Synthesis of 5''-amino-3,5''-dideoxybutirosin A. The titled compound was prepared by condensation of 3'-deoxyparomamine derivative (5) with 2,3-O-bis(p-nitrobenzoyl)-5-O-tosyl-D-xylofuranosyl bromide followed by 1-N-acylation with the active ester of (S)-4-benzyloxycarbonylamino-2-hydroxybutyric acid. The compound was slightly more active than 3'-deoxybutirosin A against Pseudomonas.


Stimulation of prolyl hydroxylase activity by bleomycin. The activity of purified prolyl hydroxylase (proline, 2-oxoglutarate dioxygenase, EC 1. 14. 11. 2) was enhanced 3 approximately 8-fold at a low concentration of ferrous ion (1 X 10(-5 M) by addition of bleomycin, a glycopeptide antibiotic with antineoplastic activity and a side effect of producing pulmonary fibrosis. The maximum stimulation was attained at a concentration of 15 microgram/ml bleomycin (about 1 X 10(-5) M), which was approximately equimolar with the ferrous ion, one of the cofactors of this enzyme. Addition of bleomycin to the assay mixture resulted in a change of the optimal concentration of ferrous ion from 2 X 10(-3) M to 1 X 10(-5) M. Changing the order of addition of ferrous ion, enzyme and bleomycin in assay medium before incubation at 37 degrees C, the stimulatory activity was varied. Blemycin A2Cu++(Cu++-chelated bleomycin), which scarcely complexed with Fe++, had no enhancing effects on the enzymatic activity. We discuss the possible reasons as to why the activity of prolyl hydroxylase was enhanced by addition of bleomycin in the assay mixture.


Urinary oligosaccharides of fucosidosis. Evidence of the occurrence of X-antigenic determinant in serum-type sugar chains of glycoproteins. Urine of a fucosidosis patient contained a large amount of fucosyl oligosaccharides and fucose-rich glycopeptides. Six major oligosaccharides were purified by a combination of Bio-Gel P-2 and P-4 column chromatographies and paper chromatography. Structural studies by sequential exoglycosidase digestion and by methylation analysis revealed that their structures were as follows: Fucalpha1 leads to 6GlcNAc, Fucalpha1 leads to 2Galbeta1 leads to 4(Fucalpha1 leads to 3)GlcNAcbeta1 leads to 2Manalpha1 leads to 3Manbeta1 leads to 4GlcNAc, Galbeta1 leads to 4(Fucalpha1 leads to 3)GlcNAcbeta1 leads to 4Manalpha1 leads to 4GlcNAc, Galbeta1 leads to 4(Fucalpha1 leads to3)GlcNAcbeta1 leads to 2Manalpha1 leads to 6Manbeta1 leads to 4GlcNAc, and Galbeta1 leads to 4(Fucalpha1 leads to 3)GlcNAcbeta1 leads to 4Manalpha1 leads to 6Manalpha1 leads to 6Manbeta1 leads to 4GlcNAc. In additon, the structure of a minor decasaccharide was found to be Galbeta1 leads to (Fucalpha1 leads to)GlcNAcbeta1 leads to Manalpha1 leads to [Galbeta1 leads to (Fucalpha1 leads to)GlcNAcbeta1 leads to Manalpha1 leads to]Manbeta1 leads to 4GlcNAc.


Antibody as an immunological probe for studying the refolding of bovine serum albumin. An immunochemical approach to the identification of possible nucleation sites. Specifically purified antibody to either domain I, domain III, or to subregions of domains I or III of serum albumin was added to refolding mixtures containing reduced serum albumin but no other refolding catalyst. It was found that the refolding of reduced albumin was greatly enhanced by the presence of specific antibody in the refolding mixture, that this enhancement was restricted to that domain for which the added antibody was directed, and that antibody-mediated enhancement of refolding in the NH2-terminal portion of each domain was delayed as compared to that seen in the COOH-terminal portion of each domain. Thus, an apparent COOH-terminal to NH2-terminal pathway of refolding within each domain was observed, which is consistent with the proposed evolutionary pathway of the albumin molecule and also consistent with the proposed presence of a nucleation center in the COOH-terminal double disulfide loop of each domain.


The antigenic structure of bovine serum albumin. Evidence for multiple, different, domain-specific antigenic determinants. Using antiserum to native bovine albumin and antigenically active fragments of the protein, we have isolated antibodies directed to each of the three domains and to several subdomains of the albumin molecule. Using albumin and these fragments as inhibitors of the reaction between 125I-albumin and any given antibody population, we have demonstrated that: (a) each domain of albumin is antigenically distinct from each of the other domains; (b) each domain possesses a minimum of two different antigenic determinants; and (c) the entire albumin molecule possesses a minimum of six different, nonrepeating, antigenic determinants.


Cross-linking studies on the conformation and dimerization of myelin basic protein in solution. Myelin basic protein was isolated from both cat and bovine central nervous system. Cat and bovine myelin basic protein, which are shown to be similar by tryptic mapping, exhibit identical behavior when cross-linked with the bifunctional reagent difluorodinitrobenzene. Myelin basic protein is cross-linked into only a dimer under certain conditions in the presence of sodium dodecyl sulfate. In contrast, many oligomers are formed when myelin basic protein is cross-linked in the absence of detergent. The formation of cross-linked dimers in the absence of other oligomer formation suggests that the protein is at least partly dimeric in the presence of sodium dodecyl sulfate. The conformation of them myelin basic protein monomer in sodium dodecyl sulfate was also studied. N-Bromosuccinimide and cyanogen bromide cleavage reactions were used to demonstrate that difluorodinitrobenzene had introduced intramolecular cross-links between the two peptides resulting from each of the cleavage ractions. However, these types of intramolecular cross-links cannot be detected under conditions in which only dimers have formed. Some of the lysine residues which are modified by difluorodinitrobenzene were identified by tryptic mapping. In several respects, the conformation of myelin basic protein in a sodium dodecyl sulfate solution appears to be similar to the conformation of the protein in the membrane.


Effect of RNA tumor virus-specific protein p30 on reverse transcriptase. Intraspecies and interspecies interaction between reverse transcriptase and p30. Reverse transcriptase and p30 were purified from various retroviruses and the intra- and interspecific interaction between the two proteins were studied. The intraspecific complex stimulates [3H]TMP incorporation into (dT)12.(rA)n severalfold above that of the enzyme itself whereas DNA synthesis in the presence of the interspecific complex can stimulate DNA synthesis about 1.5-fold. The sedimentation rate value of the intraspecies complex varies between 12 and 16 S with an estimated molecular weight of 400,000. The molar ratio of p30:reverse transcriptase within the complex is 8:1. Both complexes can be dissociated into their original protein components by exposure to salt (kcl) solution, except that 0.3 M KCl will dissociate the interspecies complex whereas 0.8 M KCl is required for dissociation of the intraspecies complex. Competition studies in which an interspecies complex was exposed to p30 autologous to reverse transcriptase within the complex resulted in the displacement of the heterologous (p30) protein and the formation of a new intraspecific complex.


Immunological studies on pancreatic phospholipase A2. Antigenic characterization of the NH2-terminal region. Rabbit antisera elicited against pure pig, horse, ox, and sheep pancreatic phospholipase A2 revealed considerable immunological differences when tested by double immunodiffusion and microcomplement fixation assays. Snake venom phospholipases did not show any detectable cross-reactions with the pancreatic enzymes. Microcomplement fixation also clearly demonstrated conformational differences between porcine phospholipase A2 and its zymogen. NH2 terminally modified analogs of porcine phospholipase A2 could be clearly distinguished using the same assay. Moreover, strong evidence was obtained that Ala1-Arg6 is a part of an antigenic determinant. Radioimmune assay, using monovalent phospholipase-specific Fab fragments revealed a maximum number of three antigenic sites of phospholipase that can simultaneously be occupied by antibody. The Fab fragments were separated into three fractions, using three immunoadsorbent columns in series. These Fab fractions showed different inhibitory properties toward micellar binding of phospholipase A2. They also exhibited different protective effects against active center modification.


Immunoradiometric measurement of the factor VIII procoagulant antigen. A fluid-phase immunoradiometric assay has been developed which identifies an antigen on the Factor VIII (antihemophilic factor) procoagulant protein. This sensitive and quantitative assay is not influenced by levels of Favor VIII-related antigen (von Willebrand factor) or other plasma proteins. There is a close correlation of procoagulant activity and immunologically detectable protein in normal and von Willebrand's disease plasmas. In contrast, several different patterns have been identified in hemophilic plasmas. Neither procoagulant activity nor procoagulant antigen is detectable in plasmas from patients with severe classic hemophilia. Patients with mild and moderate hemophilia have either comparable plasma concentrations of procoagulant activity and procoagulant antigen or relatively greater levels of immunologically detectable protein.


Serum elastase and its inhibitors in the blood of heavily burnt patients. Serum elastase and its inhibitors were determined in the sera of heavily burnt patients. Serum elastase levels were elevated at two to eight days after a severe burn-accident and returned towards normal values from the 10th day on. Both alpha1-antitrypsin and alpha2-macroglobulin levels were also elevated in the sera of heavily burnt patients. alpha1-Antitrypsin showed a parallel evolution to the elastase level but alpha2-macroglobulin followed a somewhat different time curve. Plasminogen and antithrombin were not elevated significantly. It is suggested that serum elastase may play a role in tissue degradation in burnt patients.


Effect of orally administered duodenal fluid on serum proteins in neonatal calves. This study was to determine if orally administered duodenal fluid, as a source of intestinal microorganisms, would influence absorption of gamma-globulin of colostrum in newborn calves. Duodenal fluid was obtained 2 h postfeeding from a cannulated milk-fed calf. Twenty-seven male and female Holstein calves obtained within 6 h of birth were assigned randomly to one of three treatments: 1) colostrum alone, 2) 200 ml duodenal fluid immediately followed by colostrum, and 3) 200 ml duodenal fluid followed 3 h later by colostrum. Pooled colostrum was fed at 10% of body weight in two daily feedings. Total protein, albumin, alpha-globulin, beta-globulin, and gamma-globulin of blood serum were determined prior to colostrum consumption, and again 24 and 48 h after administration of duodenal fluid. Total proteins, beta-globulin, and gamma-globulin of serum increased with age in all calves. Inocula interference with absorption was indicated by depressed values of serum in calves of treatment 3 as compared to treatment 1 calves for protein (5.28 to 6.28 g/dl), beta-globulin (.67 to .87 g/dl), and gamma-globulin (.76 to 1.33 g/dl). Protein was also lower in calves of treatment 3 (6.05 g/dl) compared to uninoculated calves (6.28 g/dl). Malabsorption of colostral proteins may be related to early establishment of large numbers of intestinal microorganisms in the newborn calf.


Absorption of colostral proteins by newborn calves fed unfermented, fermented, or buffered colostrum. Unfermented, frozen colostrum from the first three postpartum milkings of 10 cows was thawed, pooled, and treated to produce three diets: 1) unfermented, 2) fermented (7 days at 25 to 27 C), and 3) fermented (as in 2) with pH adjusted to match that of unfermented colostrum. Eighteen newborn, unsuckled Holstein calves were assigned randomly to one of the three diets. Colostrum diets were thawed and fed at 0, 8, 16, 24, and 36 h. Blood was sampled at 0, 4, 8, 16, 24, and 48 h. Minimal breakdown of colostral gamma-globulin and immunoglobulin G (IgG) occurred during fermentation. Protein breakdown during fermentation was associated primarily with the casein fraction. Concentrations of gamma-globulin in serum of calves receiving unfermented colostrum were higher than those of calves fed fermented colostrum at all sampling times beyond 0 h. Concentrations of gamma-globulin in serum of calves fed buffered colostrum were intermediate. Concentrations of IgG followed a similar trend. Health problems were not encountered, indicating potential for passive immunization of newborn calves via fermented, buffered colostrum in emergency situations.


Adrenal function and passive immunity in the dystocial calf. Dystocial calves were tested for their ability to absorb colostral immunoglobulins and establish a competent passive immunity. Twenty dystocial and 20 eutocial calves were fed 1 liter of colostrum 4 h after birth and an additional liter 12 h later. Their absorption of the immunoglobulins A, G, and M, as indicated by serum concentrations, was equivalent at 16 and 24 h postpartum. Cortisol concentrations in serum at birth were high in both eutocial and dystocial calves and were correlated negatively with environmental temperatures prior to parturition. The dystocial calves had a lower cortisol concentration in serum at birth. The differences in cortisol concentrations between dystocial and eutocial calves and between experimental blocks influenced by environmental temperature could not be related to immunoglobulin absorption.


Complete versus selective dry cow therapy for mastitis control. Two hundred and thirty-two cows were assigned alternately to complete dry cow therapy (infusion in all quarters on the day of drying off) or selective therapy (infusion in all quarters if a history of mastitis, California Mastitis Test score of +2 or +3 in any quarter, or if cell counts from bucket milk samples as determined by the membrane filter-deoxyribonucleic acid procedure were above 500,000 cells/ml). A dry cow product containing 10(6) units of procaine penicillin G and 1 g of dihydrostreptomycin in a slow release base was used. A 1% iodophor teat dip was used throughout the experiment. Infections of Staphylococcus aureus, Streptococcus agalactiae, other streptococci, and gram negative rods were eliminated from 85.4% of the infected quarters with complete therapy and 88.2% of the infected quarters with selective therapy. New infections occurred in 3.1% of quarters with complete therapy and in 6.5% of the quarters with selective therapy. Incidence of mastitis following the dry period was less with complete therapy compared to selective therapy (4.6% vs. 7.8% of the quarters). Selective therapy was as effective as complete therapy in eliminating existing infections. Complete therapy would be the choice in situations where new infections in dry period are of concern.


Studies of hypersensitivity reactions to foods in infants and children. In order to extend previous investigations of adverse reactions to foods performed at this institution, 68 children, aged 5 mo to 15 yr, were studied. All subjects reported a history of adverse reaction to ingestion of one or more of the 14 foods under study. Sixteen of 43 subjects, 3 yr of age or older, had 22 adverse reactions during 94 food challenges with one or more of the 14 foods. All reactions confirmed were to peanut or other nuts, milk, egg, and soy. Skin testing with 1:20 weight/volume concentrations of food extracts applied by the puncture technique produced a net wheal reaction 3 mm or greater in all subjects 3 yr of age or older in whom double-blind food challenges confirmed the history of adverse reaction. Thirteen of 25 children less than 3 yr of age manifested adverse reactions during 49 food challenges. Skin testing by puncture technique produced a net wheal 3 mm or greater in 9 children less than 3 yr of age in whom food challenge elicited a clinical response within 2 hr. One of 4 subjects less than 3 yr of age in whom the adverse reaction occurred more than 4 hr after food challenge exhibited a wheal to puncture skin test of 3 mm or greater. These studies suggest that at present double-blind food challenge is an indispensible tool for the unequivocal evaluation of adverse reactions to foods.


Immunogenic properties of tobacco smoke. The immunogenic capacity of tobacco smoke or tobacco smoke in combination with host proteins to stimulate antibody production in rabbits was investigated. Several antisera from rabbits immunized with tobacco smoke components reacted by immunoprecipitation with tobacco smoke or leaf antigens. The serum precipitins were present only in immune sera and had electrophoretic mobility and molecular size identical to immunoglobulin. These results suggest that tobacco smoke contains components capable of stimulating an immune response in rabbits. It is possible that these components are immunogenic in man, although their role as allergens remains to be determined.


Inferences on RNA synthesis rates during mitosis from flow cytofluorimetric RNA histograms. Flow cytofluorimetric techniques with acridine orange staining have been used to study RNA levels of cells during and immediately after mitosis. It can be inferred from the histogram data that, of the mitotic cells, those in telophase have the highest RNA content, and that the rate of synthesis increases rapidly between anaphase and telophase. These inferences correlate with results obtained from parallel labeled precursor studies.


A subpopulation of adherent accessory cells bearing both I-A and I-E or C subregion antigens is required for antigen-specific murine T lymphocyte proliferation. A murine T lymphocyte proliferation assay that used antigen-primed lymph node T cells, was antigen specific, and required exogenous accessory cells was used to characterize the accessory cells that supported proliferation. These cells were Thy 1.2 negative, radioresistant, glass-adherent, and were functional only if alive. The accessory cell function of spleen adherent cells was much greater than that of peritoneal cells. Also, the accessory cell function of spleen adherent cells was proportional to the length of time such cells were incubated with antigen and very small numbers of such cells provided accessory cell function. Cytotoxic studies with subregion-restricted anti-Ia antibodies and complement indicated that accessory cell function resided in a subpopulation of spleen adherent cells that bore both I-A and I-E or C subregion antigens. The function of such cells was not related to a selective ability (vs other spleen adherent cells) to take up antigen. These data indicate that antigen-specific stimulation of T lymphocyte proliferation requires at least one specific subpopulation of spleen adherent cells that can be phenotypically identified by its expression of Ia antigens and are consistent with the possibility that Ia antigens may be Ir gene products.


Immunochromatography on insolubilized antibodies of very low affinity: application to immunoadsorbence of bovine alpha-fetoprotein. Cross-reactive antibodies were utilized to prepare immunoadsorbents possessing a very low affinity to bovine alpha-fetoprotein (AFP). A goat anti-human AFP serum cross-reactive with bovine AFP was first depleted of antibodies reactive with bovine AFP in immunodiffusion. The remaining antibodies from this serum and gamma-globulin from a sheep antiserum against rabbit AFP, without prior absorption, were coupled to Sepharose. Chromatography of fetal calf serum on these adsorbents resulted in retardation of bovine AFP relative to other proteins. A major part of the AFP eluted from the columns with phosphate-buffered saline. The rest eluted as a sharp peak with a small quantity of 4 or 6 M urea. The elution of AFP with the initial column buffer has made it possible to prepare pure AFP that has not been subjected to the chaotropic elution buffers usually employed in affinity chromatography. Elimination of the washing step and the ease of elution has allowed purification of gram amounts of AFP. The fact that immunoadsorbents prepared from antibodies with no detectable reactivity in immunodiffusion still caused delayed elution in chromatography suggests that this procedure may be useful in search of proteins cross-reactive with a known protein.


[Alterations in the proteins found in the amniotic fluid in the course of normal pregnancy. A study carried out by immunoprecipitation tests on the amniotic fluid (author's transl)]. A fluonephelometric technique was used to study the proteins in amniotic fluid. 113 samples taken between the 8th and the 44th week of amenorrhoea from pregnancies without any fetal abnormality were tested. The levels of 8 protein fractions were estimated: albumen, IgG, IgA, alpha 1 antitrypsin, transferrin, orosomucoid, alpha 2 macro-globulin and IgM. 6 of these fractions could be estimated in almost every sample of amniotic fluid, but alpha 2 macroglobulines and IgM could only be found in a few cases. Furthermore, the fractions of the proteins most clearly shown appeared in a parallel way more or less as the total levels of proteins as estimated by Lowry's method.


Bursectomy in ovo blocks the generation of immunoglobulin diversity. Immunoglobulins made by chickens bursectomized in ovo on day 11 of incubation were studied by two-dimensional gel electrophoresis. All such bursectomized chickens have limited diversity in their immunoglobulin molecules. A range of different degrees of diversity restriction was found in individual bursectomized chickens. The limited immunoglobulin diversity was stable for at least 20 weeks in that the same spots were found over this time span. Bursectomized chickens that responded to repeated antigen challenge had sheep erythrocyte- and dinitrophenol-specific antibodies of limited diversity. Different bursectomized responders made almost identical antigen-specific antibodies. The results were interpreted as indicating that individual bursectomized birds had been blocked at different points during the developmental generation of immunoglobulin diversity, and that the genetic mechanisms that underlie the developmental diversification of clones of B cells lead to a sequential generation of very similar antibody molecules in different embryos.


Tumor-associated antigens of rat moloney sarcoma cells. I. Cell-surface antigens. The dissociated cell surface membranes of a rat Moloney sarcoma (MST), derived from a BN rat, were extracted with 2 M KI, with 6 M guanidine thiocyanate, or by papain digestion. Extracts obtained with these three reagents were fractionated on columns of controlled-pore glass, 170 A pore size. A fraction was eluted from each preparation that contained tumor-associated antigens (TAA), viral, fetal, and histocompatibility antigens. With an antibody specific for TAA, the TAA, devoid of detectable viral, fetal, and histocompatibility antigens, were co-precipitated by addition of goat antibody to rat immunoglobulin. After electrophoresis, on slab gels, three bands were detected with estimated m.w. of 185,000, 150,000, and 70,000. No such bands were detected on slab gel electrophoresis with extracts of BC5, a chemically induced tumor, of normal BN lymphoid cells, of M-MuLV, or of fetuses, after incubation with anti-TAA antibody and goat antibody to rat immunoglobulin. TAA extracts prepared with 2 M KI, 6 M guanidine thiocyanate, or papain digestion showed immunologic reactivity. Cold TAA inhibited the co-precipitation of labeled TAA by rat antibody specific for TAA; they elicited antibody in guinea pigs but not in rats; and antibodies specific for TAA were cytotoxic to MST in the presence of C.


Specificity of antisera from Lewis rats immunized with encephalitogenic fragment 43-88 of guinea pig myelin basic protein. Inbred Lewis rats were immunized with encephalitogenic fragment 43-88 of guinea pig myelin basic protein emulsified in complete Freund's adjuvant. After recovery from experimental allergic encephalomyelitis (EAE) the animals were given a booster immunization, bled, and the specificity of the individual anti-fragment antisera was examined by direct binding assays by using radioiodinated fragment 43-88 and peptides 43-67, 68-88, and 79-88. Competitive-binding experiments with these peptides in competition with labeled fragment 43-88 were also done. The results of these experiments indicated that the immunodominant region of fragments 43-88 was the carboxy-terminal half of the molecule. Individual antisera recognized different antigenic determinants within this region.


Micro-leukocyte adherence inhibition. I. Cellular basis of the mechanism of reactivity. To study the cellular basis for specific antigen-induced leukocyte adherence inhibition, enriched populations of B cells, T cells, and monocytes were prepared by a two-stage adherence separation procedure from spleen cells of normal C57BL/6J mice and mice bearing progressively growing MCA-38 tumors. The reactor cell undergoing specific antigen-induced adherence inhibition was identified as a monocyte (esterase positive, did not respond to mitogens, and did not bear Thy 1.2 antigen or surface immunoglobulin). Furthermore, an enriched population of MCA-38 sensitized B cells could program normal monocytes to undergo specific antigen-induced adherence inhibition. This programming could be abolished by pretreatment of the MCA-38 sensitized B cells with anti-immunoglobulin and complement (indirect cytotoxicity method). In contrast, enriched populations of MCA-38 sensitized T cells could not program normal nylon wool adherent cells to undergo antigen-specific adherence inhibition; and anti-Thy 1.2 serum and complement had no effect on specific antigen-induced adherence inhibition. Thus, in this murine tumor model, leukocyte adherence inhibition appears to be due to the programming of monocytes by sensitized B cells.


Specific inhibition of cytotoxic memory cells produced against UV-induced tumors in UV-irradiated mice. Cytotoxic responses of UV-irradiated mice against syngeneic UV-induced tumors were measured by using a 51Cr-release assay to determine if UV treatment induced a specific reduction of cytotoxic activity. The in vivo and in vitro primary responses against syngeneic tumors and allogeneic cells were unaffected, as was the "memory" response (in vivo stimulation, in vitro restimulation) against alloantigens. In contrast, the memory response of UV-treated mice against syngeneic, UV-induced tumors was consistently and significantly depressed. The cytotoxicity generated by tumor cell stimulation in vivo or in vitro was tumor-specific and T cell-dependent. Since the primary response against syngeneic UV-induced tumors produces apparently normal amounts of tumor-specific cytotoxic activity, UV-treated mice may not reject transplanted syngeneic tumors because of too few T effector memory cells. These results imply that, at least in this system, tumor rejection depends mostly on the secondary responses against tumor antigens and that at least one carcinogen can, indirectly, specifically regulate immune responses.


Natural killing and antibody-dependent cellular cytotoxicity are mediated by different mechanisms and by different cells. Natural killing (NK) in humans, as well as in other species, has been shown to be specific for antigenic determinants present on the surfaces of a variety of tumor cells. Physical separation of NK cells from K cells, which mediate antibody-dependent cellular cytotoxicity (ADCC), has not been successful; however, there is indirect evidence suggesting that these activities are distinct. To further study the relationship between NK and K cells, competitive inhibition techniques were employed. NK cells can be blocked via two mechanisms: 1) by direct inhibition with NK-sensitive tumor cells binding to NK receptor sites present on the effector cells and 2) by steric inhibition resulting from the binding of antibody-coated cells to the FcR on the effector cells. K cells, however, lack the NK receptor site(s) but are FcR+, and can therefore be blocked only by antibody-coated cells. We therefore postulate that NK and K cells are two separate lymphoid populations. NK cells bear receptor site(s) for NK determinants and FcR, whereas K cells bear only FcR.


Requirement for an Ia-bearing accessory cell in Con A-induced T cell proliferation. Pretreatment of murine lymphoid cells with anti-Ia and C abrogated the proliferative response of these cells to Con A, but not to PHA. Reconstitution experiments demonstrated that T cell-enriched populations failed to restore Con A responsiveness and that T cell-depleted populations were more effective in restoring responsiveness to Con A. In particular, a population of 1000 R resistant, glass-adherent, non-T spleen cells was capable of completely restoring responsiveness to Con A when added in numbers as low as 4% of cultured cells. These splenic adherent cells were found to express Ia determinants encoded by at least two genes: one in I-A and the other in I-B, I-J, and/or I-E/C, and it was demonstrated that determinants encoded in these two regions were expressed on the same cell. These results demonstrate that non-T accessory cells may be the Ia+ cells entirely responsible for the anti-Ia and C-induced abrogation of T cell proliferative responses to Con A.


Secretion rate independent evaluation of IgM antibody avidity at the level of single immunocytes. The hemolytic plaque inhibition assay has been performed on spleen cells from mice immunized with TNP-HRBC to evaluate avidity of anti-TNP IgM antibodies. At different times after immunization direct plaques were inhibited by soluble TNP-EACA, TNP61-BGG, or anti-mu antiserum. Analysis of the inhibition data provided independent estimates of antibody avidity and secretion rate. Avidity was found to increase with time, to reach a maximum when the antibody response attained the peak value, and then to decline as the response was waning. There was a decrease followed by increase of the secretion rate concomitant with the rise and fall of the antibody response and avidity.


Studies of immunosuppression by cobra venom factor. I. On early IgG and IgM responses to sheep erythrocytes and DNP-protein conjugates. The immunosuppressive activity of CVF was evaluated in mice immunized with sheep erythrocytes and dinitrophenylated proteins. Serum antibody levels to these immunogens were estimated in activity units and on a weight basis for IgG. IgM as well as IgG antibody responses were diminished in mice pretreated with CVF. However, when soluble immunogens were incorporated in CFA the suppressive effect associated with CVF was inapparent. It is suggested that C depletion per se may not fully account for the observed immunosuppression. The latter may result not only from the depression of C3 levels but also from the biologic activities of C cleavage products some of which modulate the secretory functions and state of activation of macrophages.


Antigen-initiated B lymphocyte differentiation. XIV. Nonspecific effects of antigen stimulation cause proliferation in the "pre-progenitor" subset of primary B cells. The effect of specific and nonspecific stimuli on the cycle status of subsets of primary B lymphocytes was assessed by preinjecting donor CBA mice 1 to 2 days previously with various substances, and then incubating the isolated spleen cells with high specific activity 3H-TdR before assay. AFC-progenitor activity was assessed as a response to NIP-POL antigen, either by adoptive transfer to irradiated recipients or by cell culture. Previous studies showed these assays reflected the activity of different subsets of B cells, termed "pre-progenitors" (adoptive assay) and "direct progenitors" (culture assay). Most functional primary B cells, whether assayed in culture or by adoptive transfer, were not initially in rapid cell cycle in normal adult mice. However, nonspecific stimulation for 1 day caused NIP-specific adoptive transfer IgM AFC-progenitors to enter rapid cell cycle. This effect was independent of T cells and not related to the antigenicity of the stimulus: particulate peritoneal irritants were the most effective stimulants. In contrast to adoptive transfer results. AFC-progenitors assayed in cell culture were unaffected by nonspecific stimuli, but were activated into cell cycle by specific antigen.


Comparison of the developmental kinetics of antibody- and immunoglobulin-forming cells in normal and tolerant mice. The developmental kinetics of antibody-forming cells (AFC) and of cells synthesizing immunoglobulins without detectable antibody function against the antigen injected (IFC) were compared in lymph nodes of normal mice and tolerant mice receiving an immunogenic challenge. Tolerant states to bovine serum albumin (BSA), induced in adult mice, and to human gamma-globulin (HGG), induced in newborn mice, were studied. Whatever the tolerant state induced, the following main results were obtained: 1) both AFC and IFC were suppressed in tolerant mice, and this to approximately the same extent for the two populations; 2) both the suppression of the AFC and of the antigen-induced IFC were specific to the tolerogen used.


Regulation of antibody response in different immunoglobulin classes. IV. Properties and functions of IgE class-specific" suppressor factor(s) released from DNP-mycobacterium-primed T cells. IgE class-specific suppressor factors (IgE-TsF) released from DNP-Myc-primed T cells showed their suppressor effect in an antigen nonspecific manner, although DNP-specific stimulation was required for their induction. The suppressor activity of IgE-TsF was absorbed with the alloantiserum directed to the subregions between I-A and I-E of the H-2 complex. IgE-TsF from BALB/c mice did not show their suppressor effect on the IgE response of C57BL/6J and vice versa. The suppressor activity of IgE-TsF was removed with a DNP-OA-primed B lymphocyte population including an increased number of IgE-B cells, but not with T cells. Incubation of hapten-primed B cells with IgE-TsF for 3 hr at 37 degrees C selectively abolished the anti-hapten IgE antibody response in the adoptive transfer experiment, indicating that the target cells of IgE-TsF were IgE-B cells.


Crossed immunoelectrophoresis of a herpes simplex virus type 1-specific antigen: immunological and biochemical characterization. Crossed immunoelectrophoresis of herpes simplex virus (HSV) antigens obtained from infected cells solubilized with the nonionic detergent Triton X-100 has shown that antigen number 6 (Ag-6) is found in preparations from HSV type 1-infected cells but not in HSV type 2 preparations. A monospecific antiserum was produced against Ag-6 by intracutaneous inoculation of the corresponding immunoprecipitate into rabbits. This antiserum neutralized HSV type 1 but not HSV type 2. The polypeptide composition of Ag-6 (molecular weight, 131,000 daltons) was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the immunoprecipitate, using radiolabeled antigen. The multitude of information obtained demonstrates that crossed immunoelectrophoresis can be used preparatively, since specific immunoprecipitates represent a short cut for the attainment of immunoreactive viral protein entities useful for further immunological and biochemical analyses.


Histamine release, complement consumption, and microvascular changes after radiographic contrast media infusion in rabbits. The intravenous injection of RCM into rabbits produced dose-dependent changes in SAP, MVP, and RBCV, as well as plasma histamine and complement concentrations. After infusion of 8 ml/kg Hypaque-50, SAP dropped from 86 +/- 3 mm Hg to 50 +/- 3, MVP from 42 +/- 2 cm H2O to 26 +/- 3, and RBCV from 0.98 +/- 0.11 mm/sec to 0.37 +/- 0.13. The microvascular changes appeared 10 sec after injection and persisted for 10 to 40 min. During the course of the reaction it was observed that leukocytes adhered to the endothelial walls and red blood cells shrank and finally aggregated in the microvessels. The microvascular changes were accompanied by an increase in plasma histamine concentration, with an average of 44 ng/ml after 2 min, and a drop in total plasma CH50 by an average of 46%. Infusion of 8 ml/kg hyperosmolar saline solution (4.1 gm/dl or 1324 mOsm/L) produced initial changes in microvascular parameters which returned to normal within a few seconds. At the same time plasma histamine concentration increases slightly without changes in complement. It is concluded that the hyperosmolar properties of RCM may contribute to the initial hemodynamic changes observed after RCM infusion. However, the prolonged microcirculatory disturbances produced by RCM in rabbits appear to be a direct effect of the chemotoxicity of these compounds. Part of this chemotoxicity might result form initial release of vasoactive mediators such as histamine and activation of the complement system.


Parasystole simulating ventricular bigeminy with Wenckebach-type coupling prolongation. A 65-year old male originally presented with repetitive ventricular bigeminal sequences demonstrating progressive prolongation of successive coupling intervals suggesting Wenckeback-type exit block. An even number distribution of conducted beats always intervened between bigeminal sequences. Subsequent analysis proved this to be a fortuitous "pseudo-Wenckebach" phenomenon, with the actual mechanism being continuous parasystole. Additional recording verified a parasystolic rhythm.


Lead concentration in skeletal muscle in amyotrophic lateral sclerosis patients and control subjects. The concentration of lead in the vastus lateralis muscle was determined in patients with amyotrophic lateral sclerosis and control subjects by flameless atomic absorption spectrophotometry. No statistically significant differences were found between these groups, and in both the figures were of the same magnitude as those earlier reported for normal individuals. Increased plasma lead concentrations do not seem to cause a significant deposition of lead in skeletal muscle. Therefore, plasma rather than skeletal muscle is the more likely source if pathological amounts of lead enter the motoneurones via the retrograde axoplasmic flow in amyotrophic lateral sclerosis.


ECG monitoring of oral surgery patients receiving a local anesthetic. Cardiac arrhythmias were observed on continuous electrocardiographic tracings in 36 of 225 patients who were having oral surgical procedures with local anesthesia only. The arrhythmias were serious enough in five patients to cause alteration of the treatment. A stethoscope taped to the chest of every patient for checking before and during every procedure might be just as effective as an electrocardioscope.


Combined use of alphafetoprotein and amniotic fluid cell morphology in early prenatal diagnosis of fetal abnormalities. The combined use of alphafetoprotein (AFP) measurement and amniotic fluid cell morphology was assessed in 217 pregnancies with normal outcome (including 12 where an anterior placenta was traversed), and 52 where there was a fetal defect (25 cases of anencephaly, 21 of open spina bifida, 2 of exomphalos, 2 of urogenital atresia, and 2 of intrauterine death). In each case maternal serum and amniotic fluid AFP was measured. Total, viable, and rapidly adherent cells were counted and amniotic fluid cell morphology was examined. On the basis of this experience a scheme is suggested for more precise antenatal diagnosis of fetal abnormalities.


Quantitation in biological X-ray microanalysis, with particular reference to histochemistry. Thin specimens consisting of various light and heavy elements in gelatine have been subjected to X-ray microanalysis to determine the relationship between the number of X-ray counts for a specific element expressed as a percentage of the continuum (the percentage counts) and the concentration of that element. For light elements, the relationship between the percentage counts and concentration is strictly linear. For heavier elements, the relationship is not linear, because of the increase of the continuum counts with (formula: see text). If a correction is made for the effect of (formula:see text), heavy elements also show a linear relationship between percentage counts and concentration. Within the limits of atomic number (Z = 56) and concentration (approximately 10%) studied here, it is shown that when X-ray microanalysis is carried out on bulk specimens consisting of various elements in gelatine, the relationship between X-ray counts and concentration for a particular element is linear. The problems in quantitation of the results of X-ray microanalysis caused by exogenous continuum and mass loss induced by irradiation are discussed. It is pointed out that when X-ray microanalysis is used to study histochemical and other staining procedures, allowance must also be made for the reduction in concentration of other elements in the specimen as a result of the addition of the stain to the specimen.


Presence of a mouse mammary tumor virus-related antigen in human breast carcinoma cells and its absence from normal mammary epithelial cells. Antigen(s) related to the major external glycoprotein (gp52) of mouse mammary tumor virus was detected in the human breast cancer cell line MCF-7. No such antigenic determinants were detectable in normal human mammary epithelial cells.


Videotape aids informed consent decision. Obtaining informed consent for clinical investigations represents a major legal, ethical, and moral consideration in human experimentation. Mechanisms for informing the patient vary widely, and usually no system exists to confirm the degree of information retained by the patient. A Veterans Administration Cooperative Study, begun in 1975, has used a videotape information package in addition to a standard written consent form to ensure uniformity. Each presentation was followed by a questionnaire to assess the amount of material learned before attempting randomization. Repeated showings were occasionally necessary and did not affect the rate of randomization. A videotape presentation, especially in cooperative studies, ensures uniformity, makes allowance for varying educational levels of patients, and provides documentation of the degree of informed consent.


Fetal proteins in various tumors.

Fetal proteins in various tumors. Radial immunodiffusion assay was used to measure fetal hemoglobin (HbF) concentrations in 312 patients with various malignancies. In 305 of these, alpha-fetoprotein (AFP) was measured by radioimmunoassay. The concentration of HbF exceeded 3 SDs above the normal mean in 68 of 312 patients, most notably in patients with leukemia, multiple myeloma, lymphoma, bladder carcinoma and testicular tumors. HbF was correlated with total hemoglobin concentration and with serum AFP concentration in hepatoma and bladder carcinoma.


Quantitative analysis of electrophoretically separated proteins using Coomassie blue. Electrophoresis of 125I-labelled rat albumin from 0.5 to 700 ng was performed with a 5 microliter capillary tube in which 4-40% continuous gradient polyacrylamide gel was prepared. The linear relationship was obtained by using double logarithm plots between protein amounts and densitometric areas of the protein bands stained with Coomassie blue. The radioactivities of the same gels and the protein amounts were also shown to be linear. In the case of rat gamma-globulin, the linear relationship was also obtained. As an applied example of this method, the urinary gamma-globulin excretion showed marked changes caused by the circadian rhythm in rats.


[Allorhythmias (classification and differential diagnosis)]. Allorhythmia in the broad sense is defined as a regular sequence of similar groups of ECG-complexes associated with various disorders of cardiac rhythm and conduction. The following classification of allorhythmias is suggested. A. True allorhythmias. I. Due to extrasystoles: 1) noncomplicated; 2) complicated by disorders of conduction. II. Allorrhythmias due to ectopic rhythms with capture beats: 1) paroxysmal or nonparoxysmal ectopic tachycardia; 2) escaping rhythms. III. Allorrhythmias due to impulse conduction block: 1) II degree S--A block; 2) II degree A--V-block; 2, atrial flutter and atrial tachycardia with A--V-block 3 : 2, 4 : 2, etc. B. Pseudoallorrhythmias due to regular alterations in the shape of the QRS complex: 1) transient bundle-branch block; 2) transient WPW syndrome; 3) bidirectional tachycardia. Differential diagnosis of various types of allorrhythmia is of great importance in choosing the measures and methods for antiarrhythmic therapy.


[Second increase in plasma volume after single infusion of hydroxyethyl starch (author's transl)]. 6 patients without evidence for renal, hepatic or pancreatic disease were treated with intravenous infusions of 500 ml hydroxyethyl starch (6%) over a period of 60 min. In the course of the infusion we observed an increase in plasma volume from 2.72 +/- 0.101 to 3.36 +/- 0.141. After 2 h plasma volume decreased to 3.02 +/- 0.101 but showed a second peak of 3.23 +/- 0.121 after 4 h (p less than 0.01). 24 h following infusion an increase in plasma volume of 4,8% was found as compared to preinfusion values. The second increase in plasma volume cannot be explained by the total concentration of hydroxyethyl starch since the latter decreased continuously. The increase in plasma volume was accompanied by a decrease in average molecular weight (-Mw and -Mn). It is suggested that serum amylase produces small osmotic active molecules by degradation of hydroxyethyl starch, thus leading to an increase in plasma volume. 12--24 h after the infusion of hydroxyethyl starch serum amylase was more than twice as high basal values. This is caused by the formation of a high molecular hydroxyethyl starch-amylase-complex which cannot be eliminated easily. When hydroxyethyl starch is given repeatedly to normovolemic patients, the second increase in plasma volume should be considered as a possible cause for acute hypervolemia. This is especially true for patients with myocardial insufficiency.


Protective effect of propranolol in threatened myocardial infarction. Propranolol 0.1 mg/kg intravenously followed by 320 mg orally over 27 h was given to 20 randomly selected patients within 4 h of the onset of suspected myocardial infarction unaccompanied by diagnostic electrocardiographic changes. Patients given propranolol had fewer completed infarcts as assessed by serial electrocardiograms, a lower frequency of serum-creatine-kinase levels above the normal range, and lower peak serum-creatine-kinase levels than 23 control subjects. This evidence suggests that threatened myocardial infarction can in some cases be prevented by early beta-adrenoceptor blockade.


Antenatal diagnosis of sickle-cell anaemia by D.N.A. analysis of amniotic-fluid cells. The polymorphism of a restriction endonuclease site has been used for antenatal diagnosis of sickle-cell disease. In a normal person, the beta-globin gene was contained in a Hpa I-digested D.N.A. fragment 7.6 kilobases (kb) in length. In a family where the sickle gene was contained in a variant 13.0 kb fragment, restriction endonuclease mapping was used for antenatal diagnosis. The D.N.A. from amniotic-fluid cells produced both the 7.6 and the 13.0 bk beta-globin gene fragments, indicating the diagnosis of sickle-cell trait. This confirmed the diagnosis reached after investigation of a 100% sample of fetal blood. The method is sensitive and can be performed with cells obtained from 15 ml of uncultured amniotic fluid. This approach may prove useful in antenatal diagnosis of other genetic disorders.


Controlled trial of hyposensitisation to Dermatophagoides pteronyssinus in children with asthma. Hyposensitisation with Dermatophagoides pteronyssinus tyrosine absorbate in asthmatic children with bronchial sensitivity to D. pteronyssinus was effective in a 12-month double-blind controlled clinical trial. Compared with controls, treated children used a smaller quantity of drugs while maintaining clinical and lung function improvements. In most children who improved there was no change in immediate response to D. pteronyssinus on bronchial provocation test, but the late reaction was lost in half the patients and these showed the greatest improvement in symptoms.


Renal transplantation in insulin-dependent diabetics. A joint Scandinavian report. Since 1970 renal transplantation has been carried out in 146 insulin-dependent diabetic patients with renal failure. Patient-survival at one year was 60%, and at two years it was 50%. One-year survival among 25 patients with living donor transplants was 84%. Survival was significantly reduced in patients with heart-disease, impaired vision due to diabetic retinopathy, and a long history of diabetes. Survival was not influenced by sex, age, neuropathy, or pre-transplantation dialysis. Diabetic retinopathy progressed slowly after successful transplantation, and more than 90% had stable vision one to two years after transplantation. Progression of peripheral circulatory insufficiency was common and severe enough to necessitate amputation(s) in 18 patients. One and two years after successful transplantation less than 10% of the patients with a functioning graft needed constant hospital care, and more than 50% were able to work.


Identification of Ureaplasma urealyticum (T-strain Mycoplasma) in patient with polyarthritis. A 10-year-old boy with confirmed congenital agammaglobulinaemia presented with polyarthritis while on gammaglobulin replacement therapy. Initial cultures of material aspirated from an abscess and of joint fluid were negative, and symptoms progressed despite antibiotic therapy. Synovial-biopsy material, cultured specifically for mycoplasmas, was positive for Ureaplasma urealyticum as were the blood, abscess fluids, throat-swab, and nasopharyngeal secretions. Therapy, based on in-vitro studies of antibiotic susceptibilities of the organism, resulted in the eradication of the infection and resolution of the arthritis. These findings suggest that U. urealyticum may be capable of inducing polyarthritis in man.


A diagnostic sign in states of apparent unconsciousness. Deviation of the eyes towards the ground with the patient lying on each side is proposed as a diagnostic sign in psychogenically mediated states resembling coma or epilepsy. Six cases are described in which the sign was elicited.


Cyclic A.M.P. and arrhythmias revisited. Further evidence is presented for a hypothesis linking cyclic adenosine 3', 5' monophosphate (cyclic A.M.P.) and arrhythmias: in the isolated rat heart, changes in tissue cyclic A.M.P. are accompanied by changes in the ventricular-fibrillation threshold; and in the pig, large infarcts are associated with raised tissue cyclic A.M.P. and ventricular fibrillation, whereas small infarcts are not. Data showing that changes in the metabolism of potassium, glucose, fatty acids, and lactate can influence the action-potential duration are incorporated into a revised hypothesis which allows for multifactorial arrhythmogenic mechanisms in the early stages of acute myocardial infarction.


Digoxin prescribing in general practice 1967--77. Data from a survey of general-practitioner prescribing from 1967 to 1977 were examined to see how news of the changed potency of "Lanoxin" tablets in 1972 and of unbranded digoxin in 1975 had affected prescribing patterns. A stong downward trend in average daily dose was found, equivalent to a halving in lanoxin, almost as much in digoxin, and a one-fifth fall in prepared digitalis. This trend, however, preceded the publicity on potency and bioavailability, and in the case of lanoxin was apparent during the time that bioavailability fell. It had two components--reduced frequency of tablets per day, and increased popularity of low-dose tablets. From 1972 the proprietary 250 microgram tablet of lanoxin was prescribed increasingly at the expense of unbranded digoxin, but at a lower daily frequency until 1975. The number of people treated with digoxin and lanoxin has risen overall and constitutes perhaps 6% of those over 65. The determinants of prescribing behaviour are complex.


Can the initial clinical assessment of thyroid function be improved? The clinical reasons for requesting in-vitro thyroid-function tests were studied in 500 consecutive new patients with no known history of thyroid disease. 23 patients presented with five or more signs or symptoms of thyroid disease, and 18 of these required treatment for thyrometabolic dysfunction. Of 35 subjects with three or four thyroid-associated signs or symptoms, only 1 came to treatment. Of 442 subjects with one or two signs or symptoms, 2 were subsequently treated. These results suggest that there is little value in the biochemical investigation of patients who present with minimal clinical evidence of thyrometabolic disease.


Double-blind withdrawal trial of azathioprine as maintenance treatment for Crohn's disease. 51 patients with Crohn's disease who were in good health while taking azathiprine, 2 mg/kg body-weight/day, for at least six months were allocated either to a group in which azathioprine was continued or to one in which a control tablet was substituted. The trial lasted one year unless relapse recurred earlier. The cumulative probability of relapse was nil at six months and 5% (+/-5 S.D.) at a year among those on azathioprine, compared with 25% (+/-9 S.D.) at six months and 41% (+/-11 S.D.) at a year among those in the control group (P less than 0.01). 1 patient in whom azathioprine was continued died of pancytopenia in the fourth month of the trial. Azathioprine is potentially toxic but appears to reduce the relapse-rate in Crohn's disease.


Sympathetic nervous system and blood-pressure control in essential hypertension. In normotensive subjects an inverse correlation was observed between an index of sympathetic nervous activity (the plasma-noradrenaline concentration during physical exercise) and reactivity to exogenous noradrenaline. This relationship was invariably disturbed in age-matched patients with essential hypertension. Multiple-regression analysis revealed a highly significant correlation between the combination of both factors and the height of mean arterial blood-pressure (r=0.91). The findings suggest that sympathetic nervous activity and pressor response to noradrenaline together form an important determinant of the arterial blood-pressure level. An inverse relationship could be demonstrated between plasma-renin concentration and pressor response to angiotensin II in normotensives, and this relationship was unchanged in hypertensive patients. Therefore angiotensin II does not appear to contribute directly to high blood-pressure.


Early splenomegaly in homozygous sickle-cell disease: An indicator of susceptibility to infection. 135 children with homozygous sickle-cell (SS) disease diagnosed at birth have been followed for 1--5 years. Severe bacterial infections were confined to those in whom the spleen was first palpable at or before 1 year of age and were commonest in those in whom the spleen was first palpable at or before age 6 months. Regular follow-up of children with SS disease diagnosed at birth will identify children particularly at risk of severe infections.


Acceleration of bone-marrow recovery by pre-treatment with cyclophosphamide in patients receiving high-dose melphalan. 7 patients with advanced malignant melanoma who were given cyclophosphamide (500 mg intravenously) 7 days before a high dose of melphalan (140 mg/m2) had a more rapid recovery of the peripheral white-cell count than did 4 patients who received melphalan alone. "Priming" by cyclophosphamide might be a practicable means of offsetting the bone-marrow toxicity of some chemotherapy regimens and it may permit higher doses of drugs to be given safely.


Stomach as source of bacteria colonising respiratory tract during artificial ventilation. 10 adults had intermittent positive-pressure ventilation for 3--34 days. All 10 had paralytic ileus. Microbial overgrowth in the stomach was found in 9 patients (bacterial in 7 and fungal in 2); gram-negative bacteria predominated. The trachea invariably became colonised by bacteria, mainly gram-negative organisms. In 3 instances the gram-negative bacteria were found in the stomach before they appeared in the tracheal aspirate, and in 1 case the pathogen originated in the faeces.


Renin lowers blood-pressure.

Renin lowers blood-pressure. The hypothesis that increased plasma-renin tends to lower blood-pressure is proposed. Binding of renin to blood-vessel walls is postulated to have some vasodilator action which would oppose the usual blood-pressure-raising action caused by generation of angiotensin. Many of the effects of saralasin and of converting-enzyme inhibitor on blood-pressure in relation to concentrations of renin in blood plasma and in the kidneys seem to support this hypothesis.


Campylobacter enteritis associated with canine infection. Campylobacter fetus ss. jejuni has recently been recognised as a human enteric pathogen. Five cases of campylobacter enteritis are described. All five patients had abdominal pain and diarrhoea. Two of the five patients had bloody diarrhoea and relapses. All the patients had been in contact with young dogs which had had diarrhoea. Campylobacter fetus ss. jejuni was isolated from these dogs or from their litter-mates. Canine infection with Campylobacter fetus ss. jejuni may be an important source of infection causing diarrhoea in man.


Intermittent catheterisation in the management of children with neuropathic bladder. Twenty-three children with neuropathic bladder have been treated by intermittent catheterisation during the past 3 years. Twelve are now practically dry, nine are drier than before, and two have remained wet. Urinary infections have not been a major problem, but it is too soon to assess the long-term effects on the upper renal tract. Intermittent catheterisation lightens the burden for the mothers. Four children catheterise themselves and two of them are now independent.


Endoscopic treatment of biliary-tract diseases. An international study. Data on endoscopic sphincterotomy from 15 gastroenterology centres with very wide experience show that 3618 out of 3853 (93.%) attempts at the procedure were successful. The main indication for sphincterotomy was choledocholithiasis (3070, or 84.9% cases). After sphincterotomy the stones passed spontaneously or were removed in 2779 (90.5%) cases. Bleeding, cholangitis, pancreatitis, perforation, and stone impaction occurred in 254 (7.0%) cases; the mortality-rate was 1.4%. 83 (2.3%) cases required emergency surgery. Endoscopic sphincterotomy is increasingly replacing surgery in the treatment of choledocholithiasis.


Levamisole in rheumatoid arthritis. A randomised double-blind study comparing two dosage regimens of levamisole with placebo. Multicentre study group. The therapeutic effect of levamisole in patients with rheumatoid arthritis was evaluated in a sixteen-centre double-blind controlled study which compared continuous and intermittent levamisole treatment with placebo for six months. 363 patients with classic or definite rheumatoid arthritis and active disease were evaluated. Continuous and intermittent levamisole treatments were equally effective in controlling disease activity. 20% of patients had important drug-related adverse reactions. The results demonstrated that levamisole is an active drug in patients with rheumatoid arthritis.


Cot deaths and water-sodium.

Cot deaths and water-sodium. Over a thirty-year period in Scunthorpe, during which there were two changes in the sodium content of the water supply, there were significantly more sudden deaths in infancy during the decade when sodium levels were highest. This is compatible with the hypothesis that hypernatraemia is a factor leading to cot death. Changes in the incidence of breastfeeding over the same period may have contributed to, but are unlikely to account for, the result because the pattern was different in a neighbouring district where there was no change in water quality.


Fulminant necrotising enterocolitis associated with Clostridia. 5 infants with no growth of bacteria on cultures of blood and peritoneal fluid recovered from necrotising enterocolitis after medical treatment alone. 12 infants with positive cultures required surgery. 5 of these 12, who did not harbour clostridia, had a mild clinical course and all 5 survived segmental bowel resection. The 7 infants who harboured clostridia had a more severe clinical course and 4 died. In 3 of 4 infants with Clostridium perfringens, the necrotising enterocolitis was fulminant, characterised by severe pneumatosis intestinalis, extensive gangrene, early intestinal perforation, and a fatal outcome.


Transformation of normal bone-marrow cells by a leukaemic cell line associated with a presumptive new human virus. Intracytoplasmic leukovirus-like bodies were found in the cells and culture medium of a T-cell lymphoblast line established from a leukaemic patient. When the cells were lethally irradiated and added to normal bone-marrow cells the latter were transformed into continuous replication and produced the same types of virus-like particle.


Pathogenesis of prolactin-secreting pituitary adenomas. 42 women with amenorrhoea and hyperprolactinaemia had trans-sphenoidal surgery and resection of histologically verified pituitary adenomas. 74% of these patients developed amenorrhoea and/or galactorrhoea in immediate association with the use or discontinuation of oral contraceptives or post partum. There was enough adenomatous tissue for immunocytochemical studies in 35 specimens and specific localisation of prolactin was possible in 31. There is evidence that about 10% of the population have small pituitary tumours, and the majority of these tumours, though asymptomatic, are potentially prolactin-secreting. It is suggested that oestrogens, which are known to modulate prolactin secretion in normal human beings and in animals, can induce the growth and expression of otherwise silent pituitary lesions and that this should be considered a risk of oral-contraceptive use.


Surgical treatment for recurrent herpes simplex. Superficial epidermal surgical removal of a recurrent herpes simplex lesion within 36 hours of onset nearly always prevented recurrence in the site of excision. It is postulated that the surgery results in epidermal denervation, which prevents reinoculation of that epidermal site by the virus-laden sensory neuron. The procedure did not prevent further clinical expression of the disease at other epidermal sites innervated by the same or other infected neurons.


Selective inactivation of vitamin B12 in rats by nitrous oxide. Exposure of rats to nitrous oxide rapidly inactivated the cytosol enzyme, methionine synthetase, but the mitochondrial enzyme, methylmalonyl CoA mutase, seemed to be unaffected, although both enzymes require vitamin B12.


Is pulmonary dysfunction the common denominator for the multiple effects of cigarette smoking? It is suggested that pulmonary dysfunction underlies the many diverse and apparently non-specific effects of cigarette smoking. The differences in degree as well as type of clinical expression probably derive not only from the multiplicity of constituents of the tobacco itself but also from the variation in vulnerability of different individuals and different target organs, which is attributable to other environmental exposures, previous history, and intrinsic susceptibility.


Epidemiology of respiratory viral infection among paediatric inpatients over a six-year period in north-east England. During a 6-year, hospital-based study at Newcastle upon Tyne five consecutive winter epidemics of respiratory syncytial (R.S.) virus infection occurred; the virus was identified in 1428 cases, showing that 1 in 50 live-births were admitted to hospital with R.S. virus infection. Epidemics were inversely related to temperature and to number of hours of sunshine. Parainfluenzaviruses, the second largest group of pathogens, were identified in 543 cases; most infections by this group were due to parainfluenzavirus type 3, which accounted for admission to hospital of 1 in 300 live-births. Epidemics of parainfluenza type 3 showed a summer peak (there was often a second peak in autumn) and a positive correlation with temperature and number of hours of sunshine. Epidemics of parainfluenza 1 and 2 occurred together, but only every 2 years. Influenza A epidemics occurred every winter; they coincided with, and had the same climatic correlations as, epidemics of R.S. virus infections. Influenza A was the second most frequently identified virus, and was associated with the admission to hospital of 1 in 100 to 1 in 500 live-births. Knowledge of the epidemiology of respiratory viral infections may help in the planning of preventative measures.


Hospital outbreak of Listeria monocytogenes septicaemia: a problem of cross infection? A 74-year-old man was admitted to hospital with septicaemia and meningitis caused by Listeria monocytogenes. Subsequently 3 inpatients developed listeria septicaemia. Case-to-case transmission of the infection seems possible, although the method of transmission remains obscure.


Colonic bacterial activity, biliary cholesterol saturation, and pathogenesis of gallstones. The relation between colonic bacterial metabolites in bile and saturation of bile with cholesterol was investigated. Eleven healthy men ingested metronidazole (2 g daily) for 10 days to inhibit anaerobic bacterial activity. Bile composition was determined in fasting samples aspirated from the duodenum before metronidazole was given, at the end of 10 days on metronidazole, and a month after the drug was discontinued. Bile cholesterol saturation fell in ten of the eleven subjects from a mean of 1.00 to 0.83 and rose in all eleven after the drug was stopped. At the same time the proportion of deoxycholate in bile acid decreased from a mean of 24% to 7%, returning to 22% of the total a month after metronidazole had been stopped, and the proportion of chenodeoxycholate changed significantly from 33% to 46% and back to 33%. There was little change in cholate concentrations. Deoxycholate is formed exclusively by bacterial action in the colon. Its administration increases cholesterol saturation of bile, while chenodeoxycholate reduces it. These results suggest that colonic function is important in regulating bile composition. Dietary measures which reduce the return of newly formed deoxycholate from the colon to the bile reduce cholesterol saturation and so are likely to reduce the risk of gallstones.


Strong association between membranous nephropathy and hepatitis-B surface antigenaemia in Japanese children. Renal histology in 163 Japanese children, aged 3 to 15, with proteinuria and/or haematuria showed that 11 had membranous nephropathy (M.N) and the rest had various other renal diseases. Hepatitis-B-virus surface antigen (HBsAg) was identified, by a reversed passive haemagglutination method, in the serum of all the patients with M.N. but in only 4.6% of the patients with other renal diseases. 6 of the 11 mothers of the children with M.N. were positive for HBsAg, and 1 was positive for antibody to HBsAg (anti-HBs). These findings suggest that M.N. in Japanese children is mainly, if not exclusively, caused by hepatitis-B virus and that in most instances the virus is transmitted from mother to child.


Effect of cimetidine in symptomatic gastro-oesophageal reflux. Twenty-seven patients with symptomatic gastro-oesophageal reflux received cimetidine 1.6 g daily for 6 weeks and matching placebo for 6 weeks in a randomised double-blind crossover trial. They complained of significantly more episodes of pain on placebo than on cimetidine (1186 vs 581) and consumed significantly more antacid tablets on placebo than on cimetidine (1645 vs. 1011). Cimetidine and placebo had similar effects on mucosal sensitivity to acid and on oesophagitis assessed endoscopically and histologically, suggesting that the symptomatic benefit is the result of a simple antacid effect.


An unrecognized syndrome of benign focal epileptic seizures in teenagers? 145 out of 1570 patients whose first fit occurred between the ages of 10 and 20 years and began as a focal seizure had no further fits for at least 5 years. This benign (non-recurring) form of focal seizures appears to be a distinct clinical entity. Its features, based on an analysis of the case-notes of 83 of the 145 cases, include: appearance of fit between the ages of 12--18 years in 84% cases; a higher incidence among males; an absence of family history of fits and of other factors predisposing to fits; normal electroencephalogram (E.E.G.) or non-specific, non-focal E.E.G. changes; and progression to generalised fits in 80.3%. The diagnosis can be suspected at presentation but confirmed only after a recurrence-free period without treatment.


Possible maternal effect on severity of neurofibromatosis. 62 patients with neurofibromatosis (from 54 families) whose signs or symptoms began in childhood were assessed as to the severity of disease and whether the individual was a new mutation or born to an affected father or mother. The morbidity of disease was much more severe in cases born to affected mothers than in those born to affected fathers or those who were new mutations. This finding suggests that there may be a maternal effect in neurofibromatosis similar to that which has been observed in myotonic dystrophy. This effect may be humorally mediated.


Cold-induced profuse sweating on back and chest. A new genetic entity? Two sisters whose parents shared a grandfather had cold-induced sweating. Since childhood they had sweated profusely from the back and chest when exposed to environmental temperatures of 18 degrees to 7 degrees C. They had additional abnormalities--e.g., high palate and inability fully to extend the elbows--which neither their parents nor their sibs shared. The cold-induced sweating, which could not be stopped by a beta-adrenergic blocking agent, was abolished by postganglionic blockade with atropine sulphate. This indicates the possibility of a peripheral mechanism.


Prostacyclin can replace heparin in haemodialysis in dogs. Despite the use of heparin, activation of platelets on the artificial surface of dialyser membranes results in thrombus formation, microembolisation, and thrombocytopenia. To assess the effects on these events of prostacyclin, the most potent inhibitor of platelet aggregation yet discovered, three groups of healthy greyhounds were dialysed with heparin, heparin plus prostacyclin, or prostacyclin alone. Prostacyclin, either alone or with heparin, abolished microembolisation from the dialyser (as estimated by whole-blood screen filtration pressure) and prevented thrombocytopenia. With prostacyclin, dialysis could be carried out without heparin, and there was no clotting of blood within the extracorporeal circuit nor any change in tests of coagulation.


Lack of a gastrointestinal mediator of insulin action in maturity-onset diabetes. It is suggested that hepatic uptake of orally ingested glucose depends not only on insulin secretion but also on the release of a gastrointestinal factor which mediates insulin action on the liver. In maturity-onset diabetes characterised by hyperinsulinaemia and insulin resistance, deficiency of this gastrointestinal factor may be the primary pathogenetic event leading to postprandial hyperglycaemia. Postprandial hyperglycaemia brings about an increase in insulin secretion; and hyperinsulinaemia, in turn, results in decreased binding of insulin to its receptor and in peripheral (extrahepatic) resistance to insulin.


Further experience in the treatment of severe attacks of ulcerative colitis. One hundred courses of an intensive intravenous regimen have been used in 87 patients with severe attacks of ulcerative colitis during the past 5 years, 11 of the patients having been treated more than once during separate admissions to hospital. 60% of the attacks responded swiftly to the regimen, and the patients were symptom-free at the end of the 5-day course. In 15% there was improvement but the patients were not entirely symptom-free. In 25% failure to respond resulted in emergency colectomy, the usual operation being proctocolectomy as a single-stage procedure. There were no deaths directly due to ulcerative colitis or to surgical treatment in these patients during the period of the study, the mean period of follow-up being 25 months; but 4 elderly patients died from unrelated causes. These favourable results are better than most published figures. The advantages of the intensive medical regimen are that: (i) many patients quickly go into clinical remission, which is frequently sustained; and (ii) failure to improve can be regarded as a clear-cut indication for emergency surgery.


Diarrhoea and pseudomembranous colitis after gastrointestinal operations. A prospective study. 241 patients who had gastrointestinal operations were studied prospectively. Postoperative diarrhoea occurred in 58 patients (24%) and was significantly more common after exposure to antibiotics. 9 patients (4%) had high titres of a neutralisable faecal toxin characteristic of pseudomembranous colitis. Toxigenic Clostridium difficile strains were isolated from the stools of all patients with neutralisable faecal toxin. If pseudomembranous colitis is defined as the presence of neutralisable faecal toxin, then the diagnosis is often missed by sigmoidoscopy and rectal biopsy.


Association between Streptococcus faecalis urinary infections and graft rejection in kidney transplantation. In the first month after transplantation 50% of 193 consecutive renal transplant recipients had bacteriuria. The most common organisms isolated were Streptococcus faecalis (34), Escherichia coli (28), Pseudomonas spp. (11), and staphylococcus (9). There was a significant correlation between infection with Str. faecalis and graft failure at one, three, and twelve months. This observation suggests that urinary infection with Str. faecalis may be associated with graft failure which is probably the result of immunological factors.


Kidney-graft rejection: has the need for steroids to be re-evaluated? In a group of azathioprine-treated patients whose renal allografts functioned immediately, 53 received prophylactic steroid treatment while 54 were given steroids only at the onset of the first renal failure. Three types of renal failure were identified, and their distribution in the patient groups was different, but the incidence of both reversible and irreversible renal failure episodes was identical in the two groups, suggesting that steroid treatment of early rejection episodes may not be necessary.


Isolation of a new serotype of legionnaires' disease bacterium. A new serotype of the legionnaires' disease bacterium has been isolated. The strain appears to be identical with the Philadelphia strain except for the cell-wall antigens as tested by a direct fluorescent antibody technique. Demonstration of a new serotype brings into question the diagnostic specificity of currently used reference strains.


Idiopathic cardiomyopathy, age, and suppressor-cell dysfunction as risk determinants of lymphoma after cardiac transplantation. A review of lymphomas developing in recipients of cardiac allografts has yielded significant risk factors. Frequency varied strikingly according to original cardiac disease: lymphoma developed in 6 of 37 patients with prior idiopathic cardiomyopathy (I.C.M.) but in one of 54 patients with prior coronary-artery disease (C.A.D.). All patients who developed lymphomas were aged under 40. Combination of both risk factors (I.C.M. and age less than 40) produces a sub-group with a highly significantly increased risk of lymphoma. I.C.M., but not C.A.D., is characterised by a defect in mitogen-induced mononuclear-cell suppressor activity. It is postulated that defective regulation in the immune systems of younger patients under chronic alloantigen stimulation may allow lymphoid proliferation to proceed to lymphoreticular malignancy. Immunosuppressive agents such as azathioprine may exert a co-oncogenic effect.


Laryngeal malignancy following iodine-125 therapy for thyrotoxicosis. A 52-year-old woman presented with a laryngeal sarcoma eight years after receiving two doses, each of 30 mCi, of iodine-125 for thyrotoxicosis. That extrathyroidal tissue receives a higher radiation dose of low-energy photon radiation from iodine-125 than from an equivalent microcurie dose of iodine-131 and that the tumour was of a type which rarely arises spontaneously in the larynx suggest a possible link between the development of the tumour and iodine-125 therapy.


Aspirin prophylaxis in migraine.

Aspirin prophylaxis in migraine. A prospective double-blind trial of aspirin prophylaxis demonstrated a reduction of more than 50% in headache frequency in 9 of 12 migraine patients. Response to aspirin did not correlate with age, duration of headache history, family history, or platelet ultrastructure. There is some evidence that response to aspirin is associated with raised platelet aggregation. This pilot study indicates that aspirin is effective in migraine prophylaxis.


Does ethanol intoxication promote brain infarction in young adults? 76 consecutive patients aged under 40 with ischaemic brain infarction verified by carotid angiography and/or serial brain scanning were studied. In at least 15 cases (20%) the onset of symptoms was preceded within 24 hours by a bout of alcohol drinking. Ethanol-related cases comprised 40%, 25%, and 13% of the patients in the age-groups 16-19, 20-29, and 30-39 years, respectively. Ethanol intoxication preceding the stroke was 2-3 times as common in male and 3-4 times as common in female patients as ethanol intoxication in the general Finnish population of the same ages and sex. Occasional ethanol intoxication seems to carry an increased risk of ischaemic brain infarction in young adults.


Urinary infection after micturating cystography. Out of 87 patients who underwent micturating cystourethrography (M.C.U.) 14 had infection at the time of the procedure, and infection later developed in 18 patients. The occurrence of post-M.C.U. infection was significantly influenced by whether the patient was on antibacterial treatment at the time of the procedure, but not by the sex of the patient, difficulty of catheterisation, or radiological abnormality. Hence, antibacterial prophylaxis should be given, and subsequent urine culture is mandatory.


Frapper fort ou frapper doucement: a gram-negative dilemma. Although antibiotics can clear gram-negative organisms from the circulation in a short time, large numbers of patients continue to die from gram-negative shock. Research carried out more than 25 years ago indicates that the replacement of the current antibiotic approach of "frappez fort et vite" by one of "frappez doucement" may reduce the incidence and mortality of gram-negative shock.


Hairy cell leukemia: a review.

Hairy cell leukemia: a review. Hairy cell leukemia is a chronic but steadily progressive malignancy usually of older males. Clinically, patients present with splenomegaly and/or cytopenia. The diagnosis is made by demonstration of the hairy cell in Wright's-stained peripheral blood and in bone marrow and by the characteristic histologic findings in the bone marrow biopsy and spleen sections. Infection is the most significant problem complicating the course of patients with hairy cell leukemia and the role of granulocytopenia and/or monocytopenia is undoubtedly substantial. Splenectomy has produced an objective response in improving hematologic parameters in a large number of patients and may prolong survival in those patients who respond. The precise nature of hairy cells remains unknown. The cells exhibit features of both monocytes and B-lymphocytes in morphologic, cytochemical, immunologic and functional studies. A more complete understanding of the monocytic and lymphocytic stem cells and their maturation may provide insight into the origin of the hairy cell.


Antigenic variability of Aspergillus fumigatus strains. The effect of culture media, temperature of incubation, and continuous shaking of cultures, on the reactivity and yield of antigens of Aspergillus fumigatus were evaluated. It was found that AOAC medium was superior to Czapek medium and shake cultures yielded better results than stationary cultures. However, antigens from stationary cultures in AOAC medium incubated at 30 degrees C for 3 weeks were equally as good as antigens obtained from 2-week-old shake cultures. Antigens from 11 selected strains of Aspergillus fumigatus were used to test antibody activity in 33 sera from patients with various forms of aspergillosis and 35 normal controls by the agar gel double-diffusion method. The results showed that the reactivity of individual antigens varied from 42 to 87%, indicating that antigens from more than one strain of Aspergillus fumigatus may be used. The cross-reactivity between strains were studied by two-dimensional immunoelectrophoresis. The use of polyacrylamide gel electrophoresis and crossed immunoelectrophoresis in the quality assurance of Aspergillus antigens is discussed.


Observations on the nucleolar staining by ethanolic phosphotungstic acid. In addition to the already known reactivity of heterochromatin masses and synaptonemal complexes for ethanolic phosphotungstic acid, nucleoli from Sertoli cells show a preferential electron microscopic staining of the pars fibrosa. This ultrastructural pattern can be correlated with intranucleolar differentiations observed in light microscopy after staining of semithin sections with Unna's polychrome blue.


Quantitative microspectral evaluation of the ratio of arginine-rich to lysine-rich histones in neurons and neuroglial cells. Staining of nervous tissue sections with ammoniacal silver according to Black et al. has been confirmed to be a reliable histochemical colour reaction for quantitative evaluation of arginine-rich and lysine-rich histones in cell structures on the basis of determinations of the position of spectral curve maximum. Neurons of several brain nuclei which differed in predominating neurotransmitter did not differ in the ratio of arginine-rich to lysine-rich histones while some differences in this ratio were found out in the glial satelite cells adjacent to the corresponding neurons of these nuclei. Moderate circadian fluctuations were observed in the arginine-rich to lysine-rich histone ratio, these fluctuations being rather similar in the neurons studied and in the cells of perineuronal neuroglia.


[Chromatin staining with thallium in NK/Ly ascites tumors of various ages]. Staining of the chromatin in the NK/Ly ascitic tumour was studied by electron microscopy using Mentré's thallium method. Investigations were carried out on the 2., 7., 9., and 14th days after the transplantation of the tumour. It was established, that the chromatin of the nuclei of the proliferating--2 days old--tumour cells occurs in dispers form. Later the temp of the growth decreases and as the consequence of the aggregation of the chromatin electrodense areas are formed. Authors assume, that on the base of the morphological alterations transformation of diffuse chromatin into aggregated one depression of the gene-substance might lie.


Bleomycin-induced mutation and recombination in Saccharomyces cerevisiae. Clinical preparations of bleomycins (BM) were tested for their recombinogenicity and mutagenicity at relatively high survival levels in the simple eucaryote, Saccharomyces cerevisiae. More than a dozen test loci or genetic intervals were assayed for bleomycin-induced mutation or recombination. Treatments of stationary phase diploid yeast routinely results in 25--75% inactivation. The antibiotic was mildly to very highly recombinogenic and mutagenic, with one exception. The amount of bleomycin-induced mutation, gene conversion or crossing-over depended upon the particular genetic markers assayed. The drug was also potently recombinogenic in yeast cells growing in the presence of BM. These results contrast with the finding that this antitumor agent was not mutagenic in the Salmonella/mammalian microsome mutagenicity test; possible explanation of this difference are given.


Increased plasma protein binding of propranolol and chlorpromazine mediated by disease-induced elevations of plasma alpha1 acid glycoprotein. To assess the importance of disease-induced increases in plasma concentrations of alpha1 acid glycoprotein (an acute-phase plasma protein that binds cationic drugs), we determined binding of propranolol in plasma from 53 patients and 25 healthy volunteers. Binding was increased in 10 patients with Crohn's disease (P less than 0.002), nine with inflammatory arthritis (P less than 0.002) and eight with chronic renal failure with superimposed inflammatory disease (P less than 0.01) as compared with healthy controls. The plasma binding of control subjects did not differ from that of 12 patients with chronic hepatic disease (P greater than 0.45) or 14 with uncomplicated renal failure (P greater than 0.80). Chlorpromazine binding, determined in 60 subjects, yielded similar results. Percentage of free drug and alpha1 acid glycoprotein concentration were inversely correlated (r = -0.77 with propranolol, P less than 0.001, and r = -0.69 with chlorpromazine, P less than 0.001). Increases in plasma protein binding in patients with inflammatory disease appear mediated by increases in alpha1 acid glycoprotein concentration, which may influence drug kinetics.


Surface antibodies of human myelogenous leukaemia leukocytes reactive with specific type-C viral reverse transcriptases. Purified immunoglobin G (IgG) from patients with chronic myelogenous leukaemia specifically neutralised RT from feline leukaemia virus while purified IgG from other types of leukaemias and from normal blood cells were less reactive and in some cases preferentially reacted with RT from horizontally transmitted primate type-C viruses (simian sarcoma virus-gibbon ape leukaemia virus group). This indicates the presence of a heterogeneous immune response to RT or to an RT-like molecule in humans.


Serum beta2-microglobulin in hemodialyzed patients. beta2-Microglobulin (beta2-M) concentrations were measured by radioimmunoassay in 63 patients treated with maintenance hemodialysis. Serum levels ranged from 12.5 to 92 microgram/ml and were found stable upon sequential measurements over a 6-month period. Excretion of beta2-M was achieved through urinary loss (up to 150 mg/day) and to a lesser extent by ultrafiltration across acrylopolynitrile but not cellophane dialysis membranes. Proximal tubular cells being the major site of beta2-M catabolism, stable levels in anephric patients indicated a defective production of beta2-M in uremic patients. Serum beta2-M levels were not correlated with predialysis urea, creatinine, hematocrit or middle molecule material. In vitro experiments do not support a possible toxicity of purified beta2-M but do not rule out the contribution of other low molecular weight proteins to uremic toxicity.


[Parenteral feeding during aggressive chemotherapy of various neoplasms]. Cancer patients are often extremely cachectic. Therefore, they become poor risks for adequate chemotherapy. Consequently, they are either excluded from antitumor therapy or receive only reduced dosage regimens. Since the patient's response to cancer chemotherapy depends on immunocompetence which, in turn, is related to the nutritional state, adequate nutrition is the key to effective treatment. Parenteral nutrition, which in the literature is often referred to as hyperalimentation, can overcome and prevent cachexia. We treated 19 patients with advanced malignancies of various kinds using aggressive chemotherapeutic regimens and parenteral nutrition. The tolerance for chemotherapy in our patients was improved and the patients gained weight.


[Clinical relevance of serum alpha-1-fetoprotein determinations]. History, physiological and pathological properties and clinical significance of alpha-1-fetoprotein (AFP) are reviewed in detail. Present observations suggest that additional information can be expected from AFP-determination as an index for prognosis and response to chemotherapy in patients with AFP-producing tumors. Prenatal diagnosis of fetal distress-syndrome, screening for primary carcinoma of the liver (PLC) and malignant germ cell-tumors containing yolk sac-tissue, and postoperative controls of therapeutic efficiency are mentioned as main indications for an AFP-test. Especially encouraging are the results of a 4-year prospective study, in which 108 patients with PLC have been found among 4000 patients with hepatobiliar diseases. Diagnostic efficiency of AFP, 67-gallium-scanning and celiacography is demonstrated in 80 patients with autopically verified PLC. Overall diagnostic value with a combination of AFP and 67-Gacitrate was 93.8%. Further studies have been carried out, analyzing the histological findings in 8 patients with and 8 patients without AFP-producing hepatocellular carcinomas. A comparison of diagnostic efficiency of three AFP-test-methods with different sensitivity-limits has been done.


[Radiotherapy in bronchial neoplasms].

[Radiotherapy in bronchial neoplasms]. From the radiological point of view it can be concluded that: 1. Patients suffering from lung tumors usually seek treatment in an advanced stage of the disease. 2. In about one third of the cases, there is a manifestation of extrathoracic metastases already at the commencement of therapy. 3. Significant X-ray therapy depends on a) radiosensibility of the tumor to X-rays, b) the site and extent of the tumor. Although limited in its application, radiotherapy does not only improve the situation of the patient but also leads to a regression or temporary X-ray induced standstill of the growth of the tumor. However, if it is used as the sole treatment, it would scarcely lead to a permanent improvement. As recent advances in the treatment of lung tumors show, X-ray therapy combined with polychemotherapy will not only lengthen the survival time of the patient but will also improve the patient's life in general.


[Immune diagnosis of malignant diseases. X. Value of the electrophoresis mobility test in the diagnosis of broncho-pulmonary diseases]. The frequency of bronchial carcinoma has increased significantly during the last five years. The prognosis depends very much on early diagnosis. With non-invasive methods the diagnosis can often not be certified and the dignity of a tumor can often not be judged preoperatively. With the EMT a differentiation between malignant and non-malignant pulmonary diseases is possible. The EMT is an in vitro cancer test to detect specific sensitised lymphocytes. After incubation with the encephalitogenic factor (EF) lymphocytes of patients with malignant diseases release a factor that slows the mobility of tanned and sulphosalicylic-acid stabilised sheep erythrocytes (ETS) in an electrical field. 96 patients with pulmonary diseases were checked; all malignant pulmonary diseases but one showed an inhibition of the ETS mobility, while the controls showed an acceleration; in the groups with benign pulmonary diseases most patients showed an acceleration, only in sarcoidosis in four out of twelve patients a slight ETS inhibition was registered. The differences between both groups are significant (p less than 0.001). The EMT differentiates reliably in malignant and non-malignant diseases. False-negative results are obtained during radiation and chemotherapy. In connection with other diagnostic aids the EMT is a valuable diagnostic method, by which the early cancer detection can be improved and the prognosis of the patients bettered significantly.


[Mechanisms of competency of early embryonic tissues]. The results of the author's studies of cell competence at the early embryonic stages, are summarized. The experiments with the isolation of four animal blastomeres of the newt at the eight-cell stage of development have shown that the presumptive ectoderm is determined to the development into epidermis already at this very early stage. The electron microscopi study of epidermis developing from the explanted ectoderm has shown that by its ultrastructure it does not differ from the normal larval epidermis. The loss by the ectoderm of the competence to the development under the effect of various morphogenetic factors appears to be related to the synthesis of a protein inhibitor during gastrulation. The data on the role of cell surface, adhesion and cell affinity in the early development are considered. Differences in the structure of surface between the cells experienced and not experienced the inductive influence were revealed with the help of electron microscope. The results of studying the mechanism of reaggregation of the embryonic cells using concanavalin A are also provided.


[Immunochemical study of specific "pregnancy protein" during mammalian ontogenesis]. beta1-globulins were found in the rats and guinea pigs in the extracts of placenta during the first term of pregnancy in one third of cases and beginning from the second term in all cases; they were not found in the other organs. These proteins were also present in the blood serum of pregnant rats, guinea pigs, foetuses and in the amniotic fluid, their concentration being much higher than in the placenta.


Histologic identification of mast cells in human dental pulp. Previous investigators who attempted to identify mast cells in the dental pulp have used demineralizing or tooth-splitting procedures to obtain their tissue samples. However, Eda and Langeland15 found that the fluorescence of mast cells is destroyed by acid demineralizing agents. On the other hand, tooth splitting may damage the pulp by crushing it with forceps, or cutting and heating it with burs, stones, or discs. In the present study, we used the extirpated pulps from teeth in which endodontic access openings were made by means of high-speed rotary instruments with water spray. Metachromatic staining methods failed to demonstrate mast cells in any of the non-inflamed pulp specimens. Two of the inflamed pulp specimens revealed numerous mast cells which appeared intact and well preserved with no evidence of degranulation. As to the distribution of the mast cells, there was no correlation with the number and types of other inflammatory cells observed. Although several cells present in the specimens examined were suggestive of mast cells, only those cells that revealed definitive metachromasia were included in this study.


Organochlorine residues in aquatic environments in Iran, 1974. Organochlorine pesticide residues in various organisms from different aquatic ecosystems in Iran were investigated in spring 1974. DDT levels were high in fish taken from two rivers in southern Iran, whereas low levels were detected in samples obtained from a freshwater lake in the same area. Fish from two of the reservoirs supplying Tehran with potable water contained moderate levels of DDT. The low residue level in pike collected in the Bandar-Pahlavi Mordab in northwest Iran indicates that only a small amount of organochlorine pesticides used in this area enters the pelagic food chain. Sturgeon collected at different places in the Caspian Sea showed similar accumulations of DDT in the muscles and in the eggs. Polychlorinated biphenyls (PCBs) were detected only in samples of sediment from the drainage systems in Tehran.


Chlorinated hydrocarbon pesticide residues in Pacific oysters (Crassostrea gigas) from Tasmania, Australia--1973. Pacific oysters (Crassostrea gigas Thunberg) from 19 sites in Tasmania were surveyed for pesticide residues. All samples were analyzed for dieldrin and DDT, and five samples were analyzed for hexachlorobenzene (HCB) and lindane. Only DDT was found in all samples. Dieldrin levels were high in oysters from the Tamar River, but were highest (0.39 mg/kg wet weight) in samples from Ruffin's Bay. In contrast, other residue levels  were low. Distribution of pesticides in Tamar River samples differed: dieldrin could be correlated with industrial uses upstream and DDT could be correlated with low-level widespread agricultural use.


False spurs in quantitative immunoelectrophoresis. Antigens which show reactions of identity in double-diffusion tests in gel may cause spur formation in crossed immunoelectrophoretic techniques. To differentiate these misleading spurs from spurs of double-diffusion tests which show the true immunochemical relationship between antigens, we have denoted the former type "false spurs". False spurs are often formed in tandemcrossed immunoelectrophoresis and fused rocket immunoelectrophoresis when antigens with different electrophoretic mobility are compared. On the basis of model experiments, criteria are set up for accepting a spur as a true spur, and procedures are described for avoiding formation of false spurs in quantitative immunoelectrophoresis.


Identification of different antigenic determinants within the synthetic multichain Co-polymer poly(LTyr,LGlu)-poly(DLAla) -- poly (LLys), (T,G)-A--L, as recognized by the chicken. II. Fine-specificities of the anti-(T,G) part of chicken anti-(T,G)-A--L antisera. Sera from three chickens obtained from a genetic high-responder inbred strain immunized with the multichain polypeptide poly(LTyr,LGlu)-poly-(DLAla)--poly(LLys) (T,G)-A--L) were analysed for possible restrictions in the fine-specificities of anti-(LTyr,LGlu) antibodies. A panel of synthetic hexa- and heptapeptides composed of L-Tyr and L-Glu residues linked to a C-terminal spacer tripeptide, and with L-Tyr as N-terminal, were used as inhibitors in a double-antibody radioimmunoassay. Results showed that all peptides tested possessed some inhibitional potential, although the percentage of displacement for the different sequences varied between 43% and 58%,20% and 56%, and 48% and 85%, respectively, for the three sera tested at a given inhibitor concentration. Different peptide sequences appeared as the most efficient inhibitor in the three sera tested. No simple relationship was found between substitution/elongation of inhibitor peptides and their inhibitional potential, as would have been expected from a simple conception of (T,G)-A--L possessing only one sequential determinant. Possible evidence for conformational determinants in the (T,G)-A--L antigen is discussed.