Toluene diisocyanate pulmonary disease: immunopharmacologic and mecholyl challenge studies. Selected workers exhibiting clinical "sensitivity" to toluene diiosocyanate (TDI) (wheezing, cough, and dyspnea upon entering a TDI-containing area) were studied for : (1) in vitro TDI-induced leukocyte histamine release; (2) determination of cyclic 3',5' adenosine monophosphate (cAMP) levels of lymphocytes exposed to TDI; (3) effect of TDI on the isoproterenol-induced increase of lymphocyte cAMP levels: and (4) acetyl-beta-methylcholine (mecholyl) inhalation challenge. TDI did not induce histamine release from leukocytes of "sensitive" or "nonsensitive" individuals, nor were lymphocyte cAMP levels affected by in vitro TDI exposure, TDI did, however, diminish in vitro stimulation of cAMP by isoproterenol. This effect, seen with cells of "sensitive" and "nonsensitive" individuals, appeared to be dose-dependent; there were no significant differences between the two groups. When challenged with mecholyl, 7 of 10 "sensitive" but only 1 of 10 "nonsensitive" individuals showed a greater than 20% decrease in FEV1. These results suggest that TDI-induced obstructive airways disorders may be associated with altered beta-adrenergic function.


An approach to diagnosis and treatment in the migrant allergic population. An approach to allergy diagnosis and treatment in the migrant population of the United States is derived from a review of selected aspects of pollen aerobiology and the nature and distribution of allergenic plants. Pollen distribution and importance are defined and divided into four relatively homogenous geographic regions of the continental United States. Botanic relationships between pollens are then summarized, especially as they relate to the methodology and results of studies of antigenic relationships between pollens. From this information, 13 mixes of tree pollens, 12 mixes of grass pollens, and 12 mixes of week pollens are proposed which would include the pollens of major and secondary importance found in the four defined geographic regions and which would be appropriate for puncture testing. Further grouping of antigens is described for use in intradermal testing and formulating treatment mixtures. A sample skin test sheet is presented which summarizes this information in a practical format.


Ultrastructural visualization of cellular carbohydrate components by means of lectins on ultrathin glycol methacrylate sections. A method for the visualization of cellular carbohydrate components by both light and electron microscopy using lectins on glycol methacrylate sections is proposed. This method, which is an application of the lectin-peroxidase affinity technique, solves the problem of limited penetration when it is attempted to demonstrated lectins receptors within the tissue block. Following partial dissolution of glycol methacrylate from thin sections using alcohol, they are incubated successively with lectin (Concanavalin A or wheat germ agglutinin), horseradish peroxidase (Sigma, type II), 3-3' diaminobenzidine and H2O2 and then with OsO4-Different kinds of tissues and cells have been used to test the method: mouse myocardium, rat epididymis, a protozoon Gregarina blaberae and the bacterium Escherichia coli. The localization of carbohydrate residues deomonstrated by this method within the different tissues and cells is consistent with the findings from other published studies. Controls have been performed (i.e., omission of the lectin, lectin and its inhibitor) and these demonstrate the specificity of the method.


Temperature and acid concentration in the search for optimum Feulgen hydrolysis conditions. Exposure and removal of aldehyde groups during Feulgen acid hydrolysis were studied at a wide range of temperature and acid concentrations. Temperatures between 9 and 75degreesC were found to influence only the rate of the hydrolysis reaction over the entire range from high (6 M) to low (0.05 M) HCl concentrations. The temperature dependence was high, and around +5degreesC was sufficient to double the reaction rate. The influence of acid concentrations between 0.02 and 6 M was studied, and the extraction rates that determine the peak values of the Feulgen hydrolysis curve were found to depend in the same way on the (H+) concentration. A diagram is given that makes it possible to determine the time to reach the point during hydrolysis where the maximum amount of aldehyde groups are developed for a wide range of temperatures and acid concentrations. Temperatures slightly above room temperature in combination with high acid concentration is recommended for Feulgen hydrolysis.


Structural and genetic studies on chicken 7S immunoglobulin allotypes. II. Distribution of allotypes on the 7S immunoglobulin of homozygous and heterozygous chickens. We have previously reported that chicken 7S immunoglobulin (Ig) heavy (H) chain allotypes (CS-1 locus) segregate as phenogroups in F2 progeny. Specificity CS-1.1 formed a phenogroup with CS-1.4 in inbred chicken line UCD 2, and a second phenogroup with CS-1.3 in line UCD 3. To determine whether these phenogroups were formed by combinations of specificities on the same, or on separate subclasses of 7S Ig, their distribution on the 7S Ig molecules of birds homozygous for 7S Ig allotypes was analyzed by radioimmunoassay. Anti-CS-1.1 and anti-CS-1.3 alloantisera each bound more than 94% of line UCD 3 1252-7S Ig. Similar results were obtained with alloantisera to CS-1.1 and CS-1.4 WITH 125 I-7S Ig from line UCD 2. These results indicate that both phenogroups were formed by combinations of specificities present on the same H chain. Thus, each phenogroup described, probably is the product of a single structural gene which is responsible for more than 94% of the 7S Ig H chain constant regions. In F hybrids with the genotype CS-1.3, 1.3/CS-1.2, two populations of serum 7S Ig molecules were detected by direct and sequential binding analysis with specific alloantisera. One population of 7S Ig contained specificities CS-1.1 AND CS-1.3, but not CS-1.2; while the second population was exclusively the product of one parental allele. Consistent with a genetic regulatory mechanism involving allelic exclusion, no MS Ig containing allotypes produced by both alleles was detected.


Alpha-fetoprotein and human lymphocyte subpopulations. Peripheral blood lymphocytes were incubated with varying concentrations of alpha-fetoprotein and enumerated for total and ""active'' T lymphocytes, B lymphocytes, and their proliferative responses to phytohemagglutinin. No significant effect was observed on total T or B lymphocyte proportions. However, there was a dose-related increase in proportions of the so called "active" T lymphocytes. The response of human lymphocytes to phytohemagglutinin was markedly depressed. The alteration in the proportion of active T cells and the inhibition of T lymphocyte response to phyto hemagglutinin by alpha-fetoprotein occurred at higher concentrations than are present in amniotic fluid, serum of pregnant women, or serum of adults, but well within the range reached in fetal serum. The immunoregulatory role of alpha-fetoprotein is discussed.


Characterization of suppressor cells in mice bearing syngeneic mastocytoma. Suppressor cells from syngeneic P815 mastocytoma-bearing DBA/2 mice that inhibit in vitro generation of specific anti-tumor cytotoxicity were characterized. Suppressive activity was almost completely eliminated by treating suppressive spleen cells with anti-theta serum and complement. Treatment with anti-mouse lg serum and complement or with carbonyl iron did not affect their suppressive activity. When suppressive thymocytes from P815 tumor-bearing DBA/2 mice were tested for their capacity to inhibit the generation of cytotoxicity against L1210 cells, a leukemia line in DBa/2 mice, they did not affect the activity, indicating that the supressor cells in the thymocytes of P815 tumor-bearing mice are specific to the tumor. When Ficoll-Hypaque density cell separation was carried out with cytotoxic spleen cells and suppressive spleen cells from 815 tumor-bearing mice, the dense fraction was enriched for kiler cells whereas the suppressive activitty was mainly recovered in the light fraction. Therefore, killer cells and suppressor cells in P815 tumor-bearing mice are thought to be distinct populations.


Purification of a Chlamydia trachomatis-specific antigen by immunoadsorption with monospecific antibody. This study describes the isolation and partial characterization of a Chlamydia trachomatis specific antigen. A species-specific antigen of C. trachomatis (antigen-0.65) was identified by two-dimensional immunoelectrophoresis. Antiserum specific for antigen-0.65 was prepared in rabbits by immunizing with agarose-gel precipitates excised from two-dimensional immunoelectrophorograms. Purified gamma-globulins from antigen-0.65 specific serum were coupled to the N-hydroxysuccinimide ester derivative of agarose which was then used for the immunoadsorbent purification of antigen-0.65 from Triton X-100 solubilized lymphogranuloma venereum (L2/434/Bu) organisms. The isolated antigen was immunochemically pure when tested against rabbit antiserum prepared to LGV-434 organisms by using rocket and two-dimensional immunoelectrophoresis. Antigenicity was destroyed by protease treatment and heating at 56 degrees C for 30 min, but the antigen was stable to ribonuclease, deoxyribonuclease, periodate oxidation and pH extremes of 2.2 and 10.6. Polyacrylamide gel electrophoresis of purified antigen showed a major protein band with an apparent m.w. of 155,000.


Cyclophosphamide-induced specific suppression of the protective immune response to rodent malaria. Nonspecific and specific chemosuppression of the immune response to Plasmodium berghei protective antigens were investigated. Specific immunosuppression was defined operationally as the selective suppression of the protective response to the parasite in mice injected with a combination of gamma-irradiated infected mouse erythrocytes (gammaPb) and cyclophosphamide (CY) with continued responsiveness to sheep erythrocytes (SRBC). After initial treatment (gammaPb + CY), mice were injected with gammaPb in potentially immunogenic doses. These and appropriate control animals were later challenged with nonirradiated infected mouse erythrocytes. The influence of the initial treatment regimens on the protective response was evaluated by parasitemia, and mortality was observed after challenge. Specificity of suppression was measured by evaluating the ability of mice to produce antibody to SRBC. Both specific and nonspecific suppression of the protective response to malaria were noted. Initial treatment with drug alone resulted in increased parasitemia and mortality and suppression of the SRBC antibody synthesis in drug-pretreated immunized mice as compared with immunized mice not pretreated with the drug. On the other hand, suppression of the response to the parasite, but not to SRBC, in animals pretreated with gammaPb + CY was clearly greater than that induced by drug alone. Thus, animals treated with malarial antigen and cyclophosphamide develop a measurable specific immunosuppression. These studies indicate that immunity to malaria is influenced by both cyclophosphamide alone (general immunosuppression) and cyclophosphamide in combination with antigen (specific immunosuppression) in a manner analogous to other immune responses.


Antigen recognition: the specificity of an isolated T lymphocyte population. Guinea pig lymph node lymphocytes were separated into T and B cell fractions on immunoabsorbent columns. Separated cells were functionally distinct: T cells proliferated in response to ConA, PHA, soluble and alloantigen, whereas anti-Ig reagents only stimulated B cells. The in vitro proliferative response of guinea pig lymph node T lymphocytes was then shown to be highly discriminating when elicited by a series of structurally similar synthetic DNP-oligolysine antigens. Proliferation was always most extensive in response to the homologous, immunizing antigen, and less intense to cross-reacting DNP-oligolysines. Specificity of proliferation was maintained in the absence of both B lymphocytes and antibody secreting cells, suggesting that T cell recognition is not "acquired" from B cells or secreted antibody, but is a property inherent to the T cell.


Partial characterization of nervous system-specific cell surface antigen(s) NS-2. Partial biochemical characterization of several neural tissue specific antigens isolated from a murine glioblastoma cell line was accomplished by means of radioiodination of intact cells followed by immunoprecipitation of the cell lysate with a rabbit serum specific for neural tissue antigens. Polyacrylamide gel electrophoresis of the immunoprecipitate in sodium dodecyl sulfate resolved the labeled antigens into several major components: two proteins (or glycoproteins) having apparent m.w.'s of 84,000 and 120,000 and lipid associated components which may be heterogeneous. The protein and lipid associated components apparently possess independent antigenicity because after chloroformmethanol extraction the protein components can be immunoprecipitated from the aqueous phase and the lipid associated component can be immunoprecipitated from the organic phase. Despite their independent antigenicity it is not known whether the components may be noncovalently associated on the cell surface. Although some of these antigens can be isolated from brain or glioma cells (a related tumor), non can be demonstrated in lymphoid tissues or C1300 neuroblastoma cells using identical methods. Therefore, these studies confirm our previous findings concerning the specificity of the anti-NS-2 antiserum by using cytotoxicity tests.


The mononuclear cell in human blood which mediates antibody-dependent cellular cytotoxicity to virus-infected target cells. II. Identification as a K cell. Studies were carried out to determine whether the mononuclear cell in human blood which mediates antibody-dependent cellular cytotoxicity (ADCC) to herpes simplex virus (HSV)-infected target cells has surface Fc receptors which participate in the reaction. The F (ab')2 fragment of human IgG antibody was inactive both in ADCC and in complement-mediated cytolysis, but retained the capacity to neutralize infectious virus, to agglutinate erythrocytes coated with viral antigens, and to bind to the surface of virus-infected cells. Treatment of sensitized virus-infected target cells with staphylococcus protein A, which has affinity for the Fc epitope of IgG, strongly reduced their susceptibility to lysis by ADCC in a dose-dependent relationship. These findings indicate that the Fc portion of IgG antibody to the virus is necessary for cytotoxicity. Treatment of blood mononuclear cells with either heat-aggregated gamma-globulin or HSV immune complexes inhibited effector cell activity. The presence of "third party" cellular immune complexes also strongly inhibited ADCC. Adsorption of mononuclear cells to plastic surfaces coated with soluble third party immune complexes resulted in a significant reduction in effector cell activity. These findings demonstrate that the ADCC effector cell possesses surface Fc receptors which are utilized in the ADCC reaction. The presence of Fc receptors on the surface of the effector cell indicates that it is a K cell rather than a null cell.


Reduction in basal adenylate cyclase activity during the immunologic release of histamine from guinea pig lung. Cyclic AMP has been implicated in the regulation of the immunologic release of histamine from lung and other tissues and cell types. The mechanism whereby intracellular levels of cAMP are altered during mediator release was investigated. Measurements of histamine, adenylate cyclase, and cAMP phosphodiesterase activities were made in actively and passively sensitized guinea pig lung after challenge with antigen. A transient decrease in basal adenylate cyclase activity occurred which returned to control levels after histamine release. There was no change in cAMP phosphodiesterase activity determined at substrate concentrations of 1 mM and 0.01 mM. The adenylate cyclase response did not occur under the following conditions: 1) incubation of nonsensitized lung with antigen, 2) incubation of sensitized lung with antigen in the absence of extracellular calcium, and 3) incubation of nonsensitized lung with compound 48/80. These observations indicate 1) the adenylate cyclase response and the immunologic release of histamine are intimately related, and 2) the reduction in intracellular levels of cAMP which have been reported to occur during immunologic histamine release are mediated via adenylate cyclase.


Antigen-specific T cell factors: a fine analysis of specificity. The specificity of T cell factors produced in presence of synthetic polypeptide antigens was studied. Factors prepared with either one of the three antigens: poly(Tyr,Glu)-poly(DLALa)--poly(Lys), (T,G)-A--L, poly(Phe,Glu)-poly(DLALa)--poly(Lys), (Phe,G)-A--L, and poly(His,Glu)-poly(DLALa)--poly(Lys), (H,G)-A--L, successfully cooperated with B cells for antibody production to the homologous as well as to the other two immunogens. Furthermore, the activity of a (T,G)-A--L-specific factor was removed after passage through immunoadsorbents built of Sepharose coupled to: (T,G)A--L, (Phe-G)-A--L and poly(Glu)-poly(DLAa)--poly(Lys), (G)-A--L, but not to poly (DLALa)--poly(LLys),A--L. No cross-reactivity was observed between (T,G)-A--L and poly(Tyr,Glu)-poly(Pro)--poly(Lys), (T,G)-Pro--L, at the level of T cell factors, as shown using the above approaches. These results lead to the conclusion that specificity of T cell factors, although not identical, is similar to that of antibodies.


Experimental cell-mediated interstitial nephritis induced with exogenous antigens. The capacity of intrarenal injections of bovine gamma-globulin (BGG) to elicit hypersensitivity reactions was studied in guinea pigs immunized with DNP BGG or BGG immune complexes in CFA or in rats immunized with BGG in CFA. In guinea pigs it was found that heat-aggregated BGG elicited inflammatory reactions in the renal cortex, whereas soluble BGG did not. In rats only aggregated BGG was used, and this was found to be effective. The reactions were characterized by a predominantly mononuclear cell infiltrate. Transfer experiments were performed in rats and it was found that reactivity was transferrable with lymph node cells but not with serum.


Primary in vitro antibody response from human peripheral blood lymphocytes. A method for the induction of a primary in vitro antibody response from human peripheral blood lymphocytes is presented. Upon cultivation with trinitrophenyl conjugated polyacrylamide beads (TNP-PAA), an anti-TNP response can be obtained as indicated by the appearance of direct plaque-forming cells from day 5 of culture, with a reproducible peak on day 8. These plaques correspond to cells actively producing antibody of the IgM type, as shown by their inhibition by cycloheximide and by anti-human IgM serum, but not by anti-human Fc gamma serum. Their specificity for the TNP hapten can be demonstrated by the effector cell blockade phenomenon, with highly substituted TNP-human IgG. Although the anti-TNP response induced by TNP-PAA in mouse spleen cell cultures appears T independent the same response in human PBL may involve in addition the participation of T cells, since E-RFC depletion before culture led to a markedly decreased number of plaque-forming cells. A significant response could be obtained from the PBL of all of the 30 normal individuals tested. Importantly, the response was reproducible in its magnitude in the six individuals tested in at least three different experiments. Thus, the in vitro stimulation of human PBL by TNP-PAA can be proposed as a reliable test for the study of human B cell function in a specific primary antibody response.


Antigenic specificity of opsonophagocytic antibodies in rabbit anti-sera to group B streptococci. An opsonophagocytic assay has been developed which requires human polymorphonuclear leukocytes, immune serum, and complement for optimal killing of Group B streptococci. Only with all three of these components was killing of greater than 1.0 log10 of the initial inoculum achieved, using rabbit antisera directed to homologous strains of each of the five known serotypes of Group B streptococci. Titers of specific antisera which opsonized the strains and resulted in greater than 1 log 10 reduction of colony-forming units, ranged from 1:100 (serotype Ib) to 1:3200 (serotype Ia). Cross-reactions between serotype-specific sera and heterologous strains were seen in certain instances. Type Ic strain and serotype Ic antiserum demonstrated cross-reactions with types Ia and Ib which were explainable by known shared antigens among these types. The only other cross-reaction which resulted in greater than 1 log 10 reduction in colony-forming units was when unabsorbed antiserum to strain Ia was used to opsonize a strain of serotype III. Opsonization of 10 serotype III strains was demonstrated with a single type III antiserum. Killing of nine of these strains required polymorphonuclear leukocytes, complement, and antiserum, but one strain, D136C, the reference strain, could be killed (greater than 1 log 10 reduction in colony-forming units) without either complement or specific antiserum. Inhibition studies were performed utilizing large m.w. polysaccharide antigens extracted from each serotype. These antigens inhibited opsonization of homologous strains by homologous antisera with 50% inhibition points ranging between 0.5 and 4 mug.


Complement-induced histamine release from human basophils. III. Effect of pharmacologic agents. Human serum activated with zymosan generates a factor (C5a) that releases histamine from autologous basophils. Previously we have presented evidence that this mechanism for C5a-induced release differs from IgE-mediated reactions. The effect of several pharmacologic agents known to alter IgE-mediated release was studied to determine whether they have a similar action on serum-induced release. Deuterium oxide (D2O), which enhances allergic release, inhibited in a concentration-dependent fashion the serum-induced reaction at incubation temperatures of 25 and 32 degrees C. The colchicine-induced inhibition was not reversed by D2O. Cytochalasin B, which gives a variable enhancement of IgE-mediated release, had a marked enhancing effect on the serum-induced reaction in all subjects tested. The following agents known to inhibit the IgE-mediated reaction also inhibited serum-induced release at 25 degrees C: colchicine, dibutyryl cyclic AMP, aminophylline, isoproterenol, cholera toxin, chlorphenesin, diethylcarbamazine, and 2-deoxy-D-glucose. These results suggest that the serum-induced release is modulated by intracellular cyclic AMP, requires energy, and is enhanced by the disruption of microfilaments. The lack of an effect by D2O would suggest that microtubular stabilization is not required. The data can be interpreted to indicate that IgE- and C5a-mediated reactions diverge at a late stage in the histamine release pathway.


Rapid identification of monocytes in a mixed mononuclear cell preparation. A method for identifying monocytes by the "non-specific esterase" stain is described. This method is particularly applicable to mononuclear cell suspensions obtained by Ficoll--Hypaque density gradient separations and allows rapid as well as accurate determinations.


Radioimmunoassay procedure for quantitating bacterial antibody in human sera. A RIA system was developed to detect antibodies in human sera against bacteria. Sonicates of Escherichia coli and Fusobacterium polymorphum were used as antigens to sensitize plastic-coated beads; antibodies to these antigens were detected with 125I-labeled antihuman globulin. Serum antibody titers against E. coli were determined by the serial dilution method; from the results the standard curve principle was applied in determining the relative amounts of antibodies against E. coli in serum samples tested at a single dilution. The coefficient of variation of the RIA procedure was less than 10%. Serum titers obtained by the RIA and indirect immunofluorescence test were compared; RIA was more sensitive, quantitative and objective. Absorption studies, using E. coli and F. polymorphum absorbentes against E. coli and F. polymorphum. This RIA procedure offers a combination of desirable advantages; it is sensitive, specific, objective, quantitative, and easy to perform.


Purification of rabbit T-derived (Ig-) lymphocytes. Rabbit peripheral blood cells were rosetted by means of mixed agglutination technique described by Coombs et al. and the unrosetted Ig-, T-derived lymphocytes were separated in Ficoll-Triosil gradient. The cells which did not rosette in mixed agglutination reaction represented highly purified T-derived (Ig-) lymphocytes, as evidence by their response to T and B rabbit cell mitogens, their cytotoxic reactivity versus rabbit thymus lymphocyte antiserum (RTLA), and by failure to be stained with labelled anti-rabbit immunoglobulins antibodies and antibodies against allotypic specificities of the a and b series.


Antigenic relationship between human coronavirus strain OC 43 and hemagglutinating encephalomyelitis virus strain 67N of swine: antibody responses in human and animal sera. Hemagglutinating encephalomyelitis virus of swine (HEV) was adapted to growth in suckling mouse brain. Electron micrographs of HEV-infected suckling mouse brain, prepared by negative staining and thin-section techniques, exhibited typical morphological characteristics shared with other members of the Coronaviridae. The adaptation of HEV to suckling mouse brain facilitated serologic testing by the use of common host reagents and compatible animal systems. With hemagglutination inhibition, complement-fixation, and neutralization tests, an antigenic relationship was demonstrated between human coronavirus OC 43 and HEV in specific immune and hyperimmune animal sera. Children and adults with seroconversion to OC 43 antigen had diagnostic rises in titer of antibody to HEV antigens. Individuals with seroconversion to human coronaviruse 229E and B814 demonstrated antibody to HEV but not diagnostic rises in titer. Swine with titers of antibody to HEV had lower or no detectable titers of antibody to coronavirus OC 43. Although the prevalence and geometric mean titer of antibody to OC 43 were higher than the titer of antibody to HEV in every group of normal humans tested, significant differences in antibody response to coronavirus OC 43 and HEV were seen between populations that did or did not have possible contact with swine. The evidence suggested that antibody to HEV in humans probably represented a heterologous response to infection with coronavirus OC 43. However, a heterotypic response to unknown or uncharacterized strains of coronavirus cannot be excluded.


Approaches to management of the handicapped infant. A form of management which has proven helpful in a developmental intervention program for handicapped infants is described. The use of ordinal rather than normative assessments when monitoring the infant's development and when teaching families about their infants is advocated. Two cases demonstrate ways to enhance the functioning of the handicapped infant and his family.


The physician as manager. "What" and HOW" OF PRACTICE MANAGEMENT EDUCATION. Management science and application play a pivotal role in preparing physicians for effective and efficient office practice. Integration of management theory into practice management education of family physicians may be accomplished by developing and maintaining a well-organized model practice, involving residents directly in management decisions and problem solving, using a variety of resource people in and outside the model unit, and providing quantitative analysis of practice performance. After three years of development, the Family Practice Center of Akron City Hospital has instituted a practice management curriculum whereby residents become actively involved in the management and supervision of the model practice, conduct research study into management problems, and receive training and supervision as they develop leadership and organizational skills.


Antigenic relationships of alphaviruses by a simple micro-culture cross-neutralization method. A cross-neutralization study of 22 alphaviruses disclosed two major antigenic complexes and two viruses that were distinct from all the others. Cross-reactions were common but were restricted within the complexes. Sub-groupings within a complex were also shown, and some viruses proved to be indistinguishable by neutralization testing. The results generally paralleled previously reported data. Investigations were carried out, using BHK 2I cells in a micro tissue-culture system, on all available alphaviruses.


RNA-instructed DNA polymerase associated with C-type particles produced in vivo by murine myeloma cells. C-type particles secreted in vivo by MOPC-315 myeloma cells were characterized. These particles localize at a density of 1-16 g/ml in sucrose and possess a 60 to 70S RNA and an RNA-instructed DNA polymerase. Endogenous enzyme activity requires manganese and is inhibited by ribonuclease or by the omission of any of the deoxynucleoside triphosphates. The enzyme utilizes the virus 60 to 70S RNA as a template to synthesize DNA molecules which specifically hybridize to the homologous RNA.


An antigenic subunit present in rotavirus infected faeces. It has been found by immune electron microscopy that rotavirus-infected faeces, calf or human, contain an antigenic subunit associated with the inner of the two virus capsids. This internal component represents the group specific antigen for the rotavirus group and the subunit reacts with both homologous and heterologous antiserum. It can therefore be used in diagnostic tests and in this paper its use as a reagent for immunodiffusion is described.


Induction of neutralizing antibodies and immunity in vaccinated guinea pigs by cyanogen bromide-peptides of VP3 of foot-and-mouth disease virus. The specificity of guinea pig antisera against large cyanogen bromide-cleaved peptides of the virus capsid protein VP3 of foot-and-mouth disease virus type O1, strain Kaufbeuren has been characterized by double immunodiffusion, virus neutralization and protection tests. Antibodies to purified 146S particles and the cleavage peptides of VP3 showed an incomplete cross-section against VP3 peptide antigen when reacted in immunodiffusion tests, indicating that new antigenic determinants are exhibited by the peptides which are not recognized by the antiserum against the native virus proteins. The immune response against the reduced, unfolded chain constituents of VP3 was lower in comparison to that of native virus particles but still some immunological determinants remained actively capable of inducing virus-neutralizing antibodies in immunized guinea pigs.


Fits of laughter (gelastic epilepsy) with a tumour of the floor of the third ventricle. A video tape analysis. A patient with fits of laughter due to a tumorous alteration (hyperplasia) of the floor of the third ventricle is described with electroencephalographic findings indicative of focal epilepsy (complex partial seizures = psychomotor fits). The laughter is interpreted as an inborn emotional expression with structural substrate in the hypothalamus and neighboring brain. With structures remaining intact functional disorders in this area can cause epileptic phenomena with participation of the limbic system.


Intensive immunosuppression with cyclophosphamide in multiple sclerosis. Follow up of 110 patients for 2-6 years. 140 MS patients were treated with intensive I.V. cyclophosphamide immunotherapy and 110 were followed over 2-4 years. Annual relapse rate incidence was calculated over a period of 2 years before and after treatment and repeated neurological scores were made during this period. The conclusions are that 62% of the patients were stabilized during 2-4 years and that clinical improvement of the neurological signs was observed in most of the cases. It is concluded that intensive immunosuppression is able to interfere with the pathological processes involved in the pathogenesis of disseminated sclerosis.


Peripheral neuropathy with vitamin B12 deficiency. Seven patients with neuropathy associated with vitamin B12 deficiency are reported. Four of them had other signs of malabsorption aside from the abnormal Schilling test. The neuropathy was diagnosed on the basis of the whole clinical picture and the neurophysiological findings. The pathogenesis of the peripheral nerve disease is discussed in the light of the evidence in the literature.


The pathogenesis of reactive axonal swellings: role of axonal transport. The role of axonal transport in the pathogenesis of the axonal swellings which develop at the severed ends of transected axons was studied by electron microscopic (EM) autoradiography. Proteins carried by fast anterograde transport in rat sciatic nerves were labeled with [3H]-leucine or [3H]-fucose; [3H]-leucine, [3H]-fucose, and [125I]-tetanus toxin were used to label components of retrograde transport. After the labeling procedure, the nerves were ligated and 2 to 24 hours later the animals were perfused with fixatives. The axonal swellings in both the proximal and distal stumps contained densely packed membranous organelles. The transported radioactivity in the swellings was strictly associated with these organelles, particularly pleomorphic vesicles and branched tubules derived from smooth endoplasmic reticulum. The endogenous (tritiated) substances had a similar association with the organelle collections in both the proximal stump (fast anterograde transport) and in the distal stump (retrograde transport). The exogenous marker of retrograde transport (125I-tetanus toxin) had the same autoradiographic localization. These results suggest that fast anterograde and retrograde transport are very similar processes carrying predominantly membranous organelles and constituting a system of bidirectional fast transport. The accumulations of organelles in reactive swellings are interpreted as the consequence of the acute focal interruption of this system. Studies of axonal transport provide a means for investigation of the origin and fate of axonal organelles in pathologic processes.


Cerebrovascular amyloidosis with cerebral hemorrhage. More than 1400 necropsies performed on patients with  either a nontraumatic cerebral hemorrhage (400 cases) or with dementia over the age of 55 (1010 cases), or both, have been reviewed. There were 15 cases in which a cerebral hemorrhage had occurred together with cerebral amyloid angiopathy all of whom had been demented. Eight of the 15 patients were hypertensive. The 7 non-hypertensives showing only the amyloid change included two cases of "atypical" Alzheimer's disease with acute neurological features, and 5 cases of senile dementia (aged 72 to 78 years) coupled with focal neurological disorders. In the hypertensive patients, aged 67 to 86 years, with a progressive dementing syndrome and acute neurological signs, multiple ball-like hemorrhages (7 cases) and/or cerebral hematomas (3 cases) were associated with a combination of amyloid and hyalinar (hypertensive) angiopathy, often affecting segments of the same pial and cortical vessels. From these data and recent reports on lethal cerebral hemorrhage occurring spontaneously or after neurosurgical procedures in demented old people, cerebral amyloid angiopathy, which is not necessarily associated with systemic amyloidosis or severe (pre)senile cerebral degeneration, may be considered a rare but important cause of cerebral hemorrhage in the aged. The "vascular" type of presenile dementia, occasionally complicated by focal cerebrovascular lesions or bleeds, is considered a variant of Alzheimer's disease.  The mechanism leading to formation of cerebral amyloid is unknown.


Protein profile of cerebrospinal fluid in multiple sclerosis with special reference to the function of the blood brain barrier. The leucocyte count, total protein, albumin, IgG, IgA and IgM content of the cerebrospinal fluid (CSF) of 103 multiple sclerosis (MS) patients was determined. In 54 cases a simultaneous analysis of serum was also carried out. As a sign of an intact blood brain barrier the albumin concentration was normal in 76.7%. Taking into account the relative IgG quotient in CSF and serum, and the albumin and IgG concentration gradients between CSF and serum, it was possible to reveal an elevation of IgG content in CSF of MS patients in 75 and 83%, respectively. Without a simultaneous analysis of serum this was the case only in 51.5%. In MS cases with an intact blood brain barrier the values for IgA and/or IgM were slightly elevated in 11.7%. This study demonstrates analytic methods, which support the hypothesis of IgG synthesis by cells accumulating within the CNS in MS. A correlation of the laboratory results and clinical manifestation of MS was tried.


Comparison of radiolabeled bleomycins and gallium citrate in tumor-bearing mice. Radioiodinated bleomycin is a chemically stable radiopharmaceutical that can be prepared with high specific activity using 123I. Its pharmacokinetics were compared with those of 99mTc,- 111In-, and 57Co-bleomycin, and 67Ga citrate in mice bearing a transplanted KHJJ tumor. The in vivo kinetics and stability of 123I- and 57Co-bleomycin were similar: both were acceptable, although not equivalent, tags for bleomycin and, along with 67Ga citrate, both had biologic properties suitable for tumor detection. Both 99mTc- and 111In-bleomycin dissociated rapidly in vivo and hence do not represent legitimate tags for bleomycin. However, 111In-bleomycin may have tumor-localizing properties related to its biochemical properties after the indium and chelate separate in vivo. Iodine-123 is superior to either 57Co or 55Co. Tumor-to-blood and tumor-to-liver ratios were higher for I-bleomycin than for 67Ga or Co-bleomycin. The nearly ideal nuclear properties of 123I should complement the biologic properties of bleomycin and lead to a useful tumor radiodiagnostic agent.


A radioimmunoassay for bleomycin.

A radioimmunoassay for bleomycin. A radioimmunoassay for bleomycin, suitable for monitoring serum and urine drug levels, has been developed. Antisera were obtained from rabbits immunized with a conjugate of bleomycin and human serum albumin.Bleomycin labeled with 57Co was used as the tracer. Antibody-bound and free bleomycin were separated by precipitation with polyethylene glycol. The assay could determine bleomycin levels down to 0.025 mug/ml. The assay was precise, with a coefficient of variation of 2.8% Other drugs likely to be administered in combination with bleomycin did not interfere with the radioimmunoassay.


Microprobe and microradiographic studies of hyalin bodies in odontogenic cysts. Microprobe analysis of Araldite embedded sections of hyalin bodies revealed the presence of sulphur, chlorine, calcium and in some cases iron. The results have been compared with those obtained from control tissue sections of human heel skin, a thrombus occluded vessel and mineralized spherules in a dental follicle. Microradiographic studies showed that the density of hyalin bodies increased progressively towards the core. Isodensitracing confirms the laminar configuration of hyalin bodies as seen electron microscopically. The findings conform with the hypothesis that hyalin bodies originate as an epithelial secretion.


Hyalin material bounding dystrophic calcification in the epithelial lining of  odontogenic cysts. Areas of dystrophic calcification present in the epithelial lining of two apical periodontal cysts have been shown to exhibit an outer layer of hyalin material. Similar calcific areas in the connective tissue walls do not show hyalin boundaries. Hyalin material has been found around muscle fibers present in the epithelial lining of a residual dental cyst. It is believed that the hyalin material is secreted by the epithelial cells and these observations are considered to be supporting evidence that hyalin bodied arise as an epithelial secretion.


Identification of diacetylmorphine metabolites in humans. With the techniques of column chromatography, TLC, and GLC, morphine, 6-acetylmorphine, normorphine, morphine 3-glucuronide, 6-acetylmorphine 3-glucuronide, and normorphine glucuronide were identified as metabolites of diacetylmorphine (heroin) in the urine of humans administered 10 mg iv/70 kg body weight.


Effects of halothane on ganglionic discharges. The effects of halothane on ganglionic transmission were studied by recording extracellular potentials from the postganglionic nerve of the isolated hamster stellate ganglion. Halothane, at concentrations greater than 0.1 mM, decreased the potentials evoked by preganglionic stimuli at 0.2 Hz. Halothane also blocked discharges elicited by 1,1-dimethyl-4-phenylpiperazinium, a selective nicotinic agonist, and discharges elicited by the nicotinic actions of exogenous acetylcholine. Repetitive preganglionic stimulation (30 Hz, 5 seconds) in the presence of nicotine (10(-3) M), or hexamethonium (10(-3) M), evoked asynchronous discharges in the postganglionic nerve. These discharges were suppressed by low concentrations of atropine, and were probably due to the muscarinic actions of neurotransmitter. Halothane depressed these discharges at approximately the same concentration that it depressed the compound action potential elicited by low frequency preganglionic stimulation in the untreated ganglion. Halothane had no effect on the discharges elicited by 4-(m-chlorophenylcarbamoyloxy)-2-butynyltrimethylammonium chloride (McN-A-343), a selective muscarinic agonist, or the discharges elicited by the muscarinic actions of acetylcholine. These results are most readily explained by hypothesizing that halothane acts at two sites in the ganglion. It appears to depress the postsynaptic response to the nicotinic actions of the neurotransmitter, acetylcholine. Also, it probably depresses transmitter release from the presynaptic nerve endings during repetitive stimulation.


The viscosity of mammalian nerve axoplasm measured by electron spin resonance. 1. The microviscosity of the axoplasm of can sciatic nerve was determined  by an in vitro electron spin resonance (e.s.r.) method using the spin label tempone. To identify the spin label signal as one arising only from within the axoplasm, Ni2+ was used as a line broadening agent. In one series of experiments in nerves with sheath intact the Ni2+ ion was shown to eliminate the tempone signal arising from the surface water, and in another series of experiments, with the sheath slit, to eliminate the signal from the extracellular space as well. 2. A microviscosity of less than 5 centipoise (cP), i.e. 5x that of water, was determined for the axoplasm. Changes in the viscosity of the nerve axoplasm as a function of temperature over a range of 38 degrees down to 2 degrees C were seen to follow closely the viscosity change found for a water solution. 3. The microviscosity of nerve axoplasm and its change with temperature were related to axoplasmic transport of material in nerve fibres. The results were used to exclude a large increase in viscosity at low temperatures as the cause for the cold-block of fast axoplasmic transport.


A symposium on canine biliary fever. Paper 1: relapses and immunity in canine babesiosis. Canine and bovine babesiosis are compared with particular reference to the occurrence of relapses and some immunological aspects of the diseases. Intact dogs resemble splenectomized cattle in respect of the relatively frequent occurrence of clinical relapses of babesiosis. The possible reasons for this are discussed. Attention is drawn to the fact that a sterile immunity of variable duration follows on auto sterilization of some Babesia infections and that antigenically difference strains of the parasite occur in the field.


Levels of alpha-fetoprotein in amniotic fluids of mice (curly-tail) with neural tube defects. Mutant curly-tail mice are genetically predisposed to produce offspring with neural tube defects. Estimation of alpha-fetoprotein in the amniotic fluid of fetuses of these mutants has shown that the levels are raised in fetuses with exencephaly and open spina bifida. This suggests that these mice are a valid model for studies of the aetiology and genesis of neural tube defects in man.


Inclusion of satellites in an 18/21 translocation chromosome shown by ammonical-silver staining (sat-banding) in case of partial trisomy 18. A male infant with a partial trisomy 18 and a 46,XY, --21, t(18;21)(18qter replaced by 18q12::21 p13 replaced by 21 qter) chromosome complement is described. The translocation chromosome is of special interest because it includes the satellites of chromosome 21. This was shown by differential satellite staining with the ammoniacal-silver technique.


Antigenic relationship between human and simian rotaviruses. The simian rotavirus, SA 11, and the murine rotavirus, EDIM, were investigated for antigenic relatedness to the human rotavirus, by immunoelectron-microscopy. These studies led to the recognition of two types of rotavirus antibody. One agglutinated "rough" virus particles only and was group-reactive; it appears to be widely distributed in various animal species, including human infants. The second antibody agglutinated "smooth" virus particles and was more species-specific, demonstrating only a one-way cross-reaction between the simian and human viruses; it was found only in convalescent-phase human sera and in hyperimmune rabbit sera and is probably protective. The simian rotavirus is easy to propagate in primary cell culture and in cell lines and should prove useful for serodiagnosis of human gastroenteritis. It may be a candidate for immunoprophylaxis.


Evaluation of methods for the determination of Q and K antigens of an 02:K1(L) strain of Escherichia coli. Tests made on ten colonies from a strain of Escherichia coli O2:K1 demonstrated that bacterial agglutination tests were reliable for identifying the O antigen of serogroup O2 but were unreliable for identifying the K1 antigen. The granular nature of K agglutination was not a reliable characteristic of the L type of K antigen. In contrast, indirect haemagglutination, immunodiffusion and immunoelectrophoresis tests with bacterial extracts gave consistent results with all colonies. The polysaccharide K1 antigen formed a long anodic precipitation line with two peaks, indicating its heterogenous nature, and partial fusion of this line with the O-antigen precipitation line suggested the presence of common serological determinants. In addition, a heat-labile protein antigen, possibly another K antigen, was identified by indirect haemagglutination tests and may have produced a short anodic precipitation line. The results also showed that the K1 antigen was still produced after storage of a culture for 12 years on Dorset-egg medium.


Formation of ion channels by a negatively charged analog of gramicidin A. O-pyromellitylgramicidin is a derivative of gramicidin in which three carboxyl groups are introduced at the terminal hydroxyl end of the peptide. Experiments with artificial lipid membranes indicate that this negatively charged analog forms ion-permeable channels in a way similar to that of gramicidin. If O-pyromellitylgramicidin is added to only one aqueous solution, the membrane conductance remains small, but increases by several orders of magnitude if the same amount is also added to the other side. In accordance with the dimer model of the channel, the membrane conductance under symmetrical conditions is proportional to the square of the aqueous concentration of O-pyromellitylgramicidin over a wide range. The ratio lambdaPG/lambdaG of the single-channel conductance of O-pyromellitylgramicidin to that of gramicidin is close to unity at high ionic strength, but increases more than fivefold at smaller ionic strength (0.01 M). This observation is explained in terms of an electrostatic effect of the fixed negative charges localized near the mouth of the channel. In a mixture of O-pyromellitylgramicidin and gramicidin, unit conductance steps of intermediate size are observed in addition to the conductance steps corresponding to the pure compounds, indicating the formation of hybrid channels. Hybrid channels with preferred orientation may be formed if small amounts of gramicicin and O-pyromellitylgramicidin are added to opposite sides of the membrane. These hybrid channels show a distinct asymmetry in the current-voltage characteristic.


Multiple antigens as marker substances in germinal tumors of the testis. Germinal cell tumors of the testis were studied for the presence of several tumor-associated antigens. Antisera were produced by immunizing rabbits with the purified antigens of alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and hepatoma ferritin. Indirect immunofluorescence on embryonal carcinoma with or without teratoma components demonstrated that their staining range was 1--60 per cent with antiserum against AFP, 0--16 per cent with anti-serum against ferritin, and 0-40% with antiserum against CEA. Ferritin-like substances have not been described previously in germinal tumors of the testis. No staining was seen with seminoma cells or benign testicular tissues. Raised serum levels of AFP and the ferritin-like substance were related both to the presence of tumor and to dissemination of the disease. CEA occurred transiently in serum. Eleven patients with primary tumors had no antigen in their sera and have all survived, but the median survival time for 8 patients with either antigen in preoperative sera was 12 months. Five patients with advanced tumor in whom neither AFP nor ferritin was detected had a much longer median survival time (58 mo) than did 13 patients with high levels of serum AFP or ferritin (12 mo). The presence of either AFP or ferritin in sera of patients with primary or advanced disease, therefore, seemed to indicate a poor prognosis. The determination of both substances in serum may be useful in the follow-up of patients with certain types of testicular tumors. The proportion of cells containing each antigen varied in the different tumors. Similarly, each antigen could occur independently in serum. This suggested that certain germ cell tumors contained subpopulations of cells, which differed in their production and release of the antigens studied.


Viral reverse transcriptase suppression associated with erythroid differentiation of Friend leukemia cells. The Friend erythroleukemia cell line T3-C12, which produces Friend murine leukemia virus (F-MuLV) and can be induced to synthesize hemoglobin by dimethyl sulfoxide (DMSO), was monitored for viral RNA-dependent DNA polymerase reverse transcriptase (RT) activity. The amount of viral 60-70S RNA released from DMSO-treated cells was unaffected or increased compared to that from control cells, while RT activity from treated cells was decreased. Accordingly, the specific activity in F-MuLV from DMSO-treated cells expressed as RT/70S RNA was decreased to 8% of the control activity. The 5-bromo-2'-deoxyuridine added to cultures containing DMSO reversed the differentiation process, and the F-MuLV thus treated did not exhibit the reduced RT activity normally observed in DMSO-treated virus. Cell-free F-MuLV incubated with and without DMSO showed the same RT activity, indicating that DMSO itself did not inhibit RT activity. However, when F-MuLV-containing pellets from control and DMSO-treated culture fluids were mixed, there was marked inhibition of the control RT activity, suggesting that RNase hybrid activity was stimulated or that an inhibitor was produced. Assays of F-MuLV-RNase hybrid released from control and DMSO-treated cells showed no difference in activity, indicating that a specific inhibitor of RT was produced or activated. Additions of certain nucleotide triphosphates to RT incubation mixtures did not result in any stimulation of RT activity in DMSO-treated F-MuLV, suggesting that phosphatase was not responsible for the observed inhibition. The results suggested that DMSO treatment of T3-C12 cells caused a reduction in viral RT activity by stimulating the production of an inhibitor, the nature of which is unknown.


The role of adjunctive nephrectomy in patients with metastatic renal cell carcinoma. The results of therapy for 78 patients with disseminated renal cell carcinoma are evaluated. Symptoms related to the primary tumor were noted in only 28 per cent of the patients and were not difficult to manage in those patients not undergoing nephrectomy. Adjuctive nephrectomy, therefore, is a more appropriate term than palliative nephrectomy when referring to removal of the primary tumor as part of an aggresive combined therapeutic approach. Of patients receiving an adjunctive nephrectomy those with osseous metastases only had a better 1-year survival rate (36 per cent) than those with metastases to other sites (18 per cent). Complete regression of metastases was noted in 12 per cent of patients treated with medroxyprogesterone acetate and adjunctive nephrectomy. The role of adjunctive nephrectomy combined with embolic infarction, hormonal therapy, chemotherapy and/or immunotherapy is discussed.


An improved non-intubated cutaneous ureterostomy technique for the normal and dilated ureter. Cutaneous ureterostomy is a simple procedure to perform but is attended by high morbidity owing to recurring abscesses, strictures and stenosis of the stoma. An improved technique applied to the diversion of 4 normal renal units and 3 dilated ureters is described. We have not experienced the complications mentioned in previous studies and none of the patients has required ureteral intubation in this small series with a 3-year followup.


A study of transrectal aspiration biopsies of the prostate, with particular regard to prognostic evaluation. We studied 182 transrectal aspiration biopsies of the prostate primarily to evaluate the reliability of cytologic grading as a method to determine the biological malignancy of prostatic cancer. The technique and cytologic grading are described in detail. All patients with clinical cancer of the prostate were assessed as to whether the disease was stable or progressive. A comparison was made between the clinical assessment and the cytologic grading of the prostatic material. The results show that the patients whose disease was assessed as stable tended to have a high cytologic grade and those assessed as progressive had a low cytologic grade. The importance of this method as a possible prognostic indicator is emphasized.


Rapid method for Tzanck preparations.

Rapid method for Tzanck preparations. Use of the Paragon Multiple Stain for Frozen Sections (PMS) for Tzanck preparations of herpetic lesions has several distinct advantages over procedures previously described; the method is rapid, simple, inexpensive, and results in hematoxylin-eosin-like staining. This enables a diagnosis to be made from a single, affected cell.


[Sinus extrasystole].

[Sinus extrasystole]. A rare clinical case is described pertaining to a 70-year-old female patient with atherosclerotic cardiosclerosis accompanied by a combination of sinus and ventricular extrasystole. The importance of rhythmography and the criterion of allorhythmia is emphasized as being he indices that help to improve the diagnosis of sinus extrasystole.


[Lysozyme and beta2-microglobulin in cerebrospinal fluids from healthy children and in children with diseases of the central nervous system (author's transl)]. Lysozyme is absent from normal cerebrospinal fluid (C.S.F.) and in C.S.F. from children with viral meningitis. Appreciable amounts of lysozyme were noted in C.S.F. from children with bacterial meningitis (0.23 +/- 0.14 mg/100 ml) and cerebral convulsions (0-0.82 mg/100 ml). The C.S.F.-lysozyme content is a sensitive indicator for bacterial meningitis and important in the differential diagnosis between viral and bacterial meningitis. The beta2-microglobulin content of C.S.F. in healthy children was 0.11 +/- 0.05 mg/100 ml; in children with viral meningitis 0.20 +/- 0.06 mg/100 ml and in children with bacterial meningitis 0.44 +/- 0.17 mg/100 ml. Children with cerebral convulsions had also a rise in C.S.F. beta2-microglobulin.


The antigen-induced degranulation of basophil leukocytes from atopic subjects studied by electron microscopy. Suspensions of washed leukocytes were prepared from the blood of atopic subjects and incubated with diluent, ragweed antigen E or rye grass group I antigen. Histamine release into the suspending medium was measured and directly correlated with changes in the ultrastructure of basophil leukocytes from the same tubes. Incubation of leukocytes with either diluent or an antigen to which the donor was not hypersensitive caused no significant histamine release and the morphology of the basophils was unaltered. By contrast, incubation of leukocytes with an intigen to which the donor was hypersensitive caused substantial histamine release and characteristic morphologic changes in the basophils, many of which underwent exocytotic degranulation. Degranulated human basophils showed the following features: (1) an irregular surface, to which platelets and leukocytes were often adherent; (2) reduction in the number of basophilic granules; (3) residual granular material, both in exocytotic cavities and at the cell surface; (4) coated vesicles and cisternae of smooth endoplasmic reticulum, frequently related to the plasma membrane at sites of exocytosis; (5) thin membrane-bounded granules appeared unaltered; (6) no consistent change was observed in centrioles, microtubules, 90 A filaments, mitochondria, or multivesicular bodies, and degranulated basophils appeared ultrastructurally viable; (7) in reaction cell suspensions, nondegranulated basophils often showed a more active contour than control cells; both reacting but nondegranulated basophils and degranulated basophils sometimes showed localized filamentous webs at their periphery.


Changes in blood viscosity and plasma proteins in carcinoma. Blood viscosity and plasma protein concentrations were measured in 31 patients with a variety of visceral carcinomas. The mean whole blood viscosity was not elevated over normal controls because of a significantly lowered mean hematocrit. However, when hematocrit was eliminated as a variable by adjusting the hematocrit to 45%, the mean whole blood viscosity was significantly elevated in the group with carcinoma. Both the plasma viscosity and the tendency for red cell aggregation were significantly elevated. Since blood is a non-Newtonian fluid, and its viscosity increases markedly at low shear rates, these rheological abnormalities would be most important at the low shear rates characteristic of the venous circulation. It is suggested that these abnormalities in blood viscosity and red cell aggregation may be contributing to the high incidence of venous thromboembolism seen in patients with neoplastic.


Staged surgical management of pulmonary atresia with diminutive pulmonary arteries. A particular problem in treatment is presented by patients who have atresia of the pulmonary valve and ventricular septal defect but whose pulmonary arterial tree is extremely diminutive. The pulmonary blood flow results from naturally occurring large bronchial collateral arteries. In the experience reported, satisfactory palliation was provided for all 3 patients in whom right ventricle--to--pulmonary artery continuity was constructed by placing a pericardial patch graft during open-heart operation. The ventricular septal defect was left unrepaired. Early evidence supports the hypothesis that, besides providing palliation of cyanosiis, the procedure may allow progressive enlargment of the hypoplastic pulmonary arteries. This offers hope that later second-stage completion of total repair, involving closure of the ventricular septal defect and ligation of any remaining large bronchial collateral arteries, may become feasible.


Conduit repairs of transposition complexes. A report of 14 cases. Of 14 patients with transposition complexes undergoing conduit repairs, 10 had complete transposition of the great arteries (TGA) and 4 double-outlet right ventricle. All 14 had ventricular septal defect (VSD). Ten had pulmonary stenosis, one had an atrial septal defect, and one had patent ductus arteriosus. The ages of the patients ranged from 13 months to 18 years. Six patients were treated with nine palliative operations: four systemic-pulmonary artery shunts, three atrioseptectomies, and two pulmonary banding procedures. Four patients died immediately after the operation. Among the 10 operative survivors, there were no late deaths during the follow-up periods from 5 months through 6 years. Review of the factors influencine the early operative results has stressed the importance of correct timing of operation with or without palliative treatment, increased surgical experience, and the critical evaluation of intracardiac anatomy.


Rh sytem. Genetics and function.

Rh sytem. Genetics and function. Little is known about the exact genetic control of the Rh system. The Rh antigen is a large protein molecule carrying many antigenic determinants. The structural genes controlling its production comprise a gene complex that has probably evolved by unequal crossover and mutation at the duplicated points. No convincing evidence for crossing-over within the gene complex has been found since the discovery of Rh. Studies of Rhnull families provide evidence for unlinked control genes that influence the ability of the structural Rh genes to function. It was hoped that the Rhnull bloods would provide information to establish the function of the Rh antigen, because the antigen appears to be necessary to maintain the integrity of the red cell membrane. However, the abnormalities of the Rhnull cells (increased Na+K+ pumps) have not been tied directly to their lack of Rh antigens.


[Erythrasma of the nails].

[Erythrasma of the nails]. We have studied 17 cases of pseudomycotic onychoses. This condition is frequently seen in the toe nails with the clinical aspect of hyperkeratosis of the nail bed and onycholysis. The Giemsa stained preparations have been performed with the clinical material previously heated in a 40% OHK solution and washed out with distilled water by centrifugation. The microorganism has similar or identical characteristics to those of the agent of erythrasma of the folds. Its morphology and physiological characteristics are comcon to "Corynebacterium" and "Nocardia". It is a gram positive, acid-fast organism with tendency to produce filaments with short lateral branches and fragmentation spores. Indirect inmunofluorescence identifies microorganisms present in the clinical material and that obtained in cultures.


Comparison of cromoglycate (cromolyn) and theophylline in controlling symptoms of chronic asthma. A collaborative study. 28 children with chronic asthma (15 in Denver and 13 in London) completed a 12 wk double-blind trial of treatment with sodium cromoglycate (cromolyn sodium), theophylline, and a combination of both. The three regimens were administered, each for 4 wk, in random sequence as part of a collaborative investigation of the relative efficacy of the two antiasthmatic agents. Cromoglycate was administered by inhalation in standard doses of 20 mg q.i.d. Theophylline dosage was individualized with the assistance of serum-theophylline measurements and averaged 6 mg/kg/dose q.i.d. (range 3-8--8-5 mg/kg/dose). Peak expiratory-flow rates measured twice daily on all patients averaged 75% of that predicted during cromoglycate administration, 79% during theophylline, and 81% during the combined-drug regimen (P less than 0.05). Patients had an average of 59% of days free of symptoms while on cromoglycate and 71% of days symptom-free when on both the theophylline and the combination regimens (P less than 0.025). None of the 13 patients whose asthmatic symptoms were previously controlled with cromoglycate was unable to complete the 4 wk trial with theophylline alone; 1 patient whose symptoms had been previously controlled with theophylline twice developed severe asthmatic symptoms while receiving cromoglycate, and he had to be withdrawn from that study period. No significant differences in adverse effects of the medication were observed during the 12 wk trial.


Aetiology of juvenile-onset diabetes. A prospective study. 110 people in whom insulin-dependent diabetes developed when they were less than 30 years old were studied as soon as possible after diagnosis. There was evidence for clustering of cases with BW15-positive phenotypes during the winter peak (1976) but not during the autumn peak (1975). Subjects who were BW15-positive, and in particular those who were both B8 and BW15-positive, had higher neutralising antibody titres to Coxsackle virus types B1-B4 58% of cases had islet-cell antibodies (I.C.A.), but the presence of I.C.A. was not correlated with HLA phenotypes or viral antibody titres. In 41 subjects (37%), who gave a definite history of antecedent illness, evidence indicated that this was a precipitating infection and not the initiating event producing islet-cell damage. Nearly half the subjects had had diabetic symptoms for more than 4 weeks before diagnosis.


Severe steroid-responsive nephrosis associated with hypersensitivity. Sensitivity to cow's whole milk investigated in six patients with the idiopathic nephrotic and an elemental diet was given. After proteinuria had decreased to less than or equal to 500 mg/24 hours on consecutive days patients were challenged with cow's milk. This resulted in the return of significant proteinuria, oedema, and decreased urine volume together with a decrease in serum-IgG concentrations in four patients. Acute alteration of plasma C3 complement component accompanied milk challenge in all 6 patients. There were no consistent alterations in other immunoglobulin concentrations. Intradermal skin testing with cow's milk extract was positive in all patients. These results suggest that in some individuals clinical and biochemical manifestations of the nephrotic syndrome of childhood may be related to hypersensitivity of food products.


Transitory decrease in platelet monoamine-oxidase activity during migraine attacks. A highly significant decrease in platelet monoamine-oxidase activity has been observed in migrainous subjects during a migraine attack compared with activity outside an attack. The effect did not derive from drugs commonly used in migraine therapy.


An early pregnancy factor detected in human serum by the rosette inhibition test. Modification of maternal lymphocyte activity has been demonstrated early in pregnancy by the rosette inhibition test. Normal human lymphocytes showed a similar depression of activity after incubation in serum from pregnant women, indicating that the response was caused by a serum factor. This early pregnancy factor has been differentiated from other substances which appear later in pregnancy and which may also be involved in the suppression of the maternal response. The results of this investigation suggest that the early pregnancy factor may be necessary for the continued viability of the early embryo.


A potentially toxic drug interaction between pethidine (meperidine) and phenobarbitone. The concomitant administration of pethidine (meperidine) and phenobarbitone results in enhanced sedation in a patient previously tolerant of pethidine. A complete analysis of pethidine kinetics and metabolism was performed in this patient, in four additional patients undergoing similar treatment but not receiving phenobarbitone, and in a volunteer after placebo and phentobarbitone pretreatment. The results indicate that phentobarbitone enhances the production of the toxic metabolite norpethidine by increasing N-demethylation.


Do drugs acting on the nervous system affect cell proliferation in the developing brain. Drugs which alter the balance of neurotransmitter activity may, while failing to cause gross structural malformations of the brain, produce long-lasting functional disturbances if given when the brain is developing. Subtle anatomical changes may underlie such disturbances; reserpine has been shown to interfere with cell proliferation in the brain of suckling rats, and long-term alterations in behaviour reported after treatment with reserpine may be related to this effect of the drug. Neurotransmitters, apart from their conventional role, may also function as neurohumours and be involved in the regulation of cell proliferation in the nervous system. Thus drugs influencing central neurotransmitter activity, such as phenothiazines and adrenergic agonists and antagonists, which in clinical practice are often given to pregnant mothers, may affect the developing brain through mechanisms similar to those reported for reserpine. More experimental information is needed about the influence of such drugs on cell proliferation in the brain, and about their "behavioural teratogenicity".


Virus-like particles in winter vomiting disease. In an outbreak of winter vomiting disease affecting both pupils and staff in a primary school, virus-like particles were found in 7 out of 8 faecal specimens examined by electron microscopy. The particles measured 26 nm in diameter and had a buoyant density of 1-38--1-40 g/cm3 in caesium chloride. They could not be cultured in tissue-culture or organ-culture. In immune electron microscopy tests the particles appeared to differ antigenically from the Norwalk and Hawaii agents. Two out of three patients examined more than one month after their illness were still excreting the particles.


The mast cell/heparin paradox.

The mast cell/heparin paradox. Purified heparin extracted from tissues rich in mast cells remains the ideal rapid anticoagulant in clinical practice. Nevertheless, there are grounds for doubting that an injection of commercial heparin corresponds to the release of heparin-containing granules from the mast cells. The metachromatic granule contains much more than heparin--chondroitins, heparitins, histamine (in some species 5-hydroxytryptamine also), and a variety of enzymes. Shed granules, released by trauma of any kind, are ingested by connective-tissue phagocytes and are digested. Commercial heparin, on the other hand, is taken up by cells of the reticuloendothelial system and is stored there. This apparent paradox can be resolved by conceding that the mast cell is primarily concerned with the connective tissue, as Ehrlich saw it a century ago, and that, within these broad limits, it can express itself in a variety of ways.


The preregistration year: Chaos by consensus. A questionnaire was sent to all preregistration housemen who had graduated from the University of Birmingham in July, 1975. The results showed much dissatisfaction with the workings of the houseyear--specifically, with the long, sleepless hours of work, the almost negligible educational role of the year, the lack of time for human contact with patients, and the tendious, repetitive nature of the work. It is proposed that a shift system, which wound seem to be acceptable to most housemen, would solve many of these problems, and result in a better deal for both doctors and patients.


Implications of combined treatment with 'Madopar' and L-deprenil in Parkinson's disease. A long-term study. In a clinical trial the effect of L-deprenil, a selective irreversible inhibitor of monoamine oxidase (M.A.O.) "type B" in potentiating the anti-kinetic properties of levodopa has been investigated in 223 patients. Both drugs were given orally, levodopa as 'Madopar' (levodopa plus the peripherally acting decarboxylase inhibitor, benserazide) 250 mg three times daily and L-deprenil 5 mg once or twice daily. The addition of L-deprenil to madopar therapy resulted in a statistically significant (P less than 0-01-0-001) reduction in patients' functional disability on average within 60 min after a single oral dose and lasting for 1 to 3 days. Dyskinesia occurred in 16 patients, psychosis in 14, orthostatic hypotension in 5, and nausea in 8. Reduction of the L-deprenil dose to 5 mg in these patients eliminated some of the side-effects. Two-thirds of the patients with side-effects had suffered from parkinsonism for between 7 and 15 years. 14% of the patients failed to respond to madopar-deprenil therapy. It is suggested that L-deprenil may act through inhibition of brain M.A.O. as well as by a psychostimulant effect similar to that of amphetamine which occurs through the release of dopamine. Both mechanisms would make more dopamine available at dopamine receptor sites.


A new type of penicillin resistance of Staphylococcus aureus. Penicillin--"tolerant" Staphylococcus aureus strains are resistant to the lethal action of penicillins, but are inhibited by normal (low) concentrations. They are deficient in autolytic enzyme activity which appears to be necessary for bacteriolysis and the lethal action of penicillins. This "deficiency" is caused by a large excess of an inhibitor of autolysin. Seven such tolerant strains have been isolated from blood, bone, or sputum of patients who responded poorly to penicillin treatment of endocarditis, osteomyelitis, or staphylococcal pneumonia. These isolates were of different phage-types, and most showed cross-tolerance to the killing action of cephalosporins or vancomycin, antibiotics to which they were sensitive (inhibited). They were killed at normal rates by gentamicin, cycloserine, and rifampicin. Population analysis indicated that the proportion of tolerant organisms within a resistant strain is 7% or less; their ability to inhibit autolytic activity within their own and neighbouring cells appears to account for the net decreased autolytic activity of the entire strain; 44% of the bacteraemic strains studied showed penicillin tolerance. Tolerance is thus a common, clinically important form of penicillin resistance, that differs from previously described forms of pencillin resistance, that due to beta-lactamase, and that due to "intrinsic" (e.g., methicillin resistance) mechanisms.


Early morning migraine. Nocturnal plasma levels of catecholamines, tryptophan, glucose, and free fatty acids and sleep encephalographs. Nocturnal plasma catecholamine, tryptophan, glucose, and free fatty acid levels have been measured in 19 subjects who regularly awoke from sleep with migraine. All-night polygraphic sleep recordings were also made. 13 subjects were studied on a second occasion allowing within-subject control as well as group comparison. Plasma total catecholamine and specifically plasma-noradrenaline levels were significantly higher in the three hours before the subjects awoke with migraine. No differences were found in plasma tryptophan, glucose, insulin, and free fatty acid levels in the migraine/no-migraine categories. Waking with migraine occurred significantly more often from rapid-eye movement (REM) sleep. There were no other differences in sleep pattern in the migraine/no-migraine categories.


Previous pregnancy as a protective factor against death from melanoma. Examination of the case-records of women presenting to the Melanoma Unit at Sydney Hospital over the period 1961-71 has shown that women with pregnancies before the development of melanoma had a better survival-rate from melanoma than women without previous pregnancies. The known presence of fetal antigens on melanoma cells and immunisation against fetal antigens during pregnancy suggest an immunological explanation for these results. Exposure to fetal antigens during pregnancy may protect against the dissemination of melanoma cells bearing similar fetal antigens and thus increase the survival-rate. The incidence of melanoma in males and females was approximately equal, which suggests that immune responses to tumour-associated antigens may be more effective in preventing spread of tumours than in preventing their occurrence.


Radiolabelled anti-human fibrin antibody: a new thrombus-detecting agent. Rabbit anti-human fibrin globulin (A.F.G.) was labelled with iodine (131I) and used as a thrombus-detecting agent. 131I-A.F.G. labelled thrombi were displayed by means of a gamma scintillation camera. Normal subjects and patients with thrombophlebitis of legs, acute fibrin depositions other than thrombi, and chronic varicosities were examined. The 131I-A.F.G. technique detected both formed thrombi and those that were forming and could discriminate between acute thrombosis and chronic varicosities. Thrombophlebitis and extravascular fibrin depositions were best demonstrated between 24 and 27 hours of 131I-A.F.G. injection. Radiolabelled A.F.G. in normal veins and chronic varicosities was best displayed within 6 hours of injection.


Silicon, fibre, and atherosclerosis.

Silicon, fibre, and atherosclerosis. A logical argument can be made for the hypothesis that lack of silicon may be an important aetiological factor in atherosclerosis. As silicic acid or its derivatives, silicon is essential for growth. It is found mainly in connective tissue, where it functions as a cross-linking agent. Unusually high amounts of bound silicon are present in the arterial wall, especially in the intima. Various kinds of dietary fibre have been reported to be effective in preventing experimental models of atherosclerosis, reducing cholesterol and blood-lipid levels, and binding bile acids in vitro. Exceptionally large amounts of silicon (1000 to 25 000 p.p.m.) were found in fibre products of greatly varying origin and chemical composition which were active in these tests. Inactive materials, such as different types of purified cellulose, contained only negligible quantities of the element. It is concluded that silicate-silicon may be the active agent in dietary fibre which affects the development of atherosclerosis. Two out of three samples of bran also had relatively low levels, which could explain why bran does not lower serum-cholesterol. The fact that atherosclerosis has a low incidence in less developed countries may be related to the availability of dietary silicon. Two instances are presented where silicon is reduced by industrial treatment: white flour and refined soy products were much lower in silicon than--their respective crude natural products. The chemical nature of silicon in different types of fibre is not known. It could exist as orthosilic acid, polymeric silicic acid, colloidal silica (opal), dense silica concentrations, or in the form of organically bound derivatives of silicic acid (silanolates). Possible mechanisms of action are discussed.


Incidence and severity of anaphylactoid reactions to colloid volume substitutes. All available colloid volume substitutes carry the risk of anaphylactoid reactions. In a multicentre prospective trial, 69 cases of anaphylactoid reactions have been observed among 200 906 infusions of colloid volume substitutes. The frequency of severe reactions (shock, cardiac and/or respiratory arrest) was 0-003% for plasma-protein solutions, 0-006% for hydroxyethyl starch, 0-008% for dextran, and 0-038% for gelatin solutions.


Diabetes: The quest for basal normoglycaemia. Diabetes is an endocrine deficiency disease, a logical treatment of which is hormone replacement therapy. Many patients who are thought to be controlled by diet alone continue to have high plasma-glucose levels. As the rise in the basal plasma glucose concentration is the predominant glucose abnormality of diabetes, treatment should be aimed primarily at producing basal normoglycaemia. 18 mild, maturity onset diabetics have been treated with a basal insulin supplement provided by single daily injections of insulin zinc suspension (crystalline) 'Ultralente'. Overnight basal normoglycaemia has been obtained with markedly reduced plasma-glucose levels during the day. Plama-triglyceride levels have become normal in most patients. The required insulin dose need not be determined empirically, but can be calculated from the basal plasma-glucose level and the degree of obesity. There is minimum risk of hypoglycaemia, and rigid dietary restriction is unnecessary. As mild diabetics are prone to complications, treatment with basal insulin supplements may be beneficial when diet alone fails to produce basal normoglycaemia.


High remission-induction rate in acute myeloid leukaemia. 28 adult patients with acute myeloid leukaemia (A.M.L.) received T.A.D., a high-dose sequential chemotherapeutic remission-induction regimen consisting of 7-day courses of cytosine arabinoside, 6-thioguanine, and daunorubicin. Overall response-rate was 82%. 22 patients (79%) achieved complete remission, and 1 had a partial remission. Median remission duration was 280 days and median survival 375 days. 10 patients remain in remission. These induction results are superior to those reported in most studies and indicate that disease remission can be achieved in a high proportion of patients with A.M.L. treated with an intensive multi-agent chemotherapeutic regimen, provided support facilities are adequate.


Weight-gain inhibition by lactose in Australian Aboriginal children. A controlled trial of normal and lactose hydrolysed milk. Weight-gain in 35 slightly undernourished Australian Aboriginal infants was studied in hospital (49 admissions) during a blind controlled trial of a pre-hydrolysed low-lactose milk preparation and reconstituted full-cream milk powder. Infants fed the lactose hydrolysed milk gained 70% more weight than those receiving normal milk. Better weight-gains were achieved in those on the lactose hydrolysed milk irrespective of percentage standard weight for age, the presence of diarrhoea on admission to the trial, and stool sugar concentrations. The use of low-lactose milk should be considered in nutritional aid programmes for undernourished children throughout the world.


Bromocriptine for induction of ovulation in normoprolactinaemic post-pill anovulation. 19 women with anovulation after discontinuing oral contraceptive agents and with normal plasma-prolactin concentrations were treated with bromocriptine. Ovulation and menstruation were restored in 9 of the 13 amenorrhoeic and 5 of the 6 oligomenorrhoeic patients. The success-rate (74%) indicates that bromocriptine is an effective treatment for post-pill anovulation in normoprolactinaemic women.


A second look at emepronium bromide in urinary incontinence. Response to oral and intramuscular emepronium bromide was assessed cystometrically in nine patients with urinary incontinence caused by an uninhibited bladder. Oral therapy had no effect, whereas intramuscular administration increased bladder capacity and significantly delayed the onset of bladder spasm and the desire to void. Plasma-propranolol response was delayed and concentrations were reduced after an oral 40 mg dose of propranolol in 3 patients who had received oral emepronium bromide. These results indicate that although oral emepronium bromide had some anticholinergic effect--i.e., in reducing gastrointestinal motility--absorption of an oral dose was not sufficient for the bladder to be affected.


Blood-transfusions induce prolonged kidney allograft survival in rhesus monkeys. A prospective study has been carried out in rhesus monkeys to investigate the influence of blood-transfusions on kidney allograft survival. Unrelated animals matched for 2 or 3 antigens of the A and B locus of the major histocompatibility complex were given five consecutive blood-transfusions before transplantation and received conventional immunosuppressive treatment. Transfused recipients showed a four-fold increase in mean survival time compared with the non-transfused controls. These results may contribute to a change of policy regarding blood-transfusions in transplant patients.


Association between leucocyte group-5a antigen and acute lymphoblastic leukaemia. Leucocyte group 5 has two dominant alleles (5a and 5b) which segregate independently of the major histocompatibility complex. The group-5 system was studied in a Caucasian population of controls and patients with acute lymphoblastic leukaemia. The 5a gene frequency was 0-09 in 72 controls and 0-38 in 39 patients with acute lymphoblastic leukaemia (p less than 0-001). 15 patients with acute myelogenous leukaemia and 12 patients with aplastic anaemia had 5a and 5b frequencies similar to those seen in the control population. It is concluded that 5a or a closely linked gene is involved in susceptibility to acute lymphoblastic leukaemia.


A new experimental system for the study of the pathogenesis of coeliac disease. A method is described for the differential removal of epithelial cells from human intestinal-tissue specimens. Epithelial cells can be freed of contaminating cells such as erythrocytes, and on the basis of microscopic appearance, dye exclusion tests, and short-term survival in defined media are viable. The experimental system can be used to investigate the differential cytotoxic effects,if any, of specific gluten components upon cells from normal subjects and coeliac patients.


The ocular microtremor record and the prognosis of the unconscious patient. Ocular microtremor was recorded in 41 healthy subjects and 70 unconscious patients. Abnormalities of frequency and pattern were found in all the unconscious patients, the degree of abnormality being related to outcome. The ocular microtremor record is a potential aid to prognosis in the unconscious patient.


Comparison of results from a cardiac ambulance manned by medical or non-medical personnel. During a 20-month period a "cardiac" ambulance was manned on alternate days by specially-trained ambulance personnel only, or by such personnel plus a doctor. The presence of a doctor did not lead to any reduction in the mortality of patients with heart-attacks. Although transport to hospital by the special service was associated with a low pre-hospital mortality, this was balanced by a high pre-hospital mortality in the group of patients brought to hospital by routine ambulances at times when the special vehicle was manned, but for some reason was not used. There was evidence of unintentional selection of low-risk cases for transport by the cardiac ambulance. The number of lives saved by the special service was too small to cause any significant reduction in the overall mortality from heart-attacks in Nottingham.


Effects of a heatwave on mortality-rates in elderly inpatients. The relation between the number of in-patient deaths occurring in a department of geriatric medicine and external air temperatures recorded during the heatwave of 1976 in the U.K. was investigated. There was a close correlation between the mortality-rate and the weekly average of peak daily temperatures. There was less of an increase in mortality among the elderly patients in the better insulated buildings. The total number of deaths among elderly patients increased threefold during the hottest period of the heat-wave. These results suggest that measures may need to be taken in the elderly to combat the harmful effects of heatwaves.


Clinical significance and prognostic value of the T-B immunological classification of human primary acute lymphoid leukaemias. 50 cases of primary acute lymphoid leukaemia (A.L.L.) were analysed for the presence of T and B membrane markers on bone-marrow and/or peripheral-blood cells. 26% of cases were predominantly T-cell in type, 4% were B, the remaining 70%, without detectable membrane markers, were classified as "null" cell A.L.L. Of particular interest is the correlation between this immunological classification and the prognosis, since T-cell and B-cell A.L.L. were associated with a poorer prognosis than null-cell A.L.L. in terms of both median length of first complete remission and median survival. With one exception the T-cell cases were, according to the W.H.O. classification, of either the prolymphocytic or macrolymphoblastic type of A.L.L. and were more extensive than the comparable null-cell A.L.L. In contrast, cases of the W.H.O. prolymphoblastic and microlymphoblastic types were all found to be null-cell A.L.L. and were associated with the worst and best prognosis respectively. The correlation found between the immunological classification of A.L.L. and the prognosis means that patients with a poor prognosis can be selected for more intensive therapy.


Reactivation of hepatitis b after transplantation operations. Surveillance of the staff and patients at the Cambridge Transplant and Dialysis Unit for hepatitis-B infection since 1968 has revealed the onset of antigenaemia in 6 patients in eight years. When the first serum of each patient admitted was examined for anti-HBc antibody, 23 of 380 (6-1%) patients were found positive. Since the presence of anti-HBc is taken to be evidence of previous infection, the occurence of antigenaemia in 3 of the positives when they were immunosuppressed after transplantation is believed to be due to reactivation of latent infection. This is a new factor to be considered in the control of hepatitis B after transplantation;


Non-A, non-B post-transfusion hepatitis. To clarify the role of hepatitis-A virus (H.A.V.) in the aetiology of post-transfusion hepatitis unrelated to hepatitis-B virus, we have tested and titred pre-transfusion and convalescent serum samples from 32 patients for antibody to hepatitis-A antigen (anti-HA) by quantitative immune adherence haemagglutination. 12 patients had no detectable anti-HA in either pre-transfusion or late convalescent serum; the other 20 had anti-HA in pretransfusion serum and no significant chance in titre during convalescence. This study excludes H.A.V. as the agent responsible for these cases of post-transfusion hepatitis and supports the existence of "non-A, non-B" hepatitis virus(es).


B-cell alloantigen associated with chronic mesangiocapillary glomerulonephritis. Thirteen patients with chronic mesangiocapillary glomerulonephritis (M.C.G.) defined by light and immunofluorescent microscopy were examined for possible B-lymphocyte alloantigen associations by means of antisera from multiparous mothers of M.C.G. probands. Three such sera reacted with M.C.G.-patient B-cells. One of these sera (M.C.G.3) was highly discriminative for a B-cell antigen present in 77% of M.C.G. patients and only 17% of normal individuals tested. The risk of developing M.C.G. was estimated to be 16-6 times greater in the presence of the M.C.G.3 antigen than in its absence. This is the first demonstration of an association between a specific B-lymphocyte determinant and immune-mediated glomerulonephritis.


Serum immune complexes and disease activity in lupus nephritis. Raised levels of circulating soluble immune complexes were found in sera of 21 of 29 patients with lupus nephritis. They correlated well with clinical disease activity in the group as a whole and with the course of individual patients. In 2 patients, high-dose methylprednisolone reduced levels of immune complexes and led to clinical improvement. The size of the IgG complexes was studied in 7 patients. The complexes were very large (2-5-4X10(6) M.W.) in 6, but only the 4 with diffuse proliferative glomerulonephritis had medium-sized IgG complexes (1-1-5X10(6) M.W.) as well.


Prevention of Fatal Postoperative pulmonary embolism by low doses of heparin. Reappraisal of results of international multicentre trial. The results of a multicentre trial, designed to assess the efficacy of low-dose heparin in preventing fatal postoperative pulmonary embolism, were published in July 1975. In view of inconsistencies which have now become apparent in the data from one of the twenty-eight centres which took part in the trial, the results of the trial have been re-examined, excluding the data from this centre. Of 4031 patients remaining after exclusion of these data, 2033 were in the control group and 1998 in the heparin group. 170 (4-2%) patients died during the postoperative period, 94 in the control group and 76 in the heparin group; 70-2% of deaths in the control group and 65-7% in the heparin group had necropsy examination. 15 patients in the control group and none in the heparin group were found at necropsy to have died due to acute massive fatal pulmonary embolism (P less than 0-001). Exclusion of data from the one centre did not alter already published significant differences in the total incidence of deep-vein thrombosis, nor in the frequency of operative and post-operative bleeding complications observed in the control group and the heparin group.


Primary lesion in osteoarthrosis.

Primary lesion in osteoarthrosis. The primary disturbance in osteoarthrosis is generally regarded as occurring in the articular cartilage and as resulting from a combination of ageing and mechanical factors. An alternative hypothesis is that the primary disturbance is located in the synovial lining cells. It is suggested that proteolytic enzymes which normally leak from the phagocytic (A type) lining cells are in the healthy joint neutralised by inhibitors synthesised by the B-type lining cells. Osteoarthrosis is the result of an imbalance between leakage of enzymes and provision of inhibitors.


Mechanisms for the control of body-weight. Various hypotheses for the mechanism of regulation of body-weight in human adults have been proposed in the light of the magnitude of the long-term changes in weight actually observed. One of these hypotheses has been represented in the form of a computer simulation model which has been used to demonstrate that (i) it is not necessary to postulate the existence of a set-point regulatory system, and (ii) in practice, several mechanisms, including hunger and satiety, the relative constancy of habits and customs of behaviour, and the existence of cognitive thresholds combined with a relatively simple physiological negative feedback system probably constitute the simplest hypothesis for the mechanism of weight stability.


Incidence of insulin-dependent diabetes in the first sixteen years of life. The incidence of insulin-dependent diabetes in the first 16 years of life in a nationally representative sample was 1-42 per 1000 population. This incidence is larger than that found in previous studies of diabetes in comparable age-groups and suggests an overall increase in incidence in this country. 23% of the diabetics had a history of diabetes in a first-degree relative, which is higher than reported previously. There was no evidence to suggest any association between prenatal and postnatal infections and diabetes.


Organization of the facial nerve nucleus in the cat. The location of efferent neurons in the brain stem of newborn kittens supplying the facial muscles was studied by means of horseradish peroxidase (HRP) used as a tracer of retrograde protein transport. Three to 15 microliters containing 0.3 to 1.5 mg of HRP was injected into the orbicularis oris and orbicularis oculi muscles of six kittens and in the seventh kitten, the ventral ramus of the facial nerve was transected and HRP was instilled on the cut end of the nerve. After a survival time of 24 hours, the animals were anesthetized, perfused by intracardic perfusion technique, and then they were fixed and the brain stems sectioned. Stains for peroxidase demonstrated the labelled neurons in the lateral division of facial nuclei in the ipsilateral side. The orbicularis oculi muscles were represented in the rostral pole of the lateral division of the facial nucleus dorsally while the orbicularis oris muscles were represented in the caudal pole of the lateral division of the facial nucleus ventrally. No labelled neurons were found in the nuclei of the Vth or any other brain stem nuclei. According to my knowledge, this method of localizing the neurons supplying the facial muscles has not been reported previously.


Palato-pharyngeal cine photography: a technique for developing continuing education films. A method of Cine photography has been developed to record a variety of plastic and reconstructive surgical procedures in the oral cavity and pharynx. Effective classroom teaching of surgical closure of the cleft palate and the various palatal lengthening procedures including pharyngeal flaps, has been hampered by the lack of quality teaching films demonstrating surgical techniques in color. The small size of the structures involved and the delicate nature of the surgery requires that the surgeon work at close range and directly in front of the mouth. To avoid the shadows cast by the sides of the oral cavity, the surgeon's hands and frequent change of position by the professional photographic team, a head-mounted Cine camera was employed. A "through the surgeon's eye" view for the camera was accomplished by using a parallelogram of beam-splitting mirrors. The resulting photographic film provides the classroom audience with a sense of being in the surgeon's operating position thus having a view superior to that obtained by the surgeon's first assistant. An elaborate system of counter-balancing provides the surgeon with a weightless camera, mirror, and light complex mounted on a football helmet. The football helmet merely served as an interlocking unit enabling the surgeon to compose his own movie while operating.


[Colonic histiocytosis (author's transl)]. Macrophages accumulating various substances can be detected in the mucosa of the small and large bowel under physiological and various pathological conditions. Among these the so-called PAS-positive macrophages have attracted much attention in recent times. Abundant occurrence of such cells in the intestinal mucosa has been termed "colonic histiocytosis". The occurrence of PAS-positive macrophages was investigated in 200 unselected and otherwise normal biopsy specimens of rectal mucosa; no correlation was found between the occurrence of these cells on the one hand and any intestinal or extraintestinal disease on the other. PAS-positive macrophages were mostly found close to the surface of the mucosa or to the cryptal epithelium as well as between the crypts. It is suggested to abandon the term "colonic histiocytosis" since it induces a false impression of a disease entity in the clinician (and may be related falsely e.g. to "histiocytosis X", and since the clinician may tend to attribute unnecessary importance to this harmless finding.


[Endoscopic findings in whipple's disease (author's transl)]. A case of Whipple's disease is reported in detail. Pathological changes of duodenal mucosa are demonstrated and the diagnostic importance of duodenoscopy is stressed.


[Staining the Nissl bodies in 4--10 microns thick Araldite sections with an area of about 2x2 cm (author's transl)]. For light microscopy 4--10 microns thick sections with an area of 2x2 cm o Araldite-embedded tissue (human autopsy brain) are stained in 1% aqueous methylene blue at 65 degrees C for 4--12 hours and are differentiated in 98% ethanol for some seconds or very few minutes. The Nissl bodies, nuclei and nucleoli are stained dark blue, the neuropil is nearly colourless.