Liver abnormalities in three patients with fetal alcohol syndrome. Liver abnormalities were found in three patients with fetal alcohol syndrome. The histological appearance was different in each case. Thick, sclerotic central veins were seen in two of the three cases. One patient had features typical of congenital hepatic fibrosis and cystic disease of the kidneys. Findings in these patients indicate that some cases of congenital hepatic fibrosis might be caused by high maternal alcohol ingestion in pregnancy.


Islet implantation normalises hyperglycaemia caused by streptozotocin-induced insulitis. Experiments in mice. Islet-cell deterioration in juvenile diabetes mellitus may be due to an autoimmune reaction, possibly involving both circulating islet-cell antibodies and an inflammatory process in the islets of Langerhans. Replacement of deteriorated islet cells by implantation of normal ones is now under investigation in many laboratories. The present study does not support the assumption that such islet transplants should be affected in the same way as the endogenous islets. Diabetic mice with a cell-mediated immune reaction to their pancreatic islets, induced by repeated injections of low doses of streptozotocin, were used as recipients. Isogeneic islets implanted intrasplenically in these animals were as effective in producing normoglycaemia as were those injected into animals made diabetic with a single bolus dose of streptozotocin. No inflammatory reaction was seen in the implanted islets, irrespective of the regimen of the preceding streptozotocin treatment. This finding suggests that islet-cell implantation may be attempted in insulin-requiring diabetic patients, even if the cause of the disorder is an inflammatory lesion of the patient's own islets.


Inhibition of prostaglandin synthesis as a treatment for biliary pain. Twenty patients with confirmed gallbladder disease were treated with intravenous indomethacin during 24 separate attacks of biliary pain. In all cases the pain was promptly relieved and there were no important side-effects. Indomethacin, and inhibitor of prostaglandin synthesis, may reduce intraluminal pressure in the gallbladder, and relieve pain.


Enzyme defect in primary gout.

Enzyme defect in primary gout. The rate-limiting step in the degradation of adenine nucleotides in the liver is the conversion of adenosine monophosphate (A.M.P.) to inosine monophosphate by A.M.P. deaminase, which is normally 95% inhibited. When the inhibition is released, uric acid is formed in large excess, and the biosynthesis of purines is increased. We therefore propose that congenital hyperuricaemia is caused by the presence of an abnormal A.M.P. deaminase, which is less sensitive to its physiological inhibitors. Verification of the hypothesis depends upon the availability of liver tissue from patients with congenital hyperuricaemia for kinetic analysis of A.M.P. deaminase. A call for collaboration is addressed to the medical community.


How many specialists?

How many specialists? The need for specialists cannot be adequately assessed on the basis of current practice and an estimated case-load (based on prevalence/population ratio). Specialists should declare which patients can or cannot be expected to benefit from their treatment, and they should consider the consequences of underprovision of specialist services. Specialists should also decide how much of what they normally do might equally well be carried out by generalists using the knowledge of specialists. Only then can the appropriate level of provision for various specialties be assessed, and effective deployment of the resources provided ensured.


Can patients keep their own peak-flow records reliably? Fifty patients recorded their peak expiratory-flow rate (P.E.F.R.) in hospital, unaided by nursing staff, five times a day for 5 days. Each patient's readings were randomly and independently checked on two occasions during this period. 69% of checked readings were accurate. Most patients kept satisfactory records as a table, but were less efficient in recording their results on a P.E.F.R. chart. Recording of P.E.F.R. by patients with respiratory disease saves nursing time and provides valuable clinical information.


Returned-medicines campaign in Birmingham, 1977. In a returned-medicines campaign lasting 3 weeks 362000 tablets and capsules were returned in 11400 containers from a population of 1.05 million. This yield was considered low. A comparison of hospital admission figures for childhood poisoning before, during, and immediately after the campaign suggests that the publicity and the destruction of unwanted medicines had little preventive value. The quantities of different medicines returned were roughly proportional to the quantities prescribed.


Bleomycin: its utilization in the treatment of head and neck cancer. Originally isolated as an antibiotic, bleomycin is a complex mixture of glycopeptides currently utilized against a variety of malignancies, among them epidermoid, cancer of the head and neck. Because of unique independent pharmacological properties, bleomycin may be effectively used at several points in the natural history of tumors. Use of bleomycin as a single agent, as an adjunct to surgery and irradiation and as a palliative drug in head and neck cancer, is now advocated in scattered reports. The rationale for the utilization of bleomycin at the University of California, San Diego and San Diego Veterans Administration Hospitals is discussed. In addition, examples from the authors' personal series of both response and adverse effects, suggestions for appropriate clinical monitoring to detect early toxicity, and tennets for management of side effects are included in the presentation.


Induction of C-type virus in cell lines derived from calf form bovine lymphosarcoma. For attempt to detect an etiological agent, cultures from bovine lymphosarcoma cases (adult form (ALS), calf form (CLS), and thymic form (TLS) were maintained in vitro for over a 18 month period. In two cultures from ALS, bovine leukemia virus (BLV) antigen was constantly detected. On the other hand, BLV antigen remained negative in cultures from two CLS and one TLS cases up to 40 passages. The RNA dependent DNA polymerase activities in these cultures were also negative. Treatment of a culture from CLS (3178) originated from liver tumor with 5'-iodo-2'-deoxyuridine (IdU) and dexamethasone (DXM) resulted in production of an agent serologically and morphologically similar to BLV and in alteration of cell morphology. No virus was detected in culture from TLS after treatment with IdU and DXM.


Murine model for immunoprophylaxis of cytomegalovirus infection. I. Efficacy of immunization. Murine cytomegalovirus was utilized as a model for human cytomegalovirus, which had no experimental animal, to study immunoprophylaxis of the cytomegalovirus infections. (1) Murine cytomegalovirus (MCMV) serially propagated in mouse embryonic fibroblasts had lost pathogenicity for weanling mice including neonatally thymectomized mice. (2) The cell culture-adapted MCMV was effective as a "live, attenuated virus vaccine" against challenge by virulent, mouse-passaged MCMV. (3) The immunization via intraperitoneal route protected mice from every parameter of MCMV infection. These included clinical signs, virus replication, histopathology and mortality. (4) The protective immunity was active against the virulent MCMV which was not neutralized by the rabbit anti-attenuated MCMV serum.


[The control of Aedes (Stegomyia) and related species involved in transmission of human arbovirus infections in tropical Africa (author's transl)]. In Africa, many Aedes mosquitos are involved in yellow fever and dengue transmission. Their control can be carried out either in a "prophylactic" way, when no disease occurs, or in a "curative" one, when virus is detected in the human community. In the first event, control is confounded with sanitation measures; in the second event, insecticidal control is needed against both larvae and adults. Larvae populations are destroyed by means of insecticidal deposits in the breeding-sites. Control of adults is achieved by thermal fogs or U.L.V. applications of organophosphorous compounds dispensed from ground or aerial generators. The insecticide susceptibility level of every Aedes populations involved in arbovirus transmission must be periodically determined with all the insecticides available.


[Control of malaria vectors in tropical Africa (author's transl)]. Indoor spraying with residual insecticides is at present the most effective method of malaria control. Following the failures observed during the campaigns of malaria control using D.D.T., B.H.C. and dieldrin, the W.H.O. has undertaken a wide programme for evaluating and testing new insecticides. The principal compounds tested are discussed. Only four insecticides have been held back: malathion, propoxur, fenitrothion and dichlorvos. However this compounds are very expensive and less remanent than D.D.T.


Effects of cyclophosphamide on the expression and induction of delayed hypersensitivity. Erythematous delayed reactions without induration, presumably assigned to Jones-Mote type, were characterized by the resistance to treatment with cyclophosphamide (CY) before elicitation or immunization in guinea pigs immunized with BGG in IFA or CFA. CY-treatment before elicitation converted delayed erythematous reactions from negative to positive at late intervals after immunization with BGG in IFA. Such a treatment augmented erythematous delayed reactions in animals immunized with BGG in CFA, but abolished induration at the reaction sites. CY-treatment before elicitation or immunization reduced the numbers of basophils at the reaction sites, although erythematous delayed reactions were augmented. Effector T cells responsible for delayed erythematous reaction without induration appear to persist for a long period of time after immunization in the presence of antibody production or tuberculin hypersensitivity and the expression of their function may be inhibited by suppressive mechanisms.


[Luminescent-microscopic study of soil microorganisms]. Soil microorganisms can be quantitatively assayed by means of a technique which makes use of staining preparations on slides with acridine orange. When bacterial cells were counted daily in humus-gleisolic soil, their number did not depend on time if the soil was incubated for five days. Mixed soil samples corresponding to the same time of incubation differed reliably in the bacterial number. The paper presents a scheme for determining the necessary number of samples, preparations, and fields of vision when the number of bacteria is being estimated. It is expedient to take 7 samples from a soil mixture, to make 2 preparations out of each sample, and to count bacteria in 5 fields of vision for each preparation.


A 60x computer-based Holter tape processing system. Since its introduction in 1968, the basic algorithm for automatic recognition of ventricular ectopic depolarizations, developed at Worcester Polytechnic Institute, has been implemented and modified by a number of investigators. The modified multi-template algorithm is conceptually similar to the original algorithm except that there are eight templates stored for each patient. A new template is stored whenever the match with each of the old templates yields a correlation coefficient less than 0.79. The system reads a Holter tape at 60 x real time for heart rates of 80 beats per minute, with relatively few false positives.


A dual-processor computer for arrhythmia analysis. In order to facilitate the analysis of 24-hour tape recordings of ECG for rhythm by the AZTEC technique, we have configured a dual-processor system. It samples the ECG signal from a tape playback unit at a rate of 7501.88 Hz, allowing analysis at 30 x real time. An approach to error recognition and containment for the program, which utilizes the sampling of events, is discussed. Steps are taken to reduce errors caused by human sampling of "high risk" regions of the record.


A two-dimensional clustering technique for identification of multiform ventricular complexes. A computer algorithm for the identification of multiform ectopic ventricular complexes in 24-hour ambulatory electrocardiographic recordings is described. The clustering technique established regions, based on R-R interval and ST-segment slope, in a two-dimensional probability space based on the fit of each ventricular complex. The boundaries of any overlapping regions are analyzed using a Bayesian decision rule to minimize misclassification.


Chemotherapy of head and neck cancer: combination treatment with cyclophosphamide, adriamycin, methotrexate, and bleomycin. A combination of cyclophosphamide, adriamycin, methotrexate, and bleomycin (CAMB) was explored in patients with advanced, nonresectable epidermoid carcinoma from primary sites in the head and neck, recurrent or persistent after radiation or surgery. Objective regression (greater than 50%) of measurable tumor was present in 35% of the patients. The median duration of response was 2.5 months. Median survival of responders was slightly less than the nonresponders, but the difference was not significant. Drug-related morbidity was substantial; leukopenia, mucositis, and weight loss were the most frequent major side effects. Three deaths were attributable to the regimen. The results seem comparable to those one might expect from methotrexate alone.


A detection algorithm for multiform premature ventricular contractions. This paper reports an algorithm developed to identify and quantify multiform PVCs. The algorithm clusters PVCs of similar morphology using a combination of time-domain and frequency-domain analysis. Initially, PVCs are grouped together on the basis of four time-domain-based morphological feature measurements. However, these time-domain-based clusters many times are nonunique because commonly encountered signal changes can cause substantial variations in the feature measurements of clinically similar beats. These redundant clusters are consolidated using two frequency-domain parameters: The First Spectral Moment (FSM) (center of gravity) of the amplitude spectrum, and the 5-Hz phase angle.


Semiautomated data reduction of ventricular ectopic activity: methodology and clinical application. A semiautomated ventricular premature beat (VPB) detector was developed which detects VPBs based upon a logical combination of prematurity, amplitude, and width. This system utilizes technicians to define sensitivity and criteria of VPB detection and to monitor the system's performance using a unique feedback system. Technician-assisted semiautomated scanning was found superior both to the system using preselected criteria and sensitivity of the detectors, and to traditional Holter scanning for the detection of single and repetitive VPBs. Ninety percent confidence limits of VPB frequency per hour have been established for this system.


Comparison of two radioimmunoassays and a microbiologic assay for bleomycin. Recently two radioimmunoassays have been independently developed for determination of bleomycin levels. In this study these assays are compared with each other and with a standard microbiologic assay for bleomycin. Bleomycin levels were determined in serum and urine samples obtained at varying intervals following intramuscular bleomycin injection. There were systematic differences between the assays. One radioimmunoassay indicated bleomycin levels lower than the levels indicated by the microbiologic assay with serum samples. With urine samples, both radioimmunoassays indicated bleomycin levels greater than the microbiologic assay.


The effects of prior exposure to bleomycin on the incidence of pulmonary toxicities in a group of patients with disseminated testicular carcinomas. The incidence of pulmonary toxicities in 12 patients with prior exposure to bleomycin (BLM) was compared to the incidence of pulmonary toxicities in a matched group of 73 patients with state II or IV testicular carcinomas treated with a regimen containing vinblastine, bleomycin, and cis-diamminedichloroplatinum. The comparison demonstrates that prior exposure to bleomycin constitutes a significant risk factor and that the risk is additive; ie, prior doses should be added to current doses to determine the cumulative dose-related probablity of development of pulmonary toxicities.


Immunochemical analysis of the structure of eukaryotic ribosomes: antigenic properties of rat liver ribosomes and ribosomal proteins and characterization of the antisera. Antibodies were prepared in rabbits and sheep to rat liver ribosomes, ribosomal subunits, and to mixtures of proteins from the particles. The antisera were characterized by quantitative immunoprecipitation, by passive hemagglutination, by immunodiffusion on Ouchterlony plates, and by immunoelectrophoresis. While all the antisera contained antibodies specific for ribosomal proteins, none had precipitating antibodies against ribosomal RNA. Rat liver ribosomal proteins were more immunogenic in sheep than rabbits, and the large ribosomal subunit and its proteins were more immunogenic than those of the 40S subparticle. Antisera specific for one or the other ribosomal subunit could be prepared; thus it is unlikely that there are antigenic determinants common to the proteins of the two subunits. When ribosomes, ribosomal subunits, or mixtures of proteins were used as antigens the sera contained antibodies directed against a large number of the ribosomal proteins.


Recognition of antigens by T lymphocytes. The present review briefly summarizes our knowledge of antigen-specific B and T lymphocyte receptors. Antigen-specific receptors on mammalian B lymphocytes are mainly monomeric IgM and IgD consisting of conventional immunoglobulin heavy and light chains. The nature of the T lymphocyte receptor which can specifically recognize antigens is not yet fully defined. However, it seems that conventional light chains do not participate in the build up of this receptor, and that the receptor is made up of heavy chains of a new immunoglobulin class which has to be further characterized and which we call Tau-chain. The variable region of the T lymphocyte receptors share idiotypic determinants with the corresponding B lymphocyte receptors. The possible linkage between the T cell idiotypes present on the Tau-chains and molecules which are under the control of genes of the Major Histocompatibility Complex of the species are discussed. In the last part of the review two methods for the induction of specific transplantation tolerance in adult animals are described. These methods are based on the concept that T lymphocytes reactive against alloantigens bear idiotypic determinants against which a specific auto-immune response can be initiated.


[Immunochemical properties of tryptophanyl-tRNA synthetase and its fragments]. The interaction between beef pancreas tryptophanyl-tRNA synthetase and its fragments produced after limited proteolysis, with IgG fraction of antiserum and with Fab fragment of IgG has been studied. Both the intact antibodies and Fab fragments inhibit the enzyme activity in tRNA aminoacylation and tryptophan dependent ATP-32P pyrophosphate exchange reactions. However, the enzyme inhibited by antibodies is still able to form a complex with tryptophanyl-tRNA. The enzymatically active fragment obtained after endogenous proteolysis interacts only with 1/3 of the antibodies against native enzyme. The fragment produced by trypsinolysis possess similar immunochemical properties. This fragment has almost the same molecular weight but is enzymatically inactive. Pure antibodies against tryptic fragment isolated by means of specific immunoabsorbent inhibit the enzymatic activity. The antibodies which do not interact with this fragment (2/3 of the total amount of antibodies) have no influence on the enzymatic activity. The immunochemical identity of the two synthetase fragments differing in their enzymatic activity supports the assumption that the loss of enzymatic activity of the tryptis fragment is caused by lack of a small peptide which is retained in case of endogenous proteolysis. Probably the amino acid residues of this peptide participate in formation of the active centre of tryptophanyl-tRNA synthetase. A new procedure for determination of the number of antigenic determinants in proteins is developed. It is shown by this method that beef pancreas tryptophanyl-tRNA synthetase contains 9 +/- 1 antigenic determinants.


Substance P in the vagus nerve. Immunochemical and immunohistochemical evidence for axoplasmic transport. 1. The presence of immunoreactive substance P (I-SP) in the vagus nerve of 5 species was demonstrated by radioimmunoassay. Different amounts of SP per unit weight were found: Guinea pig greater than cat greater than rabbit, rat and cattle. 2. Infranodose ligations of the vagus nerve of cats and rabbits caused an accumulation of I-SP proximal but not distal to the ligation. The results obtained by radioimmunoassay and immunohistochemistry indicate a somatofugal axoplasmic transport of SP. 3. Double ligation experiments revealed that about 37% of I-SP of the cat vagus nerve are mobile. The transport rate of this mobile I-SP was found to be 170 mm per day. 4. Locally applied colchicine resulted in a similar accumulation of I-SP as after ligations. This is evidence favouring the involvement of microtubuli in the axoplasmic transport of SP. 5. Immunohistochemical data show that SP-fibers account for about 10% of the axons in the cat vagus nerve. Most of these SP-fibers seem to be unmyelinated. 6. Supranodose extracranial ligations of the cat vagus nerve led to an accumulation of I-SP on both sides of the ligature. Part of the SP-fibers are, therefore, afferent and their cell bodies are located in the nodose ganglion. The presence of efferent SP-fibers cannot be excluded.


Axonal transport of 4S RNA in the chick optic system. The axonal transport of tRNA has been investigated in the chick optic system. Chicks were injected with [3H]uridine intraocularly or intracranially and the RNA of the retina, nerve complex, and tecta separated by polyacrylamide gel electrophoresis and then counted. The ratio of tRNA to rRNA specific activities increased with time in both the nerve complex and contralateral tectum. The ratio increased more rapidly in the nerve complex than the tectum. However, no increase was observed in the case of intracranially injected animals. This is consistent with the axonal flow of tRNA. When [methyl-3H]methionine was used as precursor, the preferential labeling of 4S RNA to rRNA which resulted more clearly showed a transport of 4S RNA from the retinal cells to the tectum. In conclusion, it was found that about 40% of the radioactive RNA observed within the optic tectum 4 days after an intraocular injection of [3H]uridine was accounted for by 4S RNA which has flowed from the retina. However, the migration of a methylated RNA molecule of size 4S, but unrelated to rRNA, cannot be entirely eliminated.


Axonal transport of lipid in goldfish optic axons. After injection of labeled glycerol, choline, or serine into the eye of goldfish, labeled lipids were axonally transported along the optic nerve to the optic tectum. Although the different precursors were presumably incorporated into somewhat different lipid populations, all three were approximately equally effective in labeling the lipids transported to the tectum, but the amount of transported material remaining in the nerve was different, being highest with choline and lowest with serine. The labeled lipids appeared in the tectum within 6 hr of the injection, indicating a fast rate of transport, but continued to accumulate over a period of 1--2 weeks, which presumably reflects the time course of their release from the cell body. Since there was a gradual increase in the proportion of labeled lipid in the tectum during this period, some other process in addition to fast axonal transport may have affected the distribution of the lipids along the optic axons. When [3H]choline was used as precursor, the transported material included a small amount of TCA-soluble material, which was probably mainly phosphorylcholine, with labeled acetylcholine appearing in only insignificant amounts. With serine, which gave rise to a large amount of axonally transported protein in addition to lipid, a late increase in the amount of labeled lipid in the tectum was seen, accompanied by a decrease in labeling of the protein fraction.


[The lupus erythematosus (LE) phenomenon. Status in 1978]. The results of 835 studies of LE cells carried out over 8 years in 563 clinical cases of various nature are reported. The LE phenomenon--i.e. LE cells, LE globs and rosettes--was encountered exclusively in patients with LES, whereas tart-cells, nucleophagocytosis A and nucleophagocytosis B, although present in initial LES, and particularly in regressing LES, were very frequent in many other conditions. It is therefore held that true LE phenomenon is pathognomonic of LES since so-called AR with LE cells can be considered a clinical variant of LES, whereas lupoid hepatitis remains a vague, uncertain syndrome.


Alpha fetoprotein levels in amniotic fluid and maternal serum and their use in screening in pregnancy. During the period January 1975--July 1977 alpha fetoprotein was measured in 263 amniotic fluid samples and 44 maternal serum samples taken in the second trimester of pregnancy. The importance of careful interpretation of results is discussed.


Intramembranous localization of bacteria in beta-hemolytic group B streptococcal chorioamnionitis. An unusual pathologic finding consisting of large colonies of bacteria, localized immediately beneath the epithelial layer of the amnion, has been observed in association with an example of group B beta-hemolytic streptococcal chorioamnionitis. Postpartum endometritis as well as neonatal sepsis and meningitis occurred. Histologic examination of the umbilical cord and placenta revealed routine features of intraamniotic inflammation, but the membranes were characterized by the presence of unusual darkly staining deposits of material immediately beneath the amniotic epithelium. Subsequent special stains revealed these to be colonies of gram-positive cocci. We have been unable to find a previous description of this observation in association with streptococcal or with other types of chorioamnionitis.


Microbial-like antigens in human leukemia. Antigens present in leukemic sera and organ extracts, but absent from non-leukemic sera and tissues, were detected by examining their reactions with anti-microbial antisera by means of counter-immunoelectrophoresis. Out of 110 different antisera used, 12 antisera, those produced against Micropolyspora, Coccidioides, Salmonella, Mycoplasma, Mycobacterium simiae, Absidia, pseudorabies virus and adenovirus, proved to react regularly with the leukemic sera. Absorption studies point to an immunological specificity of these cross-antigenicities. Interpretations and implications of these discoveries are discussed in the paper.


Anterior spinal artery syndrome--a complication of cervical intrathecal phenol injection. Spinal nerve block by intrathecal phenol-glycerine infusion is commonly employed for relief of severe pain in terminal carcinomatosis and, frequently, a dramatic regional anesthetic effect is achieved. However, nerve block by this procedure may in very rare instances give rise to serious complications. We have seen a case of terminal malignant melanoma in which clinical manifestations, indicative of anterior spinal artery syndrome, developed following the injection of 0.3 ml of 10% phenol-glycerine into the cervical subarachnoid space at the C4--C5 level for the control of severe right arm pain. This report describes the clinical course of the patient over a period of 4 months after the nerve block and the post-mortem findings along with a brief review of the literature.


[Simple methods for the quantification of elastase and its inhibitors in human sera (author's transl)]. Two methods for measuring the elastase activity and the elastase inhibitory capacity of sera or other tissue extracts are described. The elastase inhibitory capacity of 40 human sera is determined using highly purified insoluble elastin in a gelified medium and this value is correlated to the alpha1-antitrypsin concentrations of these sera quantified by radial immunodiffusion. The elastase activity of these sera were determined on high molecular weight soluble kappaelastin peptides immobilized in a gelified medium and we have found a strong dispersion of the individual values. The elastase activity is not correlated either with the inhibitory capacity, the alpha1-antitrypsin or alphai-macroglobulin concentrations of these sera. The sensitivity, specificity and simplicity of these methods render them useful for their application to clinical investigations.


[Contraceptive hormones, vascular risk and abnormal precipitation of serum gamma-globulins (author's transl)]. The monoclonal anti-ethinyl-estradiol antibody previously found in the serum of a woman on oral contraceptives, was precipitated by 25% saturated ammonium sulfate à 22 degrees C. This simple test has been used to investigate the possible relationship between abnormally precipitating gamma-globulins (GAP) and the vascular risk of the pill. Four groups of women were studied: --50 women who had never used the pill; --100 women on oral contraceptives; --30 women who had stopped the pill; --17 women had experienced venous or arterial thrombosis during oral contraception. The results obtained indicate: 1) that a GAP increase is nearly always associated with the thrombotic events (90% of the cases in group 4); 2) that the presence of GAP is seen only in part of the women population on oral contraceptives representing approximately 30% of the total population investigated as indicated by a bimodal distribution. 3) that the GAP remain increased for months and even years after the pill was discontineud. The significance of this test is discussed. It is proposed that the presence of GAP in the serum appears to be related to the presence of ethinyl-estradiol binding antibodies. This hypothesis is verified by experiments in progress.


Efficient reverse transcription of cowpea mosaic virus RNAs. Conditions are described which give an efficient synthesis of DNA copies of cowpea mosaic virus (CPMV) RNAs, using avian myeloblastosis reverse transcriptase and oligo (dT) primers. Maximum incorporation of dAMP into cDNA is attained with 0.4 to 0.8 mM of each deoxynucleoside triphosphate, 12 mM Mg++ and 60 mM K+ ion concentrations. High enzyme concentrations (up to 100 units/ml) were used. Under these conditions over 1000 pmoles of dAMP were incorporated  per reaction. The cDNA:RNA molar ratio approached 0.3 when 1 pmole CPMV RNA was used as template. The products were heterogeneous but large. Bottom component RNA (about 6000 nucleotides long) was copied into cDNA molecules ranging from about 1000 to 4000 nucleotides, and middle component RNA (about 4000 nucleotides long) was copied into cDNA mostly between 500 and 2000 nucleotides long, on average about 1500, which can be cleaved by restriction endonuclease Hae III into two fragments of 880 and 540 nucleotides.


Comparison of the methods of cathodoluminescence, electronprobe microanalysis, and calcium staining, applied to human aorta with isthmus stenosis. Electron probe x-ray microanalysis is a useful method for studying pathologic and age-related calcification mechanisms in the aorta and in muscular arteries by means of elemental analysis in microareas. In the present investigation, this method was correlated with the histochemical alizarin-S-calcium staining and with cathodoluminescence analysis in the scanning electron microscope. Portions of the proximal region of a human aorta with isthmus stenosis was shock-frozen and sectioned in a cryostat. Serial sections were investigated by calcium staining, electron probe, and cathodoluminescence microanalysis. Using quantitative electron probe microanalysis of calcium and phosphorus, it was shown that the principal regions of calcium phosphate mineralization could be located using either alizarin-S staining or cathodoluminescence analysis. The advantage of the cathodoluminescence analysis is its higher lateral resolution compared with that of light microscopy, and the fact that no special staining is required. In addition, it was possible to obtain scanning images, thus providing additional information about the topology of the tissue surface, which is necessary to decide whether or not the section is suitable for microanalysis. Quantitative microanalysis is a valuable tool for basic research on calcified arteries. The results of the combined analysis in the proximal and distal regions as well as in the stenosis will be published in a later paper.


Expression in Escherichia coli of chemically synthesized genes for human insulin. Synthetic genes for human insulin A and B chains were cloned separately in plasmid pBR322. The cloned synthetic genes were then fused to an Escherichia coli beta-galactosidase gene to provide efficient transcription and translation and a stable precursor protein. The insulin peptides were cleaved from beta-galactosidase, detected by radioimmunoassay, and purified. Complete purification of the A chain and partial purification of the B chain were achieved. These products were mixed, reduced, and reoxidized. The presence of insulin was detected by radioimmunoassay.


Fetal phenotypic expression by adult rat hepatocytes on collagen gel/nylon meshes. Hepatocytes from adult rats were maintained in primary culture for up to 10-13 days on nylon meshes coated with a thin layer of rat tail collagen gel. Their ultrastructure closely resembled that of the liver parenchymal cell in vivo, but hepatocytes in late culture exhibited a pronounced buildup of microfilaments beneath their apical cell surface. Hepatocytes in early and late cultures secreted albumin, transferrin, and alpha1-acid glycoprotein into the medium; they exhibited a 7- to 10-fold induction of tyrosine aminotransferase activity by dexamethasone; and they expressed an alkaline phosphatase that was similar to that of normal rat liver with respect to its inhibition by the liver enzyme inhibitor L-homoarginine. In addition, the hepatocytes in culture demonstrated phenotypic changes characteristic of fetal liver parenchymal cells. These changes, which paralleled an increase in DNA synthesis, included the expression of and linear increase in the activity of the fetal liver cell enzyme gamma-glutamyl transpeptidase, an increased production of alpha1-fetoprotein, and a change in the substrate specificity of fructose-bisphosphate aldolase to that of the fetal liver isozyme.


Antibodies from patients with myasthenia gravis recognize determinants unique to extrajunctional acetylcholine receptors. We have examined the interaction between sera from patients with myasthenia gravis and acetylcholine receptor (AcChoR) purified from normal and denervated rat skeletal muscles [junctional receptor (JR) and extrajunctional receptor (EJR), respectively]. Eight of ten myasthenic sera had titers against EJR that were significantly higher (1.1-2.4 times) than their titers against JR. The antireceptor titers of these sera ranged from 2 to 102 nM. Although activities of three other sera were too low (less than 1 nM) to allow accurate titrations, provisional measurements with these sera gave titers against EJR that were at least as high (1.0-1.4 times) as those against JR. Competition experiments with myasthenic sera demonstrated two classes of determinants on rat AcChoR: those that are common to JR and EJR and those that are present or exposed only on EJR. Myasthenic sera did not recognize any determinants unique to JR. Several antisera raised to purified AcChoR from eel or Torpedo electric organs or denervated rat skeletal muscle had equal titers against the two forms of receptor. Treatment of JR and EJR by various enzymatic or chemical procedures designed to alter prosthetic groups on the proteins failed to affect their antigenic reactivity. AcChoR from embryonic rats was indistinguishable immunologically from EJR of adult muscle.


alpha-Fetoprotein and albumin genes of rats: no evidence for amplification-deletion or rearrangement in rat liver carcinogenesis. Full-length radiolabeled albumin and alpha-fetoprotein (AFP) cDNAs were synthesized from pure albumin and AMP mRNA preparations by using avian myeloblastosis virus reverse transcriptase (RNA-dependent DNA polymerase). The cDNAs have been used to quantitate the number of albumin and AFP genes in different rat tissues by two independent methods, both of which yielded similar results. First, the kinetics of the association of these cDNAs with nuclear DNA from rat liver, rat kidney, and Morris hepatoma 7777 under conditions of vast DNA excess indicated that the albumin and AFP mRNA's are transcribed from "nonrepetitive DNA." Second, saturation hybridization experiments in which a constant amount of rat liver DNA or Morris hepatoma 7777 was hybridized with increasing amounts of cDNA to albumin mRNA have shown the presence of 1--2 albumin genes per rat haploid genome. The number of AFP genes obtained in similar titration experiments was approximately 2--3. This was true whether rat liver DNA or hepatoma 7777 DNA was used in the reassociation experiments. When high molecular weight DNA preparations from both these tissues were digested with the restriction endonuclease EcoRI and the fragments were transferred to a nitrocellulose filter, the albumin and AFP [32P]cDNA probes hybridized to different sets of DNA fragments. However, each probe gave the same hybridization pattern whether Buffalo rat liver DNA or hepatoma 7777 DNA was utilized.


Rapid sequence determination of late simian virus 40 16S mRNA leader by using inhibitors of reverse transcriptase. A method for the determination of the primary structure of spliced mRNA junction and leader sequences is described. By analogy to the DNA sequencing procedure of Sanger et al. [Sanger, F., Nicklen, S. & Coulson, A. R. (1977) Proc. Natl. Acad. Sci USA 74, 5463--5467], we use 2",3'-dideoxynucleoside triphosphates as chain-terminating inhibitors of the reverse transcriptase (RNA-dependent DNA polymerase) reaction. By using specific DNA restriction fragments as primers in combination with this technique, we have determined the sequence of the spliced junction between the body and the leader sequence of the 16S late mRNA of simian virus 40. The method described should be of general utility in mapping spliced mRNA regions for which the corresponding protein sequence (if any) is unknown.


Specific binding of 125I-labeled beta-hexosaminidase A to rat brain synaptosomes. Purified human beta-hexosaminidase A (beta-N-acetylgulcosaminidase; 2-acetamido-2-deoxy-beta-D-glucoside acetamidodeoxyglucohydrolase, EC 3.2.1.30) has been labeled with 125I to high specific activity with the retention of 80% of its enzyme activity. The binding of this enzyme to sonicated synaptosomes from rat brain was shown to be a saturable and specific process. Glycoproteins containing a sialic acid-terminal oligosaccharide or a galactose-terminal oligosaccharide (i.e., alpha 1-acid glycoprotein and fetuin and their asialo derivatives) were strong inhibitors of the binding. In contrast, ovalbumin, which contains a mannose-rich oligosaccharide, and mannans were poor inhibitors of the binding. Of the monosaccharides tested, sialic acid, galactosamine, mannose, galactose, and lactose were inhibitory in decreasing potency of inhibition. Optimal binding occurred at pH 7.0 in the presence of 3 mM calcium ions. The binding was a linear function of synaptosomal protein concentration between 25 and 200 microgram of protein per assay and was directly proportional to time up to 3 hr, beyond which there was no further increase in specific binding. The data suggest a unique but complex mode of interaction of glycoproteins with receptors on synaptic membranes.


Subtotal-skin electron-beam therapy once a week for inflammatory breast carcinoma. Subtotal-skin electron-beam therapy (SSEB) was employed once a week in the treatment of 22 patients with recurrent inflammatory breast carcinoma between 1971 and 1976. The entire upper torso received 400 rad once a week for 6 consecutive weeks, using 3.5-MeV electrons from a 6-MeV linear accelerator. Seventeen patients (77%) obtained complete response and 3 (14%) had partial response, for a total response rate of 91%. Remission lasted for six months or longer in 35% of those exhibiting complete response. Treatments were tolerated well. The authors suggest that this is an excellent palliative method of treating this rapidly progressive disease.


[Microspectrometric quantification of 4-hydroxypentenal binding to protein thiols in Ehrlich ascites tumor cells]. After 30 minutes in 5.10(-3) M hydroxypentenal (HPE) the microscopically determinable proteinthiols (PSH) stained with DDD-Fastblue B decrease from 1,07 . 10(-14) to 0,61 . 10(-14) moles/cell. The loss of PSH of 0,46 . 10(-14) moles has a confidential range (99%) of +/- 0,12. As HPE reacts with thiols by an addition to the C3 = C2-group, the aldehydic group remains reactive and can be recognized intracellulary and quantitatively determined with 2,4-dinitrophenylhydrazine, whereby an uptake of 0,63 . 10(-14) moles of HPE per single cell is observed (confidential range +/- 0,11). The broad overlapping of the confidential ranges indicates clearly that the loss of PSH corresponds to the uptake of HPE. From the statistical distribution diagrams it can be seen that the PSH of practically all cells take part in the reaction, if however, to very different extent; the cells with high PSH concentrations being the most reactive ones.


Quantitation of enzymes in tissue sections by estimation of hydrolytic activity and antigenic determinants. The method and instrumentation for the analysis of enzyme activity and of fluorescent antibody of antigen binding is described. It is based on the microscopic photometry of stain intensities per area of functional units. Thus it was shown that the concentration of aminopeptidase (EC 3.4.2.1) per area in procimal tubule of kidney from pig and mouse is constant. In contrast to the pig the tubules from the outer medulla of the mouse contained twice as much enzyme as those from the cortex. A non constant concentration of aminopeptidase per area was found in crypts of duodenum and in stimulated macrophages.


Chemoimmunotherapy versus chemotherapy for remission induction in patients with non-Hodgkin's lymphoma: progress report of a Southwest Oncology Group study. The Southwestern Oncology Group is conducting a controlled clinical trial for patients with all types of advanced non-Hodgkin's lymphoma in which chemoimmunotherapy (CHOP + BCG) is being compared with chemotherapy alone (CHOP + bleomycin or COP + bleomycin) for remission induction. Patients achieving a complete remission confirmed by systematic restaging are then randomly assigned to maintenance BCG or to no further therapy. As of April, 1977, 669 patients had been registered on this trial and 420 were fully evaluable. No significant differences in response rates between the three remission induction regimens are apparent. After restaging, early relapses have occurred with equal frequency in the BCG and no-further-therapy groups. Longer follow-up and further analysis will be required to fully evaluate the potential effects of BCG on remission duration or survival in this study.


Characteristics of growing bone surfaces. Both bone-forming and bone-destructing cells may appear in different forms. This conclusion has been drawn as a result of compared observations from histomorphologic, histochemical and vital staining studies. The bone-forming cells may be cuboidal and situated in one or more rows along the bone surfaces, or may be flat. The type of cell reflects the rate of bone formation. The bone-resorbing cells may be big multinucleated cells or small mononucleated cells. The latter cell type is well-known from the literature although not referred to in textbooks of histology. Flat bone-forming cells and small mononucleated bone-resorbing cells resemble each other in the light microscope. Studies of bone growth with the aid of histomorphologic descriptions of cell types have to take this fact into account. Otherwise, erroneous conclusions may easily be drawn.


Acute promyelocytic leukaemia: further evidence of the differentiation-linked expression of Ia-like (p28,33) antigens on leukaemic cells. Patients with acute non-lymphoblastic leukaemia were studied to determine if the presence of Ia-like antigens on leukaemic cells was related to the maturity of a leukaemic cell line. Ia-like antigens were present in the majority of acute myeloblastic and myelomoblastic leukaemias. 4 patients with acute promyelocytic leukaemia were Ia-negative. This finding suggests that Ia-like antigens reflect normal differentiation linked events in haemopoiesis. The presence of Ia-like antigens on leukaemic cells did not alter the patient's response to chemotherapy.


Studies on the cytophilic properties of human beta2-microglobulin. II. The role of histocompatibility antigens. The mechanism by which exogenously added beta2m binds to lymphoid cells has been explored. In the mouse it has been shown that beta2m remains associated with plasma membrane macromolecules following solubilization with NP-40 and that approximately 25-30% of the binding could be accounted for by binding to H-2 antigens. No binding to mouse immunoglobulin or Ia antigens could be detected. The sites for binding of the remainder of the cell-bound beta2m were not determined. Whereas normal human lymphocytes showed little or no capacity to bind exogenously added beta2m, it was found that phytohaemagglutinin (PHA)-stimulated cells could bind beta2m. This binding occurred optimally 2 days after PHA stimulation. Approximately half of the binding could be accounted for by binding to HLA antigens. The possible significance of these findings with respect to cellular interactions involving major histocompatibility complex gene products in the immune response is discussed.


Characterization of IgD. I. Isolation of two molecular forms from human serum. Human IgD present in the serum of normal individuals or of patients with Hodgkin's disease (having high IgD concentrations) was characterized and compared with five IgD myeloma proteins. IgD was isolated using a highly specific anti-delta insoluble immunoabsorbent from which the bound material was eluted with sodium dodecyl sulphate (SDS) or urea. The latter reagent could be removed by extensive dialysis, thus making possible the renaturation of the eluted molecules. The purity of the IgD thus isolated was confirmed by antigenic analysis. Both kappa and lambda light chain determinants were present on serum IgD, although lambda light chain was predominant with a ratio over the kappa chain of 2:1. SDS-polyacrylamide slab gel electrophoresis analysis revealed two different molecular forms of serum IgD, one (IgD) migrating identically to monoclonal IgD, the other (IgD2) having a faster mobility. The difference between the two molecules was entirely, due to the different sizes of their constituent delta chains. Peptide mapping of the two chains (delta1 and delta2 respectively) and of the delta chain of an IgD myeloma protein was carried out using 125I-labelled material. The three molecules displayed a high degree of homology, the delta2 chain differing by the presence of three characteristic extra peptides. The significance of these extra peptides is discussed in the light of the peptide mapping technique employed.


Lymphoblastoid cell lines are polyclonal activators of human T lymphocytes. Following stimulation with autologous or allogeneic lymphoblastoid cell lines (LCL) human T lymphocytes acquire two properties which suggest that LCL act as polyclonal activators. Cytotoxic activity, which has an antigen-specific component, is produced towards normal lymphocytes and LCL, and the cells become capable of mounting proliferative responses to antigens on human B lymphocytes which have accelerated secondary-type kinetics. Only weak responses to autologous cells occur. In addition, repeated restimulation with the original LCL leads to a progressive increase in the number of cells in the culture for a period of about 4 weeks. This approach may prove a useful way to grow large numbers of human T lymphocytes for further study.


In vitro sensitization of human T lymphocytes to hapten (TNP)-conjugated and non-treated autologous cells is restricted by self-HLA-D. By co-culturing human T lymphocytes with TNP-treated autologous B lymphocytes and macrophages for 10 days in vitro, sensitization to TNP-treated autologous cells could be detected in a proliferative assay. By restimulation with different types of allogeneic cells and with cells from donors compatible or incompatible for the HLA-ABC or -D determinants, results were obtained suggesting that the TNP-specific response was restricted by the HLA-D but not the -ABC antigens of the autologous priming cells. Furthermore, our experiments demonstrate that T lymphocytes can also be primed against non-treated autologous cells in vitro and suggest that the HLA-D determinants may be involved also in this auto-sensitization.


[Rational laboratory diagnosis of thyroid gland function]. The function of the thyroid can today be determined in the serum of the patient by in vitro-methods using isotopes. In borderline cases the TRH test is valuable. Scanning is necessary for the diagnosis of autonomous or toxic adenomas and is useful preoperatively. 131I-uptake, release and scanning are indicated where radioiodine therapy is planned.


[Psychopathology of infancy in pediatrics. Clinical basis. Nosographic regrouping (author's transl)]. Psychopathology in childhood, even in infancy is rich ans full of diversity. Its main clinical patterns are : 1) psychosomatic disturbances ; 2) developmental abnormalities ; 3) abnormal motor activities ; 4) straight mental manifestations. Each of these clinical categories includes several ways of psychological organization and miscellanous causes which in turn are subjected to regrouping. The purpose of the present attempt of classification was threefold : 1) screening of psychological disorders in clinical pediatrics and pedopsychiatric practice ; 2) prevention and immediate treatment for a prophylaxis of further psychopathologic organization ; 3) the use of statistical cards.


Whipple's disease. A case report.

Whipple's disease. A case report. A case of Whipple's disease in which there were some unusual features, although the results of histological investigation were characteristic of the diseases, is reported. This is followed by a brief review of the literature concerning this rare condition.


Studies of the HLA--D determinants in the Hungarian population. A Hungarian random population sample was tested for six well-known and two new HLA--D specificities. HLA--D antigen and gene frequencies in the studied population agree with the frequencies observed in pooled random Caucasians, only HLA--Dw3 being significantly elevated. The incidences of Dw1 and Dw4 are, however, lower while the incidences of the Dw5 and Dw6 alleles seem to be higher in our population sample without reaching statistical significance. As for the two new specificities, the IVAD-1 specificity has a low frequency, while IVAD-3 occurs quite frequently. HLA--B and HLA--D associations seem to be different in our population sample as compared to others. In spite of the high incidence of the HLA--Bw35 antigen, no HLA--D association was found. The two new HLA--D specificities did not show association with any of the established HLA--B antigens.


Distribution of HLA antigens in a Mexican--American population and a comparison with two similar populations from different geographical locales. The frequencies of 32 HLA antigens of the A and B series were determined in a previously unstudied population of Mexican-Americans in South Texas. The phenotype and gene frequencies for this group are presented and are contrasted with those determined in studies of Mexican/Mexican--American populations from two different locales. The statistically significant differences observed emphasize the need for indigenous controls when evaluating racially heterogeneous populations for disease-associated HLA antigens.


HLA--determination in families with hereditary ataxia. In three families with hereditary ataxia, where the inheritance pattern was autosomal and dominant, HLA antigens were determined in 25 members. In two of the families, HLA linkage of disease was suggested, whereas in the third family, the data did not directly support this concept, since two recombinational events between the postulated locus for disease and the HLA region had to be assumed. However, with this assumption, our data are compatible with those of one family described recently (Jackson et al. 1977) implying the presence on the sixth chromosome, outside the HLA region, of a locus that determines the development of spino cerebellar ataxia (SCA). Further tests with definition of enzyme markers will have to be performed before conclusions as to HLA linkage of a postulated SCA gene can be made.


Specificity of human lymphocytes primed against allogeneic cells in vitro. 1. Optimalization of culture conditions for detection of HLA--D specificity. The specificity of lymphocytes primed against allogeneic cells in vitro has been examined in order to find the optimal conditions for detection in the restimulating response of HLA--D specificity, as defined by homozygous cell typing. It was found that reducing the number of stimulating cells to less than the number of responding cells (ratio R/S = 4 : 1) in the priming culture, and increasing the number of stimulating cells at restimulation gave better discrimination. Priming with HLA--D heterozygous stimulating cells, where the responding and stimulating cells shared the other HLA--D determinant, rendered the primed cells somewhat more discriminatory than priming with HLA--D homozygous cells. The optimal length of the secondary culture was found to be about 38 h.


Association of HLA-B8, DRw3, and anti-acetylcholine receptor antibodies in myasthenia gravis. Twenty-eight patients with myasthenia gravis (MG), five with and 23 without thymoma, and 47 normal controls were typed for serologically defined HLA-A, B, C, and DRw antigens. Sera from all patients were titered for antibodies to acetylcholine receptors (AChR). The frequency of HLA-B8 and DRw3 in the non-thymoma MG patients was significantly higher than in the normal population. Most of the non-thymoma patients with AChR titers higher than the average level were positive for HLA-B8 and/or DRw3, while the majority of the HLA-B8(-) and/or DRw3(-) non-thymoma patients demonstrated AChR titers below average. These findings support the possibility of the existence of immune response genes in the HLA-B, DRw segment of the major histocompatibility complex which are concerned in the response to or recognition of autoantigens.


No significant correlation of HLA-B8 and amount of antibodies directed to acetylcholine receptor protein in patients with myasthenia gravis. Forty patients with myasthenia gravis were HLA tissue typed and the amount of anti-acetylcholine receptor protein antibody determined. Sera from seven patients were tested for antibody titer by repeated determinations and the serum concentration was found to be stable. Patients with thymoma had higher titers than patients with normal thymus histology or hyperplasia. Individuals with thymoma lacking HLA-B8 were found to have a higher concentration of antibodies than HLA-B8 negative individuals with hyperplasia. No statistically significant differences were obtained when comparing the amount of antibody in HLA-B8 positive and negative individuals. Titers in patients subjected to thymectomy more than 8 years before sampling did not deviate from those in non-thymectomized myasthenics.


Possible role of amylase enzyme in prostatic and seminal fluid. Previous quantitative assays and localization of amylase in prostatic and seminal fluid prompted us to determine serum amylase levels in benign and malignant prostatic disease. The possible role of amylase in seminal fluid in normal and pathological conditions is discussed with review of literature.


[Composition and properties of immunoglobulin G in cattle with lymphatic leukemia]. The data are presented concerning the qualitative changes in cattle immunoglobulin G with lymphoid leukosis. Protein peculiar to cattle leucosis is shown to be an immunoglobulin G subfraction which is washed out of the DEAE-cellulose column by 0.1 M of NaCl. Its molecular mass is 130,000 Daltons. The data of immunoelectrophoresis and ultracentrifugation show that it is homogeneous. The protein sedimentation constant is 7.2 S. The electrophoretic mobility is 0.18-0.19 of bull albumin mobility. The amino acid analysis of this protein shows that the content of methionine in it is more than 20% lower. This evidences for its similarity to protein characteristic of myeloma and Shvets leukosis in rats. This manifests similarly of proteins peculiar to different forms of malignant growth. This protein has common antigenic determinants with the protein peculiar to human malignant growth.


[Immunochemical approach to explaining the molecular organization and mechanism of action of Na+,K+-ATPase]. Application of immunochemical methods for elucidating the Na+, K+-ATPase molecular organization and mechanism of action is discussed. The data of some authors who have studied the purified preparations of Na+, K+-ATPase from different sources show that both the catalytic subunit of the enzymic complex and its sialoglycoproteid have antigenic determinants. Antibodies, binding with these determinants, may either change or produce no effect on the enzymic process, link with the active transport of Na+ and K+. Antibodies used as conformation-sensitive explorers may yield the interesting information on organization of the Na+, K+-ATPase complex in the membrane and its conformation in different functional states which simultaneously with the data of the kinetic analysis and reconstruction of this enzymic complex would contribute to deciphering the mechanism of the Na+ and K+ active transport through biomembranes.


[Concentration of free 17-beta estradiol in the plasm of ewes following treatment with chlormadione acetate (CAP) in 2 synchronized cycles]. Six ewes of the Merino breed were subjected to radioimmunological assay (RIA) for the study of free 17-beta estradiol during the instillation of vaginal tampons soaked with 30 mg chlormadinone acetate (CAP), and 17 and 34 days after removal of the tampons. On the day before the administration of the preparation, the concentrations of free 17-beta estradiol were comparatively low, ranging within the limits of 38.6 +/- 5.6 pg ml-1 of plasma. These values showed no significant changes during the instillation of the tampons. When the tampons were removed, three periods of increased 17-beta estradiol levels were recorded: 1. on the 1st to 3rd day after removal of the tampons with a peak of 93.2 +/- 26.7 pg ml-1, 2. on the 13th to 16th day with the highest value of 59.7 +/- 23.6 pg ml-1, 3. on the 30th to 33rd day after removal of the tampons 76.2 +/- 23.5 pg ml-1. The results showed that the endocrine activity of the ovaries, expressed by a change in the concentration of plasma 17-beta estradiol after removal of the tampons (CAP), repeated in similar time intervals as under natural conditions and was probably associated with repeated growth and ripening of the follicles of ovaries and their ovulation.


[Production of purified foot-and-mouth disease virus antigens and the specific sera against them]. It was demonstrated that the use of laboratory techniques could be contributive to the production of purified antigens of the F.M.D. virus, such a-140 S, 12 S, and VIA. The isolated purified antigens were used to immunize guinea pigs, obtaining specific antisera against them. It was found that the latter contained specific complement-fixing and precipitating antibodies, while the 140 S serum also had neutralizing antibodies. The produced 140 S serum contained certain amounts of 12 S antibodies, which was considered to be the result of a spontaneous degradation of the 140 S antigen.


[Mechanisms of the potentiating and blocking effects of the sera from tumor patients in the leukocyte migration inhibition reaction model]. In the model of the reaction of human blood leucocyte migration inhibition the in vitro study was conducted on some mechanisms of blocking and enhancement effects of the serum in 54 tumor patients. Both effects were shown to be specific to an antigen. The enhancement effect could render a nonspecific action on intact cells in the presence of the corresponding antigen. This effect is thermolabile and may occur due to the interaction with cells. The blocking effect is thermostabile and may be realizied through interaction with the antigen, cells or both simultaneously. Some possible mechanisms of the manifestation of the blocking and enhancement effects are discussed.


[Oncornavirus activation and accumulation in cell cultures under the influence of hormones]. Sex hormones (testosterone, estradiol) and thyroxine would activate irregularly the production of the specific group antigen (GS-antigen) of avian ribodesoxyviruses in the culture of "normal" chick embryonal cells (CEC, phenotype C/O, GS-). The mentioned hormones as well as hydrocortisone and insulin would not prevent the Rous sarcoma virus (RSV) infecting of CEC, render no essential action on the accumulation of RSV in the infected CEC culture, and failed to activate the formation of mature RSV in virogenic cultures of rat (XC, R--B77) and mice cells (DBA--B77).


Increased frequency of HLA-DRW4 in chronic active hepatitis. HLA-A, B, C and DRw typing was performed on peripheral blood lymphocytes of 17 adults with the diagnosis of chronic active hepatitis made by liver biopsy as the only criterion for study. An increase in the frequency of HLA-DRw4 (71 vs. 24%, p less than 0.005) was observed, but there was no increased frequency of HLA-A1, B8 or any other HLA locus specificity.


[The efficacy of radiohypophysectomy with yttrium 90 in metastatic breast cancer (author's transl)]. Radiohypophysectomy in 176 women with metastatic breast cancer, treated over the past 20 years, did not prolong life, but relieved pain in almost half of the patients. This procedure can be carried out quickly and without risk even in severly debilitated patients.


[Serum concentrations of alpha-1-fetoprotein suggestive of, or pathognomonic for hepatoma (author's transl)]. A short review of alpha-1-fetoprotein (AFP), is followed by a presentation of the serum AFP concentrations obtained in healthy subjects and in patients with hepatoma, cirrhosis of the liver or metastatic liver cancer, measured by radioimmunoassay (RIA). A calculation is made from these results of the upper limit of normal (9 ng/ml), a limit which is suggestive of hepatoma (215 ng/ml) and a limit which is pathognomonic for hepatoma (7500 ng/ml). It is concluded that the quantitative determination of AFP by RIA represents a sensitive method which provides valuable clinical information for the early diagnosis of hepatoma.


[Liver function studies under the effect of 4 sequential hormonal contraceptives]. During the first cycle of treatment the influence of four forms of sequence therapy with mestranol and ethinyl estradiol as estrogen and the two gestagens chlormadinone acetate and norethisteron acetate in women at fertile age was examined for the aminotransferases (GOT and GPT), the activity of alkaline phosphatase and alpha-amylase, for the cholesterol, total bilirubin and total protein content of the serum and for the half-life period of indocyanine green. Under the application of mestranol/chlormadinon acetate an estrogen-induced increase of the activity of the alanine aminotransferase (GPT) from 6.38 units/l to 12.14 units/l may be established, after addition of the gestagen chlormadinon acetate a decrease to 5.34 units/l was to be established. Under the sequence therapy with mestranol/norethisteron acetate only an increase of the alpha1-globulin proportion was to be ascertained. All the other changes of the tested parameters including the half-life period of indocyanine green were not essential.


Characterization of antigens on murine tumor cells reacting with alloantisera against foreign H-2 specificities: analysis by absorption with purified murine leukemia virus and normal lymphoid cells of different H-2 haplotypes. A spontaneous T cell lymphoma of DBA/2 (H-2-d) mice, SL2, was found to react with anti H-2 typing sera raised against certain foreign haplotypes as well as with anti H-2d sera. The cytotoxic anti-SL2 activity of the anti-foreign H-2 sera was detected in a newly developed microradioassay, not however, in a conventional 51Cr release test. Upon culture in vitro the reactivity of the tumor cells with the anti H-2 sera decreased. The anomalous cytotoxic anti-tumor activity of the anti-foreign H-2 sera appeared to be distinct from anti-murine leukemia virus activity, since it was not removed by absorption with either Friend of AKR leukemia virus. Partial absorption was observed with normal lymphoid cells carrying the respective foreign H-2 antigens, but not with cells of unrelated H-2 haplotypes. In each serum tested, the anti-tumor activity could also be absorbed with syngeneic H-2d lymphoid cells. These results show that the anomalous anti-tumor reactivity of certain anti H-2 typing sera, in particular of sera raised in recipients differing in H-2 from the tumor host strains, is not due to the presence of foreign (derepressed) H-2 molecules on the tumor cells. The differences observed between the tumor cells and normal cells seem to be due to unexpected antibodies in the sera reacting with public H-2 specificities which are better exposed on the tumor cells than on normal cells.


Alteration of human blood cells and changes in plasma mediators produced by radiographic contrast media. In vitro incubation of human blood cells with iodinated radiographic contrast media (RCM) produced marked effects which were dose-dependent: erythrocytes showed crenation which was reversible; neutrophil leukocytes released the lysosomal enzyme beta-glucuronidase; basophil leukocytes released histamine; and platelets released serotonin as well as beta-glucuronidase. The release reaction could not be attributed to cell lysis, as demonstrated by the release of the cytoplasmic enzyme lactic dehydrogenase (LDH). In normal human serum, RCM produced activation of the complement system with lysis of cells. This RCM-induced complement activation seemed to occur via the alternate pathway. Stabilizers and cations present in the clinically used RCM solutions did not produce any complement changes.


Temperature-induced dissociation of serum amyloid protein SAA. Serum amyloid A protein (SAA) has been shown to be unstable at elevated temperatures. While in agreement with earlier reports, molecular weights of approximately 180,000 daltons were determined by gel filtration at 37 degrees C and below, above 58 degrees C additional AA-antigenic activity was found in the void volume and at the position of approximately 12,000 daltons. The latter polypeptide resembled in size and immunoreactivity SAAL in that it had AA-antigenic determinants exposed at 4 degrees C (unlike SAA). Because the release of SAAL or a similar molecule could not be prevented by the enzyme inhibitor PMSF, a temperature-dependent dissociation of SAA is proposed. In view of the known occurrence of amyloid following febrile conditions, the change in size and immunoreactivity of AA-antigenic proteins in vitro may indicate that a similar mechanism in vivo is important in the genesis of AA-type amyloidosis.


[Antigenicity of the human trophoblast]. In this a rabbit immunological serum against human trophoblast was obtained after triple intramuscular superficial villi extract injection from chorion of 6--7 week pregnancy with Freund's adjuvant. In immunofluorescent indirect reaction to this serum made on chorion and placenta sections some most intense specific fluorescence was obtained in cytoplasm of primordial cyto- and synytiotrophoblast. Some favourable influence of antigenic differences between ovum and mother especially implantation has been suggested.


[Improvement in the tactics of systematic gamma globulin prevention of viral hepatitis taking the morbidity prognosis into account]. On the example of 4 cites of the RSFSR under conditions of expected epidemic threat a possibility was shown of directed influence on the viral hepatitis A epidemic process of preseasonal gamma-globulin prophylaxis conducted in 90% of "organized" children, aged from 1 to 12 years. The dose used was 0.75 ml of a 10% preparation. The method of Gorky Institute of Epidemiology and Microbiology was used to prognosticate the morbidity. It is recommended to improve the tactics of preseasonal gamma-globulin prophylaxis with consideration to the data of the viral hepatitis prognosis.


[Enhancement phenomenon in mice with a heterotopic heart transplant]. A possibility of enhancement induction with the aid of a preparation of lymphocyte membranes of the spleen of donor specificity in its combination with antimouse horse globulin was studied on mice with heterotopic graft of the heart. As shown, in recipients with prolongation of the graft electrical activity lymphocytes retained their reaction to donor antigens, whereas the blood serum produced an enhancement effect in its administration to syngeneic recipients.


[Treatment with inactivated cultured antirabies vaccine and antirabies gamma-globulin of persons biten by rabid wolves or those suspected of being rabid]. The authors present the results of using inactivated cultural rabies vaccine from the Vnukovo-32 strain in combination with rabies gamma-globulin for the treatment of 39 persons; of this number 28 were bitten by rabid wolves (the diagnosis was confirmed by laboratory methods), 25 had wounds of dangerous localization, and 3 were children from 7 to 15 years of age. In examining the sera of all the 39 bitten persons it was found that the scheme of combined vaccinations with inactivated cultural ribies vaccine and rabies gamma-globulin, officially acting in the USSR, in case of bites of dangerous localization led to formation of early continuous and lengthy passive and active immunity of adequate intensity.


[Makeup and properties of a polycomponent meningococcal vaccine]. The polycomponent meningococcae vaccine represented a preparation of the high-molecular fraction of meningococcus cell wall substances. Meningococcae strains for the vaccine preparation were chosen in such a way that the end preparation contained antigens of group specificity A, B, C and also other antigens detected in the cell wall of strains of epidemiological significance. Protein, group polysaccharides., lipopolysaccharides and nucleic acids were included into the vaccine composition. In doses used inhumans the vaccine was safe for mice causing no retardation in weight gain. In immunization of mice the vaccine produced formation of antigbodies to the antigens of group specificity A, B, and C, and protected them from infection with the srtrain isolated from the patient's cerebrospinal fluid. THE VACCINE PRODUCED NO HARMFUL ACTION IN ADMINISTRATION TO MAN. Antibodies to antigens of group specificity A, B, C and also to proteins and lipopolysaccharides of the meningococcus cell wall formed in the vaccinated persons. Sera of the vaccinated individuals lysed meningococci of groups A, B, and C.


[Antireticular cytotoxic serum as an agent for stimulating the immunity system]. The changes in the immunological indices characterizing the T and B immunity system and also in biological resistance of atherosclerosis patients were studied under conditons of the use of the antireticular cytotoxic serum microdoses. A possibility of employing the ACS for stimulation of the immune system was demonstrated.


[Non A-non B hepatitis].

[Non A-non B hepatitis]. The advances in the study of viral hepatitis etiology have led to differentiate certain cases which are not provoked by already know viruses. That is why these cases are called "non A-non B" Hepatitis. The morphological characteristics of this/these agents, has/have not yet been explained. The most frequent way of transmission is parenteral, and the majority of the cases are known as postransfusional hepatitis. Other ways of transmission are also mentioned. Incubation period is of approximately 2 to 15 weeks; therefore, it is an intermediate period between A and B Hepatitis. Clinical symptoms are milder compared to those presented by B type hepatitis, but they show a lower serologic response. Studies performed up to this date, seem to demonstrate that this type of hepatitis has a tendency to become chronic. Active immunization has not yielded good results; but, passive immunization with immunoglobulin has been effective. It is imperative to develop new specific laboratory techniques in order to identify the responsible etiologic agent or agents.


Histochemical demonstration of acidic glycosaminoglycans in the cell nuclei of the iris and other tissues. Using histochemical methods, the presence of acidic glycosaminoglycans in the cell nuclei of 51 human irides and a series of monkey organs was demonstrated. In general, these substances are sensitive to testicular hyaluronidase and chondroitinase ABC and also to Streptomyces hyaluronidase, when using special staining methods. The specificity of testicular hyaluronidase was tested by inhibition with heparin. By simultaneously staining with alcian blue and Feulgen, acidic glycosaminoglycans can be distinguished from the nucleic acids. Sporadically, hyaluronidase-resistant substances with a specific acidic glycosaminoglycan stainability occur. We assume the existence of various acidic glycosaminoglycans in the cell nuclei. Aging changes were not traceable with constancy.


Comparative light- and electron-microscopical study of the normal adenohypophysis in the human. The pars distalis of 1 girl and of 3 sexually mature women was studied. The glands were dissected out and fixed within a period of 30 min following death; in the aldehyde fixative, each gland was systematically divided into ten pieces. Before fixation in osmium tetroxide, each piece was again divided into several blocks. At least 60 blocks were obtained from each gland. Semi-thin sections obtained from all the blocks were stained and studied under the light microscope. Ultrathin sections were obtained from selected blocks. Under the light microscope, 6 types of secretory cells and 2 types of non-secretory cells were characterized. At the ultrastructural level, 7 types of granulated cells and 2 types of non-granulated cells were distinguished. The range of the granule size for each type of sectetory cell was determined by applying a mathematical model and a computer program that corrected the size distribution curve in such a way that only the diameter of the equatorial sections of the granules, that is the real granule sizes, was recorded. By comparing the observations made in the ultrastructural study with those performed in adjacent semi-thin sections it was possible to correlate the cell types characterized ultrastructurally with those distinguished under the light microscope. In addition, the study of the semi-thin sections made it possible to quantitatively analyze the different cell types, while the ultrastructural characteristics suggested the probable functional role of each of these cell types.


Ectopic atrial tachycardia on swallowing. Report on favourable effect of verapamil. A female patient who suffered from atrial tachycardia associated with the ingestion of food or drink was examined in our department. No signs of organic heart disease were discovered, oesophageal motility was normal, but X-ray revealed a small hiatal hernia. The arrhythmia started with an atrial extrasystole arising well outside the functional refractory period of the AV node, and it could be reproduced by inflation of a balloon. It is suggested that the arrhythmia is induced by a mechanical effect of the passage of food on the left atrial wall. Several drugs were tried in order to stop or relieve the complaints. None of them prevented or stopped the atrial tachycardia but verapamil and edrophonium chloride caused 2:1 AV block, and follow-up study has shown that sufficient doses of verapamil are able to relieve the patient's complaints.


Some Golgi data on visual cortex of the rhesus monkey. The rhesus monkey's visual cortex was studied on Golgi material. The terminal arborization of the geniculate fibres and non-specific vertical fibres have been analysed. The interneurons (intrinsic neurons) of the area described in detail and classified on the basis of their axonal and dendrite arborizations. The stellate neurons in layer IV are discussed.


Cellular and humoral immunity in viral hepatitis. Cellular and humoral immunity combine to determine the outcome following exposure to hepatitis virus and are implicated in the proposed pathogenetic mechanism for acute and chronic hepatitis. Although antibody to HBsAg is found in virtually all following recovery from hepatitis B, a cell-mediated response to HBsAg can be detected in most patients during the acute phase, and it has been suggested that this may cause the acute hepatic damage by an attack on virus-infected cells. Patients who have chronic active hepatitis also frequently have cell-mediated immunity to HBsAg, regardless of whether the antigen can be detected in their sera; thus, previous exposure to hepatitis B may be important in initiating the disease even in antigen-negative cases. Cell-mediated responses to liver-specific lipoprotein, a membrane antigen, occur transiently in many patients who have acute hepatitis and are persistent in virtually all with untreated chronic active hepatitis. The relative importances and precise mechanisms of these immune responses in the pathogenesis of acute and chronic hepatitis remain to be determined.


A rapid (4--6-hour) urine-culture system for direct identification and direct antimicrobial susceptibility testing. This study evaluates a new direct rapid system for urine cultures, including detection and quantitation of positive specimens by Gram stain, direct identification by 4--6-hour incubation of sediment with reagent strips, and antibiotic susceptibility testing by direct (3--4-hour) disk-elution methods. Of 987 routine urine specimens, 121 had significant (less than or equal to 10(5) colony-forming units/ml) gram-negative bacilluria, of which 89% were detected by the Gram stain. Direct rapid identification was correct in 94%. Results of direct disk-elution antimicrobial tests showed overall agreement with results of standard disk diffusion of 93% of tests, and major discrepancies in 4%. For urine specimens with gram-negative bacilluria, this system permitted detection, quantitation, identification, and antimicrobial susceptibility testing in four to six hours with reasonable, though not complete, accuracy.


Diagnostic value of biochemical analysis of pleural effusions. Carcinoembryonic antigen and beta 2 microglobulin. Pleural effusions from 105 patients with malignant and nonmalignant diseases were examined for tumor cells, content of CEA, beta2 microglobulin, ceruloplasmin, alpha2 macroglobulin, orosomucoid, lysozyme, and hexosaminidase. Only CEA and beta2 microglobulin determinations were of diagnostic value. CEA concentrations greater than 11 ng/ml were found only in malignant effusions. Beta 2 microglobulin values were increased in pleural effusions due to lymphoma or immune diseases. Measurement of CEA and beta2 microglobulin in addition to the cytologic examination could increase the diagnostic significance of the analysis of pleural effusions.


The nature of mutation in Krabbe disease. Galactosylceramide beta-galactosidase cross reacting material was demonstrated in brain, liver, and skin fibroblasts from patients with Krabbe disease. The mutant enzyme was antigenically identical to the normal enzyme and exhibited similar electrophoretic mobility. Normal quantities of the catalytically deficient enzyme were measured in the patients' tissues by a sensitive single radial immunodiffusion assay, indicating that the mutation is in structural gene for the enzyme protein.


Infant outcome following labor induction. A matched control study was undertaken in which 156 children were examined between ages 23 and 62 months after births associated with spontaneous labor, oxytocin-induced labor, or prostaglandin E2 (PGE2)--induced labor. Physical development was not adversely affected by labor induction based on height and weight percentiles. The frequency of neurologic or developmental abnormalities not attributable to postdelivery events was the same overall in induced and spontaneous labors (19.2 per 1,000), but those abnormalities occurring after labor induction all followed use of oxytocin. None followed PGE2 despite case-selection criteria which specifically chose PGE2 cases from among those with documented adverse drug-related reactions.


Differences in mouse ovarian cells as distinguished by horseradish peroxidase labelling. The extracellular space of mouse ovarian follicles and stroma contained horseradish peroxidase (HRP) reaction product one minute after intravenous injection of the tracer. In addition to pinocytotic uptake of the tracer, non-vesicular staining with HRP reaction product, heretofore unrecognized, was noted in a variety of ovarian cell-types. This diffuse staining was correlated with changes in cellular morphology suggestive of degeneration. These findings are discussed in relation to the composition of cell populations comprising follicles and ovarian stroma and alterations in cell function.


Streptococcal pharyngitis: diagnosis by gram stain. Group A beta-hemolytic streptococci were isolated from 49 (10.4%) of 472 patients with pharyngitis. Throat culture results, interpreted by five observers of varying experience, showed the mean sensitivity, specificity, and predictive value of a positive Gram-stained smear of pharyngeal secretions as 73%, 96%, and 71%. Assignment to a high-risk group by clinical algorithm gave sensitivity, specificity, and predictive value of only 45%, 83%, and 23%. The Gram-stained smear is the most accurate method of early diagnosis of streptococcal pharyngitis.


Testicular germ-cell neoplasms: recent advances in diagnosis and therapy. The diagnosis and treatment of testicular neoplasms have been facilitated by identification of the tumor-associated proteins alpha-fetoprotein and human chorionic gonadotropin. These circulating tumor markers, present in 85% to 90% of patients with nonseminomatous testicular cancer, reflect tumor presence and reliably indicate response to therapy. Alpha-fetoprotein is produced by embryonal carcinoma and yolk-sac tumors; human chorionic gonadotropin is produced by syncytiotrophoblastic giant cells and the syncytiotrophoblastic component of choriocarcinoma. Refinements in staging techniques and definitions have improved prognostication. Effective therapy for seminoma (cure rate, greater than 90%), early-stage (stage I, stage IIN1-2) testicular carcinoma (cure rate, 65% to 87%), and advanced (stage IIN3-4, stage III) testicular carcinoma (complete remission rate, 50% to 74%) has been shown in clinical trials. Adjuvant chemotherapy/radiotherapy trials for limited stages of testicular carcinoma, and further experience with intensive chemotherapy-based trials for advanced stages may further improve the prognosis for all testicular germ-cell neoplasms.


[Antigenic study of "Serratia marcescens" isolated in France.II.--Characterization of O antigens and description of 5 new O factors, occurrence of serotypes and labelling of new H factors (author's transl)]. The somatic O-antigens of 583 French isolates of Serratia marcescens were studied with the aid of the tube O-agglutination technique sensitized by centrifugation. Flagella antigens were identified by the H-immobilization test. Five new O-antigens (O16 to O20) were found. An antigenic factor (Co) common to isolates of serotypes O12:H9, O14:H12, O14:H20, and O13:H17 is described. Agar cultures of serotypes O12:H9 and O14:H12 dissociated into two colonial types: iridescent colonies, and non-iridescent colonies. Non-iridescent colonies, heated at 100 degrees C, are agglutinated by anti-Co serum, whereas heat-treated iridescent colonies are not. Close relationship between serogroup antigens O6 and O14 observed by traub and Kleber is confirmed. Serogroup O9 was subdivided into two subgroups. In France, 49 different serotypes were identified, with a predominance of serotypes O14:H12, O13:H17 and O3:H12. Recently, several new H-antigens were independently described by Traub and Kleber, and by us. To avoid confusion, these new H-antigens have been herein redesignated in accord with Dr Traub.


The effects of thyroxine and climatic factors on colostral gammaglobulin absorption in newborn calves. Observations of 68 Friesian and Holstein X Friesian calves in a single herd with low neonatal mortality gave the following results: --The calves which will suffer from diarrhoea but survive were in a hyperthyroid state (high levels of hormonal iodine, T3 and free thyroxine index) compared with the healthy animals. --The concentration of plasma globulins, after colostrum intake was lower in diarrhoeic subjects calves than in the healthy ones. --For the whole group of animals, plasma hormonal iodine, at birth, was negatively correlated with the concentration of plasma globulins at 48 hours (r = 0,37, P less than 0,05). Thus, by reducing the absorption capacity of colostral globulins, an excess of thyroid hormones at birth could increase young calves sensitivity to various infections. To test this hypothesis, 12 Holstein X Friesian calves, born in the same stable and then transferred to outside individual boxes, were used. Six animals received thyroxine injections at birth and after 24 hours. All the calves received colostrum in the same conditions. The following results were obtained. --All the treated calves became ill (1/6 of the controls), independantly of their plasma IgG1 concentrations. --The capacity of calves to acquire colostral IgG1 varies considerably between individuals (maximum IgG1 concentrations and, probably, duration of intestinal absorption of IgG1). --The T4 injections at birth do not noticeably after IgG1 absorption. --Thyroxinemia at birth, reflecting the foetal concentration, is negatively correlated (r = 0,74, P less than 0.01) with the period of IgG1 absorption. --The outside temperature at birth is negatively correlated with the maximum IgG1 concentration (r = 0.78, P less than 0.01). These results indicate that a hyperthyroid state at birth, and, probably, during foetal development compromise the calves health: --by direct or indirect action, the intermediates of which are not known, --by reducing the period of intestinal absorption of immunoglobulins in addition. Moreover climatic factors such as ambient temperature at birth may influence acquisition of passive immunity.


Immunoglobulin transfer to calves and health problems in large bovine units. The serum immunoglobulin levels were studied in 215 calves born on 4 farms. Each farm had at least 60 cows. There was a great variation in the immunoglobulin levels at 48 hours. In those cases where the quantity and Ig concentration of colostrum was measured it was found that the serum Ig level was correlated with the total amount of Ig ingested. Where only the serum level was measured it was found that suckled calves had higher levels than bucket-fed calves. Immunoglobulin levels were not correlated with the incidence of diarrhoea or pneumonia nor with the viability of calves although calves with less than 8 mg/ml IgG1 showed a slightly higher incidence of diarrhoea. The globulin concentrations in colostrum were not influenced by the breed, the season, the number of calvings, the length of the dry period and the level of feeding during this period but the time of the first feeding or milking proved to be of prime importance.


About the importance of colostrum for the newborn calf. 1. Between December and April there was a decrease in the concentration of gamma-globulins in the blood serum of 2 to 3 day old calves. 2. Calves with more symptoms of enteritis or omphalitis had lower concentrations of gammaglobulin. 3. Calves with higher body temperatures had lower concentrations. 4. Calves from primiparous cows had lower concentrations than calves from pluriparous. 5. Calves from young dams had lower concentrations than calves from older dams. 6. Calves, which were born by caesarian section had lower concentrations than calves which were born spontaneously or with other assistance.


Colostrum immunoglobulin concentration in cows: relationship with their calf mortality and with the colostrum quality of their female offspring. Samples of colostrum were taken from 180 suckling cows (beef cows) from the same herd, during the 3 hours immediately after calving over a period of 4 consecutive years. Total proteins in colostrum-whey were estimated by the biuret method, and concentrations of gamma-globulins determined by electrophoresis. The significance of the close relationship between calf mortality and gamma-globulin levels in the maternal colostrum was studied. An attempt was made to define levels suitable for the health of the calves. Twin birth, age at calving and food intake towards the end of the gestation period, whatever their effect on calf mortality rate, did not bring about any significant variation in the levels of colostral gamma-globulins. On the other hand, however, cows suffering from various infections had lower levels of colostral gamma-globulins, and produced a higher calf mortality rate. A high degree of repeatability in gamma-globulin levels was observed in colostrums produced by the same cow during successive calvings. A correlation between colostral gamma-globulin levels of a particular cow and those of her female offspring was also found. This result, which should be controlled on a larger number of animals, suggests the possibility of an approach of the problem of calf mortality, using a sanitary and genetic selection designed to reduce the number of cows producing colostrum with low levels of gamma-globulins.


[Separation of the biosynthesis products of a mutant strain of Actinomyces chrysomallus var. carotenoides and the identification of actinomycin antibiotics]. An orange antibiotically active substance isolated from the mycelium of a mutant strain of Actinomyces chrysomallus var. carotenoides was identified as a mixture of actinomycins according to its light absorption spectra, circular dichroism spectra, IR spectra and chromatographic comparison with the standard samples. A scheme for successive extraction of the biologically active substances from the mycelium resulting in isolation of a fraction enriched with antibiotic substances and a fraction enriched with pigments is presented. A method for separation and purification of 3 groups of biologically active substances from the mycelium enriched extract was developed.


Effect of 5-azacytidine on cytoplasmic ribosomal and messenger ribonucleic acids in BSC-1 cells. 5-Azacytidine (5-AzaCR) inhibited the accumulation of 28S and 18S ribonucleic acids (RNAs) in the cytoplasm of treated cells. The inhibition of 28S and 18S RNAs in the cytoplasm of BSC-1 cells was dependent upon the concentration of 5-AzaCR employed and the time of exposure. At a concentration of 200 mug/ml for 2 h, 5-AzaCR inhibited the cytoplasmic 28S and 18S RNAs by 80 and 70%, respectively. The 28S and 18S RNAs that appeared in the cytoplasm of treated cultures had no altered secondary structure, as analyzed by polyacrylamide gel electrophoresis. The inhibitory effect on cytoplasmic 28S and 18S RNAs was found to be reversible, and removal of 5-AzaCR from treated cultures allowed the accumulation of cytoplasmic 28S and 18S RNAs to almost normal levels by 20 h. 5-AzaCR appeared to have no effect upon the synthesis and processing of polyadenylic acid-containing messenger RNA in treated cultures. However, the formation of the 80S ribosomal subunit appeared to be inhibited in drug-treated cells. Moreover, 5-AzaCR treatment caused a disaggregation of polyribosomes and an accumulation of 80S ribosomes.


Immunochemical study of a human myeloma IgG1 half molecule. The serum of a patient with multiple myeloma contained an IgG1 kappa monoclonal protein which existed in two molecular species: one with and one without inter-heavy chain covalent bonds, the latter dissociating into half molecules without reduction. The half molecules were present in the urine together with a kappa Bence-Jones protein. This peculiar protein was discovered because the serum and urinary IgG formed double percipitin lines when analysed by immunoelectrophoresis with an antiserum to gamma chains, the inner line being due to residual normal IgG. The isolated half molecule, as well as the major constituent of the 7 S IgG fraction, failed to precipitate with most antisera specific for the Fc fragment of IgG. The half molecule lacked the Gm(non a) marker and other antigenic determinants of the third constant region of gamma1 chains. No isotypic or allotypic antigenic determinant of another immunoglobulin class or subclass was detected. The molecular weights of the 7 S molecule, the half molecule and its covalently linked heavy and light chains were about normal, suggesting that they did not have a large deletion which could have caused the lack of interheavy chain covalent bonds. The hinge peptide appeared normal after high voltage electrophoresis of the peptic-tryptic digest of the reduced and alkylated half molecule. The carboxy-terminus of the heavy chain and the amino acid composition of the molecule were similar to those of IgG1 myeloma proteins. Two cysteinyl peptides of the CH3 domain showed on a diagonal peptidic map an electrophoretic mobility somewhat different from that of the corresponding peptides of an IgG1 myeloma protein. Another peculiar feature of this protein was the presence of galactosamine. Idiotypic determinants of the half molecule were present in the 7 S fraction, suggesting that the 7 S IgG molecules and the half molecules were derived from the same clone of tumour cells. Lack of material precluded further characterization of the structural abnormality--probably located in the third constant domain of the heavy chain--responsible for the absence of most antigenic determinants of the Fc region of IgG1 and for the formation of half molecules. This abnormality could be a small deletion undetectable by molecular weight measurements or an unidentified exchange of genetic material. Family members of the patient could not be studied in order to investigate whether this immunoglobulin abnormality reflected a minor genetic variant or a mutational event.


Oxygen content determined by acrylamide polymerization: screening of anticancer agents, generation of oxyhemoglobin dissociation curves, and potential applications. Many investigators have endeavored to accurately measure oxygen content produced or consumed from substrates or tissues. Most of the techniques currently available are time consuming or exceedingly complex. Many require expensive apparatus and demand the skills of a highly trained technician. We have deveoloped a rapid and sensitive method of measuring oxygen content or consumption. This method is based upon the time for polymerization of acrylamide gels. The time of acrylamide polymerization is directly proportional to the oxygen content of the test medium. We have used this method to generate oxyhemoglobin dissociation curves which closely resemble those published by Severinghaus and Duvelleroy, as well as those we determined by the conventional Van Slyke analysis. We have also used this method to measure the oxygen consumption of tumor cells and to evaluate the effects of Actinomycin, cyclohexamide and cytosine arabinoside on Walker 256 ascites tumor. The results correlate with the known in vivo effects of these drugs on this tumor cell line. Therefore, because of its sensitivity and adaptability this method may be useful in a variety of clinical and biological situations.


[Physiopathological study of coupled electric stimulation]. The charges of left ventricular function provoked by coupled electrical stimulation were studied in 17 patients with severe chronic aortic incompetence and 9 controls. These results were compared with those obtained after isolated extrasystole in 24 cases of aortic incompetence and 10 controls, and during paired electrical stimulation in 12 cases of aortic incompetence. Left ventricular function increased uniformly after post-extrasystolic potentiation whatever the mode of stimulation. The preload did not change significantly, the increased ventricular function being mainly due to increased contractility. Coupled electrical stimulation mobilised the greatest contractility reserve (ejection fraction : +32 % in controls and +37 % in aortic incompetence and averaged circumferentiel fibre shortening +55 % in controls and +47 % in aortic incompetence). The contractility reserve is inversely proportional to the initial ejection fraction except when its value is less than 35 %. The myocardial response then becomes variable so that left ventricles with probable irreversible hypocontractility may be distinguished from those whose ventricular funciton would improve after surgical correction.


A comparative immunological study of catalases from coagulase-positive staphylococci. Protein homology studies with catalase as a reference point were carried out with coagulase-positive staphylococci belonging to Staphylococcus aureus, S. intermedius and S. hyicus. Antisera against catalases of S. aureus ATCC 12600 and S. aureus ATCC12601 reacted very weakly employing double immunodiffusion and quantitative microcomplement-fixation assay with cell-free extracts or catalase enriched preparations of S. intermedius or S. hyicus. The differences between coagulase-positive staphylococci could be confirmed by using the antiserum against S. intermedius H 11 catalase. Within the strains of the species S. intermedius immunological distances ranging up to 25 indicate a heterogeneity which justify the separation of the biotypes E and F on a subspecies level. Coagulase-positive strains of S. hyicus revealed neither a close relationship to S. aureus nor to S. intermedius.