Fate of transforming bacteriophage HP1 deoxyribonucleic acid in Haemophilus influenzae lysogens. The biological fate of temperate phage HP1 deoxyribonucleic acid (DNA) was followed after uptake by defectively lysogenic competent Haemophilus influenzae cultures. The similar inactivation kinetics of three single phage genetic markers and of their triple combination indicated a complete rather than partial destruction of about half of the adsorbed DNA molecules. Intracellular DNA breakdown products were tentatively identified by hydroxyapatite column chromatography as short single strands and extensively damaged short double strands. Integrated donor DNA (after single-strand insertion?) was still highly efficient for triple-marker co-transformation. This suggests that whole or nearly whole donor DNA molecules were integrated. Some donor DNA was never integrated but remained largely unaltered. This DNA fraction did not contain significant amounts of recipient prophage marker activity. It is concluded that it had not participated in some kind of reciprocal recombination event involving the recipient chromosome. Since very similar phage DNA marker inactivation rates were observed after adsorption by competent nonlysogenic recipients (transfection), the relationship between biological inactivation of adsorbed donor phage DNA and its integration in lysogenic recipients is not clear.


Single-strand regions in the deoxyribonucleic acid of competent Haemophilus influenzae. The deoxyribonucleic acid (DNA) of competent wild-type Haemophilus influenzae and rec1 mutant cells contains single-strand regions, as judged by alkaline sucrose sedimentation, benzoylated naphthoylated diethylaminoethyl-cellulose fractionation, and digestion with an enzyme specific for single-strand regions in DNA. In contrast, the DNA of competent rec2 cells does not contain single-strand regions. Since transforming DNA does not associate with recipient DNA in the rec2 mutant as it does in wild type and rec1, it is concluded that the single-strand regions in the DNA of the competent cells are important for an early step in recombination between cell DNA and transforming DNA.


Pediococcus cerevisiae mutant with altered transport of folates. A Pediococcus cerevisiae mutant that actively accumulated folate (PteGlu), in contrast to the wild-type, was also found to exhibit changes in the pattern of uptake of 5-methyl-tetrahydrofolate (5-CH3-H4PteGlu) and amethopterin. Most of the 5-CH3-H4PteGlue accumulated through a glucose- and temperature-dependent process, and a concentrative uptake was also found in gluocse-starved cells and in cells incubated at OC. About 75% of the accumulated 5-CH3-H4PteGlu exchanged with amethopterin. In contrast to the wild type, the mutant accumulated both diastereoisomers of 5-CH3-H4PteGlue by glucose-dependent and glucose-independent processes. Amethopterin and PteGlue competitively inhibited the uptake in both processes, with an apparent lower affinity of the carrier for PteGlu than for the analogue. p-Chloromercuribenzoate strongly inhibited the uptake (75%). The p-chloromercuribenzoate-nonsusceptible and temperature-independent uptake was also competed by amethopterin. Metabolic poisons like sodium azide, potassium fluoride, iodoacetate, and 2,4-dimitrophenol inhibited the glucose-dependent process. Uptake, in the absence of glucose, was enhanced by sodium azide and potassium fluoride.


Capsular polymer of Haemophilus influenzae, type b. I. Structural characterization of the capsular polymer of strain Eagan. The capsular type-specific antigen of Haemophilus influenzae, type b, has been reported to have a unit structure composed of D-ribose and phosphate. Recently, the presence of ribitol was found in preparations of type b capsular antigen. Our analytical results show equimolar proportions of ribose, ribitol, and phosphate. Periodate oxidation studies, paper chromatography of acidic and alkaline hydrolysates, and NMR spectral data indicate the structure of the capular antigen of H. influenzae b, strain Eagan to be a polyribosylribitol phosphate polymer.


The occurrence of actinlike filaments in association with migrating pigment granules in frog retinal pigment epithelium. In the retina of the frog and certain other animals, melanin pigment granules move in response to light so as to shield photoreceptor outer segments. The granules are contained within the cells of the pigment epithelium (PE) which lie as a continuous sheet between the neural retina and the choroid. Moderate illumination of the eye causes the melanin granules to move from a region within a PE cell body into numerous fingerlike extensions of the cell which interdigitate with the receptor outer segments. This migration takes many minutes and is reversed when the light falling on the eye increases in intensity. Several reviews are concerned with the early descriptions of this phenomenon (6,30) and with more recent experiments (1,5,19). The mechanism of the pigment granule motion is undetermined although there are studies concerning PE ultrastructure (8, 23, 31), scanning electron microscopy of the fingerlike extensions of the PE cells (27), the role of the PE in photoreceptor phagocytosis (32), the nature of the pigment granules (19), and the action spectrum of the light which induces the migration (16). This study reports the presence of a system of microfilaments associated with the pigment granules in the fingerlike extensions processes of the PE cells. We demonstrate by heavy meromyosin (HMM) labeling that the filaments are actinlike in character and suggest that these filaments could be responsible for the migration of the melanin pigment granules.


On the connection between the transverse tubules and the plasma membrane in frog semitendinosus skeletal muscle. Are caveolae the mouths of the transverse tubule system? The transverse tubular system (TTS) of skeletal muscle fibers represents the morphological basis for the inward spread of conduction of the electrical signal that triggers muscle contraction. A historical account of the main steps contributing to the elucidation of the structure and function of the TSS has been presented by Huxley (1971). While the localization of the TSS and its association with the sarcoplasmic reticulum (SR) is well documented; there is still a need further to develop our knowledge of the morphology of the connection between the TSS and the plasma membrane. It is generally believed that the TSS opens directly to the extracellular space and that there is continuity between its membrane and the sarcolemma. However, direct observation of such a connection has been clearly shown only for the myotome of fish (Franzini-Armstrong and Porter, 1964). In other muscle fibers, only indirect evidence of the connection has been provided by experiments showing penetration of extracellular tracers into the TSS. These extracellular markers were also observed inside another membrane-bounded compartment consisting of round profiles named "caveolae" (Yamada, 1955) or "pinocytotic vesicles" (Ashurst, 1969). The present study deals with the communication between the TTS, caveolae, and plasma membrane (Peachey, 1965); Ezerman and Ishikawa, 1967; Schiaffino and Margreth, 1968; and Rayns et al., 1968). A detailed study of the caveolae compartment was undertaken with ruthenium red as an electron-dense tracer. As a result of this study, we propose that in certain species the caveolae compartment represents the transitional region in the connection between the TSS and the sarcolemma.


[Hemobilia. (Apropos of 5 cases)].

[Hemobilia. (Apropos of 5 cases)]. Hemobilia or hemorrhage through the biliary tract is increasing in frequency. With spreading knowledge of the syndrome, the diagnosis is now rarely missed. There is also a real increase due to traffic accidents which often cause liver injuries. The typical triade with digestive hemorrhage, biliary colic and jaundice should always arouse suspicion of hemobilia. Hepatic angiography is the best and most accurate diagnostic method. Accidental or operative trauma constitute the major cause of macroscopic hemobilia where as microscopic hemobilia is a very frequent symptom in gallstone-disease. In this report five cases of different ethiology are described. Three were caused by abdominal trauma. The fourth case illustrates the risk of hemobilia from instrumental exploration of the common duct. Even when this is done carefully it might cause a hemorrhage with formation of obstructing clots. In the last patient there was severe hemobilia due to errosion of the cystic artery by a gallstone, penetrating into the duodenum. The treatment given in the five cases are examples of different methods which may be used, according to the nature of the lesion. In the three cases of traumatic hemobilia one healed spontaneously under angiographic control, one was cured by local hemostasis in the central liver rupture and the third had a successful hepatic resection. In the case with post-operative hemobilia, an obstructing clot had to be removed from the common duct. Simple cholecystectomy cured the patient with hemorrhage from the eroded cystic artery.


[Indications for portacaval anastomoses in portal hypertension due to alcoholic cirrhosis. (Role of anatomo-pathological examination.)]. The authors report their experience of 134 cases of porta-caval anastomosis for alcoholic cirrhosis. From their experience, they draw up the logical indications for this operation, i.e. in order to ensure better survival than that of patients treated in other ways. They suggest routine study of surgical biopsy, even as an emergency. This biopsy permits them to recognise which cases are liable to be progressive; in severe cases, surgery should not be undertaken. Thanks to this selection, the operative mortality is reduced to that of any other severe operation (6 p. 100) and later survival is improved owing to absence of recurrent hemorrhage.


Studies on the reproducibility of glass bead antibody affinity columns. Rabbit antibovine spleen DNase II and antihuman parotid amylase IgG were coupled to zirconium-clad (MAO, Corning) or plain (GAO, Corning) glass beads. (These were challenged with DNase II or amylase (human parotid or pancreatic), respectively. Although columns of the beads bound the enzymes whereas control columns did not, recoveries from the immune adsorbents were not only not quantitative but extremely variable. The columns also shed material absorbing in the ultraviolet. The antiamylase IgG-MAO column bound amylase so firmly, yet without inactivating it, that an insoluble enzyme reactor was formed. For these experiments, amylase was labeled with 14C in vitro without loss of activity.


Quantitative determination of indolic compounds in the rat brain using p-dimethylaminocinnamaldehyde as reagent. A method is proposed for determining the metabolites of radioactive 5-hydroxytryptophan and of endogenous tryptophan in the rat brain. The compounds are separated by thin-layer chromatography and made visible with p-dimethylaminocinnamaldehyde (DACA) reagent. The conditions studied are those which allow the use of DACA reagent for the quantitative determination of tryptophan metabolites in brain tissue. Amount of 5 ng of serotonin and 20 ng of tryptophan can be determined by densitometry.


Antiglobulins and glomerulonephritis. Classification of patients by the reactivity of their sera and renal tissue with aggregated and native human IgG. Renal biopsies and sera from 41 consecutive patients were studied to determine if antiglobulins were found more frequently in patients with severely diseased glomeruli. Patients were classified into three groups: A, 12 patients with normal renal function and minimal histological evidence of glomerular disease; B, 18 patients with normal renal function but distinctly abnormal biopsies (16 cases) or proteinuria greater than 16 g/24 h (2 cases); and C, 11 patients with both decreased function and abnormal histology. Positive latex fixation tests for rheumatoid factor were found in none of group A, four (22%) of group B, and five (45%) of group C patients. Sera heated 56 degrees C for 30 min contained precipitins reactive with heat-aggregated IgG in none of seven group A, five of ten (50%) group B, and four of ten (40%) group C patients. The quantity of 135I-labeled patient globulin which bound to immunoadsorbents coated with Cohn fraction II in competition with an equal quantity of 131I-labeled globulin from pooled plasma of normal donors was also measured. Patient globulins bound in significantly greater quantity (greater than or equal 2 SD) than the control in none of the group A, 7 of 18 (39%) group B, and 7 of 11 (64%) group C patients. Renal biopsies from 18 patients were also studied for the ability to fix fluorescein-conjugated heat-aggregated and native human IgG. None of nine tissue specimens from group A or B patients fixed either fluorescein-conjugated protein whereas tissue from eight of nine group C patients showed glomerular localization of one or both reagents. Severity of disease as judged by renal function and glomerular histology correlated with the presence of tissue-fixed and serum antiglobulins. Thus, detection of antiglobulins in glomeruli and sera of patients with glomerulonephritis may indicate a relatively poor prognosis and raises the possibility that antiglobulins may be implicated in some way in the pathophysiology of human glomerulonephritis.


Simple screening tests for the diagnosis of isolated clotting factor defects. With special reference to 'contact factor' defects. Reagents may be prepared from normal plasma and used with the prothrombin time and partial thromboplastin time tests to distinguish isolated defects of factors I, II, VII, VIII, IX, X, XI, or XII.


Liver disease in infancy: histological features and relationship to alpha-antitrypsin phenotype. Sixty-nine specimens of liver tissue from 53 infants with neonatal hepatitis or its sequelae were examined without knowledge of the alpha1-antitrypsin phenotype. Distinctive, diastase-resistant, PAS-positive, pure magenta-coloured, sharply defined globules, 2-20 microns in diameter were found in periportal and paraseptal hepatocytes in all liver biopsies from eight alpha1-antitrypsin deficient (PiZZ) infants biopsied after the age of 12 weeks. Such globules were not seen in biopsies from PiZZ individuals aged less than 12 weeks nor in individuals of normal alpha1-antitrypsin phenotype (PiMM). No other specific histological abnormality was found in PiZZ individuals, but in them giant-cell transformation was infrequent and liver damage was more severe, three of 14 cases developing cirrhosis in contrast to four of 27 PiMM subjects. The pathogenesis of liver disease in PiZZ individuals is discussed.


A diallel cross analysis of genetic determinants of copulatory behavior in rats. A dialled cross analysis was aimed at obtaining information regarding genetic influences on the copulatory behavior of rats, and permitting considerations of adaptive significance. Rats of 4 inbred strains, ACI, F344, LEW, and WF, and all possible F1 crosses were used. Of 385 males tested, 73 failed to mate. The F1 rats were more likely to mate than were rats with inbred genotypes. Overdominance was generally apparent for low frequencies of mounts and intromissions preceding ejaculation across 5 series and 3 tests. A trend for directional dominance toward low scores on various latency measures of copulatory behavior also was apparent. According to the theory relating directional dominance to adaptation, it would appear generally adaptive for rats to copulate rapidly and to ejaculate after relatively few mounts and intromissions.


The problem-oriented record: clinical application in a teaching hospital. A dental team-care concept that incorporates the problem-oriented system has been instituted at The Medical College of Pennsylvania. The program, as described, is designed to achieve the following goals: 1) to enhance communication between doctors and auxiliaries and thus maintain continuity in patient care and improve the quality of care; 2) to identify all problems related to the care of a patient; 3) to evaluate the educational and technical ability of the residents and students; 4) to achieve an effective dental auxiliary utilization program; 5) to increase faculty involvement in the delivery of patient care; 6) to organize an effective system of peer review; 7) to maintain complete, accurate and systematic medical-dental records; and 8) to encourage an interdisciplinary approach to health care delivery.


Lymphokine production by C3b-stimulated B cells. Trypsin cleavage of guinea pig C3 (60 sec, 20 degrees C) yields a fragment which stimulates guinea pig lymphocytes to produce a chemotactic lymphokine. These digested C3 preparations possess only minimal inherent chemotactic properties. The response is completely inhibited by prior adsorption of the trypsin-derived C3 fragments with insolubilized anti-C3. The active C3 fragment is C3b as demonstrated by the elution of activity in the exclusion volume of Sephadex G-75 (m.w. greater than 50,000 dalton). The C3b-dependent cellular-derived chemotactic factor is present in the supernatants of B cell cultures and totally absent in those of T cell cultures. Generation of this lymphokine occurs in the absence of cellular proliferation.


Radiosensitivity of T and B lymphocytes. III. Effect of radiation on immunoglobulin production by B cells. Radiation injury in defined populations of B cells was investigated utilizing an allotype congenic transfer system. The amount of donor immunoglobulin present in the recipient's serum was found to be directly proportional to the number of viable cells injected, and on this basis approximate D37 values for the inoculated B cells were determined in several experiments and found to fall in the 70 to 145 rad range depending upon the specific experimental conditions. Since the sensitivity of T cells to radiation-induced interphase death can be modified by prior exposure to select mitogens and antigens, an attempt was made to demonstrate a similar phenomenon with respect to B cells. The results indicate that the radiosensitivity of B cells can be slightly influenced by prior incubation with mitogens and only equivocally changed by activation with antigen.


Syngeneic adoptive immunotherapy and chemoimmunotherapy of a Friend leukemia: requirement for T cells. The aim of the study was to determine which cell mediates adoptive immunotherapy and chemoimmunotherapy of a syngeneic transplantable Friend virus-induced leukemia (FBL-3). An adoptive immunotherapy model was developed in which adult C57BL/6 mice given a lethal dose (10(4)) of FBL-3 on day 0 were saved by treatment on day 1 with C57BL/6 spleen cells or peritoneal exudate cells (PEC) immune to FBL-3. Cells passed through a nylon wool column to remove B cells and macrophages or treated with carbonyl iron to remove phagocytic cells remained effective, whereas cells treated with anti-theta serum and complement were far less effective. For adoptive chemoimmunotherapy, mice inoculated with 10(7) FBL-3 were treated 5 days later with cyclophosphamide (CY) plus immune spleen cells. CY, with or without non-immune cells, prolonged survival but all mice died with leukemia, whereas mice given CY plus immune cells survived tumor-free. As an adjunct to CY, immune cells passed through nylon wool or treated with carbonyl iron remained quite effective whereas cells treated with anti-theta serum and complement were far less effective. Thus, immune thymus-derived lymphocytes were required for the adoptive immunotherapy of an early leukemia or chemoimmunotherapy of a disseminated leukemia.


Evidence for cell-receptor activity in lymphocyte stimulation by staphylococcal enterotoxin. A wide dose-response curve and the inhibitory effect on mitogenicity of specific antitoxin suggest that polyclonal lymphocyte activation by staphylococcal enterotoxin requires direct interaction of toxin with lymphocyte receptors of low avidity for the protein. Staphylococcal enterotoxins A, B, and C1 demonstrated equivalent mitogenic activity. Lymphocyte receptors involved in enterotoxin activation thus appear to be specific for nonantigenic regions of the toxin molecule. Monosaccharide (hapten) inhibiton data indicate that lymphocyte receptors for staphylococcal enterotoxin lack alpha-mannoside, galactose, acetylgalactosamine, acetylglucosamine, and fucose (or closely related saccharides) as determinant sugars and thus differ significantly in structure from lectin cell receptors.


Characteristics of mesenteric lymph node cells homing to gut-associated lymphoid tissue in syngeneic mice. A subpopulation of cells in murine mesenteric lymph nodes, about 15% of those synthesizing DNA at any given time, homes specifically to the gut and mesenteric nodes of syngeneic recipients within 1 day of i.v. transfer. In contrast, cells from Oeyer's patches or peripheral lymph nodes do not. A large proportion of the B blasts which home to the small intestine has surface Ig, but lacks complement receptors. Thy-1-positive T blasts home to the gut to a lesser extent than B blasts. However, it is probable that equal fractions of B and T blasts home to mesenteric nodes. Homing is not affected by measures calculated to interfere with the combination of cell surface IgA and secretory component.


Human lymphocyte subpopulation: early and late rosettes. In the process of forming SRBC rosettes of human lymphocytes, two types were distinguished, the early and late rosettes. The former appeared immediately whereas the latter required further incubation at 4degreesC. In this study, the two types of cells were separated by gradient centrifugation and studied separately. It was found that the proportion of caps in the late rosettes was much greater than in the early ones. Treatment of the former by trypsin, AET, and neuraminidase decreased this proportion so that it resembled the late one. It was postulated that some of the differences in the early and late RFC lie in the differences in the content of membrane sulphydryl and sialic acid groups and distribution of SRBC receptors.


A method for detection of Ia antigens in the absence of appropriate H-2 recombinants. A method is described which obviates the use of H-2 recombinant strains for production and detection of Ia antibodies. The antibodies are produced by immunization with spleen cells in a strain combination in which the donor differs from the recipient either in the K end of the H-2 complex or in the whole complex. If the right schedule is used, this immunization produces antibodies against both H-2 and Ia antigens. The H-2 antibodies are absorbed out with erythrocytes or T lymphocytes rendering the antiserum specific for Ia antigens. The presence of Ia Ia antibodies is asserted by determining the tissue distribution of the antigens detected with the absorbed antiserum. Another antiserum is then prepared in the same strain combination by immunization with tissue that does not contain Ia but does contain H-2 antigens (e.g., a sarcoma of the proper genotype). The second antiserum contains only H-2 antibodies and the presence of these antibodies is again asserted by determining the tissue distribution of the corresponding antigens. The molecular distinctiveness of the putative Ia and H-2 antigens is then demonstrated by the newly developed technique of antibody-mediated induction of resistance to cytotoxicity (lysis). If the antigens detected with the two antisera move independently in the cell membrane, and if the antigens detected with the first antiserum do indeed have Ia-like properties, it is concluded that the antiserum detects Ia antigens. This method should prove to be useful for detection of Ia antigens in H-2 haplotypes for which no intra-H-2 recombinants are known, and for detection of Ia-like antigens in other mammalian species, particularly in man.


T cell products activating stem cells: further studies on the origin and action of the factor(s). We studied the capacity of bone marrow hemopoietic stem cells to form colonies (colony forming units, CFU) in the spleens of irradiated recipient mice following incubation of the cells with T cell-derived mediators in short-term culture in vitro. The mediators were a) stem cell-activating factor (SAF) present in crude form in the supernatant from phytohemagglutinin (PHA); stimulated lymphocytes, and b) immunoenhancing factor (IEF) obtained in partially purified form from the supernatant of antigen-stimulated lymphocytes and characterized by its ability to enhance antibody formation in vitro. Both SAF and IEF increased the number of CFU in the cultured bone marrow cell suspension. However, only SAF, and not IEF, significantly stimulated DNA synthesis in the cultured cells, Furhter more, SAF appears to activate CFU in vitro, rather than merely to promote the survival of active CFU stem cells. Experiments with SAF and bone marrow from different strains of mice indicated that the biologic activity was not restricted by K and Ia regions of H complex.


Interaction between lymphocytes and inflammatory exudate cells. I. Enhacement of thymocyte response to PHA by product(s) of polymorphonuclear leukocytes and macrophages. Thymocytes of C3H/He mice were poorly triggered to induce DNA synthesis by phytohemagglutinin but fairly well triggered when they were mixed with small number oble product(s) of these cells. Peritoneal exudate cells were mainly harvested at 3 hr, largely consisting of macrophages, after intraperitoneal injection of 0.2% sodium caseinate. Addition of 2(2) to 2(6) x 10(3) of 3-hr exudate cells, 2(2) to 2(4) x 10(3) of 48-hr exudate cells, or 2(2) to 2(4) x 10(3) of 96-hr exudate cells to syngeneic thymocyte culture (3 x 10(6) resulted in marked enhancement of DNA synthesis by thymocytes stimulated with 1 mul PHA. Similar enhancement of DNA synthesis was also observed in the presence of 200 mul of cellfree supernatant fluid of peritoneal exudates of 3 hr or 9 hr after casein stimulation. Conversely, two hundred microliters of 0-hr, 48-hr, or 96-hr peritoneal fluid showed a slight suppressing effect on thymocyte response and 50 to 100 mul of these exudates showed no enhancing effect. Furthermore, 50 to 800 mul of culture supernatants from 1.6 x 10(6) cells/4 ml of 3-hr exudate cells, 96-hr exudate cells, or purified macrophages also caused a similar enhancement of DNA synthesis by thymocytes. On the other hand, excess numbers of exudate cells (2(7) to 2(8) x 10(3) of 3-hr exudate cells, or 2(5) to 2(9) of 96-hr exudate cells) or excess amounts of culture supernatants (800 mul from 6.4 to 12.8 x 10(6)/4 ml of 3-hr cells, or 200 mul from 12.8 x 10(6)/4 ml, 400 mul from 6.4 x 10(6)/4ml, or 800 mul from 3.2 x 10(6)/4 ml of 96-hr cells) diminished the enhancing potency on thymocytes. The cooperative function by polymorphonuclear leukocytes or by macrophages on the lymphocyte response was thus postulated.


RNA and protein synthesis in spontaneous rosette formation by T lymphocytes. Formation of rosettes with sheep red blood cells (SRBC) by peripheral blood lymphocytes and thymocytes has been studied. Trypsinization of these cells abolishes the capacity to form SRBC-rosettes. The process of re-establishment of this capacity to form SRBC-rosettes, in vitro, has been shown by use of metabolic inhibitors to require transcription, translation, and protein synthesis. These observations are interpreted in terms of the T cell markers as the expression of a definitive process or step in lymphoid cell differentiation.


A simple radioimmunoassay for the enumeration of rosette-forming cells. A simple radioimmunoassay for the enumeration of Ig bearing (Ig+) lymphocytes by rosette formation with anti-Ig, antibody coated erythrocytes (Ab-E) is described. The method is based upon labeling lymphocyte populations with 51Cr, rosetting them with Ab-E, separating the rosetted from unrosetted cells by centrifugation through a Ficoll-Hypaque layer, counting the radioactivity of the unrosetted cells, and counting the radioactivity of the unrosetted cells in a rosetting system with unreactive uncoated-E. This permits the calculation of the percentage of rosette-forming Ig+ cells. The assay eliminates the subjectivity and tediousness of counting and distinguishing between rosetted and unrosetted cells under the microscope. Being also sensitive and reliable, this radioimmunoassay may, after suitable modifications, replace the conventional counting of other types of rosettes.


Visualization by immune electron microscopy of viruses associated with acute respiratory disease. A sensitive and rapid method for detecting adenovirus and influenza viruses has been demonstrated by using both the direct and indirect immune electron microscopy technique. The indirect method was from 4 to over 32 times more sensitive than the direct method. The technique appears to have the sensitivity approaching tissue culture methods, but is much more rapid, requires less laboratory support personnel and space, and should lend itself to detection of noncytologic agents. These data suggest a new role for the electron microscope in diagnostic virology.


A modified assay for the detection of human adult active rosette forming lymphocytes. A modified procedure is described for the detection of a sub-population of peripheral blood T-cells in normal human adults. This sub-population of T-cells has been called the active rosette forming cell by others. The advantages of this modified procedure compared with that previously described are: 1) the elimination of 60 mon incubation period for lymphocytes prior to the assay and 2) the elimination of the need for fetal calf serum in the assay. The mean percentage of RFC in the peripheral blood of 80 healthy adult controls using the modified procedure is 25.2+/-5.5% in buffer lacking FCS. The results were highly reproducible and comparable to the results obtained using the procedure previously described. It was concluded that a 60 min pre-incubation of lymphocytes and the use of FCS are not necessary when the appropriate SRBS: lymphocyte ratio is used in the determination of human adult active RFC. The use of this procedure in evaluating the immune competence of cancer patients is discussed.


A simultaneous method for detection and quantitation of T- and B-lymphocytes. Assay for quantitation of B- and T--lymphocyted from small volumes of heparinized man blood has been developed by simultaneously reacting Ficoll-Hypaque purified mononuclear cells with antobody-coated chicken erythrocytes to for rosettes with B-lymphocytes, and sheep erythrocytes which formed non-immune rosettes with Tlymphocytes. Distribution of various lymphocyte populations in normals are T-cells, 60.9+/-7%, B-cells 16.4+/-4%, and lymphocytes with both receptors, 1.6+/-0.6%.


Detection of specific antigen-sensitized T-lymphocytes in human tonsils. Tonsillar lymphocytes from children immunized against rubella were cultured with various mitogens, including phytohemagglutinin and rubella virus. Sheep red cells were subsequently added to detect rosette-forming T-lymphocytes, and the suspension tested by autoradiography to identify transformed cells. With PHA, 60--80% of the cells were transformed, of which 37% were rosette-forming T-cells. With rubella antigen only 31% of lymphocytes were transformed, but almost all of these formed rosettes. It is concluded that PHA stimulates B- as well as T-cells alone; such stimulation may therefore be a more reliable test of T-cell function and of cell-mediated immunity.


Effect of previous infection on antibody response of children to vaccination with capsular polysaccharide of Haemophilus influenzae Type b. Children who had recovered from meningitis, orbital cellulitis, or epiglottitis caused by Haemophilus influenzae type b were immunized with capsular polysaccharide vaccine derived from that bacterium; some healthy siblings and adults who had not had H. influenzae infections were also vaccinated. Of 10 children who had had H. influenzae meningitis previously, only one had an antibody response to the vaccine. One child with prior H. influenzae orbital cellulitis also failed to respond. None of the children had detectable H. influenzae polysaccharide antigen in their bloodstream at the time of immunization. Two children who had had H. influenzae epiglottitis and six of seven controls without histories of H. influenzae infections responded immunologically to the vaccine. One of eight vaccinees under two years of age showed a response, and eight of 12 over two years responded well (P = 0.02). All four nonresponders over the age of two years had had H; influenzae meningitis or cellulitis. Children who had had H. influenzae meningitis responded less well to the polysaccharide vaccine than did other recipients of the vaccine; this difference could not be explained solely on the basis of age;


Modification of rat uterine monoamine oxidase activity by steroid hormones. The monoamine oxidase (MAO) activity in the ovariectomized rat uterus was significantly increased above control levels in animals given testosterone: 33% (P smaller than 0.01) with tryptamine or 34% (P smaller than 0.05) with tyramine as substrate. Activity was also higher in hydrocortisone-treated animals: 30% (P smaller than 0.05) with tyramine or 25% (P smaller than 0.05) with tryptamine as substrate. Progesterone injection increased MAO activity toward tyramine by 20% but towards tryptamine by only 8%. The differences are not statistically significant but are believed to be real since they were reproducible. MAO activity in oestradiol-treated animals was 11% less than in the controls for both substrates. Although they are not significant differences, they were reproducible. No change in MAO activity was observed in the cerebellum, hypothalamus or anterior pituitary of ovariectomized rats after steroid treatment. At oestrus the enzyme activity in the uterus was lower than at dioestrus or prooestrus when beta-phenylethylamine was the substrate. When 5-hydroxytryptamine was used to measure enzyme activity, the same values were found at oestrus, dioestrus and prooestrus. Ovariectomy did not cause any changes in MAO activity in any of the tissues. Effects of the steroids in vivo were probably not due to a direct action on the enzyme since only at high concentration did they have any effect on the mitochondrial enzyme activity of the uterus in vivo.


Genetic control of immune responses in vitro. VI. Experimental conditions for the development of helper T-cell activity specific for the terpolymer L-glutamic aicd60-L-alanine30-L-tyrosine10 (GAT) in nonresponder mice. Mice which are genetic nonresponders to the random terpolymer of L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) not only fail to develop GAT-specific antibody responses when stimulated with soluble GAT either in vivo or in vitro, but develop GAT-specific T cells which suppress the GAT-specific plaque-forming cell response of normal nonresponder mice stimulated with GAT complexed to methylated bovine serum albumin (MBSA).Thus, both responder and nonresponder mice have T cells which recognize GAT. However, nonresponder mice can develop GAT-specific helper T cells if immunized with GAT bound to MBSA or to macrophages. The relevance of Ir gene-controlled responses is discussed.


Detection of antigens specific for B-lymphoid cultured cell lines with human alloantisera. Human sera were tested for cytotoxicity to pairs of long-term tissue-cultured cell lines. Each pair had been derived from the same individual and one of the pairs possessed the characteristics of either "T" or "B" cells. The alloantisera used were HL-A-typing reagents or sera obtained from Amish multiparas. Selected cytotoxicity was found against the  B-cell lines by direct testing. Cytotoxicity was abolished by absorption with B-cell line but not by absorption with the T-cell lines. The results suggest that a group of allotypic antigens may be expressed exculsively on human B cells.


Non-physician development of problem lists from office records. It has been argued that conversion of office records to the problem-oriented medical record entails a prohibitive cost in money and physician time. This study reports an evaluation of the cost of preparing problem lists from existing ambulatory patient records by non-physician personnel. The problem lists constructed by non-physician personnel were judged by physicians to be accurate, and the cost was much less than that required when physicians reviewed charts and prepared problem lists themselves. The method described here is an accurate and cost-effective way to begin conversion of outpatient records to P.O.M.R.


Effects of sudden changes in external sodium concentration on twitch tension in isolated muscle fibers. When [Na] was suddenly introduced to single muscle fibers (Xenopus or frog), which had been pretreated with Na-free solution (Tris-substituted), the time-course of twitch recovery was very variable, half-time ranging from less than 1 S to 5 S. The [Na] vs. twitch height relationship was also variable. In small Xenopus fibers, decreases of [Na] to 50% increased the twitch, while in large Xenopus fibers twitch height remained constant or decreased as [Na] was decreased to 50%. The apparent diffusion constant (D') of Na+ or K+, calculated from the time-course of twitch recovery and the [Na] vs. twitch relation, and from the time-course of the slow repolarization upon sudden reduction of [K] was about 1-1.5 X 10(-6) cm2/S. This is one order of magnitude smaller than the diffusion constants in an aqueous solution. Even if the tortuosity factor of the T system is taken into account, there remains a substantial discrepancy. Although our value of D' is subject to various errors, if we accept the value, the twitch recovery is predicted to be either very quick or slow depending upon the variation of [Na]-twitch relation and fiber size. Thus, both quick and slow twitch recoveries can be explained by the diffusion time of Na+ in the T system, and therefore the results are consistent with the idea that the T system is excitable.


Psychiatric complications following coronary bypass surgery. Previous studies of psychiatric complications following open heart surgery have included few if any patients who had coronary bypass surgery. This experiment reports the relative incidence of psychiatric complications in a sample of 97 open heart surgery patients of whom 51 patients (53 per cent) had coronary bypass surgery. The results suggest that the incidence of psychiatric symptoms following coronary bypass surgery is significantly lower (16 per cent) than that following cardiac valvular surgery (41 per cent). Several possible reasons for this large discrepancy in incidence of psychiatric complications are considered.


Acute reduction of brain serotonin and 5-HIAA following food consumption: correlation with the ratio of serum tryptophan to the sum of competing amino acids. In a series of experiments designed to test further our hypothesis that brain tryptophan and 5-hydroxyindole levels vary post-prandially as a function of the serum tryptophan to competitor ratio (i.e., ratio of serum tryptophan concentration to the sum of the concentrations of competing neutral amino acids), rats fasted overnight were allosed to consume for two hours single meals containing carbohydrates, fats, and various amino acids: Diet 1 contained no amino acids; Diet 2 contained five neutral amino acids known to compete with tryptophan for uptake into the brain; Diet 3 lacked tryptophan and the five competitors, but contained twelve non-neutral amino acids found in dietary protein; Diet 4 contained tryptophan and these same twelve non-neutral amino acids. The diet-induced modifications in brain tryptophan and 5-hydroxyindoles followed closely the changes in the serum tryptophan/competitor ratio, but not in serum tryptophan alone: The ingestion of Diet 4 raised serum tryptophan, but not the serum ratio, brain tryptophan or 5-hydroxyindoles; Diet 3 did not raise serum tryptophan, but did elevate the serum ratio, brain tryptophan and 5-hydroxyindoles. Diet 2 caused major reductions in serum tryptophan, the serum ratio, and brain tryptophan and the 5-hydroxyindoles. This diet might provide a simple, attraumatic means for lowering brain serotonin in studies of the physiology or serotonergin neurons. These studies provide further evidence that the effect of insulin on brain tryptophan uptake is not direct, but instead mediated via insulin-induced changes in the serum tryptophan/competitor ratio.


Babinski response: stimulus and effector. This is an electromyographic study of the activity in flexor and extensor muscles of the big toe in 22 patients with a Babinski sign and 49 controls, after mechanical or electrical stimulation of the sole. The results indicate: (1) the Babinski sign is mediated by the extensor hallucis longus (EHL), and not by the extensor hallucis brevis; (2) electrical stimuli may fail to activate the EHL in these patients, and conversely may evoke EHL reflexes in control subjects; (3) in skin reflexes, electrical and mechanical stimuli are not freely interchangeable.


Radiological abnormalities in temporal lobe epilepsy with clinicopathological correlations. In 73 patients with drug-resistant temporal lobe epilepsy submitted to an unilateral anterior temporal lobectomy the radiographs were studied to see if there were any correlation with the pathology subsequently found and with the outcome of the operation. A small middle cranial fossa, focal calcification, and temporal horn displacement are often better indices of the underlying pathology than temporal horn dilatation alone. In a small number of cases, however, radiological changes were seen on the side opposite to an unilateral EEG focus, thus suggesting bilateral disease.


Hemianopic colour blindness.

Hemianopic colour blindness. A man developed cortical blindness after cerebral infarction in the distribution of both posterior cerebral arteries. When he recovered from this condition, he was found to be colour blind in the left visual field, but not in the right. This unusual situation resulted in apparently contradictory performances on hemifield and free-field tasks of colour discrimination, naming, and recognition. The contradictions may be explained by interhemispheric competition between a hemisphere which could discriminate colours and a hemisphere which was colour blind.


Intracranial hydatid cysts. Study of 17 cases. The authors report 17 cases of intracranial hydatid cyst out of 500 brain tumors seen in 20 years, and analyze clinical, investigative, diagnostic, and operative findings.


Portsmouth syndrome: review of the literature and clinicopathological correlation. Hereditary and acquired abnormalities of platelet function are recognized more frequently.  Recent advances in platelet physiology have led to new tests of platelet function.  Assessment of platelet adhesiveness and aggregation have allowed more definitive classification of platelet dysfunction.  Platelet abnormalities will not be diagnosed before surgery.  It would be impractical to perform these tests for platelet function as screening procedures on all patients; however, they should be considered as an important part of the laboratory screening for abnormal postoperative bleeding.


Comparison of the effect of various antisera and cobra venom factor on inflammatory reactions in guinea-pig skin. I. Non-specific inflammation due to the intradermal injection of turpentine. Guinea-pigs were treated with agents which lowered the serum complement levels and the effect on the inflammatory reaction to intradermal turpentine was studied. A comparison was made between two antisera to beta1C/beta1A globulin which had been prepared in different ways. One was made using C3 fixed to zymosan particles as the antigen, and the other using chemically extracted beta 1C/beta1A globulin. The antisera to beta1C/beta1A globulin (zymosan) was found to have the greater anti-inflammatory activity. The effect of each on the parameters of complement studied, and on the circulating platelet count, was much the same. An antiserum to serum factors fixed to zymosan during C3 activication was prepared free of anti-beta1C/beta1A globulin antibodies. This was found to have some of the anti-inflammatory activity of the anti-beta1C/beta1A globulin (zymosan), as well as lowering total complement levels. Anti-gamma globulin andheterologous immune complexes also lowered serum complement levels and were antiinflammatory. However, all the above agents were also found to reduce the number of circulating platelets. This was in contrast to CVF which reduced complement levels by 90 per cent. but had no effect on platelet numbers. CVF also reduced the inflammatory response but was no more effective than the other agents. In view of these findings a role for the participation of the complement system, possibly involving the alternate pathway of activation of C3, is discussed as well as the participation of platelets in the reaction.


The influence of dental plaques on the microvasculature of the oral mucous membrane. This investigation was designed to explore the effect of plaque, obtained at different stages of accumulation, on the microvasculature of the hamster cheek pouch. Five groups of three dental students followed an oral hygiene abstinence program for 22 days. At day 2, 9, and 22, plaque was sampled from different anterior teeth, pooled and suspended in a reduced diluting fluid. Each of the three pooled plaque suspensions was then introduced into the right or left cheek pouche of five hamsters. Microvascular changes in the pouches were then observed and recorded photomicrographically until vascular reconstitution occurred. Plaque and gingival indices were taken, and the microbial composition of the plaque was determined according to gram-staining characteristics and morphology. The results indicate that the microvascular response was not a function of age and composition of plaque. This finding is based on the observation that 2-, 9-, and 22-day-old plaque induced similar microvascular damage which required approximately the same recovery period of 9 days to reconsitute normal microvascular function.


Microdetermination of ergocalciferol (vitamin D2) in pharmaceutical preparations by differential spectroscopy using trifluoroacetic acid in the absence of vitamin A. A differential spectroscopy method for the determination of microgram quantities of ergocalciferol, using trifluoroacetic acid and hydrogen peroxide, was applied to commercially available pharmaceutical preparations. Tablets were powdered and extracted with methanol after being made basic with diethylamine. The methanol was concentrated, chloroform was added, and the mixture was chromatographed on neutral alumina using chloroform as the eluent. Ergocalciferol was determined in an aliquot of the eluate by differential spectroscopy and was compared with a reference ergocalciferol standard treated similarly. The method applied to low potency formulations (2.5-6 mug/tablet) is simple and quantitative, needs less than 5 hr for completion, and has a precision of less than +/- 2%. A simple and accurate chromatographic method for the determination of ergocalciferol in stabilized powders and high potency tablets, which precludes the necessity of solvent-solvent extraction, was also developed. The results are comparable with those obtained by the rat bioassay and the USP XVIII chemical assay.


Tetrodotoxin binding to normal depolarized frog muscle and the conductance of a single sodium channel. 1. We have examined the binding of tritium-labelled and unlabelled tetrodotoxin to frog twitch muscle. Bio-assay as well as radioisotope experiments show a saturable component of tetrodotoxin binding with a binding capacity of about 22 p-mole/g wet wt., and a dissociation constant of about 5 nM. 2. If the observed uptake of tetrodotoxin by muscles represents one-to-one binding of the drug to sodium channels, the channel density is about 380 channels/mum2 of a muscle fibre's surface membrane. On the basis of this result and electrical measurements of sodium conductance in frog muscle, we calculate that the conductance of a single sodium channel is of the order of 10(-12) reciprocal ohms. This is one to two orders of magnitude less than previous estimates. 3. We have looked for an effect of membrane depolarization on saturable tetrodotoxin binding, and have found none. This suggests that there is little molecular interaction between the "gating" portion of the sodium channel molecule, and that which binds tetrodotoxin.


Patterns of antinuclear antibodies and lupus-activating drugs. Patterns of antinuclear antibodies (ANA) occurring in individuals consuming lupus-activating drugs who have not developed systemic lupus erythematosus (SLE), may give insight into their mode of action as SLE triggering agents. We have studied the antigenic specificity of ANA induced by isoniazid (INH), anticonvulsants and chlorpromazine. ANA found in INH treated subjects are primarily directed at soluble nucleoprotein (sNP), an antigen which is physicochemically altered in vivo by INH. Antibodies to INH altered sNP were found in 78 per cent of 214 subjects receiving INH, while none had anti-DNA antibodies. Different anticonvulsants give rise to different patterns of ANA. Antibodies to Sm antigen were found only in patients receiving hydantoins. Antibodies to native and denatured DNA were found in 14 per cent and 22 per cent respectively, of 170 patients receiving anticonvulsants. Antibodies to denatured DNA were most frequently found in patients receiving chlorpromazine, which correlated with the known reactivity of this drug to denatured DNA.


2-Halo derivatives of 3'-acetamido-3'-deoxyadenosine. 9-(3-Acetamido-2,5-di-O-acetyl-3-deoxy-beta-D-ribofuranosyl)-2,6-dichloropurine (VI) prepared by the mercuric cyanide catalyzed reaction of 3-acetamido-2,5-di-O-acetyl-3-deoxy-D-ribofuranosyl chloride (III) with 2,6-dichloropurine, was converted by standard reactions to 3'-acetamido-2-chloro-3'-deoxyadenosine (VII) and 3'-acetamido-3'-deoxy-2-fluoroadenosine (X). The 2-chloroadenine nucleoside VII was not cytotoxic, but the 2-fluoroadenine nucleoside X was moderately so, and its cytotoxicity to a subline of H.Ep.-2 cells resistant to 2-fluoroadenine indicates that its activity is due to the intact nucleoside.


Synthesis and antiinflammatory activity of some 1,6-methano[10]annuleneacetic acids. Some new approaches to the 1,6-methano[10]annulene system are described. The routes were used to prepare 1,6-methano[10]annulene-3-acetic acid and the alpha-methyl analog. The compounds showed antinflammatory and analgesic activity, though less than that of corresponding naphthalene compounds; the possible effect of the chirality of the annulene on the observed biological activity is discussed.


Cytophysiological basis of disruptive pigmentary patterns in the leopard frog Rana pipiens. II. Wild type and mutant cell-specific patterns. A new pattern index, Ip, is introduced and used to compare patterns of wild type, burnsi, and kandiyohi chromatophores in the leopard frog, Rana pipiens. Wild type chromatophores are hyperdispersed over distances within cellular contact, and it is concluded that this hyperdispersion results from contact-mediated negative interactions. The hyperdispersion is less strong in spot cells than interspot, and extends over larger areas in burnsi than in wild type epidermis. Over areas greater than chromatophore size, patterns are either random or clumped. Patterning of kandiyohi melanophores is clumped into aggregates small enough to be within the range of cellular contact, suggesting a lack of contact inhibition among these cells. The possible roles of cellular properties and the extracellular environment in pattern determination are discussed.


Evidence for diaphragms in the pores of annulate lamellae and the nuclear membrane. Interpretation of cross and tangential sections of the annulate lamellae and nuclear membrane of Rana pipiens oocytes provides evidence in these structures for the existence of disphragms spanning the pores. The evidence appears to rule out explanations ascribing such diaphragms to an optical artifact. More detailed description is given of a component of the pore complex only briefly described heretofore and now called the "intracisternal ring." The varied results and interpretations of studies of the pore complex in various cells are discussed.


Massive postpartum right renal hemorrhage. All reported cases of massive postpartum right renal hemorrhage have involved healthy young primigravidas and blacks have predominated (4 of 7 women). Coagulopathies and underlying renal disease have been absent. Hematuria was painless in 5 of 8 cases. Hemorrhage began within 24 hours in 1 case, within 48 hours in 4 cases and 4 days post partum in 3 cases. Our first case is the only report in which hemorrhage has occurred in a primipara. Failure of closure or reopening of pyelovenous channels is suggested as the pathogenesis. The hemorrhage has been self-limiting, requiring no more than 1,500 cc whole blood replacement. Bleeding should stop spontaneously, and rapid renal pelvic clot lysis should follow with maintenance of adequate urine output and Foley catheter bladder decompression. To date surgical intervention has not been necessary.


Colonic neoplasms following ureterosigmoidostomy. Attention is drawn to the occurrence of colonic tumors at the site of ureterosigmoidostomy. A case of carcinoma is described, the literature is reviewed and regular long-term followup is emphasized.


Clinical studies on ampicillin-cloxacillin for intravenous injection (Rectocillin 'Kyowa') (author's transl). (1) Ampicillin-cloxacillin for intravenous injection (Rectocillin 'Kyowa') was administered to 9 patients 1 g or 2 g daily for protection of postoperative infections, and good result was obtained in all cases. Eight out of 9 cases were with renal insufficiency. No side effect was encountered. (2) Rectocillin was administered to 14 patients with infections. The treatment was remarkably effective in 4 cases, and effective in 6 cases. In the cases with renal insufficiency, a daily dose of 1 g was effective. The dose administered to the patients with normal renal function was 2 g or 4 g daily. Neither clinical nor laboratory findings showed evidence of side effect.


Rod late receptor potential and rhodopsin concentration of an isolated frog retina. The relation of the threshold of the late receptor potential (late RP) and ERG b-wave with the rhodopsin concentration in the rod outer segments of an isolated bullfrog retina were studied by simultaneous recordings of electrical responses and spectral change. The curve indicating log threshold rise of the late RP with the decrease of rhodopsin showed two phases separated by a kink, which was found at 50% rhodopsin concentration; the b-wave threshold, however, was linearly related to rhodopsin concentration. From the intensity response curves (IR curves) at various rhodopsin concentrations, the amplitude decrease of both waves following bleaching light adaptation was compared and the mode of the conversion from the late RP to the b-wave was discussed.


The variation in thermoelasticity with sarcomere length in frog's striated muscle. The effect of lowering temperature on the resting tension of frog's striated muscle was studied at various sarcomere lengths, using whole muscle, single-fibre and skinned-fibre preparations. And the temperature coefficient of tension, beta=(1/P)(dP/dT) (P, tension; T, temperature) was investigated. In whole sartorius muscles in Ringer solution, beta was negative over the whole range of sarcomere lengths investigated. In the presence of 2 mM procaine the rubber-like thermoelasticity (beta greater than 0) was revealed at medium lengths. At shorter (greater than 2.3 mum) and longer (greater 2.7 mum) lengths, beta stayed negative. In single muscle fibres suspended in Ringer solution with mM procaine, beta was positive over a wider range of lengths (2;3-3.4 mum), and the peak positive value of beta was obtained at the length of 2.6 mum. In skinned fibres suspended in a relaxing solution, beta stayed positive up to the length of 4.2 mum, and the peak value of beta was obtained at the length of 3.0 mum which was considerably longer than in single fibres. The results substantiated A. V. Hill's view on the thermoelasticity of the muscle; there are components with positive beta (contractile apparatus) and those with negative beta (connective tissue and sarcolemma), and at high elongations the positive coefficient is masked by the increasing importance of the negative coefficient.,


[Carcinofetal antigens. II. Carcinoembryonic antigen (CEA). (author's transl)]. CEA is a beta1-glycoprotein (mol. w. approx. 200 000) which in embryonic life is usually found as a cell membrane associated antigen in the gastrointestinal (GI) tract and pancreas. Furthermore, it is secreted into body fluids. In healthy adults a very low serum concentration may be found. The clinical significance of CEA lies in its increased formation in primary and secondary adenocarcinomas of colon and rectum and pancreatic carcinoma, where values of 20 ng/ml and more are observed. However, other gastrointestinal (e.g. oesophagus, stomach, gall-bladder) and extragastrointestinal tumors (e.g. lung, breast, urogenital, prostatic, ovarial carcinomas) as well as non-malignant diseases mainly of the GI tract (e.g. hepatitis, cirrhosis, pancreatitis, colitis, diverticulitis) may provoke less frequent and lower increases in the CEA level. Healthy smokers also tend to show a slight increase in CEA concentration. A certain relationship exists between the CEA level and the size and extent of the tumor so that a decrease following operation may account for complete tumor removal, whereas a persistent or recurring increase in the CEA level is highly suspicious of metastases and/or recurrent tumor. Difficulties in proving and purifying CEA are mainly caused by multiple cross-reactions of CEA with other substances, e.g. blood group substances (A, B, Lea, Leb) and normal or other antigens (NGP, NCA, CEX, CCEA 2, NCA 2, CCA-III, FSA, BCGP). The radioimmunoassay is the most suitable method to determine CEA levels in body fluids. The 3 procedures used differ in the precipitation of the specific immune complex by ammonium sulphate (AS), Z-gel (ZG) or a second antibody (SA). Depending on the method, the upper normal limit in serum or plasma corresponds to approximately 2.5 (AS, ZG) or 12.5 (SA) nanogramme/milliliter. CEA determination in the urine is of interest in patients suffering from bladder carcinoma.


Selective arterialization of coronary veins for diffuse coronary occlusion. An experimental evaluation. The selective arterialization of coronary veins as a surgical therapy for diffuse coronary arteriosclerosis was studied in canine and sheep experiments. The arterialized blood can be delivered promptly to the selected region of the myocardium and an adequate runoff exists for this mode of revascularization, so that myocardial edema and hemorrhage do not occur. The retrograde blood flow through an anastomosis between the internal mammary artery (IMA) and great cardiac vein (GCV) is excellent, with a predominantly diastolic flow pattern. Follow-up studies indicate significant but partial protection of the myocardium against diffuse LAD occlusion. The size of infarcts is decreased. However, the focal or small transmural infarcts observed are usually located near the apex of the heart. The studies with radioactive microspheres (15 plus or minus 5 mu diameter) revealed that the degree of capillary trapping of microspheres is very much less when the microspheres are injected retrograde into the vein than when injected into the artery. This may indicate that significant "shunt" blood flow exists when the coronary vein is arterialized. Thus this study demonstrates both the potential and the limitation of the selective arterialization of coronary veins in revascularizing patients suffering from diffuse coronary arteriosclerosis.


Resection of acute posterior ventricular aneurysm with repair of ventricular septal defect after acute myocardial infarction. Three patients with true posterior myocardial infarctions and ventricular septal defects were treated by posterior infarctectomy, closure of the defect, and appropriate combinations of mitral valve replacement and coronary grafting. Aortic balloon pumping was not used. The technique of infarctectomy and ventricular septal defect closure is illustrated. Two of the 3 patients have excellent long-term results.


[Genesis of vestibulo-autonomic disorders in space flight]. Some considerations on the mechanisms of vestibulo-vegetative disturbance in space flight are given on the basis of clinical observations, experience of otoneurological clinic, simulation experiments and examinations of cosmonauts. The starting point in these disturbances was a significant fact of blood redistribution in weightlessness and subsequent changes in hemodynamics, metabolism, etc. The body reactions to weightlessness seem to prepare pronounced vestibulo-vegetative reflexes to threshold and subthreshold vestibular stimuli induced by head and body movements in flight. Some aspects of the vestibular selection and training of cosmonauts are discussed from this point of view.


Bridge saphenous vein graft.

Bridge saphenous vein graft. Single aorta-coronary artery vein grafts (bridge grafts) were constructed to two coronary branches with a side-to-side anastomosis in 250 patients. Most of these grafts were constructed between circumflex branches (96 grafts), circumflex and diagnol branches (47 grafts), and anterior descending and diagonol branches (79 grafts). The aim of the bridge graft is to decrease the number of anastomoses, decrease the operative time, and improve graft patency. The hospital mortality rate in this group of patients was 1.2 per cent, and the incidence of postoperative myocardial infarction was 3.6 per cent. One hundred ten patients were restudied after surgery; the average time of restudy was 1 year. Ninety-two grafts of 83.6 per cent had two anastomosis patent; 6 grafts (5.4 per cent) had one anastomosis patent; and in 12 grafts (10.9 per cent), both anastomoses were occluded. One hundred twenty-six associated grafts were studied all the same time; the patency rate was 84.1 per cent. From this experience, we believe the bridge graft is a useful procedure for bypassing the small coronary artery branches.


Multiple coronary artery aneurysms resulting in myocardial infarction in a young man: treatment by double aorta-coronary saphenous vein bypass grafting. A 26-year-old Japanese man was treated for a transmural myocardial infarct caused by multiple aneurysms of the left main (LMC), left anterior descending (LAD), and the right coronary arteries (RCA). He underwent successful double aorta-coronary saphenous vein bypass grafting. The etiology of the aneurysm remains uncertain but an inflammatory origin is most probable. Review of the literature has indicated that this is the seventh case of coronary artery aneurysms without arteriovenous fistulas to be managed by grafting techniques with the saphenous vein. This experience has suggested that young patients presenting with anginal pain or myocardial infarction whould be carefully examined for coronary artery aneurysms. Since most of the patients developed myocardial infarction probably from thrombotic occlusion or embolism of the distal vessel, this lesion should be considered for surgery whenever anatomically feasible. Coronary artery reconstruction by grafting techniques, with or without resection of the aneurysm, is the treatment of choice. Although surgical treatment has provided good clinical amelioration to our patient as well as the patients previoulsy reported, a careful long-term follow-up should be continued for patients with multiple coronary artery aneurysms of doubtful origin.


Aneurysm of saphenous vein bypass graft to coronary artery. A few cases of aneurysmal dilatation of autogenous vein grafts to peripheral arteries have been reported. However, to our knowledge, no case of this complication in coronary artery vein bypass grafts have been found. We are presenting a case of a vein graft aneurysm which appeared 6 months postoperatively. The patient had had an aortic valve replacement and a vein bypass graft to the right coronary artery.


Aorta-coronary artery saphenous vein bypass surgery: clinical and angiographic results. In a series of 500 consecutive patients undergoing aorta-coronary artery saphenous vein bypass surgery, operative mortality was 2.5% (1% with one-vessel disease, 2% with two-vessel disease, and 3% with three-vessel disease). Transmural myocardial infarction occurred within 30 days after operation in 67 cases (13%) and caused 10 of the 16 deaths in that period. Among 484 patients followed 1 to 58 months (median, 26 months), there have been 20 deaths. Of the 464 survivors, 65% had complete relief of angina, 24% were improved, and 11% were unimproved. In 162 patients who underwent postoperative graft angiography between 1 and 42 months after surgery, a strong positive relationship existed between clinical response and completeness of myocardial revascularization as defined by the presence of a patent graft to all major coronary arteries with greater than 50% stenosis. A similar relationship was found between postoperative multistage treadmill exercise response and completeness of myocardial revascularization. Thus, 82% of patients completely revascularized were asymptomatic at the time of postoperative graft visualization, and 91% had a negative treadmill exercise response.


Fluorescence histochemical observations on the uptake and metabolism of tryptophan in the endocrine cells of the hypophysis. The present work was undertaken to study the significance of the uptake of precursors of biogenic amines, L-dopa and 5-hydroxytryptophan, in the cells of the pars distalis of the mammalian hypophysis. The results of our own earlier studies suggested that L-dopa and 5-hydroxytryptophan may be taken up by the cells of the pars distalis which possess in their cell membranes the system for active transport of amino acids. In the present study, an effort is made to demonstrate the uptake of the amino acid, tryptophan, which is generally used for the protein synthesis. It was observed that after the administration of tryptophan the small cells of the pars distalis exhibited specific formaldehyde-induced fluorescence characterizing tryptophan and its metabolites. It was also noted that after the administration of tryptophan blue fluorescence was observed in some cells of the pars distalis prior to formaldehyde vapour treatment. The blue fluorescence may be due to the presence of quinoline metabolites of tryptophan formed in the cells. This new observation offers good possibilities to study the metabolism of tryptophan at the cellular level. The results of the present work support the suggestion that L-dopa or 5-hydroxytryptophan is taken up by cells of the pars distalis which possess the mechanism for general active transport of amino acids in the cell membrane.


Impaired interaction (adhesion-aggregation) of platelets with the subendothelium in storage-pool disease and after aspirin ingestion. A comparison with von Willebrand's disease. Possible defects in the interaction of platelets with the subendothelial surface were evaluated in six patients with storeage-pool disease, nine patients with von Willebrand's disease and seven normal subjects who ingested aspirin. Citrated blood was perfused through a chamber containing everted segments of rabbit aorta previously denuded of endothelium by means of a ballon catheter. With normal blood, 83.3 +/- 1.9 per cent (S.E.M.) of the surface was covered by adherent platelets. Platelet adhesion was normal after aspirin ingestion (89.7 +/- 4.6 per cent) and decreased in some patients with storage-pool disease. The most striking defect in both circumstances was the virtual absence of platelet thrombi. In contrast, decreased adhesion (57.3 +/- 3.4 per cent), but normal thrombus formation, was characteristic of von Willebrand's disease. These types of defects in platelet adhesion and aggregation may account for the hemostatic defects in a variety of bleeding disorders. The findings further suggest the possible usefulness of aspirin as an antithrombotic agent.


[Paradoxical vestibular reaction in patients with consciousness disorders (nystagmographic recording)]. In 32 patients with coma of varying intensity and aetiology the effect of light on caloric nystagmus was studied. During consciousness disturbances a light stimulus provoked or increased the intensity of induced caloric nystagmus. This reaction was thus a reverse (paradoxical reaction) of that observed in waking state. Photic stimulation may provoke the rapid phase of nystagmus through facilitating impulses coursing from the subcortical or cortical visual centres to Cajal's nuclei and then through the reticular formation to the vestibulo-oculomotor system. In waking state these impulses are inhibited while in precomatic state they may become prevalent. The paradoxical reaction disappears in deep coma together with all vestibular reactions.


Evaluation of intracranial disorders in children by computerized transaxial tomography: a preliminary report. Computerized transaxial tomography (CTT) is a nonivasive roentgenologic method that demonstrates the configuration of the intracranial contents, including the cerebral parenchyma and the ventricular system. Of 207 children examined by CTT, 53 later had neuroradiologic contrast studies or neurosurgical intervention, or both, and two came to autopsy. The neuroradiologic, surgical, and pathologic findings corresponded with the CTT findings in patients with large ventricles, dupratentorial tumors, intracranial hematomas or cysts, and epidural collections. The correlation was less concordant in patients with intracranial vascular malformations or lesions involving cranial bones. CTT promises to be valuable for diagnosis of many intracranial lesions in children.


[Diagnostic difficulties in cases of colloidal cysts of the 3rd ventricle]. The authors report two cases of colloidal cysts of the third ventricle discussing clinical neurological syndromes and diagnostic difficulties in the assessment of pneumoencephalography stressing the value of positive contrast encephalography.


Oligodendroglial toxicity by serum and lymphocytes from patients with multiple sclerosis. The gliotoxic effect of multiple sclerosis serums and lymphocytes was investigated by the measurement of Cr51 release from prelabeled bovine oligodendroglia. There was no difference in glial toxicity between multiple sclerosis patients and normal controls except for a depression of Cr51 release from bovine oligodendroglia in the presence of autologous serum plus lymphocytes in the multiple sclerosis patients compared with the normal controls. This correlated with the phase of the disease and may be due to the presence of a lymphotoxic factor in the active multiple sclerosis serums.


Alpha-1-antitrypsin deficiency in New Zealand. A severe deficiency of the serum protein alpha-1-antitrypsin can be expected to occur in 1 in 750 European New Zealanders. It can usually be identified by a faint or absent alpha-1 band on serum protein electrophoresis. Forty-seven cases are presented. 31 phenotype ZZ and 16 phenotype SZ. Eighteen have developed emphysema usually by age 40 years, two show childhood liver disease. One adult died of liver disease and three of the emphysema patients had liver abnormalities at post mortem. The remainder, mainly aged less than 30 years, are as yet asymptomatic. Individuals at risk should be protected from respiratory irritants (cigarettes, dusty environments and chest infections) and liver toxins (e.g., alcohol). The partial deficiency state (MZ) which occurs in 4 percent of the population also predisposes to respiratory and perhaps liver disease.


Effect of methylergonovine on puerperal prolactin secretion. Serum prolactin concentration was measured by radioimmunoassay in 29 women, in the first 1 1/2 hours postpartum. Fourteen women received 0.2 mg methylergonovine maleate (Methergine) intramuscularly after the delivery of the placenta. Fifteen women who served as controls received only saline. The rise in serum prolactin concentration seen in the control women (266.4 ng/ml +/- 40.8 SE) was significantly greater than that seen in methylergonovine-treated patients (141.0 ng/ml +/- 29.0. SE).


Nasotracheal intubation in epiglottitis. Significant numbers of patients with epiglottitis have been treated using nasotracheal intubation. Evidence is accumulating that this procedure is safe, effective and reliable when used in this disease. Nasotracheal intubation should be considered a suitable alternative to tracheostomy in epiglottitis.


Acetylcholine receptor: modification of synaptic gating mechanism after treatment with a disulfide bond reducing agent. Reduction of a 'reactive' disulfide bond in the postsyraptic membrane of the frog neuromuscular junction by dithiothreitol (DTT) decreases both the sensitivity of the membrane to applied acetylcholine (ACh) and the amplitude of the single 'shot effect'. Analysis of ACh induced conductance fluctuations in voltage clamped frog endplates indicates that DTT reduces both the amplitude gamma and duration tau of the elementary conductance events. The mean control value of gamma was 18.5-10(-12) omega-1 with no significant dependence on temperature. The mean control values pi were 2.3 msec at 7-9 degrees C and 0.94 msec at 20-22 degrees C. At 7-9 degrees C 1m7 DTT (20-50 min after application) reduced gamma to 61% of the control value and at 20-22 degrees C to 39%, while tau was reduced to 70% at both temperature ranges. The dose-response curve for iontophoretically applied ACh indicates that neither the total number of ionic channels nor the cooperativity within the receptors are changed. However, the affinity of ACh for the receptor sites was reduced. All effects of DTT were fully reversed by the oxidizing agent 5,5'-dithie-bis-(2-nitro-benzoic acid) (DTNB).


Chloride transport in isolated skin of Rana esculenta. Using a modified Ussing chamber, transepithelial Cl transport in isolated skin of Rana esculenta was determined throughout the year. Unidirectional 36-Cl fluxes were measured in the absence of electrochemical gradients across the skin. The correlations between unidirectional Cl influx and Cl efflux respectively and the Cl concentration in Na containing solutions were not linear in the 0 to 90 meq/1 range. The net Cl influx calculated from these two correlations was, in the same concentration range, also not linearly correlated and was significantly different from zero...


Cerebellar control of vestibular neurons of the frog. Intra- and extracellular potentials were recorded from vestibular neurons of the frog following stimulation of the ipsilateral cerebellar cortex (auricular lobe). Single neurons were identified as vestibular neurons by their location within the borders of the vestibular nuclei and by their activation via stimulation of the anterior branch of the VIIIth nerve. 2. Stimulation of the cerebellar auricular lobe provoked in some vestibular neurons apparently pure IPSPs with latencies as short as 1.5 msec suggesting a monosynaptic linkage between Purkinje cells and vestibular neuron. Vestibular-evoked responses were inhibited by cerebellar conditioning stimuli for as long as 50 msec. 3. Cerebellar stimulation also elicited an EPSP-IPSP sequence or occasionally pure EPSPs in vestibular neurons. These EPSPs were probably generated by axon reflex activation via the excitation of axons of primary and secondary vestibular neurons terminating in the cerebellum since they persisted after chronic VIIIth nerve section. Some vestibular evoked resonses were facilitated by cerebellar stimuli for 40-50 msec. 4. Occasionally an inhibitory effect was also induced in vestibular neurons by paired ipsilateral VIIIth nerve stimulation; it's latency of onset and time course suggested that a vestibulo-cerebello-vestibular loop was mainly responsible for the inhibition.


Tonic properties of the Flexor carpi radialis muscle of the male frog (Rana temporaria). The mechanical acitvity of the isolated flexor carpi radialis muscle (FCRM) of the mature male frog (Rana temporaria) was compared to that of the sartorius muscle. Muscles were stimulated directly by massive shocks at 20 degrees C and isometric tension was recorded during single twitch, twitch series, long tetani and long tetanus series. Some groups of muscles were poisoned with IAA-N2 or FDNB. The FCRM showed a high resistance to fatigue during a tetanus series and a "fatigue contracture" during a twitch series. The rate of the tetanic tension rise was smaller by five to six times than in the sartorius muscle (0 to 50% Po) and the twitch/tetanus ratio was always very small. During continuous activity and after the blocking of recovery metabolic pathways, FCRM used its energetic stores two to three times slower than the sartorius muscle. These stores did not seem to be more important. The results indicate that the FCRM is not a "tonic" muscle but, quite possibly, is composed of several types of fibre like many other frog muscles. However, some characteristics of mechanical response cannot be explained by the common classification into two types of fibre.


Late sodium current in the node of Ranvier. Voltage clamp experiments carried out on nodes of Ranvier of myelinated fibres of Rana esculenta showed that a small fractoon of sodium channels fail to inactivate. Thus during long lasting depolarizing pulses there is a small Na-current superimposed on the leakage and potassium currents. This late Na-current appears more marked in sensory fibres than in motor ones.


[Sharp's syndrome: a new entity amongst the connective tissue diseases?]. Sharp and coworkers have coined the name "Mixed connective tissue disease" to an association of symptoms seen in different connective tissue diseases. Those symptoms are associated with a special antibody directed against ribonucleoproteins (RNA-P). The presence of this antibody accounts for a high titer of antinuclear fluorescent antibody, of the speckled type. The most frequents symptoms in the association described by Sharp are Raynaud's phenomenon, swollen fingers, non deforming arthritis. We have observed those symptoms without any further symptoms of connective tissue disease, but with the presence of anti-RNA-P antibody. We suggest to coin the name of Sharp's syndrome to that clinical association. The significance of anti-RNA-P, and their correlation with a remarkable benignity of the disease, is discussed.


Blue dextran: influence on chromatographic profile and immunoreactivity of human follicle-stimulating hormone (HFSH). When FSH is chromatographed on G-100 Sephadex in the absence of Blue Dextran, it elutes as a single peak in the region of monomeric FSH. The addition of Blue Dextran causes a significant portion of FSH, iodinated or uniodinated, to elute in the region of the void volume. When standard curves for FSH are performed under identical conditions, with tracer 125I-FSH from the void volume, and from the FSH monomer region, maximal immunoreactivity was significantly greater for the Blue Dextran-associated tracer.


Gelfoam embolization of the left gastric artery for bleeding ulcer: experimental considerations. A bleeding gastric ulcer was surgically created in 18 dogs, and the left gastric artery was successfully catheterized by percutaneous techniques in 15. Nine of these dogs were treated with vasopressin infusion which did not arrest the hemorrhage. A total of 11 dogs (five of them following unsuccessful vasopressin therapy) underwent embolization with strips of Gelfoam, and hemorrhage stopped in ten. This technique of embolization is concluded to be of value in the management of gastric hemorrhage.


Release of prostaglandin F1alpha and F2alpha from superfused platelets: quantitative evaluation of the inhibitory effects of some aspirin-like drugs. The release of PGF1alpha and PGF2alpha from superfused blood platelets was studied by the combined use of two radioimmunoassay systems with different specificities. PGF1alpha only accounted for approximately 30% of the total immunoreactivity. A substantially similar pattern of release was obtained with platelets of rat and human origin, although the latter released considerably lower amount of both compounds. Indomethacin, Femoprofen, Ditazole and Aspirin all inhibited PGF2alpha release from rat platelets in descending order of potency. Hydrocortisone was partically inactive. The release of PGF1alpha and PGF2alpha was inhibited to the same extent by both Indomethacin and Fenoprofen. Moreover, a quite similar inhibitory effect by the same drug on rat and human platelets was found in preliminary experiments. In agreement with a previous similar finding, Aspirin displayed a higher inhibitory activity than that reported in other tissues. The use of superfused platelets seems to provide a simple and reproducible model for studying pharmacologic influences upon PG formation.


Cold-haemagglutinin disease with an autoantibody exhibiting different specificities at different temperatures. A case of chronic cold-haemagglutinin disease is reported in which an agglutinin apparently carrying two specificities was present. At first, specificity was anti-not-I and anti-I respectively: in the course of time anti-I was replaced by anti-A-1. Both anti-I and anti-A-1 could be demonstrated at room temperature only while specificity was anti-not-I at 4 degrees C. The antibody displayed haemolytic activity at room temperature and gave stronger reactions when treated biphasically. The same pattern of specificity was apparent in haemolysis tests, i.e. anti-not-I in the biphasical reaction 4 degrees C goes to 37 degrees C and first anti-I and later anti-A-1 at room temperature and at 22 degrees C goes to 37 degrees C. Anti-A-1 was not neutralized by A bloodgroup substance of animal origin nor by secretor saliva.


Antibody response by cultured spleen fragments from carrier-primed mice to hapten-protein conjugates. Hapten-protein conjugates stimulated very poor anti-hapten responses in mouse spleen fragment cultures from unimmunized mice, whereas hapten coupled to type III pneumococcal polysaccharide or polylysine induced good responses. When the donors of the fragments were primed with the carrier protein, hapten-protein conjugates induced a strong anti-hapten response. Both the true primary and the carrier-primed response in vitro consisted mainly of IgA antibodies of 9-13S. In carrier-primed responses also IgM was produced at the beginning and IgG at the end of those responses.


Effects of treating immune lymphocytes with a proteolytic enzyme (papain): reduction in immune potential and recovery after incubation. Immune spleen cells were treated with papain, washed, and boosted with homologous antigen (4-hydroxy-3-iodo-5-nitrophenylacetic acid coupled to chicken globulin) for 1 hr at 4 degrees C. When transferred to irradiated mice, they produced up to 20-fold less anti-hapten antibody than non-papain-treated cells. The lymphocytes could recover their ability to respond if incubated at 37 degrees C after papain treatment but before antigen boosting. Incubation for 30 min at 37 degrees C gave complete or almost complete recovery. Although papain usually reduced the response, in 31% of experiments the reduction was not significant. Possible reasons for this variability are discussed.


Genetic control of the murine cell-mediated immune response in vivo. I. H-2-linked responsiveness to the terpolymer L-glutamic acid-60-L-alanine-30-L-tyrosine-10. Various inbred and congenic strains of mice were immunized with the linear terpolymer L-glutamic acid-60-L-alanine-30-L-tyrosine-10 (GAT). Using a radioisotopic footpad assay to measure cell-mediated immunity in vivo, mice with H-2-a, H-2-b, H-2-d, and H-2-k histocompatibility alleles showed a positive reaction, whereas mice with H-2p and H-2-s alleles failed to respond. The ability of "responder" lymphocytes to show an immune response resides in the thymus-derived (T) lymphocyte population. Unfractionated spleen cells from H-2-q nonresponder mice, on transfer, showed no reactivity, whereas T-cell-enriched preparations were active.


Surface markers on human B and T lymphocytes. VII. Rosette formation between peripheral T lymphocytes and lymphoblastoid B-cell lines. Almost 100% of peripheral T lymphocytes are shown to have the capacity to form rosettes with human lymphoblastoid B-cell lines, predominantly at 4 degrees C and with lines having surface-bound IgG. Blast-transformed T cells retained this capacity and formed rosettes even at 37 degrees C. Unstimulated T cells bound less readily to B-cell blasts, stimulated by pokeweed mitogen for 72 hr. Even though rosettes, formed at 4 degrees C, were stable for several hours at 37 degrees C, no T-cell-mediated cytotoxicity could be detected during overnight incubation. Extreme pH values and trypsinization decreased rosette formation, whereas neuraminidase treatment enhanced the reaction. Rosette formation was independent of bivalent cations and unimpaired in the presence of inhibitors (NaF, NaN3), undiluted human or fetal calf sera, protein A, sonicated sheep erythrocyte membranes, and normal or heat-aggregated human IgG. Anti-Ig, anti-beta2-microglobulin, or anti-T cell sera did not influence rosette formation.


The protective role of thymus-derived lymphocytes in arbovirus-induced meningoencephalitis. The inflammatory response in mouse brain and the elimination of virus from the brain following intracerebral inoculation of a group A arbovirus has been shown to be T-cell dependent. Virus persists in the brain of T-cell depleted mice, and inflammation is depressed. Virus persists in the brain of T-cell depleted mice, and inflammation is depressed. Inflammation is restored by transfer of immune cells but not by immune serum, and the transferred cells are effective in reducing virus titres in the absence of circulating antibody. Transferred antibody is not efficient in protecting infected mice. The cells that restore inflammation can come from mice immunized with a group A arbovirus of the same subtype but not from mice immunized with more distantly related viruses. Macrophages may be important effector cells working in collaboration with T cells.


Are fetal cells in maternal blood mainly B lymphocytes? In 10 blood samples from mothers who were studied after the delivery of a male infant and who had Y-body-containing cells in their circulations (mean value, 0.06%) the proportions of surface-Ig- and Y-body-positive lymphocytes were determined after passage through nylon wool. In each case one part of the sample was treated with pronase before the nylon wool incubation and the other was not. Passage through nylon wool of maternal lymphocytes not treated with pronase resulted in a drastic decrease of fetal cells, since only 1 Y-body-containing cell was found in 1 of the 10 maternal blood samples studied, as compared with 28 Y bodies in the 10 samples not passed through nylon wool. In lymphocytes pretreated with pronase, 7 fetal cells were recovered after passage through nylon wool, although only in 5 of the 10 samples. Thus most fetal cells in maternal blood adhere to nylon wool, as do B lymphocytes, but this adherence is to some extent affected by pronase incubation.


Interactions between ricinus agglutinin and human IgM and IgG. Ricinus agglutinin, purified until homogeneous, precipitates serum glycoproteins with terminal nonreducing galactose residues including IgM and IgG. Almost 100% of IgM reacted with anti-IgM and ricinus agglutinin in quantitative precipitin tests. In similar tests, almost 100% of polyclonal IgG was precipitated by excess anti-IgG, whereas only about 10% reacted with ricinus agglutinin. In quantitative precipitin analyses and affinity chromatography experiments with insolubilized ricinus agglutinin and isolated monoclonal IgG1 and IgG3 proteins, only IgG3 proteins reacted with ricinus agglutinin.


Deficient lymphoid cell-mediated, PHA-induced cytotoxicity in rheumatoid arthritis patients. Lymphoid cells from patients with rheumatoid arthritis were compared with those from healthy blood donors and from nonrheumatoid arthritis patients for the ability to manifest in vitro cytotoxicity against target cells in the presence of phytohemagglutinin (PHA) or anti-target cell antibodies. The PHA-induced cytotoxicity in the rheumatoid patient group was significantly lower than that of the blood donors (P less than 0.01) and of the nonrheumatoid patients (P less than 0.05). The rheumatoid arthritis patients appeared to fall into two groups, one with normal and one with distinctly subnormal PHA-induced cytotoxicity. No obvious differences were observed betes, or the proportion in peripheral blood of T lymphocytes (E-RFC) or Fc-receptor-bearing lymphocytes (EA-RFC). There were no significant differences between the groups with regard to antibody-dependent cytotoxicity.


[Hemophilia A: early detection of women carriers by Laurell's quantitative immunoelectrophoresis]. Using one-stage quantitative factor VIII assay and the quantitative immunoelectrophoretic method of LAURELL a good correlation has been found between factor VII activity and protein concentration. In 80% of the known hemophilia A carriers the protein concentration was about twice as high as in normals as compared to the factor VIII activity, whereas about 20% of the known carriers have the same ratio between factor VIII protein and factor VIII activity as normals. The reliability of the test and its usefulness for the detection of hemophilia A carriers are discussed.


[Alpha 1 antitrypsin deficiency. Physiopathological consequences]. Alpha-1-antitrypsine, a glycoprotein synthesized in the liver, exists in different phenotypic variants. The Z allele, when heterozygotic, causes a diminution of protein in the blood; when homozygotic it causes an almost complete absence of blood protein. It appears that in instances of deficiency the hepatocyte is unable to secrete the protein it synthesizes, and this leads to intracellular accumulation of protein (visible on histological examination as granules of amorphic P.A.S.-positive material). The deficiency is accompanied by pulmonary manifestations of the destructive emphysematic type. The lesions are probably related to the absence of anti-protease activity in the lung tissues: proteolysis of the lung in animals reproduces the lesions observed in man. Studies on large populations have shown that, in people exhibiting a total or intermediate deficiency in alpha-1-antitrypsine, cigarette smoking represents a significant risk factor in that it increases the probability of parenchylmal destruction.


[Experimental studies on the vascular effect of adrenaline and POR-8 infiltrations in the jaw region]. The infiltration of a vasoconstrictor causes bleeding to diminish in the surgical field. Adrenalin is such a vasoconstrictor, but because of its metabolic action, acidosis develops in the tissue followed by decreased oxygen tension, a reactive hyperemia. This can of course cause postoperative hemorrage and edema.


Epidemiology and aetiology of cancer of the uterine cervix including the detection of carcinogenic N-nitrosamines in the human vaginal vault. Cancer of the uterine cervix occurs with high frequency in black females of several populations of Southern Africa. It accounts for 40-50% of all cancers in Black females in the Johannesburg area and for over 40% of those in women in the rural lowveld area of the Transvaal. The aetiology of this cancer has several distinct features, almost all of which concern some or other aspect of coitus. Age at first coitus and at first marriage, and promiscuity, are very strongly associated with the development of the disease, and age, race, religion, culture, socio-economic status, extent of genital hygiene and venereal disease also play a major role. In spite of current belief, circumcision of the male partner is at best weakly associated with the development of the disease, and so are menstruation, coital habits and pregnancy. Certain aetiological features are selectively discussed; these include Herpesvirus type II, 'rogue' spermatozoa and the recent isolation of a group of potent carcinogens, the nitrosamines, in infected discharge samples taken from the vaginal vault of patients attending gynaecological clinics.


Tuberculosis control in an urban Black community. A tuberculosis case-finding survey of an urban Black community is described. The programme included health education of the community leaders, tuberculin testing of all scholars at the schools, and of the pre-school and non-schoolgoi  ng children in their homes. The insignificant reactors to the tuberculin skin test were BCG-vaccinated. Isoniazid prophylactic therapy of the significant reactors was instituted and their contacts were radiologically investigated. The various results are to be found in the tables in the main body of this review.


Plasma expansion in surgical patients with high central venous pressure (CVP); the relationship of blood volume to hematocrit, CVP, pulmonary wedge pressure, and cardiorespiratory changes. There was no correlation of blood volume measurements with central venous pressure (CVP) or hematocrit determinations and only minimal suggestive trends with wedge pressure in a large series of postoperative patients; the lack of correlations emphasize the unreliability of venous pressure and hematocrit determinations to predict blood volume alterations. To evaluate the physiological problems, to define optimal therapeutic goals, and to measure therapeutic effectiveness of volume loading with an oncotically active agent, we measured the hemodynamic and oxygen transport responses to 500 ml. of 5 percent albumin given over 1 hour in 22 patients with CVP greater than 15 cm. H2O. The patients were separated into two groups according to the CVP response to volume therapy. The CVP decreased in 14 (64 percent) of these patients (Group 1), but it increased slightly but not significantly in eight (36 percent) patients (Group 2). In Group 1 patients, there was increased flow, improvement of tissue perfusion as reflected by increased oxygen consumption, and augmentation of the ventricular function. In Group 2 there were slight increases in mean flow, mean pulmonary arterial pressure, and mean transit time and slightly decreased pulmonary vascular resistance; there was appreciable improvement in left ventricular function without significant deterioration of right ventricular function. The high initial central venous pressure is not a reliable index of either hypervolemia or cardiac failure in critically ill patients. It is concluded that a trial of volume loading with an oncotically active agent with frequent auscultation of the chest and careful observation of the CVP trends will give the maximum diagnostic as well as therapeutic information.


Plasma components which interfere with ristocetin-induced platelet aggregation. Normal human plasma contains a component or components which interfere with ristocetin-induced platelet aggregation. Preliminary examination suggests a protein (or proteins) which binds ristocetin and competes more effectively for ristocetin than do the proteins involved in ristocetin-induced platelet aggregation. The presence of this protein in normal human plasma also prevents ristocetin-induced precipitation of plasma proteins at levels of ristocetin necessary to produce platelet aggregation (0.5-2.0 mg/ml). Serum contains an apparent two0fold increase of this component when compared with plasma. Heating serum at 56 degrees for one hour results in ad additional 2 to 4 forl increase. The presence of a ristocetin-binding protein in normal human plasma requires that this protein be saturated with ristocetin before ristocetin-induced platelet aggregation will occur. Variations in the ristocetin-binding protein(s) will cause apparent discrepancies in ristocetin-induced platelet aggregation in normal human plasmas.


The antiglobulin microcytotoxicity assay in HL-A genotyped families. HL-A genotyping was accomplished in 30 families (8 black, 21 white, and 1 American Indian) based on serological results obtained by our ususal lymphocytotoxicity assays. Each family was further tested by an antiglobulin microcytotoxicity method. Segregation patterns obtained by the latter method, compared with those of the former, showed few discrepancies. HL-A-identical siblings were serologically similar by the antiglobulin assay with frequency of discordant reactions at the same level as that of our regular two-stage lymphocytotoxicity assay. The antiglobulin method was shown to be highly reproducible with 1.3% discordance between duplicate tests. Many sera employed in routine cytotoxicity testing gave positive reactions with all family members in the antiglobulin assay (39% all positive by antiglobulin versus 16% by the regular cytotoxicity test), so that this method has limited usefulness for routine HL-A typing. The antiglobulin assay may have particular value, however, for identifying HL-A haplotypes in families, especially non-Caucasian, which give infrequent positive reactions in the usual lymphocytotoxicity assays.


Ag-F: serological and genetic identification of a new locus in the rat governing lymphocyte membrane antigens. A new genetic locus in the rat (Ag-F) is described. It controls expression of lymphocyte membrane antigens as determined by allospecific cytotoxic antibody. It is linked by approximately two recombination units to the gene for albinism and is therefore in linkage group I. It is suggested that Ag-F is the homologue in the rat of mouse H-1. It appears to be highly polymorphic and yields antigens which are highly cross reactive serologically. Disparity at Af-F is the probable cause of alloantibody responses attributable to reciprocal immunization between the Lewis and Fischer strains.


[Effect of insulin of frog skeletal muscle respiration]. The respiration of the isolated frog sartorius muscle was measured polarographically. The endogenous respiration was seen to increase by 8 and 6 times in 20 mM KCL and 0.05 mM 2,4-DNP, resp., and by 40 percent in 10mM pyruvate or lactate. Insulin stimulated the endogemous respiration from 27 to 38 mm-3 O2/hr. per gramm of wet weight. In the excess of exogenous lactate and pyruvate, the degree of the insulin stimulated respiration did not change. It is suggested that the increase of the endogenous respiration by insulin cannot be accounted for by the mobilization of the substrate of glycolysis.