Serum cortisol and dehydroepiandrosterone sulfate responses to adrenocorticotropin stimulation in premature infants. ACTH stimulation tests were performed in 15 premature infants in a serial fashion at the ages of 5--10 days and 27--31 days. Six of the 15 had subsequent ACTH stimulation tests at 6--8 weeks and/or 12--13 weeks. The pre- and post-ACTH serum cortisol and dehydroepiandrosterone sulfate (DHAS) levels were determined by radioimmunoassay. The mean basal levels of cortisol, 55 ng/ml, and DHAS, 4108 ng/ml, were significantly higher (P less than 0.05 and P less than 0.025, respectively) at 5--10 days than those of 24 ng/ml and 1858 ng/ml, respectively, at 27--31 days. The mean net change (delta) of cortisol after ACTH at 5--10 days, 95 ng/ml, increased significantly to 148 ng/ml at 27--31 days. However, deltaDHAS did not differ significantly between the two periods (1514 ng/ml vs. 972 ng/ml). Therefore, deltaDHAS/deltacortisol was lower (P less than 0.05) at 27--31 days than at 5--10 days. No further significant changes were observed after 4 weeks of age in the levels of the two steroids. There was little correlation of basal levels between cortisol and DHAS, nor between deltacortisol and deltaDHAS at any age period we studied. There were four infants whose mothers had prenatal steroid treatment for the prevention of hyaline membrane disease and their values were not different from the other infants.


Renin-like (angiotensinogenase) activity in human eccrine sweat. The presence of renin or renin-like activity (RLA) was demonstrated in human eccrine sweat incubated with purified sheep angiotensinogen, using rat bioassay and angiotensin I radioimmunoassay. Following cholinergic stimulation, sweat RLA was found to range between 0 (unmeasurable) and 266 ng/ml.h, i.e. RLA-values of sweat can be about 10 times higher than those of plasma. Therefore, renin synthesis in sweat glands could be assumed. RLA following activation of beta-adrenergic receptors by the administration of isoprenaline (Aludrin) did not exceed the mean values obtained by cholinergic activation. After beta-adrenergic receptor blockade by propranolol (Dociton), RLA became unmeasurably low. Higher RLA-values were found after local injection of dibutyryl-c-AMP (90--210 ng/ml.h). The results indicate a beta-adrenergic regulation of RLA-release in human sweat glands. Human sweat glands appear to be useful for studying extrarenal renin release.


Egg-drop syndrome 76 in Danish poultry.

Egg-drop syndrome 76 in Danish poultry. After a more general mention of Egg drop Syndrome 76 (EDS 76) an account is given of 3 cases of EDS 76 in broiler parent flocks. In all cases the animals involved originated from Ireland and were imported as day-olds, either directly from Ireland or via Sweden. Serological examinations indicate that the infectious agent has not previously been present in Danish hen flocks, but that it is presumably stationary in Danish flocks of ducks. In 2 of the 3 cases of EDS 76 animals from 2 different foreign firms were involved, and everything indicates that the infection has been carried by chickens from one of the firms and spread horizontally to the other. In the first case 12 weeks lapsed from the first to the last of 6 flocks in the same locality were attacked by SDS 76. An example is also given of trans-ovarial spread of EDS 76-virus to broiler flocks which at the age of 10--20 days were attacked by a disease similar to gangrenous dermatitis. In the course of the following few weeks an intensive rise took in the frequency of positive reaction to EDS 76. It is assumed that the EDS 76-virus has been of importance to the development of the said disease in these broiler flocks.


[Marrow scintigraphy in Paget's disease of bone (author's transl)]. Marrow scintigraphy using 99mTc colloids was performed in 20 patients with Paget's disease of bone and compared with skeletal scanning in each of them. As long as the regions explored were haematopoietically active, despite the advanced age of the patients, there was decreased marrow uptake in regions of increased uptake on the skeletal scan. Whilst increased uptake of pyrophosphate reflects bone hyperosteogenesis, decreased uptake of colloids reflects marrow fibrosis, and early histological sign of the disease. This scanning technique could be a new criterion in the surveillance of the therapeutic effectiveness of calcitonins or of diphosphonates.


[Epidemiology of cytomegalovirus infections (author's transl)]. Improvements of serological techniques allow seroepidemiologic surveys of cytomegalovirus infections. Intrauterine contamination is not unfrequent (1%) but pathological consequences of these infections in the fetus had only been observed after primary infections of the mother. Infections in the first days of life are frequent. The mother is almost exclusively the source of contaminations. The frequency of these infections is influenced by socio-economic factors. In adolescents and adults, contaminations seem related to closed person to person transmission (sexual behavior, kissing...).


SV40 viral minichromosome: preferential exposure of the origin of replication as probed by restriction endonucleases. Isolated SV40 minichromosomes [1-3] were treated with different single-cut restriction endonucleases to probe the arrangement of nucleosomes in relation to the SV70 DNA sequence. While Eco RI and Bam HI each cut 22-27% of the SV40 minichromosomes under limit-digest conditions, Bgl I, which cuts SV40 DNA at or very near the origin of replication [4,5], cleaves 90-95% of the minichromosomes in a preparation. Similar results were obtained with minichromosomes which had been fixed with formaldehyde before endonuclease treatment. One possible interpretation of these findings is that the arrangement of nucleosomes in the compact SV40 minichromosomes is nonrandom at least with regard to sequences near the origin of DNA replication.


The same amount of DNA is organized in in vitro-assembled nucleosomes irrespective of the origin of the histones. The four histones H2A, H2B, H3 and H4 from calf thymus, CHO and sea urchin gastrula cells were associated by stepwise dialysis from 2 M NaCl with SV40 DNA Form I. The in vitro-assembled chromatins were visualized by electron microscopy and the size of the DNA fragments generated by digestion with DNase II was determined. Irrespective of the origin of the histones, the size of the smallest DNA band generated at early times of digestion was about 190 base pairs, whereas oligomeric DNA bands were multiples of 140 bp. These results support our previous proposal that the four histones H2A, H2B, H3 and H4 are able to organize more than 140 bp of DNA, but do not provide any evidence that the variability of histones H2A and H2B plays a role in the variability of the DNA repeat length of native chromatins.


Physical properties of inner histone-DNA complexes. Chicken-erythrocyte inner histone tetramer has been complexed with several natural and synthetic DNA duplexes by salt-gradient dialysis at various protein/DNA ratios. The resulting complexes, in low-ionic-strength buffer, have been examined by electron microscopy, circular dichroism, and thermal denaturation. Electron microscopy reveals nucleosomes (nu bodies) randomly arranged along DNA fibers, including poly(dA-dT)-poly(dA-dT), poly(dI-dC)-poly(dI-dC), but not poly(dA)-poly(dT). Circular dichroism studies showed prominent histone alpha-helix and "suppression" of nucleic acid ellipticity (lambda less than 240 nm). Thermal denaturation experiments revealed Tm behavior comparable to that of H1- (or H5-) depleted chromatin. Tm III and Tm IV increased linearly with G + C%(natural DNAs), but were virtually independent of the histone/DNA ratio; therefore, the melting of nucleosomes along a DNA chain is insensitive to adjacent "spacer" DNA lengths. This suggests that Tm III and Tm IV arise from the melting of different domains of DNA associated with the core nu body.


Definition of the boundaries of the origin of DNA replication in simian virus 40. We have determined by use of DNA sequencing techniques the exact location of the deletion in d1 892, a viable deletion mutant of Simian virus 40 (SV40) reported to map very near the unique replication origin or SV40. With the help of this localization we have narrowed down the boundaries of the replication origin to 85 nucleotides within the sequence of SV40.


The turnover of tRNAs microinjected into animal cells. Red cell-mediated microinjection has been used to study tRNA turnover in SV3T3 mouse cells and TC7 cells, an African green monkey kidney line. The turnover of endogenous tRNA, measured by labeling with 3H-methionine, was first-order with half-lives of approximately one day in SV3T3 and two days in TC7 cells. 32PtRNA isolated from E. coli or TC7 cells turned over at the same rate as endogenous tRNA when injected into either SV3T3 or TC7 cells. This demonstrates that cellular processes, not properties inherent to tRNAs, are responsible for the difference in tRNA turnover observed between SV3T3 and TC7 cells. These results further indicate that the mechanism of tRNA turnover in mammaliam cells does not distinguish prokaryotic from eukaryotic tRNAs. In contrast to unmodified tRNA, glyoxalated tRNA was rapidly degraded upon injection. Thus altered tRNA's, like altered proteins, are turned over more rapidly in animal cells.


Escherichia coli DNA topoisomerase I catalyzed linking of single-stranded rings of complementary base sequences. Eco DNA topoisomerase I (E. coli omega protein) has been observed to catalyze the formation of double-stranded, covalently closed DNA from complementary single-stranded DNA rings, a novel reaction which is topologically forbidden without the enzyme-catalyzed breakage and rejoining of DNA backbone bonds. Incubation of a mixture of single-stranded PM2 DNA rings of complementary base sequences with omega yields a species with a sedimentation coefficient in an alkaline medium characteristic of a covalently closed circular double-stranded DNA. Buoyant density measurements in CsCl at alkaline pH also identify the product as a covalently closed duplex ring. If the omega-catalyzed reaction is stopped short of completion, highly negatively supercoiled molecules are formed which sediment more slowly in an alkaline medium than the final duplex product. As the reaction proceeds the mean sedimentation rate of the intermediates increases. This is in agreement with the expectation that the linking number between the two complementary rings increases gradually during the course of the reaction from zero to that of a relaxed covalently closed circular DNA duplex. The possible role of DNA topoisomerases in genetic recombination is discussed.


Studies on spin labeled ribonucleic acids encapsulated by viral proteins. Spin labeled poly rA (sl-poly rA) was encapsulated by the coat proteins of two plant viruses having different morphologies: TMV, a rigid rod and CCMV, an icosahedral sphere. Electron microscopy showed that the resultant particles were morphologically similar to the parent virus from which the coat protein was obtained. Encapsulation produced progressive immobilization of the spin label. The motion of the spin label attached to TMV-sl-poly rA appears anisotropic with a correlation time about the long axis of approximately 5 x 10(-6) sec. Exogenous nuclease had no effect on the epr spectrum of this nucleo-protein complex. The epr spectrum of CCMV-sl-poly rA was isotropic with a correlation time less than 5 x 10(-7). CCMV-sl-poly rA was partially degraded by T2 ribonuclease. Theoretical calculations of correlation times for the motion of the nucleo-protein particles were similar to the experimentally derived values suggesting that the nucleo-protein particles are tightly packed with little potential for internal motion.


Identification of specific fragments containing the 5' end of poliovirus RNA after ribonuclease III digestion. The small protein (VPg) covalently linked to the 5' end of poliovirus Type 1 (PV-1) RNA has been labeled in vitro with 125I using the Bolton and Hunter reagent. The RNA is not degraded under the conditions used and nearly all the label enters VPg and not the poly-nucleotide chain. When this 125I-labeled RNA is cleaved with RNase III at low monovalent salt concentrations, one major 125I-labeled fragment, approximately 100 nucleotides long, is produced. The corresponding fragment from similar digests of 32P-labeled RNA has also been identified. The 32P-labeled fragment changes electrophoretic mobility after protease treatment indicating that it contains VPg. Furthermore, the RNase T1 oligonucleotide known to be at the 5' terminus of poliovirus RNA is found in T1 digests of the purified fragment. These results confirm that the fragment is derived from the 5' end of the RNA. This fragment will be useful in studies concerning the initiation of protein synthesis during poliovirus infection.


Nucleotide sequence of the leader RNA of the New Jersey serotype of vesicular stomatitis virus. Sequence for the leader RNA Synthesized by the New Jersey serotype of vesicular stomatitis virus is presented and its complementary sequence representing the 3'-terminal sequence of the genome RNA is deduced. Comparison with the leader RNA sequence of the serologically distinct Indiana strain reveals that the 3'-terminal region of the genomes of two viruses is highly conserved.


Myocardial perfusion studies--direct imaging of acute myocardial injury with 99mTc-pyrophosphate. Imaging of acute myocardial injury is possible with a large number of agents. All of these agents share similar patterns of uptake in acutely injured myocardial tissue. The technique appears to be a reliable way of ruling in or out the diagnosis of acute myocardial infarction.


General features of persistent virus infections. Persistent virus infections are discussed from the virus point of view in terms of the bodily sites in which the infection persists. Glands and body surfaces are thought to be significant because they give the virus protection at the topographical level from immune forces, and because they are appropriate sites for the shedding of virus to the exterior. Germ cells are relevant sites because infection can thus be transmitted vertically from generation to generation in the host. The central nervous system, however, is generally a 'dead end' from which there is no shedding to the exterior. Persistance in blood may be relevant when continued arthropod transmission becomes possible. Most persistent viruses infect lymphoreticular tissues, and this is interpreted by suggesting that it results in an impaired immune response to the infecting virus, which in turn favours persistence. It is suggested that the biological function of virus transformation and the integration of viral into host cell DNA is that it enables the infection to persist in the host and undergo reactivation. Papovaviruses, adenoviruses and oncornaviruses are considered from this point of view.


The effect of aflatoxin B1 on the utilization of cholecalciferol by chicks. The official A.O.A.C. (1975) vitamin D3 chick assay of bone ash was used in a study of the effect of aflatoxin B1 (AFB1) on calcification and the utilization of cholecalciferol. U.S.P. vitamin D3 reference oil (D3) was mixed into the assay diet to give 0, 50, and 100 ICU D3/kg of diet. At each level of D3, AFB1 (Calbiochem) was mixed into the diet to give concentrations of 0, .5, 1.0, 5.0, 10.0, and 20 ppm. Individual bone ash values were determined at 3 weeks of age. These bone ash values were evaluated by a multiple regression analysis for two independent variables. A highly significant regression equation demonstrated a significant interaction between AFB1 and D3 on bone calcification. The equation indicates that 1 ppm of AFB1 in the ration increases the D3 requirement of the chick by 8.84 ICU/kg of diet.


Persistence in herpes simplex virus infections. Diseases of man caused by the virus of herpes simplex fall into two broad categories. The primary disease occurs only once in any individual's life and is caused by transmission of virus from an already infected human. Thereafter, the individual may be subject to recurrent herpetic disease, the manifestations of which are different from the primary disease. Recurrent disease varies in severity from trivial, to incapacitating and frankly lethal (as in diseases resulting from the virus's neurotropic and oncogenic properties). The source of the virus in recurrent herpetic disease has never been conclusively resolved, but is almost certainly endogenous to the patient. Theories, case reports and experiments exist to show that endogenous virus may, in periods of clinical quiescence, be latent (or persistent) at the site of the recurrent lesions itself, or more remotely in nerve tissues related to the site of recurrence.


[Effect of synthetic somatostatin on basal and stimulated growth hormone and prolactin secretion in vitro]. The effect of synthetic somatostatin on the basal and stimulated secretion of growth hormone and prolactin under conditions of incubation of the adenohypophysis (ADH) tissue in vitro was studied. The labeled growth hormones (GH) and prolactin (Pl) secreted was assayed by the method of electrophoresis in polyacrylamide gel as modified by the authors. Synthetic somatostatin (10 and 100 nM) suppressed the basal and stimulated by 2--0-dibutyril AMP, theophylline, and prostaglandins of E series GH labeled secretion. In doses of 100 nM the inhibitor also suppressed the basal and the stimulated by 2--0-dibutyril AMP and theophylline release of labeled Pl. Apparently, the inhibitory action of somatostatin involves the reduction of the ADH activity of adenylatecyclase.


Cyclic nucleotide-binding proteins detected by photoaffinity labeling in nucleus and cytoplasm of bovine liver. A photoaffinity labeling method was used to characterize and compare cyclic nucleotide-binding proteins of bovine liver cytosol with binding proteins of the nucleus. After photoaffinity labeling of cytosol with 8-azido cyclic [(32)P]AMP, autoradiographs of sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed two major labeled proteins of 47,000 and 52,000-55,000 daltons. DEAE-cellulose column-derived fractions suggested that the larger protein was the regulatory subunit of peak II cyclic AMP-dependent protein kinase and the smaller protein was the regulatory subunit of peak I kinase. The smaller protein was largely present as the free regulatory subunit. The two binding proteins differed in their ability to bind cyclic GMP. Binding to both proteins was abolished by excess unlabeled cyclic AMP but not by 5'-AMP. Photoaffinity labeling of a 0.14 M salt extract of nuclei and a nonhistone chromosomal protein preparation revealed two major binding proteins with the same molecular weight and competition profiles as those of the cytosol. Detergent-washed nuclei gave similar results. Several minor binding proteins were observed in both cytosol and nucleus. One protein (36,000 daltons) was unique to the nucleus and had low affinity for 8-azido cyclic AMP. Photoaffinity labeling with cyclic [(3)H]GMP revealed a cytosol protein, absent from the nucleus, of 31,000 daltons and the ligand was competed for by both cyclic GMP and 5'-GMP. These studies suggest that the major specific cyclic AMP-binding proteins of bovine liver are the type I and type II regulatory subunits of cyclic AMP-dependent protein kinase and are present in both nucleus and cytoplasm.


Formation of protein micelles from amphiphilic membrane proteins. The membrane penicillinase (penicillin amido-beta-lactamhydrolase, EC 3.5.2.6) from Bacillus licheniformis, the Semliki Forest virus spike proteins, and the Sendai virus glycoproteins have each been isolated as soluble protein aggregates that are virtually free of lipid and detergent. The sedimentation coefficients of the complexes were 18 S, 29 S, and 43 S, respectively. Mixed aggregates containing both the virus glycoproteins and the penicillinase could also be formed. Such protein micelles may serve a number of useful purposes in membrane research.


[Participation of prostaglandins in the mechanism of hypothalamo-hypophyseal regulation of thyroid gland function]. Prostaglandins E (PGE) content was studied in the hypothalamus, hypophysis, thyroid gland and blood of rats after thyroliberin injections, thyrotropin administration, and thyroidectomy in experimental hyperthyroidism. Changes in the PGE level, cyclic adenosine monophosphate (cAMP), and in thyroxin secretion in the thyroid gland of man under the effect of thyrotropin and acetylsalicyclic acid were studied. The effect of acetylsalicylic acid on thyroxin and triiodothyronine secretion in healthy persons and those suffering from thyrotoxicosis was investigated. Analysis of the results obtained indicated that PGE played a significant role in the mechanism of the thyroid gland function regulation.


Antipain inhibits thyroxine-induced synthesis of carbamyl phosphate synthetase I in tadpole liver. The increased activity of carbamyl phosphate synthetase I [carbamoyl-phosphate synthase (ammonia); ATP: carbamate phosphotransferase (diphosphorylating), EC 2.7.2.5] in tadpole liver observed during thyroxine-induced metamorphosis was markedly inhibited by intraperitoneal injection of the microbial protease inhibitor antipain (0.1 micrometermol/g of body weight, twice daily). A somewhat less than maximal inhibition was seen when antipain was given only during the first 2 days of thyroxine treatment. On the other hand, little inhibition was observed when the inhibitor was given after the third or fourth day of thyroxine treatment. Antipain also inhibited thyroxine-induced increases of ornithine transcarbamylase (EC 2.1.3.3), arginase (EC 3.5.3.1), and succinate-cytochrome c reductase (EC 1.3.99.1) activities. Among other microbial protease inhibitors tested, chymostatin was nearly as effective as antipain, leupeptin was less effective, and pepstatin was ineffective. Analysis of the total liver protein and of the immunoprecipitate by sodium dodecyl sulfate/polyacrylamide gel electrophoresis showed that the inhibition was due to decreased amount of the enzyme protein. Antipain had no significant effect on leucine incorporation into total protein of tadpole liver. These results indicate the involvement of a proteolytic step in the pretranscriptional events in thyroxine-stimulated enzyme induction.


Quantitative determination of the lateral diffusion coefficients of the hormone-receptor complexes of insulin and epidermal growth factor on the plasma membrane of cultured fibroblasts. Fluorescent derivatives of insulin and epidermal growth factor bound to 3T3 mouse fibroblasts are mobile on the cell surface, with similar diffusion coefficients, D approximately (3--5) x 10(-10) cm2/sec at 23 degrees C. Increasing the temperature to 37 degrees C results in rapid receptor immobilization. The immobilization is attributed to aggregation of hormone-receptor complexes, their internalization, or a combination of both processes.


Adenosine analogs inhibit adipocyte adenylate cyclase by a GTP-dependent process: basis for actions of adenosine and methylxanthines on cyclic AMP production and lipolysis. Adenylate cyclase in purified membranes from rat adipocytes is inhibited by low concentrations of purine-modified adenosine analogs, particularly those modified in the N6 position. Such inhibition is antagonized competitively by methylxanthines, but not by other cyclic nucleotide phosphodiesterase inhibitors, and it is dependent on "inhibitory" concentrations of GTP in the assay medium. Ribose-modified adenosine analogs inhibit adenylate cyclase through a process that is neither dependent upon the GTP concentration nor antagonized by methylxanthines. These results explain the potent effects of adenosine and methylxanthines on fat cell metabolism and demonstrate the importance of GTP in mediating inhibition by agents that act at cell surface receptors.


Rapid intramolecular coupling of active sites in the pyruvate dehydrogenase complex of Escherichia coli: mechanism for rate enhancement in a multimeric structure. In the absence of CoA and presence of pyruvate, the lipoic acid residues covalently bound to the lipoate acetyltransferase core component (acetyl-CoA:dihydrolipoate S-acetyltransferase, EC 2.3.1.12) of the pyruvate dehydrogenase multienzyme complex of Escherichia coli become reductively acetylated. A study of a series of reassembled complexes varying only in their content of pyruvate decarboxylase [pyruvate:lipoate-oxidoreductase (decarboxylating and acceptor-acetylating) EC 1.2.4.1] showed that the initial direct reductive acetylation of lipoic acid residues can be followed by extensive intramolecular transacetylation reaction between lipoic acid residues on neighboring polypeptide chains of the lipoate acetyltransferase core [Bates, D. L., Danson, M. J., Hale, G., Hooper, E. A. & Perham, R. N. (1977) Nature (London) 268, 313-316]. Pulsed-quenched-flow measurements of the rates of the acetylation reactions in the various complexes now demonstrate that the intramolecular transacetylation reactions are not rate-determining in the normal reaction mechanism of the enzyme. There is therefore the potential for rapid multiple coupling of active sites in the lipoate acetyltransferase core. The rate constant for the overall complex reaction, measured by stopped-flow fluorimetry, is found to be approximately twice that for the reductive acetylation reaction measured by pulsed-quenched flow. This result could mean that CoA is an allosteric stimulator of the reductive acetylation part of the overall reaction or that there are two active sites on each chain of the lipoate acetyltransferase component working in parallel. A system of rapid functional connection of active sites in a multienzyme complex ensures that sequential reactions can be successfully coupled even under conditions of low substrate concentrations for the different steps. The substantial rate enhancement thus achieved offers a plausible explanation for the unusual complexity of the quaternary structure of the enzyme.


Ca2+-dependent protein phosphorylation system in membranes from various tissues, and its activation by "calcium-dependent regulator". Analysis of membranes from a variety of tissues has revealed a widespread distribution of a protein phosphorylation system dependent on the presence of both Ca2+ and "calcium-dependent regulator" (CDR). This protein phosphorylation system has been studied in some detail in nervous tissue. Neuronal membranes contain a protein phosphorylation system that requires Ca2+ and a soluble heat-stable protein [Schulman, H. & Greengard, P. (1978) Nature (London) 271, 478--479]. This protein has been purified to homogeneity from bovine cerebral cortex, with use of an assay based on its ability to stimulate Ca2+-dependent protein phosphorylation in membranes. This protein kinase activator appears to be identical to CDR of cyclic nucleotide phosphodiesterase. Throughout its purification, this single entity was found to activate both Ca2+-dependent protein kinase and cyclic nucleotide phosphodiesterase. The kinase activator purified here and authentic CDR were equally effective in their ability to activate Ca2+-dependent protein kinase.


Sequence of oxygen binding by hemoglobin. A nitroxide spin-label probe was attached directly to a propionic acid group of heme in either the alpha or the beta chain of hemoglobin. The electron paramagnetic resonance (EPR) spectrum of the spin label is altered by the spin-state change of the heme iron to which the spin label is attached. These hybrid hemoglobins showed normal optical and functional properties, indicating that the attachment of the spin label did not perturb the function of hemoglobin. Upon deoxygenation of alpha-heme-spin-labeled hemoglobin, EPR signals changed proportionally with oxygen saturation (determined by measuring absorption spectra). This result indicates that there is no binding preference between the alpha and beta chains of hemoglobin. However, the cross plot for the fraction of the EPR changes vs. the fraction of oxygen saturation deviated significantly from the diagonal straight line in response to the addition of 2,3-diphosphoglycerate and inositol hexaphosphate. The deviation indicated that the EPR change precedes the optical change at low oxygen tension. This result implies that, in the presence of organic phosphate, oxygen binds preferentially to the alpha subunit of deoxyhemoglobin. This conclusion was supported by the result obtained with beta-heme-spin-labeled hemoglobin: the direction of the deviation for beta-heme-spin-labeled hemoglobin in the presence of diphosphoglycerate and inositol hexaphosphate was opposite to that obtained for alpha-heme-spin-labeled hemoglobin. However, the curve deviated even in the absence of organic phosphate. This deviation for beta-heme-spin-labeled hemoglobin can be explained by the intersubunit interaction of hemoglobin. From these results, it was concluded that, in the absence of organic phosphate, oxygen combines with the alpha and beta chains with equal probability whereas, in the presence of organic phosphate, oxygen binds preferentially to the alpha chains of hemoglobin.


Rotational motion of the sarcoplasmic reticulum Ca2+-ATPase. Using saturation transfer electron paramagnetic resonance, we have detected the rotational motion of a spin label rigidly attached to the sarcoplasmic reticulum Ca2+-ATPase (ATP phosphohydrolase, EC 3.6.1.3). At 4 degrees C, the spectrum indicates an effective rotational correlation time of 60 microsec, determined by comparison with reference spectra obtained from theoretical calculations and from experiments on model systems. This motion appears to correspond to rotation of the enzyme with respect to the membrane, because the motion persists when the membrane fragments are immobilized by sedimentation and the motion stops when the polypeptide chains, but not the membrane vesicles, are crosslinked by glutaraldehyde. The rotational mobility of the enzyme increases with increasing temperature, and this increase becomes more gradual when the temperature exceeds 20 degrees C; the same kind of temperature dependence has been observed previously for lipid fluidity and enzymatic activity.


Induction of DNA synthesis in terminally differentiated myotubes by the activation of the src gene of Rous sarcoma virus. Mononucleated myogenic cells from 11-day-old chicken embryos were infected with tsLA24 or tsNY68, temperature-sensitive transformation mutants of Rous sarcoma virus. The infected mononucleated myogenic cells were incubated at the nonpermissive temperature (41 degrees C) and allowed to develop into multinucleated myotubes. These myotubes have withdrawn from the cell cycle, and no DNA synthesis was observed as long as the cultures were maintained at the nonpermissive temperature. However, when the incubation temperature of these cultures was lowered to the permissive temperature (36 degrees C) for expression of the src gene, DNA synthesis was induced in multinucleated myotubes. For this induction of DNA synthesis, cells infected with tsLA24 had to be incubated at the permissive temperature for at least 50 hr, while the induction of DNA synthesis in cells infected with tsNY68 required less than 20 hr. Induction of DNA synthesis was observed by autoradiography as well as by measuring incorporation of [3H]thymidine into the macromolecule fraction in these myotube cultures. For the maintenance of capacity to induce DNA synthesis, constant presence of the src gene product is necessary, because when the temperature of these cultures was returned to 41 decrees C, the myotubes lost the capacity to induce DNA synthesis. During the process of DNA induction one biochemical marker of muscle (creatine kinase) remained unchanged.


Infectious murine leukemia virus from DNA of virus-negative AKR mouse embryo cells. DNA from virus-negative AKR mouse embryo cells is infectious for NIH 3T3 cells if the transfected cells are treated with 5-iododeoxyuridine (IdUrd) either before or after addition of the DNA. The virus isolated after transfection of the AKR DNA is an ecotropic murine leukemia virus (MuLV) indistinguishable from endogenous AKR MuLV. The AKR DNA is not infectious in the absence of IdUrd treatment of the recipient cells. DNA from AKR cells treated with IdUrd before DNA isolation is not infectious unless the recipient cells have been treated with IdUrd. Transfected DNA from NIH mouse cells is not infectious even when the recipient cells have been treated with IdUrd. DNA from cells chronically infected with AKR MuLV or Rauscher MuLV is infectious with or without IdUrd treatment of the recipient cells, but the infectivity is not enhanced by IdUrd. The results indicate that the endogenous AKR MuLV DNA genome is potentially infectious. The data are consistent with an IdUrd-sensitive restriction in the recipient NIH 3T3 cells that prevents viral replication from endogenous AKR MuLV DNA but does not prevent viral replication from MuLV DNA of productively infected cells.


Translation of animal virus RNA in the cytoplasm of a plant cell. Isolated Acetabularia crenulata nuclei were injected with Mengo virus RNA solution and then implanted into anucleate posterior Acetabularia mediterranea cell fragments or fused with Acetabularia ryukyuensis cytoplasts. The injected animal virus RNA was actively translated in the plant cell cytoplasm. Mengo virus proteins were detected and localized in Acetabularia cytoplasts by use of an immunofluorescence method on the first to fifth day after injection.


Genetics of the large, external, transformation-sensitive (LETS) protein: assignment of a gene coding for expression of LETS to human chromosome 8. Techniques have been developed to analyze the genetics of the large, external, transformation-sensitive (LETS) protein (fibronectin). External membrane proteins of human-mouse somatic cell hybrids with reduced numbers of human but not mouse chromosomes were labeled by lactoperoxidase-catalyzed iodination. Cell surface proteins were identified after sodium dodecyl sulfate/polyacrylamide gel electrophoresis by autoradiography of the dried gel. The LETS protein was identified in parental human cells, and LETS segregated in human-mouse cell hybrids formed from human WI-38 fibroblasts and a mouse L-cell line not expressing LETS. The LETS protein segregated concordantly with the chromosome 8 enzyme marker glutathione reductase (EC 1.6.4.2) and human chromosome 8. These findings demonstrate that a gene, LETS, encoded on chromosome 8, is responsible for the LETS protein expression in humans. Because LETS has been implicated in tumorigenicity and cellular transformation, it is of interest that rearrangement or modifications in the number of chromosome 8 have been associated with certain forms of cancer.


Human antibodies reactive with purified envelope antigens of primate type C tumor viruses. Human sera from healthy individuals have been shown to react with viral antigens in preparations of detergent-disrupted C type viruses from monkeys. In this report, it is demonstrated that (populations of) these human antibodies react with highly purified envelope glycoproteins of the simian sarcoma virus-simian sarcoma-associated virus complex and the Friend leukemia virus complex. Several immunological parameters influencing human antibody binding to C type tumor virus antigens have been characterized. These parameters indicate that human antibodies tend to bind to what is probably a subset of the antigenic determinants on the virus envelope antigens and that different human sera recognize the same antigenic determinants on the virus envelope antigens tested. The possible origin of these antibodies is discussed.


Reversal of renovascular hypertension by antibodies specific for angiotensin-converting enzyme. Goat antibodies developed against pure rabbit pulmonary angiotensin-converting enzyme (peptidyl dipeptidase, EC 3.4.15.1) were administered intravenously to rats with two-kidney Goldblatt hypertension and to normotensive animals. In the hypertensive model these antibodies were associated with a sustained, immune-dependent decrease of blood pressure to normal values. A smaller, but also immune-specific, reduction of blood pressure was observed in the normotensive group. The data suggest that heterologous antibody directed against angiotensin-converting enzyme may provide a biologically specific probe for examining the contribution of the renin-angiotensin system to normal and pathologic circulatory states.


Isolation of host-range variants of mouse mammary tumor viruses that efficiently infect cells in vitro. Host-range variants of mouse mammary tumor virus (MMTV) have been isolated that have the ability to productively infect cells in vitro with high efficiency (at multiplicities of infection </=1) and with extremely short latent periods to the production of de novo virus (as short as 4 days after infection). These variants of the highly oncogenic MMTV of RIII, C3H, and GR mice were obtained by serial virus passage in feline cells. The resultant variant stocks react in group-specific radioimmunoassays for the MMTV major external glycoprotein (gp52) and major internal protein (p28), possess a protein profile similar to that of wild-type MMTV, and contain a virion-associated DNA polymerase with a magnesium cation preference. Addition of dexamethasone and insulin to culture media enhances the titer of de novo MMTV to levels of approximately 10(10) particles per 75-cm(2) flask (containing 5 x 10(6) cells) per 24 hr. Variant stocks exhibit no evidence of contamination with either murine or feline type C retroviruses, as assayed by various techniques. The variants of MMTV derived from C3H and RIII mice exhibit differential host ranges that include the ability to productively infect feline, canine, bat, mink, murine, and human cells. Use of these MMTV host-range variants now facilitates the study of the complete replicative cycle of MMTV as well as an elucidation of the interaction of MMTV with various hormones, physical or chemical carcinogens, and tumor promoters in the initiation and promotion of mammary neoplasia.


Electron reactions with cytochrome c in ethylene glycol/water glass at-196 degrees C. Low temperature gamma-irradiation and spectroscopy are used to study electron reactions with cytochrome c in aquo organic glass at-196 degrees C. Spectral data suggests that cytochrome c is reduced by electron at 196 degrees C. Raising the glass temperature reveals further changes in spectrum, suggesting that conformational changes may occur in cytochrome c molecule during stabilization of reductive process.


Effects of inhibition of prostaglandin-synthesis on renal electrolyte excretion and concentrating ability in healthy man. In five healthy subjects inhibition of prostaglandin (PG)-synthesis with indomethacin did not significantly alter glomerular filtration, urinary flow rate or sodium and potassium excretion during control urine collection periods or i.v. hypertonic saline infusion. Saline administration was accompanied by a fall in urinary PGEI-excretion from 0.58 +/- 0.14 to 0.26 +/- 0.09 ng/min (p less than 0.05). While indomethacin had no effect on basal urinary osmolality (Uosm), renal concentrating ability following hypertonic saline or i.v. administration of 100 mU lysine-vasopressin significantly increased in the presence of indomethacin with Uosm rising from 805 +/- 25 to 970 +/- 53 mosm/L (p less than 0.01) and from 839 +/- 47 to 996 +/- 62 mosm/L (p less than 0.01), resp. Since this was not accompanied by respective changes in urinary excretion of cyclic adenosine monophosphate (cAMP) mechanisms other than PG-antagonism of vasopressin, such as decreased medullary washout of solute, may contribute to enhanced renal concentrating ability following inhibition of PG-synthesis with indomethacin.


Who becomes chronic?

Who becomes chronic? Chronic social disablement is caused by three types of factor: impairment, e.g. slowness in schizophrenia; social disadvantage, e.g. lack of opportunity to develop social or vocational skills; and an underconfidence or unduly low self-esteem which is reactive to impairment and disadvantage. The last of these factors is particularly evident in 'institutionalism', a condition in which the individual comes to acquire a contentment with institutional life and wishes to lead no other. Many long-stay patients in large mental hospitals used to be 'well-institutionalized' but it became recognized that retraining and rehabilitation could lead to successful resettlement outside hospital. For a time these striking successes suggested to some theorists that abolishing the hospitals would abolish disablement as well but it is now quite clear that this is not the case. Chronic impairments still occur and create a continuing need for sheltered environments. The frequency and type of problems still arising are discussed in the light of recent surveys in England. One small group requires highly-staffed accommodation, others need less supervised day and residential settings; all need long-term care. It is emphasized that some people living at home with relatives also have chronic mental disabilities as have a high proportion of the destitute. Such problems are less frequent than formerly but they still require detailed medical and social attention.


When schizophrenia comes marching home.

When schizophrenia comes marching home. Deinstitutionalization of the chronically mentally ill has only recently been recognized as a phenomenon which may not be in the best interests of the patients involved. The reasons for this include the lack of adequate community-based resources for domiciliary, treatment, and rehabilitative services, plus the response of society to deviant behavior. However, the most fundamental problem is likely to be the severity of the illnesses with which we are concerned, so that the solution cannot be as simple as the sending "home" of the long-term patients. Prevention of institutionalization is seen as a more feasible goal than its cure. This requires a comprehensive program incorporating, among other things, a recognition of the necessary role of the mental hospital, and the need to improve the quality of care provided therein.


Bile duct obstruction in hepatocellular carcinoma (hepatoma)--clinical and cholangiographic characteristics. Report of 6 cases and review of the literature. Direct cholangiography revealed 6 cases of hepatoma where tumor growth within the bile ducts caused obstructive jaundice. Characteristic features included bulky obstructing intraluminal masses in the proximal extrahepatic ducts. Distal common duct defects usually signify hemobilia and clots as tumor complication. Review of the literature disclosed only 22 cases in which common duct involvement was a predominant clinical feature. Hepatoma should be included in the different diagnosis of a cholangiographic filling defect in the proximal extrahepatic bile ducts. The recent widespread use of endoscopic and fine needle transhepatic cholangiography should aid in preoperative diagnosis.


Experimental hyperthyroidism in rats suppresses in vitro prostaglandin metabolism in lung and kidney. Metabolism of prostaglandin (PG) F2alpha and PGE2 was depressed 40--62% in 100,000 g cytoplasmic supernatants of lungs and kidneys prepared from rats made hyperthyroid by 18 daily L(-) thyroxine injections (200microgram, s--c). These hyperthyroid rats had elevated serum thyroxine levels, cardiac hypertrophy and thyroid atrophy. There were no differences in soluble protein concentrations, NAD+ utilisation by endogenous enzymes and substrates, or in the NAD+ dependence of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) between the supernatants prepared from hyperthyroid rats and saline-injected controls. Thyroxine did not inhibit PG metabolism in vitro up to 260 micrometer. These results suggest that thyroxine specifically decreases intracellular levels of PG-metabolising enzymes, especially of the rate-limiting 15-PGDH. Metabolism of PGF2alpha and PGE2 by 15-PGDH was faster in smaller rats and declined with increasing animal weight. These studies imply that some of the clinical features of hyperthyroidism in man might be caused by deficiencies in PG metabolism.


Stimulatory effect of prostaglandins on the production of hexosamine-containing substances by cultured fibroblasts (4) adenosine 3':5'-cyclic monophosphate independent stimulation by prostaglandin F2alpha. The mechanism of the stimulatory effect of prostaglandin PG) F2alpha on the production of hexosamine-containing substances by cultured fibroblasts was studied with special reference to adenosine 3':5'-cyclic monophosphate (cAMP). At the stationary phase, the cells were exposed for 6 hrs to PGF2alpha, E1, cAMP or dibutyryl-cAMP in a wide range of concentrations. cAMP itself showed a slight stimulation on the production of hexosamine-containing substances, and the effect was enhanced by using the dibutyryl derivative. PGF2alpha had much a greater capacity than either the exogeneous cAMP or the dibutyryl-cAMP for enhancing the production of hexosamine-containing substances. To know whether cAMP is involved in the stimulatory effect of PGF2alpha, intracellular cAMP level was concomitantly measured in both PGF2alpha and PGE1 treated cultures. Although the cellular cAMP level in PGE1 treated cultures was much higher than that in the PGF2alpha treated cultures, the stimulatory effect on the production of hexosamine-containing substances in PGE1 treated cultures was always much smaller than that in the PGF2alpha treated cultures. Moreover, PGF2alpha had a significant stimulatory effect on the production of hexosamine-containing substances even at a low concentration as 100 pg/ml, which is small enough not to increase any cellular cAMP level. From these results, it was concluded that the stimulatory effect of PGF2alpha on the production of hexosamine-containing substances by cultured fibroblasts is not mediated by cAMP and is caused by a mechanism different from that caused by cAMP.


Prostacyclin: a potent stimulator of adrenal steroidogenesis. The relative potencies of various prostaglandins were investigated in trypsin-dispersed cat adrenocortical cells. Prostacyclin proved to be the most potent steroidogenic prostaglandin, being 100-1000 times more potent than PGE2. This stimulant effect of prostacyclin was only partially dependent upon the presence of extracellular calcium and was associated with increased levels of cyclic AMP. These data suggest a possible role for prostacyclin in corticosteroidogenesis.


Development of tolerance to the ACTH-releasing effects of beta-endorphin. Acute intracisternal injection of human beta-endorphin results in increased plasma concentration of adrenocorticotropic hormone (ACTH). Repeated injections of beta-endorphin are associated with the development of tolerance with regard to this ACTH-stimulating effect.


Crystalline cytoplasmic inclusions in the liver cells of two mongrel dogs. Crystalline inclusions were found in the cytoplasmic matrix of the liver cells in 2 out of 5 healthy mongrel dogs. The crystals were rectangular, with fine granular structure and free from the surrounding membrane. Their appearance was different from the intramitochondrial crystalline inclusions described in human and dog livers, as well as from those observed in the livers of other species. The significance of this unique finding remains unclear, but it is suggested that these inclusions represent crystalized protein.


Induction of chicken interferon by avian infectious bronchitis virus. The ability of nine strains of avian infectious bronchitis virus (IBV) to induce chicken interferon has been investigated using Semliki Forest virus for the tests. The Beaudette, H120 and Connecticut 46 strains induced interferon in the allantoic fluids of embryonated hens' eggs, the highest titre (1 : 30) being associated with Beaudette; but these as well as the Massachusetts M-41 and H52 strains failed to yield interferon in primary monolayer cultures of chick kidney cells as did all nine strains in organ cultures of chick embryo trachea. None of six strains of IBV investigated was susceptible to the inhibitory effects of chicken interferon.


Parainfluenza-3 virus: difference in capacity of neuraminidase-weak and strong strains to infect young calves and to elicit cellular immune response. Calves less than four weeks old could not be infected with a neuraminidase-weak strain of parainfluenza-3 virus (Pi3) but were successfully infected with either of two neuraminidase-strong strains. The criteria for infection were virus excretion, cell-mediated and antibody-mediated immune responses. In the lymphocyte stimulation test, calves infected with the neuraminidase-strong Pi3 strain Tüb-E6 responded more strongly to antigen prepared from this strain than to antigen from the heterologous Pi3 strain Um-23. The non-immunoglobulin haemagglutination inhibition activity of the liquid phase of nasal secretions of newborn calves decreased after treatment with Vibrio cholerae neuraminidase. For virus-bound neuraminidase the liquid phase from newborn calves was a richer substrate than the liquid phase from older animals.


The distribution of antibodies to Border disease virus among sheep in England and Wales. Within a sample of the sheep population of England and Wales, 10.8 per cent of 3506 individuals had immunodiffusion test antibody to bovine viral diarrhoea mucosal disease virus antigen. There were marked differences between various geographical regions in the proportion of sheep with antibody, and Border disease may be more common in some areas than disease records indicate.


Effects of swab materials and transport media on Aujeszky's disease virus. The effect of swab materials on the recovery of Aujeszky's disease virus from various transport media held at 4 degrees C was investigated over a five day period. No significant loss in infectivity was found in control preparations, approximately 50 per cent of infectivity was recovered from fluids containing applicator wire and approximately 10 per cent from fluids containing polyester fibre or cotton wool. Virus recovery from fluids containing wooden applicator sticks ranged from no virus recovery in protein free media to from 1 to 10 per cent in protein containing media. Freezing followed by thawing was the most effective of the physical methods used for eluting virus from swab materials.


[Fisher's syndrome. Peripheral or central origin (author's transl)]. The syndrome described by M. Fisher in 1956 includes ophtalmoplegia, ataxia, and generalized loss of reflexes. It is classically considered to be of peripheral origin and its relation to Guillain and Barre's syndrome in its mesencephalic form is debatable. The authors review 5 cases and discuss the question of a probable central origin. They base their opinion on the pathognomonic features of these cases and those in the literature, as well as the results of their oculographic and electromyographic studies. They stress the importance of the nature of the ataxia; the severe equilibrium disturbances noted in these patients could result, contrary to usual thinking, more from a central vestibular syndrome than from a cerebellar lesion.


The pharmacology of phagocytosis.

The pharmacology of phagocytosis. The biochemical mechanisms underlying the processes of chemotaxis, adhesion, phagocytosis and lysosomal enzyme secretion are described. Particular attention is drawn to the roles of aerobic glycolysis, the hexose monophosphate shunt, cyclic adenosine monophosphate, cyclic guanosine monophosphate and the microtubular and microfilament systems. The way in which drugs modify these pathways is discussed with reference to agonists and antagonists of beta-receptors, agonist and antagonists of muscarinic receptors, prostaglandins, colchicine, Cytochalasin B, and to steroidal and non-steroidal anti-inflammatory agents. The possibility that anti-inflammatory agents produce a significant effect in this manner is considered.


Dental maturity in hypopituitarism, and dental response to substitution treatment. In 25 patients with hypopituitarism the relation of skeletal and dental maturity and the effects on it of substitution therapy for 2-4 years were analyzed. Dental age was retarded less regularly and to a lesser degree than skeletal age and statural growth. In most patients dental age was within the range of 0-2 s.d. All components of dental development seemed equally retarded. Changes in dental delay during GH treatment were variable, but in most cases parallel to the changes in statural and skeletal delay. When treatment was discontinued the lag in dental age increased, showing a response similar to that of skeletal age.


Erythrocytosis and Wilms' tumour.

Erythrocytosis and Wilms' tumour. A Wilms' tumour was diagnosed in an 18-year-old male patient with erythrocytosis. After radical excision of the tumour and postoperative irradiation and chemotherapy, the erythrocytosis disappeared and did not recur during a 2-year observation period. The levels of erythropoiesis-stimulating activity in serum and in the renal mass suggest the tumour as the source of this activity. The rarity of the association is discussed and a review of the literature is given.


Illnesses during the first two years of life and their association with perinatal cytomegalovirus infection. In order to find out whether perinatal cytomegalovirus (CMV) infection causes clinical symptoms or signs or influences the general morbidity of a child, a prospective study was performed on 147 children during their first year of life. 48 infants were infected with CMV perinatally. Reports of clinical infections during the second year were available from a total of 108 infants, and serum samples for viral antibody screening at the age 24 months from 111. No specific symptoms or signs could be attributed to perinatal CMV infection. None of the symptoms previously described in connection with CMV infection in childhood were observed. Urinary tract infections were, however, noticed in the group of perinatally infected children. Judging from the prevalence of illnesses and the frequency of elevated antibody titres against different agents, perinatal CMV infection does not seem to influence the general morbidity of a child. In general, the frequency and distribution of illnesses were the same as previously reported by Finnish authors. Breast-feeding did not protect against infection. The children of CMV seronegative mothers were not resistant to other infections, although all of them escaped perinatal CMV infection.


[Importance of numeric scintigraphy of the hips during primary aseptic osteonecrosis of the femoral head in adults]. The authors have studied 58 cases of primitive aseptic osteonecrosis of the hips, 35 cases of coxarthrosis, 12 algodystrophies and 11 cases of coxitis, using numerical scintigraphy with Technetium 99m pyrophosphate. They have studied the ration of uptake by the femoral head over the uptake by the soft issues. The values obtained are compared to those observed in the study of normal hips. The result is that the technique offers the possibility of establishing, in a more differential manner, a diagnosis of lesion of the hips at an infraradiologic stage.


Rotavirus infections in families. A clinical and virological study. Among 25 family members of 8 children with acute rotavirus gastroenteritis (8 siblings and 17 adults) gastroenteritis was recorded in 9 (5 siblings and 4 adults), and minor symptoms in 8 (2 siblings and 6 adults). A rotavirus infection was diagnosed in 7 of the family members with gastroenteritis and was probably the cause of the disease in the remaining 2 in this group. Four of the 8 family members with minor symptoms were infected with rotavirus, whereas no infection was detected among the 8 family members without symptoms. Serological findings sugggested that infants and young children underwent a primary infection with rotavirus, whereas older children and adults probably were reinfected. Adults as well as children with rotavirus infection excreted virus and may have served as sources of infection.


The effect of alpha-adrenergic stimulation in stress incontinence. The urethra is innervated by adrenergic fibres and its smooth muscle is equipped mainly with alpha-adrenoreceptors. Norephedrine chloride, which is an alpha-stimulating agent, has been proposed as therapy for stress incontinence, since it was shown to increase the maximum urethral pressure at rest. For further study of the effect of norephedrine chloride on the urethal closure pressure at rest and in a dynamic situation, we examined ten severely stress-incontinent women before and after three weeks of treatment with this agent (100 mg by mouth twice daily). The urethral closure pressure at rest, between coughs of varied strength and at the precise moment of stress were recorded. The margin to leakage, the tone of the urethral wall and the transmission of pressure from abdomen to urethra were also among the estimated factors. No improvement was found in any of these respects. Alpha stimulation in this form therefore seems ineffective in severe stress incontinence and is not an alternative to surgical treatment.


The pineal gland: a biological clock in vitro. Circadian rhythmicity was studied by following the course of N-acetyl-transferase activity in the pineal glands of chickens in vitro. The results indicate (i) a daily change during day 1 of organ culture in constant dark that was dependent on the time the chickens were killed, (ii) equivocal persistence of the daily change in constant dark during 6 to 7 days of organ culture, (iii) an effect of light, (iv) inhibition by adrenergic agents and cycloheximide, and (v) stimulation by dibutyryl adenosine 3',5'-monophosphate and related compounds.


Nicotinamide adenine dinucleotide splitting enzyme: a characteristic of the mouse macrophage. Murine macrophages are endowed with nicotinamide adenine dinucleotide splitting activity that is markedly higher than that of other cells, tissues, or organs of the mouse. This enzyme therefore can be used as a biochemical marker for distinguishing macrophages from other cells of the lymphoreticular system and from polymorphonuclear leukocytes.


Cellular analysis of long-term habituation of the gill-withdrawal reflex of Aplysia californica. Long-term habituation training in Aplysia californica produces a profound depression in the efficacy of synaptic transmission between mechanoreceptor neurons and gill motor neurons. This depression persists for more than 3 weeks. Thus a critical synaptic site for plasticity underlying long-term habituation is the same as that for short-term habituation. For this simple form of learning, short- and long-term memory share a common locus and aspects of a common mechanism: synaptic depression.


Synaptic phosphoproteins: specific changes after repetitive stimulation of the hippocampal slice. Repetitive stimulation (100 pulses per second for 1 second) of the Schafer collateral-commissural system of the rat hippocampus induces long-term potentiation of synaptic strength and produces significant changes in the subsequent endogenous phosphorylation of a 40,000-dalton protein from synaptic plasma membranes. This effect is not observed after stimulation in calcium-deficient media or after simulation at the rate of one pulse per second for 100 seconds. These findings provide evidence that repetitive synaptic activation can alter the phosphorylation machinery of the synaptic region and suggest a biochemical process which may be involved in the production of neuronal plasticity.


Octopamine receptors, adenosine 3',5'-monophosphate, and neural control of firefly flashing. An adenylate cyclase activated as much as 25-fold by low concentrations of octopamine has been identified in the firefly lantern. The relative potency of octopamine and various other amines in stimulating this enzyme, and effects of antagonists in blocking octopamine activation, correlate well with the known effects of these agents in affecting light production. In addition to suggesting a role for adenosine 3',5'-monophosphate (or pyrophosphate) in the neural control of firefly flashing, identification of this potent enzyme should facilitate the characterization of phenylethylamine receptors in excitable tissue.


[Acute leukemia and primary Vaquez' polycythemia. 20 cases]. The authors report the clinical and hematological course of 20 patients with polycythemia vera complicated by acute leukemia. This was responsible for 35,8% of the 53 deaths in the series of 103 patients treated with radioactive phosphorus. It occurred on average 12 years after the first treatment. The data in these cases are compared with those in the literature. The role of ionising radiation and/or the myelo-proliferative syndrome itself in the onset of acute leukemia is discussed.


[Evans' syndrome during acute myelomonocytic leukemia. 2 cases]. The immune abnormalities observed during acute myeloblastic leukemia often remain undiagnosed for they generally have no practical consequences. The association of peripheral thrombopenia and a positive direct Coomb's test, during two cases of acute myelo-monocytic leukemia should be recognised owing to the difficulty of interpretation and the therapeutic consequences.


[Multiple myeloma and acute leukemia. Simultaneous evolution of plasmacyte and myelomonocytic clones]. The authors report two cases of acute myelo-monocytic leukemia occuring during the course of multiple myeloma treated by local radiotherapy and melphalan. Both patients underwent a complete remission of their myeloma for 27 and 78 months. The myeloma relapsed suddenly in the form of an acute leukemia. In one case, the onset of acute leukemia was preceded by a syndrome of marrow failure with numerous crown-shaped sideroblasts and an excess of myeloblasts in the marrow. This stage lasted two years. The biochemical abnormalities of the red cells usually associated with refractory anemia and preleukemic conditions were present in the other case.


[Extramedullary lymphosarcoma, erythroblastopenia and gastric adenocarcinoma. Apropos of a case]. The authors report the case of a patient with lymphosarcoma and erythroblastopenia who died following a surgical operation for gastric carcinoma. The erythroblastopenia, corrected by radiotherapy of the lymphosarcoma, reappeared during the relapse. The link between these two diseases seems undoubted. The later appearance of a gastric carcinoma suggested the predisposing role of the first neoplasm, and/or its treatment, through an immunological disorder.


[Collagen : physiological approach to skin healing,. Its application to the practical treatment of leg ulcers (author's transl)]. Collagen gel has been studied, during a comparative trial, as a topic for cicatrization on a series of twenty patients with severe leg ulcers rebellious to the usual methods of treatment. A complete healing was obtained in 16 cases out of 20, after a period of 8 to 60 days. Collafilm Gel must only be applied to clean, uninfected wounds. It's action seems noticeable by the appearance of network cicatrization, the mechanism and signification of which is being discussed by the authors.


[Radiological signs of tumours of the adrenal glands (author's transl)]. The authors discuss the radiological signs in 18 patients with an adrenal tumour. 7 of them had a Cushing's syndrome, 10 others a phaechromocytoma and the last had primary hyperaldosteronism. The diagnosis was made from the history, the clinical picture, hormone estimations and pharmacodynamic tests, whilts in the majority of cases the tumour was localised by radiodiagnosis. In all cases, there was hypertension, permanent in tumours of the adrenal cortex, paroxysmal or permanent in the cases of pheochromocytomas. We emphasise the importance of retro-pneumoperitoneum, as the radiological investigation of choice, in the localisation of adrenal tumours, especially pheochromocytomas, and in Cushing's syndrome. In cases of pheochromocytoma, one should follow carefully the blood pressure, during special radiological investigations, in view of the danger of a sudden rise or fall in blood pressure, the first is treated with phentolamine, the second with noradrenaline solution. Finally, a scan using I 131 19-iodocholesterol may be valuable in diagnosis and localisation of adrenal tumours; it has in particular given very encouraging results in the differential diagnosis of adrenal tumours with the clinical presentation of Cushing's disease.


[The importance of quantitative left ventriculography in coronary heart disease (author's transl)]. Regional impairment of left ventricular contraction in chronic stage of coronary artery disease is best demonstrated by using left ventriculography. Moreover, left ventricular volumes and ejection fraction can be computed from this angiography. Changes in these volumetric parameters are closely related to the degree of left ventricular dysfonction and to the adaptation mechanisms due to ventricular asynergy. Since left ventricular dysfonction has a high prognostic value in coronary artery disease (CAD), left ventricular volumes and ejection fraction should be measured as a routine of angiographic evaluation of CAD.


[The failures of surgery in peptic ulcer. Report of 62 reoperations (author's transl)]. 62 reoperations were performed in 54 patients for failure of surgery for chronic ulcer. In 15 cases there was a recurrence of an ulcer left in position, in 32 cases there was an anastomotic ulcer, in 4 cases, severe hemorrhage for severe inflammation of the stoma without recurrence of the ulcer and in 11 cases, there were severe functional disorders. The authors are convinced that in the treatment of recurrent ulcer, vagotomy should always complete gastrectomy and vice versa. It is because they did not follow this advice in the early stages that they had to reoperate certain patients several times for new ulcer recurrences. The results of reoperation for functional disorders when indicated in a gastrectomised patient were mediocre in the vagotomised patients.


[Effect of sustained release alprenolol in hypertension uncontrolled by chlorothiazide and dihydralazine. Study in double blind (author's transl)]. In 20 hypertensive patients with functioning renal graft, sustained release alprenolol or placebo was given orally for 2 months, in combination with chlorothiazide and dihydralazine, after previous failure of these 2 last drugs. Blood pressure was normalized with alprenolol during the length of the study, but is was not with placebo. Mean plasma renine level decreased of 45 p. cent.


[A new treatment of Huntington's chorea. Report of three cases (author's transl)]. The authors report their experience in three cases of Huntington's chorea treated with tiapride (Tiapridal). A real efficacy and an interesting effect of the drug were observed on choreic hyperkinesias. No regression of the other symptoms were noted and the course of the disease not changed.


Hepatic carcinoma with opisthorchiasis.

Hepatic carcinoma with opisthorchiasis. Eighty-seven cases of primary hepatic carcinoma associated with opisthorchiasis were reviewed. The prevalence of liver carcinoma among 154 cases of liver fluke infection was 56.6%. The tumours were classified histologically as cholangiocarcinoma in 67 cases (77%), hepatocellular carcinoma in 9 (10.3%), mixed hepatocholangiocarcinoma in 4, squamous carcinoma in 2, and undifferentiated carcinoma in 5. Metastases, found in 71 cases, occurred most frequently in the regional lymph nodes and lungs. There were numerous or moderate numbers of liver flukes in most of these cases.


[Neopergonal treatment in male hypogonadotropic hypogonadism (author's transl)]. Male hypogonadotropic hypogonadism is a rare disease but a caracteristic one of currently isolated gonadotropin deficiency. 15 subjects have been treated during 6 to 52 monthes with Neopergonal (225 UI a week) + H.C.G. (15 00 IU a week). We observed spermatogenesis onset in 11 patients, sufficient 9 of them, poor in 2 others.


[Risk factors in aorto-iliac surgery (author's transl)]. The authors report a statistical analysis of 163 operations of aorto-iliac vascular surgery. A detailed study of their 14 deaths showed the various causes of mortality (immediate post-operative thrombosis, acute renal failure, digestive complications, septic cardiac, pulmonary, hemorrhagic and cerebro-vascular accidents). This analysis, compared with the findings in all the operated patients showed the main factors of risk in this type of surgery (age over 70 years immediate and late reoperations, heart lesions, renal, pulmonary and late lesions, the risk of sepsis). The indicate the means of prevention of such accidents and the therapeutic attitude when they occur. They conclude that the contra-indications are relative, but should be observed in order to lower the risk of this surgery below 5 p. cent mortality rate.


[Eosinophilic pleurisy. Apropos of 35 cases]. Eosinophilic pleuritis are inflammatory effusions containing more than 10% of eosinocytes. More frequent in men, the course of illness is acute our subacute but pleural sequelae are seldom. They can be due to all inflammatory process, thoracic trauma, tuberculosis and viral diseases are predominant. Unexplained etiology represents 25% of cases, so "called autonomous pleuritis". Pleural eosinophilia could be explained by eosinophilotactic action of red cells or by activating products induced during hypersensibility reaction.


Selective and reconstructive surgical procedures for carcinoma of the breast. Eighteen hundred and fifty-nine patients with primary carcinoma of the breast from New York Medical College-Flower and Fifth Avenue Hospitals were treated by a moderate selective surgical approach between 1950 and 1975. Seven hundred and eleven patients with potentially curable carcinoma of the breast were observed for ten or more years. Based upon strict criteria of evaluation, the series did not have an increased number of prognostically favorable cancers compared with that of other series. The results obtained were most rewarding regarding absolute gross ten year survival rates, local recurrence rates, percentage of skin grafts, management of the other breast, arm and shoulder function and cosmetic appearance, especially in relation to reconstruction of the breast in properly selected patients.


Small hemorrhages vs. small calcifications in brain tumors: difficulty in differentiation by computed tomography. The difficulty in differentiating multiple small hemorrhages from multiple small calcifications in brain tumors by computed tomography (CT) is discussed. Illustrative CT scans are presented and the theoretical basis for this problem is elaborated. The difficulty is attributed to the relatively large size of the voxel and the ensuing partial volume effect, particularly with small intraparenchymal lesions of different sizes and attenuations.


[New therapeutical possibility in a geriatric practice (author's transl)]. Thirty four patients whose ages ranged for 60 to 101 were treated with "tiapride" in a geriatric hospital. The patients' tolerance of the drug was excellent even the very elderly whose circulatory or respiratory state was often rather poor. The results obtained were good for the cases of acute or chronic agitation. They were satisfactory as regards a certain number of abnormal movements and some painful syndromes. However the number of these cases was too small for the results to be considered significant.


Multicentric tracheobronchial and oesophageal granular cell myoblastoma. Two patients with multiple intrathorcic granular cell myoblastomas are described. In one case multiple tumours were present in the major airways and oesophagus. The patient presented with recurrent pulmonary infections and stridor due to airway obstruction. In the other case dysphagia caused by multiple oesophageal granular cell myoblastomas was the major symptom. Granular cell myoblastoma is a rare tumour of neurogenic origin with a characteristic histological appearance. The pattern of multiple tracheobranchial and oesophageal tumours is uncommon and forms the basis of this report.


A study of cyclic nucleotide metabolism and the histology of rat liver during 3'-methyl-4-dimethylamino-azobenzene carcinogenesis. II. Cyclic AMP metabolism. We have studied cAMP metabolism in rat livers undergoing carcinogenesis induced by dietary 3'-methyl-4-dimethylaminoazobenzene. A correlation between the biochemical and the histological changes described in the companion paper has been made. In this study, we saw 100% incidence of cholangiocarcinoma by 10 weeks. During weeks 1--10, the biochemistry of tumor-free areas of the livers only was studied; during weeks 11-13, the increased size of the tumors made possible a biochemical study of the tumor tissue as well as the non-tumor tissue, and a comparison between the two was made. Alterations in all parameters of cAMP metabolism were seen from the earliest stages of treatemnt. Most striking were those of adenylate cyclase activity which preceded and accompanied tumor formation, and were seen in both non-tumor and tumor tissue. In the first few weeks of treatment, small acidophilic glycogen-deficient hepatocytes appeared in the periportal areas of the liver lobules. During this time, there was an increase in maximal isoproterenol stimulation of adenylate cyclase and to a lesser extent in the basal activity of the enzyme; increases in phosphodiesterase activity were seen, and were greatest in weeks 1, 2; cAMP levels were diminished in weeks 1, 2 and slightly but not significantly elevated at week 3. From week 4 onwards an even smaller glycogen-deficient cell population appeared in perilobular areas amongst the acidophilic hepatocytes, and tumors began to appear elsewhere in the livers; at this time, there were further marked increases in the basal activity and isoproterenol responsiveness of adenylate cyclase, and the appearance of increased Gpp(NH)p responsiveness of the enzyme; the increase in phosphodiesterase activities seen at week 3 (smaller than that seen in weeks 1, 2) was sustained but did not further increase; cAMP levels were now significantly elevated also, but they did not rise steadily as did the activity of adenylate cyclase. There was a marked difference between the adenylate cyclase activities in non-tumor tissue from tumor-bearing and non-tumor-bearing livers in weeks 4--10, but there was no difference between the phosphodiesterase activities or cAMP levels in these two groups. Adenylate cyclase activity was extremely high in both non-tumor tissue of tumor-bearing livers from weeks 4--10 and tumors from weeks 11--13. Although phosphodiesterase activities were most elevated in the tumors, there were extremely high cyclic AMP levels in these tissues. The difference between the cAMP levels of tumor and non-tumor tissue was striking. Our findings are discussed with respect to the two-state model of carcinogenesis...


Hormonal activation of mammary gland peroxidase. Ultrastructural cytochemistry was used to detect an endogenous peroxidase in the rat mammary gland. The enzyme was identified only during the latter half of pregnancy and during lactation, indicating its possible dependence upon hormones. To test this hypothesis, specific hormones associated with the development and differentiation of the mammary gland were used both in vivo and in vitro in an effort to induce, or unmask, the activity of the enzyme. Estrogen injected into nonpregnant rats induced some peroxidase activity in the mammary glands of a few animals. Two hormone combinations tested in organ cultures of mouse mammary gland were able to activate the enzyme: (1) dexamethasone + insulin and (2) dexamethasone + insulin + prolactin.


A new approach to the difficult assessment of aldosterone secretion in anephric patients. A new method for the assessment of endogenous formation of aldosterone in anephric patients is described. (1, 2-3H) aldosterone was administered i.v. to patients 1-2 days before hemodialysis, and then the specific activity (SA) of tetrahydroaldosterone glucosiduronate, the major aldosterone metabolite, was measured in the dialysate using a specific radioimmunoassay. The aldosterone secretion rate was determined from the extent of isotope dilution by endogenous metabolite. Aldosterone secretion rates measured in 10 patients were for the most part low. The secretion rate determined in blood from the aldosterone metabolic clearance rate and plasma aldosterone concentration closely approximate secretion rate values obtained by the isotope dilution method in 3 of 4 patients. In 2 patients in whom ACTH was administered chronically, radio-labeled aldosterone was administered at the start of the study and then the day to day aldosterone secretory response to ACTH was determined from the SA of tetrahydroaldosterone in blood. Aldosterone secretion continuously increased for as long as ACTH was administered.


The differentiation of invasive and non-invasive Entamoeba histolytica by isoenzyme electrophoresis. Cultures of 85 stocks of Entamoeba histolytica were compared by electrophoretic patterns of three enzymes: glucosephosphate isomerase, phosphoglucomutase and L-malate: NADP+ oxidoreductase (oxaloacetate-decarboxylating). Four groups of E. histolytica stocks have been distinguished. 18 of these stocks were derived from individual patients with clinical amoebiasis and all of these were of one enzyme group, which did not occur among the other stocks.


Leishmania donovani: ultrastructural localization of diaminobenzidine reactivity in the amastigotes. Intracellular amastigotes of Leishmania donovani obtained from spleens of infected hamsters were studied by means of the diaminobenzidine technique for the presence of cytochromes and the activities of cytochrome oxidase and peroxidase. In the absence of H2O2, the oxidation of DAB, evidenced by electron-dense deposits localized on the cristae, inclusions, and enveloping membranes of the mitochondria and kinetoplast, revealed the activity of the cytochrome oxidase and the presence of the cytochromes. The increased deposition of DAB oxidation especially on the enveloping membranes in the presence of H2O2 suggests the activity of a peroxidase, probably cytochrome c peroxidase.


[Effect of single exposure to the carcinogen 4-dimethylaminoazobenzene on several properties of rat liver mitochondria]. The hepatospecific carcinogen 4-dimethylaminoazobenzene (DAB), applied as a single interperitoneal injection, induced no changes in the activity of mitochondrial and cytoplasmic malate-dehydrogenase in the rat liver. The same carcinogen and non-carcinogenic isomer 4-diethylaminoazobenzene brought about decreased activity of cytochromeoxidase in isolated rat liver mitochondria. During 18 days after a single interperitoneal injection of DAB the swelling-contraction properties of isolated liver mitochondria were seen altered in the presence of succinate and ATP whereas DAB exerted no influence on mitochondria from the kidney, which organ is not a target-tissue for carcinogenic action.


[Morphology of the surface of normal and virus transformed cells in vitro]. The cell surface morphology of two cell lines--from the mink lung (Mv1Lu) and from the Kirsten sarcoma virus transformed derivate (Ki-Mv1Lu)--was studied by scanning electron microscopy. Marked differences are seen in cell morphology of these two lines at high cell densities. Mv1Lu cells at high densities had uniform flat polygonal shape with microvilli at their surface. A marked diversity in cell morphology was characteristic of Ki-Mv1Lu cells at comparable cell densities: variation in shape, in thickness degrees, and in the expression of cell surface ultrastructure (microvilli, blebs, filopodia). No dependence of Ki-Mv1Lu cell morphology from cell densities was observed. At low cell densities of Mv1Lu cells, cells with the morphology differing from the typical pattern of confluent Mv1Lu cells were seen. Morphological diversity of these cells was comparable with that of Ki-Mv1Lu cells. Nothing has been found in cell surface morphology that could be absolutely specific for transformed cells only.


[Electron microscopic study of glycocalyx formation in different functional states of the frog bladder epithelial cells]. The apical part of the urinary bladder granular cells contains oval granules filled with a homogenous substance; close to the plasma membrane granules with tubular element are disposed. A preliminary 30 min fixation of the bladder epithelium with 0.1--0.5% glutaraldehyde followed by 2.5% glutaraldehyde post-fixation rather increased the number of granules with the orderly distributed inner material. The membrane of these granules includes in to the plasma membrane. The loosening of the inner material takes place and the fibrillar elements similar in structure to the glycocalix fibrilles attach to the external surface of the cell plasma membrane.


[Effect of cAMP on the structural and functional properties of the erythrocytes]. Cyclic AMP inhibits the anion transport and decreases the osmotic resistance and deformability of erythrocytes with the normal level of ATP. With ATP-depleted erythrocytes cAMP exerted the opposite effects on the corresponding characteristics. In addition, it was observed that the pattern of cAMP effect on the cell form depends on the basal level of ATP. These effects may be associated with the two types of structural rearrangements of erythrocyte membranes established earlier: a cooperative transition not connected with protein kinase system, and a non-cooperative one caused by protein phosphorilation.


[Correlation of Na,K-ATPase activity and protein synthesis in nerve cell membranes exposed to acetylcholine]. Acetylcholine (10(-6)--10(-3) M) added to the rat brain homogenate increased that activity of microsomal Na, K-ATPase and (14C)-amino acid incorporation in microsomal proteins. Actinomicin D (5.10(-5) M) eliminated the effect of acetylcholine. It is concluded that acetylcholine induced the synthesis of either Na, K-ATPase itself or some other proteins involved in the enzyme activity regulation.


[Effect of the critical fragmentation of erythrocyte membranes]. After sonification of erythrocyte membranes, some changes were registered in these including a loss of their ability to structural rearrangements caused by cAMP (ESR-spectroscopy and luminescence data), an increase in cAMP binding and aggregation of intramembrane particles (freeze-fracture data). These findings suggest a non-identity of the structural organization in membranes and in their fragments. The cooperative nature of membrane structural modification at ultrasonic fragmentation is shown.


[Formation of heterosymplasts in human reticular cell cultures]. The cell fusion has been studied in human reticular cell cultures J-96 and J-41 treated with the Sendai virus or with polyethylene glycol 1000 and 6000. The J-96 cells have a high alkaline phosphatase activity, in J-41 cells the enzyme is not detectable. No heterogenous alkaline phosphatase activity was seen in the protoplasm of symplasts 18 hours after virus cell fusion. It has been shown with polyethylene glycol treatment that during the fusion of cells J-96 and J-41 the enzyme activity was spreading over the symplast protoplasm.


[On corticosteroid control of NAD splitting in rat liver]. Hydrocortisone increases the NAD-glycohydrolase activity in the liver of intact rats. Actinomycin D does not influence the stimulating effect of hydrocartisone with respect to the NADase activity of the liver. The degree of activation of NAD enzymic splitting with administration of 200 mg/kg of nicotinamide depends on the initial hormonal background: with hypercorticoidism it is higher and with hypocorticoidism it is lower than the level found in the intact animals which were given the same dose of the vitamin. An inverse correlation between the steroid-dependent shifts of the NADase activity and the content of NAD in the liver may evidence for their interdependence. A conclusion is drawan on the paramount importance of corticosteroid control of the nucleotide splitting in vivo for formation of NAD cellular pool.


Oral calcium tolerance and urinary cyclic AMP in urolithiasis. Oral calcium tolerance and urinary cyclic AMP testing was used in the evaluation of 61 unselected patients with stones. The oral calcium tolerance test was easy to perform and was useful in defining several distinct metabolic abnormalities contributing to calculous formation. Oral calcium tolerance testing is more precise than twenty-four-hour urinary calcium determination and should provide a means of determining proper medical treatment of urolithiasis. Urinary cyclic AMP was disappointing as a measure of parathormone activity.


Recognition of virally transformed cells by lymphocytes from patients with prostatic cancer. Data presented describe the first assay using human peripheral blood lymphocytes (PBL) against two unique virally transformed cell lines in vitro. Human cells transformed by a cytomegalovirus (CMV-Mj) isolated from normal human prostate tissue were used as target cells in microcytoxicity assays with lymphocytes from 100 patients. Three target cell types were used: control human embryonic lung cells (HEL), transformed HEL cells (CMV-Mj-HEL-2), and transformed HEL cells retrieved from tumors induced in athymic nude mice (CMV-Mj-HEL-2, T-1) by injection of CMV-Mj-HEL-2 cells. PBL preparations from 84% of all patients tested significantly killed CMV-Mj-HEL-2, T-1 cells. However, only PBL from patients with prostatic carcinoma were cytotoxic for CMV-Mj-HEL-2 cells significantly more often than for control HEL. The implications of this approach are discussed.


Adult renal myoepithelial hamartoma.

Adult renal myoepithelial hamartoma. A renal myoepithelial hamartoma presented as a lucent filling defect with gross hematuria in an adult female. Preoperative studies caused conflicting impressions. The predominance of smooth muscle and incorporated tubuloepithelial elements characterize the tumor as a hamartoma of myoepithelial type. Pertinent review of the literature confirms the rarity of this lesion in adults.


[Hyperlipemia and lipoprotein blood spectrum of rabbits of different age with administration of cholesterol]. Hyperlipemia developing in impuberal, young and old rabbits with administered cholesterol is characterized by a considerable prevailence of the cholesterol level over the triglyceride one. The degree of shifts in lipids depends on the age, it is most pronounced in old animals and the least pronounced in impuberal ones. The amount of blood serum cholesterol bound with lipoproteids of high density lowers and most considerably in old rabbits. Separation of blood serum lipoproteids by electrophoresis in polyacrylamide gel detects in rabbits with hyperlipemia a sharp decrease as compared to the norm in the intensity of alpha-lipoproteids disc. This decrease is most pronounced in animals of older age groups. The presence of the intermediate fraction between pre-beta- and beta-lipoproteids is also found in the same animal by the separation especially often in old animals.


[Characteristics of surface-active substances effect on K+-dependent phosphatase activity of brain tissue]. The K+-acetylphosphatase and K+-p-nitrophenylphosphatase activities in the fraction of brain microsomes were studied as affected by anionic (sodium desoxycholate and sodium dodecyl sulphate) and nonionic (triton X-100 and digitonin) surface-active substances. The most activating concentrations of these substances are determined and their similarity with those for Na+, K+-ATPase is marked. According to the character of the effect on the K+-phosphatase and Na+, K+-ATPase activities, the studied surface-active substances are grouped on the basis of the molecule configurations, rather than ionogenic factor. Their activating effect is supposed to result from an increase in the number of functioning catalytic centres rather than the molecular activity of the enzyme. It is shown that the digitonin high concentrations may completely inhibit the Na+, K+-ATPase activity and to some extent retain the K+-acetylphosphatase activity.


[Contents of catecholamines and corticosteroids in tissues of quinea pigs with C-hypovitaminosis]. On the 12-14th day of the scorbutigenic regime simultaneously with a decrease in the level of ascorbic acid in the guinea pig tissues to content of catecholamines and 11-oxycorticosteroids changes as well. The amount of adrenalin in the adrenal tissue drops, that of epinephrine in the brain tissue and liver rises. The content of glucocorticoids in adrenals and blood plasm increases. Against a background of vitamin C deficiency administration of ACTH does not cause any deviations in the level of catecholamines in tissues, of 11-oxycorticosteroids in the adrenals tissue and increase insignificantly the content of the latter in blood plasm.


[Effect of potassium orotate on metabolism in chickens under different provision with vitamin D3]. Vitamin D3 induction of the vitamin-D3-dependent proteins biosynthesis and certain indexes characterizing the rachitic state in animals were studied as affected by potassium orotate. Introduction of potassium orotate to the rachitogenic diet in combination with vitamin D3 is shown to normalize the processess of bone mineralization and to increase intensity of chicken growth. In duodenum mucosa with rachitis orotate normalizes the activity of alkaline phosphatase, raises the content of calcium-binding protein and stimulates the latter formation after administration of vitamin D3; orotate favours redistribution of the purine and pyrimidine nucleotides content. Radioactive orotic acid is subjected to intensive metabolism in mucosa and is converted to nucleotides of pool and RNA.


[Effect of several drugs and nonspecific substances on the uterine microflora of cows during the puerperal period and at the time of impregnation]. A total of fifty Bulgarian Brown cows were used to test the effect of some hormonal and therapeutic preparations in combination with unspecific agents, having an irritation effect on the reticuloendothelial system, to establish their action on the quantitative and qualitative changes in the microbial flora of the uterus and the impregnantion of cows after calving. It was found that treatment after normal calving with 200,000 IU vitestrol and 20 IV hypophysin, and after rejection of the placenta with 2 g chloramphenicol, 15 g ac. citricum or sodium citrate and 0.2 g pilocarpinum hydrochloricum, coupled with the injection of 30-40 cm3 Filatov's tissue emulsion 8n the 5th day lowered the microbial count in the uterus by to 30.12% from the 1st to the 5th day and by 6.46 to 12.78% from the 10th to the 20th day. Parallel drop was established in the number of microbial species by 42%. Besides, it was noted that the cases of retentio secundinarum among the test cows and the number of cows with acute endometritis after calving decreased by 12%, on an average, the service period became shorter by 12.04 days, and the rate of conception at first insemination rose by 12% as compared with the controls.


[Clinico-epizootologic studies in Gumboro disease]. The disease was established on a poultry dressing combine, affecting birds at the age of three to eleven weeks. It ran its course with clinical symptoms and epizootiology that were characteristic of it. A total of 8778 birds or 10% succumbed to the disease. Its notification on a newly built poultry dressing combine made it reasonable to believe that possibility existed of its transmission through the hatcheries. The outbreak occurred almost simultaneously with the inadequate feeding that was admitted on the combine. The cyclogramme concerning the admission of birds and its strict application were shown to influence the course of the epizootic process. Clinical and epizootiological investigations coupled with virological and histopathological studies rendered it possible to draw the conclusion that the birds on the combine were affected with infectious bursitis, identified as Gumboro disease. It was established for the first time in this country.


[Immune response of pigs to Aujeszky disease virus and swine influenza virus]. Explored was the possibility of simultaneous vaccination of pigs against the Aujeszky's disease virus and the swine influenza virus. Used were strain MK-25 against the former and strain 3sb against the latter. It was found that at the simultaneous subcutaneous or oral treatment with the two antigens equally effective immunity was built as in the case of vaccination with each one of them used alone. No antagonism was established between the two antigens during the time of immunity building in the body.


Chronic lathyrism and atheromatosis in the rat. Study of the V.L.D.L. and plasma and arterial wall lipids. Temporary chronic administration of Beta-amino-propionitrile (B.A.P.N.) produced morphological and biochemical changes of the aortic wall of rat as well as abnormalities of the plasma lipid levels. A hyperlipidic diet resulted in the blood plasma lipid abnormalities as B.A.P.N. intoxication. Nine weeks of B.A.P.N. followed by 42 weeks of a hyperlipidic diet increased the aortic cholesterol level and induced an atheroma. The diet alone produced only an endothelial lipid overload. The structure of arterial wall played the decisive role in atherogenesis.


Malignant fibrous histiocytoma of the renal capsule. Light and electron microscopic study of a rare tumor. This light microscopically pleomorphic tumor, which occurred in the renal capsule of 35-year-old female was diagnosed as a malignant fibrous histiocytoma. Ultrastructurally, the tumor showed two major components; fibroblast-like and histiocyte-like cells. This report stresses the rarity of such neoplasm in the kidney and also the usefulness of electron microscopy in establishing the diagnosis.


Primary oat-cell carcinoma of the larynx. A primary oat-cell carcinoma of the larynx in a 63-year-old man is reported. The oat-cell pattern appeared intermingled at one edge with a squamous carcinoma. The origin of this mixed tumour is considered together with the literature of extrapulmonary carcinomas having an oat-cell pattern.


An epidemiological review of Japanese encephalitis. Twenty-five years ago, Japanese encephalitis (JE) was known as an endemic, mosquito-borne disease in East Asia. Today, the causative virus is known to be distributed from maritime Siberia to the north, eastern India to the west, the Archipelago of Japan presumably the Philippines to the east, and from Indonesia to the south. Since the late-1960s, the geopathological status of JE epidemics has undergone considerable changes. The sizes of JE epidemics in Japan and China (Province of Taiwan) have steadily declined. In fact the JE virus itself appears to be disappearing from Japan. Long-term prediction of JE epidemics is more difficult for Korean Peninsula, nevertheless, reported JE morbidity rate in the Republic of Korea has remained at a relatively low level since 1969. In contrast to the trend in East Asia, new epidemic foci of JE have been emerging in the northern part of Tropical Eastern South Asia starting in 1969. Of particular importance are the continued high incidence (annual morbidity rate: 8.67-22.04/100 000) of reported JE in the northern part of Viet Nam between 1969 and 1974, and the high incidence (14.7/100 000) recorded in Chiang Mai Valley, Thailand, between 1969 and 1970. Apparently, the epidemic in Chiang Mai Valley spread to the neighbouring Shan State of Burma in 1974. Another JE epidemic broke out in West Bengal State, India in 1973. The occurrence of JE in the endemic zone south of these areas has remained sporadic. An increasing number of pathogens have been shown to cause signs and symptoms clinically indistinguishable from JE. In this review, the quality and international comparability of available JE statistics are also examined. Only a few countries and areas with reasonably developed statistical and laboratory services are able to provide national JE statistics in a form ready for epidemiological analysis. A practical surveillance system for JE needs to be organized in those countries where JE is a newly emerging health problem.


Tumor cell interactions in vitro microtubules, 100 angstrom filaments, and contractile microfilaments of tumor cells involved in "emperipolesis". An increase in the number of examples of emperiopolesis, i.e., cells within cells, was observed subsequently to addition of Bt2cAMP to spinner flask cultures of JB-1-E tumor cells. A conspicuous arrangement of microtubules and 100 angstrom filaments in the tumor cells involved in emperiopelesis was observed. Absence of emperipolesis in cultures treated with cytochalasin B indecates a possible role of the contractile microfilaments in the events leading to emperiopolesis. The significance of and the term emperipolesis are discussed.


Nephroblastoma and neuroblastoma--histology and prognosis. Statistically evaluating the influence of a histological grading, respectively of morphological differences on prognosis of nephroblastomas and neuroblastomas, better chances for survival become evident not only for earlier clinical stages, but also for nephroblastomas with high differentiation, or neuroblastomas with signs for differentiation. Only for neuroblastomas a relevant predeliction of tumors with signs of differentiation for the early clinical stage I is present. Combined subclassification according to clinical stages and histological grades results in 3 risk groups with different chances for survival. These 3 groups may play a role for specific therapeutic considerations.


Does lateral specialization apply to the frog's brain? An electron microscope observation. The ultrastructure of polymorphic crystal-like inclusions occurring in the cytoplasm of neurons of only the medial portion of the left habenula has been studied in the adult frog Rana esculenta and in the tadpole with the use of three types of fixatives: osmium tetroxide, a mixture of aldehydes and potassium permanganate.


[Benign multilocular cystic nephroma (author's transl)]. A case of benign multilocular cystic nephroma in a 12 month old male infant is reported. The patho-anatomical features of this rare renal lesion are demonstrated. Its possible histogenesis and relationship to nephroblastoma are discussed.


[Neurologic changes in systemic lupus erythematosus]. All the 200 observed cases of lupus erythematosus showed neurological changes. Among these patients in 17 cases lesions of the nervous system were the main manifestations. Certain neurological syndromes correlated with the degree of activity of the lupoid process. Prognostically unfavorable were developing strokes, convulsive syndromes, symptomatical psychoses, cerebral hypertensive syndrome, lesions of the spinal cord.