Dose-response curve of glutamate applied by superfusion to crayfish muscle synapses. Single muscle fibers were space clamped to a membrane potential of -75 to -80 mV, and the synaptic currents elicited by L-glutamate (gEPSCs) were recorded. The bathing solutions flowing across the fibers at high speed could be switched rapidly and repeatedly through valves actuated by solenoids. Glutamate solutions were applied for periods of 7 s or 1 s, and the responses to repeated applications were averaged. For glutamate concentrations of 10-50 mumol/l, applied for 7 s, the gEPSCs reached a steady state. In this concentration range the amplitude of the gEPSC rose steeply proportional to the power n=2.5 to n=6 (average of 12 experiments n=4.0) of the glutamate concentration. At higher concentrations, after rising for a few seconds the gEPSC was reduced by desensitization. At 500 mumol/l glutamate complete desensitization was reached with an approximate time constant of less than 1 s. The glutamate concentration that elicited a half maximum gEPSC was K=70 mumol/l. If glutamate was superfused only for 1 s, similar dose-response curves were observed. In these experiments n was between 4 and 6. The results obtained by superfusion agree quantitatively with those published for electrophoretic applications.


[Changes in plasma level of corticotropin after intravenous injection of metyrapone. Value of this test in pituitary pathology]. The Metyrapone was given, the morning, in perfusion intravenous of saline serum over 2 hours. A.C.T.H. levels were determined before and at 2, 4, 8 and 24 hours. Sixteen normal subjects adults served on controls with 1 g of Metyrapone. Sixteen other normal subjects with 2 g of Metyrapone are best responses. With this maximum dose 2 g were studied nine hypophysal adenomas with three low responses, three normal and three high responses; thirteen hypophysectomised subjects with very low peak value at 4 hours, and only two responses higher than the controls, five Cushing's syndromes with variable responses. The I.V. Metyrapone test seems to offer several advantages: it eliminates the questions about gastro-intestinal absorption of Metyrapone (oral) and the difficulties of urine collection. With the A.C.T.H. dosage on 4 hours, this is a rapid test able to put in combination other hypophysal tests.


[Thecal tumors of the ovary. 14 cases].

[Thecal tumors of the ovary. 14 cases]. Out of 524 tumours of the ovary seen over a 20 year period, the diagnosis was that of a thecal tumour in 14 cases. In addition to the symptoms common to all ovarian tumours, in 7 cases there was metrorrhagia, including 4 post-menopausal. Vaginal cytology after the menopause was abnormally young in 6 cases. In 7 cases out of 13 the endometrium was hyperplasic. In only 5 cases were urinary oestrogen levels increased. At operation, the tumour was bilateral in 3 cases and ascites was present in 4. Histological findings were as follows: 6 thecomas, 4 fibro-thecomas, 1 luteinised thecal tumour, 3 tumours with granular cells and 1 case associated with a Brenner tumour. Two of these "mixed tumours" were malignant, with a fatal outcome. All the others were cured by operation. In young women in whom conservative procedures were used there were 4 subsequent pregnancies. The following questions were posed: The coexistence of ascites with tumours totally free of secretory cells (3 cases); The existence in true thecal tumours of signs of hyperoestrogenism (5 out of 6) whilst fibro-thecomas are not associated with any abnormal production of oestrogen.


Hematologic and oncologic implications of alcoholism. Hematologic complications of alcoholism are common. Folic acid deficiency can lead to pancytopenia. Iron-deficiency anemia, various hemolytic states, and abnormalities in both function and number of platelets can occur. There is a great deal of interest in the adverse effects of alcohol on pyridoxine (vitamin B6) and folic acid metabolism. Malignant disease often complicates alcoholism and should always be suspected.


Facial nerve injury. A short review.

Facial nerve injury. A short review. Despite considerable advances in technique, experience and skill, the precise place of surgery in the treatment of facial nerve injury remains uncertain. The mechanism of delayed facial palsy is not yet clear, and there is still debate about the value of tests for early evidence of denervation. Recent literature has been reviewed.


Synthesis and some biological properties of 6-aminopenicillanic derivatives. The properties of 33 6-aminopenicillanic derivates were described, the majority of which and particularly all 3,4-disubstituted phenyl derivatives, are new compounds. These derivatives were synthesized by three different methods consisting in treating of 6-aminopenicillanic acid (6-APA) with appropriate phenylthio -- and phenoxyalkanecarboxylic acids. The method consisting in use of aryloxyketenes is new and claimed by the patent applications. All synthesized compounds were screened for their biological activity against 21 different strains of pathogenic microorganisms of species: Staphylococcus, Sarcina, Streptococcus, Escherichia, Proteus, Klebsiella, Neisseria, Pseudomonas, Bacillus subtilis and Candida albicans. In the present paper only the most interesting results of microbiological tests and some data concerning pharmacological investigations performed on rats, were presented. Among selected compounds both substances 30 and 32 showed animals weight growth stimulating activity.


The effect of apomorphine, amantadine and dimethylaminoadamantane on the level of cyclic AMP in the rat striatum. The content of cyclic AMP (cAMP) in the slices of rat striatum and cerebral cortex was tested after incubation with various concentrations (10(-6)--10(4) M) of dopamine (DA), apomorphine (APM), amantadine (AMD), and dimethylaminoadamatane (DMAD), and incubation with DA, AMD and DMAD in combination with KCl (43 mM) or haloperidol (HP) (10(-5) M). APM, AMD, and DMAD act synergistically with DA, elevate the c-AMP content in the striatum less than DA dose and do not affect the level c-AMP in the slices of cerebral cortex. KCl potentiated the action of DA, but inhibited that of APM, AMD, and DMAD. HP was most effective in blocking the action of DA, and blocked more weakly the action of APM AMD, DMAD, and the action of DA, APM, AMD, and DMAD in the presence of high concentration of KCl. The results indicate that APM, AMD, and DMAD, are less specific stimulants of central dopaminergic structures than DA, and that the increase of c-AMP content in the slices of rat striatum caused by APM, AMD, and DMAD is due to depolarizing action of these compounds.


Characterization of the 3' terminus of RNA isolated from vesicular stomatitis virus and from its defective interfering particles. The 3' termini of RNA from vesicular stomatitis virus and from three widely dissimilar defective interfering particles of the virus are PypGpU-OH. The possible relevance of these findings to autointerference and to replication of vesicular stomatitis virus is discussed.


Mapping of sequences with 2-fold symmetry on the simian virus 40 genome: a photochemical crosslinking approach. Sequences with 2-fold axes of symmetry have been detected and mapped on the simian virus 40 (SV40) genome by their ability to form hairpin turns in single-stranded SV40 DNA. Supercoiled SV40 DNA (SV40 I) was digested with restriction enzymes EcoRI and HpaII. The resulting linear DNA molecules with lengths of the complete SV40 genome were then denatured and photochemically reacted with 4,5',8-trimethylpsoralen (trioxsalen) at 16.0 +/- 0.5 degrees and different ionic strengths. Secondary structures on the single-stranded SV40 DNA were crosslinked and their positions analyzed by electron microscopy. There were no observable hairpin turns on the denatured SV40 DNA when it was photoreacted in 1 mM Tris-HCl/0.1 mM EDTA at pH 7.0. In 20 mM NaCl, one specific hairpin turn was detected at 0.17 +/- 0.02 map units on the map of EcoRI-digested SV40 DNA, where the 3' ends of early 19S mRNA, late 19S mRNA, and 16S mRNA of SV40 have been mapped. In 30 mM NaCl there are five more major hairpin turns besides the most stable one. The centers of four of these specific hairpin turns were mapped at 0.26 +/- 0.02, 0.68 +/- 0.03, 0.84 +/- 0.02, and 0.94 +/- 0.01 units on the map of EcoRI-digested SV40. The fifth one is at or near the unique EcoRI cleavage site on SV40 DNA. The possible functions of these sequences are discussed in terms of the nature of the promoter sites, the replication origin, the processing of RNA precursors, and regulation at the translational level.


Cellular uptake and nuclear binding of insulin in human cultured lymphocytes: evidence for potential intracellular sites of insulin action. Human cultured lymphocytes (IM-9) were used to demonstrate that insulin can enter the intact cell and bind to the nucleus. When these lymphocytes were incubated with 125I-labeled insulin, specific cellular uptake reached a maximum within 2 min and remained at a plateau for 90 min or longer. Partially purified nuclei from such cells contained approximately 15-20% of the total cellular radioactivity. Nuclei freed of all other cellular fractions (by washing the partially purified nucleic with Triton X-100) bound approximately 7% of the total cellular radioactivity. In contrast to the rapid uptake of labeled insulin into the intact cell, specific binding to the nucleus was half-maximal after 5 min of incubation and maximal after 90 min. Both the cellular uptake and subsequent nuclear binding of labeled insulin were progressively inhibited by increasing concentrations of unlabeled hormone. Independent evidence for the nuclear binding of insulin was obtained by preparing autoradiographs of lymphocytes incubated for various times with labeled insulin. Such preparations strongly suggest that insulin binds to the plasma membrane, enters the cytosol, and then binds to the nucleus.


Gene cloning for the isolation of enzymes of membrane lipid synthesis: phosphatidylserine synthase overproduction in Escherichia coli. We have screened a bank of 2000 E. coli strains carrying hybrid ColE1 plasmids [Clarke, L. & Carbon, J. (1976) Cell 9, 91-99] for those that correct the temperature sensitivity of a mutant in CDP-1,2-diacyl sn-glycerol:L-serine O-phosphatidyltransferase (EC 2.7.8.8, phosphatidylserine synthase). Two hybrid plasmids of this kind (pLC34-44 and pLC34-46) were identified and characterized. Strains carrying these plasmids overproduce the synthase by 6- to 15-fold, as demonstrated by assays of extracts and purification to homogeneity of the overproduced enzyme. The overproduced synthase, like the wild-type enzyme, is found associated predominately with the ribosomal fraction of crude cell extracts. Because the membrane phospholipid composition of these overproducers is not greatly altered, we suggest that the synthase is normally present in excess.


Partial reaction of peptide initiation inhibited by phosphorylation of either initiation factor eIF-2 or 40S ribosomal proteins. Preparations of the hemin-controlled repressor (HCR) from rabbit reticulocytes contain 3':5'-cyclic-AMP-independent protein kinase activity for the smallest subunit of the peptide initiation factor eIF-2 and for proteins of reticulocyte 40S ribosomal subunits. Binding of the ternary complex formed between Met-tRNAf, GTP, and eIF-2 to 40S ribosomal subunits is shown to be inhibited by phosphorylation of either the ribosomal subunits or eIF-2. The protein kinase activity responsible for phosphorylation of eIF-2 has been separated from the activity for phosphorylation of 40S ribosomal subunits and shown to independently block the same partial reaction of peptide initiation. It appears that different enzymes are involved, each capable of regulating peptide initiation at the same step but by a different mechanism.


Role of 3':5'-cyclic-AMP-dependent protein kinase in regulation of protein synthesis in reticulocyte lysates. The initiation inhibitor of reticulocyte lysates has been shown by others to be associated with a 3':5'-cyclic-AMP-independent protein kinase that catalyzes the phosphorylation of the small (38,000 daltons) subunit of the polypeptide chain initiation factor eIF-2. This factor forms a ternary complex with Met-tRNAi and GTP which, on interaction with a 40S ribosome, gives rise to a 40S complex. Ternary complex formation is inhibited by prior incubation of partially purified eIF-2 with reticulocyte inhibitor and ATP. The relation between phosphorylation and inactivation of eIF-2 is indicated by the lack of inhibition when ATP is omitted. Translation in hemin-containing reticulocyte lysates is also inhibited by cyclic-AMP-dependent protein kinases or their catalytic subunits. They act by converting proinhibitor (inactive eIF-2 kinase) present in lysates to inhibitor (active eIF-2 kinase). This reaction is analogous to the conversion of inactive phosphorylase kinase to active phosphorylase kinase.


Mechanism for acute control of fatty acid synthesis by glucagon and 3':5'-cyclic AMP in the liver cell. Labeling experiments with chicken liver cell monolayers and suspensions show that glucagon and N6, O2-dibutyryladenosine 3':5'-cyclic monophosphate (dibutyryl cyclic AMP) block fatty acid synthesis from acetate without appreciably affecting cholesterogenesis from acetate or acylglyceride synthesis from palmitate. Neither acetyl-CoA carboxylase [acetyl-CoA:carbon-dioxide ligase (ADP-forming), EC 6.4.1.2] activity assayed in the presence of citrate nor fatty acid synthetase activity is decreased in extracts of cells treated with glucagon. However, the cytoplasmic concentration of citrate, a required allosteric activator of acetyl-CoA carboxylase, is depressed more than 90% by glucagon or dibutyrl cyclic AMP. Pyruvate or lactate largely prevents the inhibitory action of these effectors on fatty acid synthesis by causing a large increase in cytoplasmic citrate level. Thus, it appears that glucagon, acting via cyclic AMP, inhibits fatty acid synthesis by blocking the formation of citrate, an essential activator of acetyl-CoA carboxylase.


Purified DNAs are transcribed after microinjection into Xenopus oocytes. The possibility of using DNA-injected Xenopus laevis oocytes and eggs for studying the control of transcription in eukaryotes has been investigated. When purified DNA of simian virus 40 (SV40) is injected into Xenopus laevis oocytes, tritiated RNA precursors are incorporated into DNase-I-resistant, RNase-A- and alkali-sensitive material that hybridizes specifically to SV40 DNA. This viral transcription continues for at least 5 days and occurs only when the injected DNA is directed to the nucleus of the oocyte. The quantity of SV40-specific RNA produced is roughly proportional to the amount of DNA injected; above 1 ng per oocyte, most of the nonribosomal RNA made in successfully injected oocytes is virus-specific. Transcription also occurs, although at a lower efficiency, after injection of the DNA into unfertilized eggs. The DNAs of adenovirus 5, cloned Drosophila melanogaster histone genes, and even bacteriophage phiX174 replicative form, bacteriophage phi80plac, and the ColE1 plasmid are also transcribed after injection into oocytes or eggs.


Synthesis and glycosylation in vitro of glycoprotein of vesicular stomatitis virus. Coupling of ribonucleoprotein particles from L cells infected with vesicular stomatitis virus to a pre-incubated ribosomal system obtained from uninfected HeLa cells allowed synthesis of two proteins. G1 (molecular weight 63,000) and G2 (molecular weight 67,000), and all other proteins of vesicular stomatitis virus except the spike protein G (molecular weight 69,000). Analyses of the tryptic peptides showed that G1, G2, and G had identical peptide sequences. The synthesis of G2 required the presence of membranes; only G1 was synthesized in the absence of any membranes. G2 but not G1 was shown to be a glycoprotein by affinity chromatography on a concanavalin A-Sepharose column. Removal of sialic acid residues from G by neuraminidase resulted in a product having an identical mobility to G2. Digestion of G2 or G with a mixture of neuraminidase (EC 3.2.1.18), beta-galactosidase (EC 3.2.1.23), and beta-N-acetylglucosaminidase (EC 3.2.1.30), however, produced a protein of molecular weight 65,000. These data suggest that G2 is the desialated G and is formed by glycosylation of G1, which is the unglycosylated polypeptide backbone of G.


Unified mechanism for relay and oscillation of cyclic AMP in Dictyostelium discoideum. A modified version of an allosteric model for adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] previously analyzed for sustained oscillations of adenosine 3':5'-cyclic monophosphate (cAMP) in Dictyostelium discoideum [Goldbeter, A. (1975) Nature 253, 540-542] is examined to see whether it can account for the relay of cAMP pulses. Oscillations occur around a nonequilibrium, unstable stationary state when system parameters are in a certain domain. It is found that relay can occur outside this domain, in a restricted set of parameter values for which the solution ultimately tends to a stable steady state. A suprathreshold level of extracellular cAMP is needed to elicit relay which consists in a pulsatory synthesis of intracellular cAMP. Theoretical predictions are compared with the results of experiments on cAMP relay and oscillation in aggregation-competent cells of D. discoideum. The model suggests an explanation for the emergence of aggregation centers and for a sequence of developmental events observed in interphase amoebae.


Electron spin resonance absorption of tissue constituents. The electron spin resonance spectra at g = 2 of the structural and soluble proteins of mouse liver have been investigated separately. The structural materials have signals an order of magnitude stronger. Radicals with important similarities to those occurring in natural tissue can be induced by treating casein with methylglyoxal or crotonaldehyde. The structural proteins of cancer give little or no signal. The color of the proteins and their electron spin resonance signal seem closely related.


Generation of macrophage migration inhibitory activity by plasminogen activators. Medium from cultures of simian virus 40-transformed mouse 3T3 cells (SV3T3) inhibits the migration in vitro of peritoneal exudate cells (macrophages) from guinea pigs while medium from untransformed 3T3 cultures does not [Hammond, M. E., Robbin, R. D., Dvorak, A. M., Selvaggio, S. S., Black, P. H. & Dvorak, H. F. (1974) Science 185, 955-957]. The present paper describes the generation of migration inhibitory factor (MIF)-like activity for peritoneal exudate cells from guinea pigs after incubation of a serum-free harvest fluid from SV3T3 cells with guinea pig serum. Inhibited macrophages lose a densely staining material from the cell surface coat compared with uninhibited guinea pig peritoneal exudate cells. The factor in SV3T3 harvest fluids which generates the migration inhibitory activity appears to be plasminogen activator, i.e., a serine protease, because (i) plasminogen activator activity and the factor which generates MIF-like activity copurify, and co-chromatograph on Sephadex G-200 columns, and (ii) plasminogen activator activity and capacity to generate MIF-like activity are simultaneously lost upon treatment with [3H]diisopropylfluorophosphate. In addition, a purified preparation of a known plasminogen activator, human urokinase, can also generate MIF-like activity upon reaction with guinea pig serum. Because transformation of 3T3 cells by SV40 increases their plasminogen activator secretion, enhanced secretion of plasminogen activator by SV3T3 cells may explain why formation of MIF-like activity is observed in SV3T3 but not 3T3 cultures. These results reveal a biochemical pathway whereby a product secreted by virus-transformed cells affects one function of a cell central to the host's immunological defense system.


Transfer of the gene for thymidine kinase to thymidine kinase-deficient human cells by purified herpes simplex viral DNA. Transformation of human cells from a thymidine kinase (ATP:thymidine 5'-phosphotransferase, EC 2.7.1.75)-negative to a thymidine kinase-positive phenotype has been achieved by using purified DNA from herpes simplex virus type 2. The specific activity of the DNA was in the range 0.5 to 2.0 transformants per microng and the efficiency of gene transfer was up to 1 transformant per 10(5) recipient cells. Several transformed lines able to grow continuously in medium selective for thymidine kinase-positive cells have been established. All of these lines express a thymidine kinase activity of viral origin but they differ from each other in the stability of enzyme expression. Subclones derived from a given transformed line inherited the degree of stability of the parental line.


Microinjection analysis of envelope-glycoprotein messenger activities of avian leukosis viral RNAs. Virion RNA from the avian leukosis virus Rous-associated virus 2 (RAV-2) and poly(A)-containing RNAs from RAV-2-infected chick embryo fibroblasts were microinjected into fibroblasts transformed by the Bryan high-titer strain of Rous sarcoma virus (RSV), which is deficient in viral envelope glycoprotein. Production of infectious RSV following these injections depended upon the viral envelope-messenger activity of the injected RNA. This system constituted a sensitive and rigorous assay system for viral envelope-messenger RNA. It was found that 21S mRNA from RAV-2-infected cells expressed the highest activity, while 35S mRNA expressed comparatively little. In addition, RAV-2-virion RNA expressed little messenger activity. The rate of formation of infectious RSV following 21S mRNA injections reached a peak near 9 hr, which was followed by a rapid decline. Evidence has been obtained that a small fraction of both 35S virion RNA and 35S mRNA from virus-infected cells was encapsulated into virus particles following their injection into virus-producing cells.


Quantitative determination of transformed cells in a mixed population by stimultaneous fluorescence analysis of cell surface and DNA an individual cells. Cell-surface labeling with fluorescamine indicates that the fluorescence of Balb 3T3 A31 cells in considerably decreased after both viral and chemical transformation. This phenomenon, coupled with the technique of flow microfluorometry, enabled nontransformed and transformed cells to be distinguished. A second fluroescent probe, propidium iodide, which intercalates into DNA, was used in combination with fluorescamine in order to obtain a ratio of cell-surface labeling to DNA content. This manipulation allowed enhanced resolution of two populations and the detection of small numbers of transformants in a predominantly normal population.


Mapping of inverted repeated DNA sequences within the genome of simian virus 40. Single-stranded, linear DNA of simian virus 40 (SV40) created by denaturing the endonuclease EcoRI- or Hpa II-generated, linear, double-stranded products from form I DNA of SV40 was analyzed for regions of inverted repeated sequences by visualization with the electron microscope. Six hairpin loops were found at positions 0.11-0.30 (two loops forming a "rabbit ears" structure), 0.47-0.52, 0.63-0.68, 0.70-0.76, and 0.90-0.96. The nucleotide sequences within all of these inverted repeats may be related since the looped regions can crosshybridize with one another and, thus, the SV40 genome may contain regions of interspersed repeated and unique sequences. The map positions of the 3' and 5' ends of the early and late messenger RNAs, as determined by others, lie within regions of inverted repeated sequences. Previously recorded recombination events that occurred either within the SV40 genome or between SV40 DNA and other genomes have apparently occurred frequently at positions of inverted repeated sequences within the SV40 DNA.


Immunoprevention of x-ray-induced leukemias in the C57BL mouse. An attempt to prevent irradiation-induced thymic lymphomas in C57BL mice was made by inducing active immunity to endogenous type-C virus with inactivated Rauscher murine leukemia virus (MuLV) or inactivated Gross MuLV or by transferring passive immunity to endogenous type-C virus with goat anti-Gross MuLV IgG. Control groups received the following immunogen or treatment: inactivated simian sarcoma virus, complete Freund's adjuvant, normal goat IgG, and diluent, in both irradiated and nonirradiated C57BL mice Active immunity to the 70,000 molecular weight glycoprotein AKR-gp70 by immunization with Rauscher MuLV and passive immunity to AKR-gp70 by passive transfer of goat anti-Gross-MuLV IgG was measurable throughout some of the latent period of tumor development; in these two groups a significant reduction in tumor incidence was observed, as compared to the other experimental and control groups. Thus, the present findings support the concept of a type-C virus etiology of irradiation-induced leukemias and demonstrate the applicability of immunologic techniques directed against the endogenous type-C virus in the prevention of this disease.


Application of imidazole as a selective inhibitor thromboxane synthetase in human platelets. Human platelet suspensions release a rabbit-aorta-contracting substance (previously identified as thromboxane A2) during aggregation produced by arachidonic acid, prostaglandin endoperoxide, thrombin, and collagen. Incubation of platelets with imidazole did not interfere with the aggregation produced by these agonists but markedly reduced the generation of the rabbit-aorta-contracting substance. We find that imidazole inhibited the conversion of exogenous or endogenous prostaglandin endoperoxide into thromboxane A2-Imidazole selectively inhibits thromboxane synthetase in intact human platelets, because this agent blocks the conversion of [14C]arachidonate into [14C]thromboxane B2 but does not inhibit the conversion of [14C]arachidonate into [14C]prostaglandin E2. The inhibition of thromboxane synthetase by imidazole is not the result of an alteration in platelet 3':5'-cyclic AMP levels. These results illustrate the utility of imidazole as a pharmacological tool and demonstrate the two unique and dissociable properties of the endoperoxides themselves--their ability to aggregate platelets and their enzymatic conversion to the potent vasoconstrictor thromboxane.


Relationship between serum sex hormones and glucose, insulin and lipid abnormalities in men with myocardial infarction. Fifteen patients who had had a myocardial infarction before the age of 43 were compared with thirteen age-matched normal subjects. Twelve of the patients and three of the controls had a delayed glucose and insulin peak in the glucose and insulin areas than normal curves. When the measurements of the four patients with the largest areas under the glucose tolerance curve were separated, significant correlations were observed in the remaining patients and controls. The ratio in serum of the concentrations of estradiol-17beta to testosterone (E/T) correlated with serum glucose area (r equals + 0.69, P is less than 0.001), insulin area (r equals + 0.80, P is less than 0.001), and the ratio of insulin area to glucose area (I/G) (r equals + 0.64, P is less than 0.005) in the glucose tolerance test. Serum cholesterol concentration correlated with E/T, insulin area, and I/G, and serum triglyceride concentration correlated with glucose area, I/G, and serum cholesterol concentration. The hypothesis is presented (i) that in men who have had a myocardial infarction, an abnormality in glucose tolerance and insulin response and elevation in serum cholesterol and triglyceride concentrations are all part of the same defect (glucose-insulin-lipid defect), (ii) that this glucose-insulin-lipid defect when glucose intolerance is present is the "mild diabetes" commonly associated with myocardial infarction but is based on a mechanism different from that of classical diabetes, (iii) that this glucose-insulin-lipid defect is secondary to an elevation in E/T, and (iv) that an alteration in the sex hormone milieu is the major predisposing factor for myocardial infarction.


Induction of deoxycytidine deaminase activity in mammalian cell lines by infection with herpes simplex virus type 1. Herpes simplex virus type 1 induces deoxycytidine deaminase (cytidine/deoxycytidine aminohydrolase, EC 3.5.4.5) activity when it lytically infects a number of mammalian cell lines. The deaminase activity is induced in a mouse cell line that is deficient in this enzyme. The induction of the enzyme in this mutant cell line does not occur in the presence of actinomycin D and the induced enzyme is more thermolabile than the enzyme of the wild-type mouse cell line. Furthermore, a new deoxycytidine deaminase species with a characteristic electrophoretic mobility that is different from that of the host cell enzyme is found in cell extracts prepared from a human cell line infected with herpesvirus. These results strongly suggest that the virus-induced deoxycytidine deaminase is coded by the viral genome. Because a deficiency in this enzyme is conditionally lethal for cells growing in a medium containing 5-methyldeoxycytidine as the sole source of thymidylate, this enzyme can be utilized as a selective marker for selecting mutant cells that have regained deoxycytidine deaminase activity as the result of infection by ultraviolet-inactivated herpes simplex virus.


Insulin and fetal growth.

Insulin and fetal growth. This review has examined the evidence from both clinical and experimental data that insulin has a key role in stimulating fetal growth. Human disorders where excessive insulin secretion and beta cell hyperplasia are present result in fetal overgrowth. Experimental models confirm an important anabolic effect of insulin in utero. Contrasted with this data is the evidence of intrauterine growth retardation occurring in association with insulinopenia or total absence of fetal insulin. Without the anabolic effect of insulin, no amount of substrate will induce optimal growth. It is evident from both the clinical and experimental data that sensitivity to insulin (probably individual receptor sites) develops in the latter stages of pregnancy. This point of sensitivity to the anabolic action of insulin has yet to be identified in a number of fetal tissues.


Bactericidal mechanisms of the granulocyte. Antimicrobial action of polymorphonuclear leukocytes depends on an array of substances carried in their cell membranes and cytoplasmic granules. These substances mediate killing in several systems. Some depend on molecular oxygen while others are independent of it. Some of the systems that depend on oxygen also require myeloperoxidase. The different systems seem able to act in primary or in reserve capacities backing each other up in times of stress or failure. Thus a deficiency in one system does not necessarily leave the polymorphs completely incapable of antimicrobial action although impairment may be severe as in chronic granulomatous disease. In general a poorly functioning polymorph is better than no polymorph at all.


Extent of mitogen receptor occupancy and modulation of mitogen receptor exposure: possible mechanisms for the regulation of cell growth. 125I-Insulin was used as a model mitogen to examine the relationships of mitogen receptor occupancy and exposure in controlling cell replication. Labeled hormone was bound to substratum-attached, confluent fibroblasts with two affinities, K1 approximately equal to 2 X 108 M-1 and K2 approximately equal to 0.8 X 107 M-1. Approximately 9,000 receptors per cell were calculated from a scatchboard plot analysis with 80% of them of the affinity type. Treatment of confluent fibroblasts with 1.0 to 10 microng/ml of trypsin for 10 min increasd the number of exposed K2 sites by a factor of 2 to 3. Culturing the fibroblasts in the absence of serum for 12 to 24 hr also increased the quantity of exposed K2 sites to 60,000 per cell. The addition of unlabeled insulin to untreated, trypsin-treated, or serum-starved fibroblasts resulted in a stimulation of 2-deoxyglucose transport and thymidine incorporation activity that was proportional to the observed level of 125I-insulin binding. The quantity of exposed insulin receptors on uninfected fibroblasts decreases as the cell culture density increases. Hormone binding to B77 virus-transformed fibroblasts also decreases with culture density but plateaus at a density of 6 X 105 cells/plate. This resulted in a 2- to 3-fold difference in the level of exposed receptors between the uninfected and virus-transformed cells in confluent cultures, and proportionally higher rates of sugar transport and thymidine incorporation activity. Trypsin treatment and 12 hr of growth in the absence of serum did not result in an increase in the level of recepto exposure in the virus-transformed cells. The results of this study suggest that the pleotypic events associated with the stimulation of cell replication as represented by sugar transport and DNA synthesis are dependent upon and proportional to mitogen receptor occupancy. The control of cell replication, however, appears to be linked by a presently unknown mechanism with the degree of exposure of mitogen recipotrs. Receptor concentration is high and is similar in rapidly growing uninfected and virus-transformed cells, but the subsequent decrease observed with an increase in culture density reaches an early plateau for the transformed cells. This difference in exposed receptors could provide the growth advantage that is the hallmark of transformed cells.


Further studies on the C5-derived chemotactic factor for tumor cells. A factor has been studied that is chemotactic in vitro for Walker carcinosarcoma and Novikoff hepatoma cells of rats and for murine mastocytoma cells, but not for neutrophils. This chemotactic factor is generated by the incubation of normal serum with a crude extract from tumor cells. The generation of the tumor cell chemotactic factor is time and temperature dependent and results in greater than 30% reduction of serum complement activity. The tumor cell chemotatic factor appears to be a small cleavage product of the fifth complement component (C5) which binds to serum globulin. This has been shown by the use of agammaglobulinemic serum. By the use of isolated C5 fragments there is direct evidence that the tumor cell chemotactic factor is structurally derived from a larger C5 leukotactic fragment. The study of tumor cell chemotaxis, particularly the involvement of the complement system in this phenomenon, may suggest a novel approach to the investigation of the mechanism of metastasis in the malignant process.


Initial evaluation and management of patients with suspected pituitary tumors. While pituitary tumors are not as rare as was once thought, it is difficult to assess how many are of clinical significance. Trans-sphenoidal pituitary exploration is a technique which can be performed with low operative morbidity and mortality, and when instituted early can prevent subsequent visual and endocrine impairment from an expanding lesion. Thus early recognition has increased importance.


Adenosine 3'5' cyclic monophosphate metabolism in patients with severe depressive illness. The daily excretion of adenosine 3'5' cyclic monophosphate (c-AMP) in a group of 19 patients with a severe depressive illness was found to be significantly decreased when compared with that from a group of euthymic patients being treated for other disorders in the same ward. The daily excretion of the depressed patients increased during the period of treatment and recovery from the illness. Treatment with a tricyclic antidepressant caused a greater increase than electroconvulsive treatment (ECT). There was no difference between the mean plasma c-AMP concentration of the depressed and euthymic groups. The mean CSF-c-AMP concentration was not different from the mean plasma c-AMP concentration in 12 patients with severe depression. There was no direct correlation between the CSF and plasma concentrations within patients. It was concluded that there may be a reversible disturbance in the renal metabolism of c-AMP in patients with severe depression.


[Statistical research on the lipides electrophoresis and on double pre-beta lipoprotein (author's transl)]. On 442 healthy subjects statistical research on cholesterol, triglycerides and lipoprotein electrophoresis on agarose was carried out. The results of statistical elaborations concerning average and standard deviation of the three lipoproteic bands (beta, pre-beta and alpha) are explained. 22 cases with double pre-beta lipoprotein (both normal and hyperlipoproteinaemic subjects) are described. The importance of this anomaly and its correlation with coronary atherosclerosis are pointed out.


Tissular cycli AMP levels after treatments with prostaglandins. In this study both prostaglandin A1 (PGA1) and prostaglandin F2alpha (PGF2alpha) have been shown to be effective long-lasting stimulators of the cyclic AMP (cAMP) synthesis in the liver, intestinal mucosa and brain, whereas prostaglandin E1 (PGE1) was found to have a similar effect on the cerebral cAMP synthesis and a dissimilar effect (decrease) on the hepatic one. A lack of sensitivity of the intestinal mucosa cAMP to PGE1 was also observed.


The postoperative myelogram. Radiographic evaluation of arachnoiditis and dural/arachnoidal tears. Either arachnoriditis or dural/arachnoidal tears may cause symptoms in the postoperative spinal patient. Surgery and myelography as causes of arachnoiditis are discussed. Intradural arachnoid cyst formation and intramedullary cavitation may present as unusual sequelae of arachnoiditis. Extra-dural cysts and cerebrospinal fluid fistulas resulting from dural/arachnoidal tears are unusual postoperative complications presenting striking myelographic features. Their mechanisms of formation, clinical significance, and radiographic features are discussed.


The role of the blood in metabolism of prostaglandin E1 in the cat lung. We found that when 15-keto-PGE1 was added to cat blood, it was converted to 13, 14-dihydro-15-keto-PGE1 (dihydro-keto-PGE1) by a NADH-dependent enzyme associated with some formed element(s) in the blood. When PGE1 was injected into the pulmonary artery of blood-perfused lungs, the only metabolite detectable in the pulmonary venous blood was the dihydro-keto-PGE1. However, when the lungs were perfused with an artificial perfusate containing no blood cells, a small amount of 15-keto-PGE1 was detected in the venous effluent. Therefore it would appear that a blood-borne delta13 reductase was partially responsible for the conversion of PGE1 to dihydro-keto-PGE1 on passage through blood-perfused cat lungs.


Inhibition of PGE1-stimulated cAMP accumulation in human platelets by thromboxane a2. The prostaglandin endoperoxide PGH2, HHT, HETE, thromboxane A2, and thromboxane B2, which are all products of arachidonic acid metabolism of human platelets, were tested for their ability to modulate platelet cyclic nucleotide levels. None of the compounds tested altered the basal level of cAMP or cGMP, and only PGH2 and thromboxane A2 inhibited PGE1-stimulated cAMP accumulation. Thromboxane A2 was found to be a more potent inhibitor of PGE1-stimulated cAMP accumulation and inducer of platelet aggregation than PGH2.


Free and conjugated dihydroxyphenylacetic acid: effect of alterations in impulse flow in rat neostriatum and frontal cortex. Stimulation of the nigro-neostriatal dopamine pathway results in an accumulation of both free and conjugated dihydroxy-phenylacetic acid (DOPAC) in the rat neostriatum. Drugs which have previously been shown to alter impulse flow in central dopaminergic neurons also produce predictable changes in the levels of both free and conjugated DOPAC in both the neostriatum and, in most cases, in the frontal cortex. Drugs such as the antipsychotics which increase impulse flow in the nigro-neostriatal dopamine neurons increase both free and conjugated DOPAC levels in both the neostriatum and frontal cortex. Drugs which reduce impulse flow, such as d-amphetamine and apomorphine, cause a reduction in free DOPAC in both the neostriatum and frontal cortex but reduce DOPAC conjugate only in the neostriatum. Pargyline, a monoamine oxidase inhibitor, causes an extensive depletion of free and conjugated DOPAC in both the striatum and frontal cortex, indicating that these metabolites are rapidly cleared from both of these brain areas.


[Study of 67Ga distribution in neoplasms and in liver by a cell fractionation method]. Subcellular distribution of 67Ga was quantitatively determined to evaluate the role of lysosome in accumulation of 67Ga in malignant tumor tissue and liver. The following animals and transplanted tumors were used: rats implanted with Yoshida sarcoma and hepatoma AH109A; mice implanted with Ehrlich tumor. 67Ga-citrate were injected to the rats intravenously and to the mice intraperitoneally. Ten minutes to 48 hours after the administration of 67Ga-citrate, the animal were sacrificed, and the tumor tissues and liver were excised. Subcellular fractionation of tumor tissues and livers were carried out according to the method of Hogeboom and Schneider. Radioactivity of each fraction was counted by a well type scintillation counter, and protein of each fraction was measured according to Lowry's method. In Yoshida sarcoma and Ehrlich tumor, most of the radioactivity was localized in the supernatant fraction, and small amount of radioactivity was localized in the mitochodrial fraction (lysosome contains in this fraction). But in the liver, most of the radioactivity was concentrated in the mitochondrial fraction and the radioactivity of this fraction was increased with the passage of time after administration. Twenty-four hours later, about 50% of total radioactivity was accumulated in this fraction. In the case of hepatoma AH109A, radioactivity of mitochondrial fraction was increased with the passage of time after administration, and about 30% of total activity was concentrated in this fraction at 24 hours after administration. From these results it is concluded that lysosome doses not play an important role in the tumor concentration of 67Ga and lysosome plays an important role in the liver concentration of 67Ga. In the case of hepatoma AH109A it is presumed that lysosome plays considerably important role in the tumor concentration of 67Ga, hepatoma AH109A having some nature of liver.


[Effect of the bilateral olfactory bulbs removal on the daily fluctuations on the plasmatic corticosterone levels (author's transl)]. The influence of the bilateral destruction of the olfactory bulbs on the circadian rhythm of plasmatic corticosterone in rat was investigated. Twentyfive days after bulbectomy, the values of corticosterone in the morning and in the evening were not significantly different. The possible involvement of the stria medularis, habenula, septum and preoptic area in the determination of this phenomenon is discussed.


Autonomic and cardiovascular effects of chronic delta9-tetrahydrocannabinol administration in mongrel dogs. Chronic administration of delta9-tetrahydrocannabinol (delta9-THC) 1mg/1kg, s.c., twice a day for 7 days failed to produce any major changes in the pulmonary or systemic hemodynamics and in the myocardial contractility of the mongrel dogs. Chronic delta9-THC treatment did not result in any significant alterations either in the transmission in the lumbar sympathetic chain or in the activity of autonomic receptors within the cardiovascular system. Further systemic pressor responses to bilateral carotid occlusion and reflexly mediated alterations in the perfused hindlimb vascular resistance were essentially identical in both the treated and placebo groups. Pressure-flow curves obtained from the perfused hindlimb preparations suggested that in contrast to the acute studies, neurogenic tone to the hindlimb vasculature was unaltered by chronic delta9-THC and intrinsic tone of the vascular smooth muscle was significantly depressed in the treated animals; in addition it appears that the tone due to circulating catecholamines was significantly enhanced in treated animals. The results of this investigation demonstrated that several acute cardiovascular and autonomic effects of delta9-THC may not be evident following chronic THC-treatment, however, prolonged use may demonstrate certain new pharmacological properties and/or mechanism of actions which cannot readily be seen in the acute studies.


Enhancement of the cardiac phosphorylase activating effect of dibutyryl cyclic AMP by thyroid hormone. The injection of dibutyryl cyclic AMP into the perfused rat heart resulted in dose-dependent increases in contractile force and phosphorylase a activity. In hearts from hyperthyroid animals both responses were markedly enhanced. The data indicate that the hyperthyroid state may produce changes in the heart making it more responsive to cyclic AMP. Such a change could occur at the level of protein kinase. The data may also indicate that, in hyperthyroidism, the heart is more capable of taking up dibutyryl cyclic AMP or of converting it to an active product.


Affinities of opiate agonists and antagonists for the enkephalin receptors of rat brain. The binding of 3H-enkephalin (methionine-enkephalin) to membranes of rat brain is inhibited by enkephalin and levorphanol with IC50 values of 5 and 1.6 nM, respectively. Dextrorphan, the optical isomer of levorphanol, is over 6,000 times less effective. Opiate agonists, morphine, dihydromorphine and l-methadone and opiate antagonists, naltrexone and naloxone are less effective inhibitors of 3H-enkephalin than in 3H-dihydromorphine and 3H-naloxone binding. However, opiates without the oxygen bridge as in the structure of morphine, such as levorphanol and the benzomorphans show affinities for the receptors of 3H-enkephalin equal or greater than their affinities for the receptors of 3H-opiates.


Composition of some urinary calculi of ruminants in Western Australia. Forty ruminant urinary calculi, selected as being essentially inorganic and mainly obtained from sheep grazing in the drier wheatbelt areas of Western Australia, were examined by optical and X-ray diffraction techniques. Four mineral types-silica (SiO2-nH2O), weddellite (CaC2O4-2H2O), calcite (CaCO3) and aragonite (CaCO3)--were found. These minerals were present respectively in 30, 17, 13 and 1 of the 40 calculi examined and were the sole component in 12, 0, 7, and 0 calculi. One calculus was found to be composed of organic material which was subsequently shown to consist mainly of 4'-O methyl equol (4'-methoxy-7-isoflavanol, C16H16O3) with a small amount of equol and a trace of formononetin. This is the first report of a calculus of this composition. Determinative data useful for identification of 4'o-methyl equol, equol and a related substance are presented in an appendix.


Immunoglobulins in the serum and nasal secretions of lambs following vaccination and aerosol challenge with parainfluenza 3 virus. Serial changes in the concentrations of IgM, IgG and IgA were compared in specific pathogen free (SPF) lambs which had been vaccinated with live or inactivated parainfluenza 3 virus (PI 3) by either intramuscular (IM) or intranasal (IN) routes followed by aerosol challenge with PI 3. In the serum, an increase in IgM was associated with the primary antibody response to the aerosol challenge, whereas increased IgG was associated with the secondary antibody response. No changes in immunoglobulin concentrations were observed in the nasal secretions of lambs administered live or inactivated virus IM or IN without adjuvant. Marked increases in IgG were found in the serum and nasal secretions of lambs vaccinated IM with inactivated virus in Freund's complete adjuvant (FCA) and fractionation by gel filtration confirmed that the antibody was associated with IgG in both these fluids.


The immunodepressive effect of infectious bursal agent on vaccination against Newcastle disease. Immunodepression due to an infectious bursal agent (IBA) infection depends on the age of the birds, the time of Newcastle disease (ND) vaccination and the IBA strain used. The immunodepressive effect of IBA on ND vaccination can be avoided by vaccinating the chicks against ND at day old or by using attenuated strains of IBA in all commercial vaccines.


[Contribution of superselective arteriography and embolization in maxillofacial surgery. Apropos of 2 cases]. After describing the technique of embolisation and its therapeutic indications,the authors present two cases of different indications:--embolisation as the sole treatment,--pre-operative embolisation of a haemorrhagec tumour. These two cases illustrate two applications of the technique of embolisation:--Medical therapeutic value: making possible the reduction or stabilisation of the size of a vascular tumour difficult to excise surgically, in addition to eliminating the complications (haemorrhage, local trophic disturbance, pain);--Surgical interest: elective lesional embolisation such as is carried out at present greatly facilitates the surgical procedure in operations which may be associated with severe bleeding. Problems of healing are avoided. The procedure is carried out at the same time as selective arteriography. When in the hands of a skilled team, scarcely any risk is involved.


[Psychosomatic insomnia].

[Psychosomatic insomnia]. In presenting a case of extreme hyposomnia, psychosomatic insomnia is elaborated as a special type of primary insomnia. The case study of a 60 years old man is based on psychiatric examinations, an intersive one-week observation including polygraphic sleep recordings, and on reviewing medical data over a period of 35 years. In this case, the insomnia developed during a life situation with social stress and continued over 30 years with a gradual sleep reduction to 2-4 hours. Our sleep recordings confirmed a total sleep time of nearly 3 hours, a marked rhythmicity of sleep and day-time activities, fragmentation of sleep, and psychogenic extrasystoles, all symptoms having been reported by the subject previously. Autonomic functions indicated a good efficiency of NREM sleep, whereas a first night effect with subsequent adaptation revealed a good regulatory function of the sleep-waking-system. In addition to a detailed documentation of this extraordinary case, an interpretation is undertaken in order to explain, how the insomnia developed and continued. Psychodynamic aspects show a set of characteristics which are most typical for psychosomatic syndroms. The authors expect, that the knowledge about psychosomatic insomnia will be helpful in diagnosis and treatment of severe insomnias.


[Uremic neuropathy. Study of the motor conduction rate in patients treated with maintenance hemodialysis and peritoneal dialysis]. Forty-four patients, treated with different systems of dialysis (peritoneal dialysis, two-weekly and three-weekly hemodialysis) have been controlled by electroneurographic, electromyographic and ematochimical examinations during a six months to five years period. The results can be summarized as follow: a) motor nerve conduction velocity of the peroneal nerve is reduced proportionally to the clinical status in all patients. Motor nerve conduction velocity of the ulnar nerve is reduced only in the most severe cases; b) there are no significant correlations between the examined ematochimical data and the maximal motor nerve conduction velocity; c) there is a slight improvement of the maximal motor nerve conduction velocity of the peroneal nerve when passing from a twelve hours two weekly dialytic treatment to a five hours three weekly hemodialytic treatment. Motor nerve conduction velocity is therefore a reliable index of insufficient or adequate dialysis. Moreover it is confirmed the efficacy of a treatment with short and frequent dialytic sessions.


[Early mobilization in the acute stage of myocardial infarction long term results]. A report is presented on the continuation of a controlled study on early mobilization after acute myocardial infarction performed at the Cantonal Hospital of Geneva. Detailed follow-up studies were made in the patients from the original study 4 years on average after the myocardial infarction. It is well known that early mobilization offers many advantages over prolonged bed rest. The present study demonstrates that early mobilization after acute myocardial infarction involves no longterm risks.


Problems in the diagnosis of Cushing's syndrome. The diagnosis of florid Cushing's syndrome is usually made without difficulty but diagnostic problems may arise. Five such cases are described. Difficulties may occur when the features of the syndrome are incomplete. Three such cases were encountered. In each only one clinical feature was present; these respectively were hypertension, osteoporosis and obesity. The diagnosis was confirmed, however, biochemically and eventually histologically and there was a good response to surgery in each case. Another diagnostic problem, both clinically and biochemically is the obese, hirsute, hypertensive female. Two such cases are described, in whom Cushing's syndrome was diagnosed clinically and biochemically but in whom there was no response to adrenalectomy. Retrospectively the validity of the original diagnosis is questioned. It is concluded that Cushing's syndrome may present in a very incomplete form and should be considered in the differential diagnosis, even if only one feature is present. It is stressed that obesity, hirsutism, hypertension and depression are commonly found in association with normal adrenal function. Urinary free cortisol and cortisol response to insulin induced hypoglycaemia may be of value in distinguishing these cases from those with endocrine disease.


Tumor cell collagenase and its inhibition by a cartilage-derived protease inhibitor. Human osteosarcoma and mammary carcinoma cells were cultured separately in a medium supplemented with fetal calf serum, until they were confluent. The medium was then replaced by serum-free medium supplemented with heparin. Both cell cultures secreted collagenase, and this activity was inhibited by a cartilage-derived protein of low molecular weight. Since cartilage is rarely invaded by neoplasms, the presence of this inhibitor may play an important role in the regulation of tumor invasion.


Studies on the mechanisms of abortion induction by Trichosanthin. Radix trichosanthis, an abortifacient drug of mid-gestation, is extracted from the root tuber of Trichosanthes kirilowii Maxim, Cucurbitaceae. Its purified effective principle is a basic protein of molecular weight of approximately 18,000 and is named trichosanthin. By authorization it has been proved to be very effective in abortion induction of mid-gestation, particularly effective in curing ectopic pregnancy, hydatidiform mole, and invasive mole, and it has also some therapeutic action on choriocarcinoma. From the analysis of the experimental results on its initial site of action, the morphological and functional injury of trophoblast cells of placenta and of cultures in vitro and the effect on prostaglandin synthesis, the following conclusions are drawn concerning the mechanisms of abortion induction by trichosanthin: (1) Trichosanthin exerts its action directly on the placental trophoblasts and possesses a certain degree of specificity; (2) It selectively causes the necrotic denaturation of the syncytiotrophoblasts of placental villi, which makes fragments of the disintegrated cells clumped in the blood sinus, hence the coagulation of blood and the circulation hindrance, and tissue necrosis over large areas follows. The necrosis of placental villi is the primary response, and circulation hindrance secondary; (3) Structural injuries have been reflected on the impairment of functional activities; the concentrations of HCG and steroid hormones fall rapidly below the threshold values of threatened abortion. Serious structural and functional injuries bring about destructive disturbances on the normal endocrine relationship between the mother and the fetus and on metabolic exchanges. It is further postulated that through certain unknown mechanism the synthesis of prostaglandins increases, uterine contraction is initiated and abortion ensues. In summary, trichosanthin, a plant protein discovered from Chinese medicinal herbs, is a drug effective in abortion induction and against trophoblastic neoplasms. Preliminary elucidation of the mechanisms of abortion induction by trichosanthin has afforded a basis for the clinical application with better efficacy and its possible abortifacient use in early pregnancy and for the discovery of newer cancer chemotherapeutic agents.


Human breast cancer: biologically active estrogen receptor in the absence of estrogen? The human breast cancer cell line MCF-7 does not require estrogen for growth, but paradoxically its growth is inhibited by antiestrogens. Our results show that, unlike normal target cells, MCF-7 cells carry most of their estrogen receptors in their nuclei even when these receptors are not charged with estrogens. The receptors for androgen and for progesterone, on the other hand, are localized in the cytoplasm as usual. Therefore, it is possible that the growth of these abnormal cells is stimulated by estrogen receptor in spite of the absence of the hormone and that the binding of antiestrogen molecules antagonize this stimulation.


Cyclic GMP accumulation causes degeneration of photoreceptor cells: simulation of an inherited disease. Guanosine 3',5'-monophosphate (cyclic GMP) metabolism in developing eye rudiments of Xenopus laevis embryos in culture is disrupted by the phosphodiesterase inhibitor isobutylmethylxanthine. At low concentrations of inhibitor the rudiments develop normally, but at higher concentrations of the inhibitor, cyclic GMP accumulates in the rudiments and the retinal photoreceptor cells degenerate selectively. The isobutylmethylxanthine-induced photoreceptor degeneration is associated with an accumulation of cyclic GMP and, in this respect, it stimulates an early biochemical defect in the inherited degenerative disease of rd mice.


Chlamydiae (with phages), mycoplasmas, and richettsiae in Chesapeake Bay bivalves. Intracytoplasmic chlamydia-like organisms, some with phages, rickettsia-like organisms, and mycoplasma-like organisms have been found in clams and oysters from the Chesapeake Bay area by electron microscopy. None of these organisms have been previously detected in mollusks, nor have phages been previously observed in Chlamydia sp.


Pontine reticular formation neurons: relationship of discharge to motor activity. The discharge correlates of pontine reticular formation units were investigated in unrestrained cats. In agreement with previous investigations using immobilized preparations, we found that these cells had high rates of activity in rapid eye movement sleep, and responded in waking to somatic, auditory, and vestibular stimuli at short latencies, many having polysensory responses and exhibiting rapid "habituation." However, despite the sensory responses of these cells, most unit activity could not be explained by the presence of sensory stimuli. Intense firing occurred in association with specific movements. Units deprived of their adequate somatic, vestibular, and auditory stimuli showed undiminished discharge rates during motor activity. Discrete sensory stimuli evoked sustained unit firing only when they also evoked a motor response. We conclude that activity in pontine reticular formation neurons is more closely related to motor output than to sensory input.


Drug tolerance in biomembranes: a spin label study of the effects of ethanol. Ethanol in vitro increased the fluidity of spin-labeled membranes from normal mice. Membranes from mice that had been subjected to long-term ethanol treatment were relatively resistant to this fluidizing effect. The data suggest that the membranes themselves had adapted to the drug, a novel form of drug tolerance.


Hormone-induced cyclic guanosine monophosphate secretion from guinea pig pancreatic lobules. Carbamylcholine (30 micronM) increased the concentration of guanosine 3',5'-monophosphate (cyclic GMP) in guinea pig pancreatic lobules about eight-to tenfold over the basal concentration in 30 seconds with a concomitant increase in the rate of amylase secretion. The concentration of cyclic GMP rapidly declined to a plateau value of about 16 percent of the peak level in 10 minutes. Cellular cyclic GMP decreased, mostly because the nucleotide was secreted into medium; cellular adenosine 3',5'-monophosphate (cyclic AMP), however did not change, nor was this nucleotide secreted into the medium. An immunocytochemical technique showed that cyclic GMP was distributed in the apical plasmalemma membrane and lumen of the pancreas. Carbamylcholine increased the cyclic GMP fluorescence in tha apical plasmalemma membrane within 30 seconds, and in zymogen granules and the plasma membrane in the apical part of acinar cells in 10 minutes. The islets of Langerhans did not show any change in cyclic GMP. Fluorescence of cyclic AMP in pancreatic lobules was not altered by carbamylcholine and was localized along the apical portion of plasmalemma and cytoplasm. Cyclic GMP  may thus participate either in the process of exocytosis or in the activation of enzymes secreted from the pancreas.


Cytochrome c: immunofluorescent localization of the testis-specific form. Mouse testes contain a unique form of cytochrome c. As demonstrated by the indirect immunofluorescence technique, the testis-specific cytochrome c is detectable in the primary spermatocyte and in cell types comprising the later stages of spermatogenesis. Interstitial cells, Sertoli cells, and spermatogonia contain the somatic form of cytochrome c, as does heart muscle.


Cerebrospinal fluid production: stimulation by cholera toxin. Large increases in the production of cerebrospinal fluid have been observed after the intraventricular administration of cholera toxin. Because cholera toxin stimulates adenylate cyclase, the data suggest that adenosine 3',5'-monophosphate plays a role in cerebrospinal fluid production.


Synapse formation between two clonal cell lines. Clonal neuroblastoma x glioma hybrid cells frequently formed synapses with clonal mouse striated muscle cells. Clonal myotubes were similar to cultured mouse embryo myotubes with respect to acetylcholine sensitivity and other membrane properties examined. However, acetylcholine sensitivity measurements indicate that acetylcholine receptors of clonal myotubes are distributed more uniformly over the cell surface than the receptors of cultured mouse embryo myotubes.


Gating of neuronal transmission in the hippocampus: efficacy of transmission varies with behavioral state. Electrical stimuli were applied to the angular bundle of the freely moving rat, and the neuronal responses were recorded ipsilaterally in the dentate gyrus and the CA1 field of the hippocampus. The number of neurons responding monosynaptically in the dentate gyrus was relatively small when the animal was alert and not moving but was much greater both during slow-wave sleep and during rapid eye movement sleep. In Ca1, however, the trisynaptic population response was considerably smaller during rapid eye movement sleep and when the animal was alert than during slow-wave sleep. These findings are interpreted in terms of a set of behaviorally dependent "neural gates". Measurement of the synaptic current at the dentate gyrus induced monosynaptically by stimulation of the angular bundle further suggests that the mechanism by which gating occurs at this level is either a tonic inhibitory synaptic influence exerted upon the granule cells during the alert state, a tonic excitatory influence during slow-wave sleep, or both.


The complementary role of computerized axial transmission tomography and radionuclide imaging of the brain. Computerized axial transmission tomography and radionuclide imaging are complementary procedures, and the following recommendations are made as to their use. Where there is no real clinical suspicion of intracranial disease, either modality can be used for "rule out" screening; the choice can frequently be made on the basis of which modality is cheaper or more quickly available. It should be remembered that "quicker" is often "cheaper". Total cost is determined, not only by the cost of the procedure, but also the per diem costs incurred in waiting for that procedure. Thus the more expensive modality may, in effect, be cheaper if delays are shorter. Screening of the elderly patient, particularly when atrophy or communicating hydrocephalus is of clinical concern, should be by the CT method because of its ability to visualize cerebrospinal fluid spaces. When clinical signs and symptoms point to intracranial abnormality, both modalities should be utilized. If either study done first is normal, use of the other modality is mandatory. When the first study is positive with pathognomonic findings for a specific disease, which totally explains the patient's neurologic problems, the second study need not be employed. Such examples might include the fresh cerebral hemorrhage demonstrated by CT imaging, the AV malformation defined by dynamic-static radionuclide imaging, or multifocal metastatic lesions defined by either. However, when the clinical picture is not totally and satisfactorily explained by the demonstrated disease, the other modality should also be employed. Under many circumstances, neither study will be so reliable, specific, and free of false-negative or false-positive findings as to warrant ignoring the additional information potentially available from the other study.


Computerized cranial tomography and radionuclide imaging in the detection of intracranial mass lesions. Computerized cranial tomography (CCT) and radionuclide imaging (RI) of the brain are both accurate techniques for detecting intracranial mass lesions. CCT is superior in detecting low-grade gliomas, cystic lesions, parasellar tumors, and brain stem lesions. Overall, CCT detection rates are slightly higher than those with RI, but the use of iodinated contrast media with CCT increases the risk of this examination. There is a significant difference in the generally binary (positive/negative) type of information offered by RI and the more specific information offered by CCT about the pathologic nature of a lesion and its precise location. In the evaluation of patients with suspected intracranial mass lesions, CCT is generally the preferable initial diagnostic test. However, RI may still serve as a satisfactory screening examination in certain well-defined clinical situations.


Hyperkalemia due to selective hypoaldosteronism. Hyperkalemia secondary to hyporeninemic hypoaldosteronism with a normal glucocorticoid function was diagnosed in a 47-year-old man with moderate renal insufficiency. Mineralocorticoid administration corrected the hyperkalemia. A probable explanation for hyporeninemia and hypoaldosteronism in this syndrome is that the primary defect is an inability to release renin and the resultant angiotensin deficiency leads to an aldosterone deficiency.


Current chemotherapy of schistosomiasis japonica in the Philippines. For the past several decades, the drug being used for the treatment of schistosomiasis in the Philippines has been Stibophen. It is administered intramuscularly at a dose of 1 ml per 10 kg body weight with a maximum of 5 ml every other day after 2 initial daily smaller sensitivity doses at a total dose of 45 to 70 ml fof adult patients. In recent years, a number of drugs for the treatment of schistosomiasis have been developed. These were evaluated clinically either in the hospital or in field trials in Leyte. Unfortunately, none of these were found to be suitable for mass treatment on account of toxicity to prolonged course of treatment. In view of the pressing need for a safe and effective schistosomicidal agent, the search for a better drug is imperative.


Drug trial of Schistosoma japonicum enfection in Indonesia. A limited drug trial was carried out on 42 cases with schistosomiasis japonica from an endemic area of Central Sulawesi. The drugs used were niridazole and stibophen. The effects of treatment were reported and discussed. The results of this study offer promise for treating S. japonicum infection in Central Sulawesi on a larger scale.


Comparison of some methods for the detection of antigen-antibody reactions in amoebiasis. The indirect hemagglutination test (IHA) and counterimmuno-electrophoresis (CIE) were used to test for antibodies to Entamoeba histolytica in human sera using antigens from axenic cultures of the HK9 strain. Correlation between the test was excellent with most sera from patients with amoebiasis demonstrating precipitin lines by CIE at IHA titers considered diagnostically positive, larger than or equal to 1:128. Precipitin reactions with positive sera were also compared by CIE, immunoelectrophoresis (IEP) and two-dimensional electrophoresis is (2D-IEP). The greatest number of antigen-antibody components were demonstrated by 2D-IEP. Further studies utilizing 2D-IEP should be of value in the antigenic analysis of E. histolytica.


Future geriatric needs in South Africa. Hospital and teaching aspects. Noteworthy factors in geriatric care, derived from experience in a geriatric clinic, are that symptoms are often wrongly attributed to the ageing process; the aged are often overtreated and subjected to unnecessary diagnostic procedures; and functional abilities of the elderly and social factors are important in planning comprehensive care for the aged. To render total care the services of a visiting sister attached to the clinic are an absolute necessity. The elderly are often prematurely discharged from hospital. The combination of multiple pathology, functional derangement and social factors necessitates a period of aftercare which entails physiotherapy, occupational therapy and the services of a social worker. Medical students, nurses, students in social work, psysiotherapists, and occupational therapists should be enlightened on gerontology and geriatrics during their undergraduate years.


Feto-maternal amino acid patterns and cyclic AMP in the human placenta with abnormal pregnancies, particularly with SFD. To clarify the causes of SFD from the view-point of placental function, investigations were made on feto-maternal amino acid circumstances and on how cyclic AMP behaves in the placenta, particularly in relation to the transport of amino acid across the placenta. Amino acids were measured by gas liquid chromatography (hydrogen-flame ion detector), c-AMP by the binding protein method, adenyl cyclase activity by Krishna's method, and proteins by Lowry's method. Results show: (1) The levels of maternal amino acids were indistinctive between the SFD group and the normal pregnancy group. (2) The feto-maternal ratio of amino acid concentrations (f/m ratio) was lower in the SFD group than in the normal control. (3) The level of c-AMP in the placenta was lower in the SFD group than in the control. (4) The lower level of placenta c-AMP in the SFD placenta seems partly attributable to the decreased adenyl cyclase activity. (5) There was a positive correlation (gamma=0.61) between the content of c-AMP in the placenta and the f/m ratio of amino acid concentrations. These findings suggest a decline in placental active transport of acids in SFD; adenyl cyclase and c-AMP in the placenta presumably play a key role in such course.


Biochemical differences between human malignant and benign insulinoma tissues. Five cases of malignant insulinoma and 2 cases of benign insulinoma were studied lipid-chemically. Tissues were collected by surgical operation or biopsy under peritoneoscopy. The total lipid was extracted from each tissue, and one part of each total lipid was separated into phospholipid, triglyceride and other lipid fractions by a thin-layer chromatography (TLC) on silica gel. The fatty acid composition and fatty acid content of each lipid fraction were measured by a gas-liquid chromatography (GLC). The most remarkable difference between malignant and benign isulinoma tissues was a higher percentage value of eicosatrienoic acid in the phospholipid of malignant insulinoma tissues when compared with that of non-malignant insulinoma tissues; the values mentioned above distributed between 9.82 and 3.32 in 5 malignant cases, but were 2.89 and 2.57 in 2 benign cases. Those changes in the phospholipid fatty acid composition of malignant insulinoma tissues may represent one of the mechanisms of malignant growth in the malignant neoplastic tissue.


Plasmodium chabaudi-infection of mice: specific activities of erythrocyte membrane-associated enzymes and patterns of proteins and glycoproteins of erythrocyte membrane preparations. Membrane preparations of erythrocytes from normal and P. chabaudi-infected mice and membrane preparations of P. chabaudi-infected and uninfected erythrocytes from infected mice and separated by zonal centrifugation were characterized by the pattern of proteins and extracted glycoproteins obtained by SDS-polyacrylamide gel electrophoresis and by the specific activities of membrane associated enzymes. The protein pattern of the membrane preparation of infected erythrocytes showed similar differences from membrane preparations of normal erythrocytes as those described by Weidekamm et al. for P. berghei. The pattern of glycoproteins extracted by the chloroform-methanol method showed characteristic differences as compared to the controls. A new band (PASi) with a molecular weight of about 165,000 corresponds with the protein band IIa. In membrane preparations of normal erythrocytes and of nonparasitized erythrocytes separated from parasitized erythrocytes by zonal centrifugation was no difference in specific activities of ATPase, adenylate kinase and acetylcholinesterase. Adenylate kinase activity was markedly increased and acetyl-cholinesterase activity was slightly increased in membrane preparations of infected cells. Specific activities of ATPase of membrane preparations of normal and parasitized erythrocytes did not show significant differences. There was a decrease in enzyme activity of ATPase and an increase of acetylcholinesterase in Triton X 100 containing samples. Specific activities of an acid phosphatase were lower in membrane preparations of parasitized cells than in the controls.


Apolipoprotein B (apoB) retention in atherosclerotic intracranial arteries. Low (LDL) and very low (VLDL) density lipoproteins retained in grossly normal and atherosclerotic human intracranial arteries have been quantitated using an electro-immunoassay directed against apolipoprotein B (apoB), the major protein of these two lipoprotein fractions. Buffer-homogenates of grossly normal arteries contained apoB amounts ranging from less than 0.04 to 1.58 microng/mg tissue dry weight, while those of atherosclerotic plaques gave values ranging from 0.80 to 3.9 microng per mg tissue dry weight. These results were consistent with immunofluorescence studies localizing apoB in these arteries. Plaques also contained a remaining fraction of tightly-bound apoB as evidenced by positive immunofluorescence in sections of pellets from buffer homogenates. This was in contrast to the negative results from grossly normal arteries. These results would suggest that retention of apoB by intracranial arteries correlates positively with vessel lesions. Arterial apoB is present in both grossly normal regions and plaques in a loosely-bound form, possibly representing intact lipoprotein. ApoB is also present in a tightly-bound form in plaques.


Dibutyryl cyclic adenosine monophosphate effects in the ischemic-hypoxic cat. The effects of dibutyryl cyclic adenosine monophosphate (dB-cAMP) were studied in fifty cats, twenty anesthetized with pentobarbital and thirty with halothane. Nasopharyngeal temperature and Paco2 were maintained at normal values. Somatosensory evoked response was monitored and used as an indicator of cerebral cortical function. Ischemic hypoxic injury was produced by an orthopedic tourniquet snugly applied around the animal's neck and inflated for a period of fifteen minutes. This method produces a reliable and reproducible injury. Times for recovery of the evoked response to 10% of control value, as well as immediate and long-term animal survival, were noted. The dBcAMP was administered at the end of the hypoxic insult. Treated animals recovered the evoked response earlier than the untreated controls and had better immediate and long-term survival rates.


Helium pressure alteration of function in squid giant synapse. The squid giant synapse, which permits intracellular electrical measurements in a single, excitatory synapse, was exposed to helium pressures up to 204 atm. By stimulating presynaptically and recording postsynaptically with an intracellular electrode it was found that pressure alters, but does not prevent, synaptic transmission of action potentials. Synaptically transmitted action potentials are prolonged in the same way as in the directly stimulated axon. However, slowing of the excitatory postsynaptic potential and marked increases in synaptic fatigue were observed at pressures as low as 35 atm. These changes may contribute to high pressure nervous effects by interfering with information transfer within the nervous system.


Herpes simplex virus nuclear nonvirion antigens detected by anticomplement immunofluorescence. The finding of a nuclear antigen by anticomplement immunofluorescence in cells treated with cytosine-arabinoside after infection of Herpes Simplex Virus (HSV), opens a new approach to the problem of the role of this virus in certain human cancers. Complement-fixing tests of HSV markers with cancer and control human sera as well as with hyperimmune guinea pig antisera are discussed, suggesting another parameter for studies of squamous cell carcinomas. The finding of HSV antigens in selected tumors as the expression of repressed viral genome proves a continuing release of virus specific message and supports the important role of the virus in the development of the tumor.


Herpes simplex virus tumor-associated antigens in cancer patients. Data are reported on the HSV nonstructural antigens detected in GPK and RK cells after infection with the same strain of virus. Both the HSV types 1 and 2 NV antigens consist of more than one component for which the immunized guinea pigs produce distinct antibodies. It was possible to separate by PAGE, HSV-induced markers not only from cells undergoing lytic infection by the virus but also from viable cells from squamous cell carcinoma of the head and neck and the urogenital tract. These fractions were tested with sera from cancer patients, and the percentages of their CF reactivity are reported. The specificity of the antibody to the antigen from the cancer cells was less high than that of the antibody to the antigen from HSV-infected cells. It is suggested that the use of these PAGE separate antigens would eliminate the need for removal of the virion antibody from the cancer sera prior to testing them for the NV-specific antibody.


[Obtaining pig pulmonary macrophages for the cultivation of swine cytomegaloviruses]. A method of obtaining and cultivating pig pulmonary macrophages (PPM) is described and documented. The results obtained with its use in the cultivation of pig cytomegalovirus of the ADRI-1 reference strain are shown. In PPM cell cultures, the virus was demonstrated cytologically cytologically and by electron microscopy. After 18 passages on cell cultures, the virus, applied intranasally, infectious to colostrum.


Allergy in cattle after foot-and-mouth disease vaccination. BHK cell derivatives, saponin and aluminium hydroxide, all of which are commonly present in foot-and-mouth disease vaccines, were injected subcutaneously into 10 cattle and the serum levels of anti-BHK reagins and passive haemagglutinating antibodies were followed. The reaginic antibodies rose to a peak titre one to two weeks after the stimuli and waned during the third week. They had a serum half life of about three days, assuming exponential decay, and were generally undetectable four weeks after last contact with antigen. Passive haemagglutinins were slower to develop and two or more stimuli were usually required to produce detectable antibody levels. They were also slower to subside and were demonstrable for at least 10 weeks after last contact with antigen in most cases. Clinical reactions provoked by the intradermal injection of lysate into sensitised cattle were not correlated with the serum reagin or passive haemagglutinin levels or their ratio to one another at time of the reactions. The reasons for this are discussed.


[Effect of chemical modifiers on the antigen-binding capacity of antibodies]. The effect was followed up of the chemical modifications "carbamylation" and "benzylation" on the antigen-fixing activity of the foot-and-mouth disease immunoglobulins G and M. The chemical agents used - potassium cyanate and 2-hydroxi-5-nitrobenzylbromide--modified a considerable number of side lysine chains and tryptophane radicals, however, had no effect on the precipitation activity of the foot-and-mouth disease antibodies IgG and IgM manifested with the respective antigens. The lowered ability of the modified (to a higher degree) antibodies to form precipitations with the homologous virus was due to secondary reactions between the two components of the system, the functional groups of the active center remaining intact. The higher affinity of the IgM antibody to the homologous antigen was due to its polyvalent capacity (as compared to the bivalent immunoglobulin G).


[Study of foot-and-mouth disease virus inhibitors in cell cultures and experimental animals]. Studied was the inhibiting action of some synthetic agents conditionally denoted No. 3 (benzamidazol), No. 76, and No. 78 (imidazolins) on the reproduction of the foot-and-mouth disease virus in cell cultures, newborn mice and guinea pigs. It was irrefutably demonstrated that all three agents produce an inhibiting effect on the virus. This effect was enhanced by the combined use of these inhibitors. It was found that best effect on the virus' replication produced the combination of agent No. 3 and some of the other two inhibitors. Discussed is the mechanism of action of these compounds.


[Effect of somatotropic hormone on certain indices related to carbohydrate and fat metabolism in sheep]. Investigated was the effect of the somatotropic hormone (STH) at doses of 0.3 mg/kg and 1 mg/kg liveweight on the amount of insulin, glucose, and free fatty acids (FFA) in the serum up to the 12th hour following treatment. The activity of glucose-6-phosphatase and the amount of glycogen were studied in tissue samples taken through biopsy of the liver at the 2nd, 4th, 6th, and 8th hour after treatment with STH. The content of blood sugar decreased, and that of insulin increased in the course of one hour following treatment. The values shown by FFA first dropped (at the end of the 1st hour), and then rose by the 6th hour after treatment. The amount of glycogen and the activity of glucose-6-phosphatase increased at the 6th hour following treatment with STH. The variations shown by the investigated indices depend on the size of the STH doses.


[Action of actidione on the multiplication of Aujeszky's disease virus]. Studied was the effect of actidione on the propagation of the Aujeszky's disease virus (strains 2,7,10--virulent,, and strain MK--avirulent virus mutant). It was found that at a concentration of 2 microng/cm3 actidione discontinues the reproduction of the most virulent strain 2 when the antibiotic was added immediately after the adsorption of the virus on the cells. The decrease in the virulence of the virus strain was associated with the decrease in the concentration of the antibiotic needed for the inhibition of its propagation. Thus, the reproduction of the more slightly virulent strain 10 was fully inhibited at actidione concentration of 0.75 microng/cm3, while that of the avirulent strain MK was discontinued at 0.4 microng/cm3. The preliminary cultivation of the cells with 1 microng/cm3 actidione for 24 hours and the adsorption of the virus on the cells jointly with actidione showed no effect on the vitality of the virus particles.


[Demonstration and type determination of Clostridium perfringens isolated from meat semipreserves]. Investigated were a total of 92 samples of pasteurized cans of different batches. Six strains of Clostridium perfringens were isolated from a sample of pasteurized ham. To demonstrate a toxin and present its type differentiation a strain was investigated with the use of dermonecrotic test after Williams along with the cross toxin neutralization after the internationally accepted method, and the neutralization of the lecithinase activity after Williams. The use of native toxins at the type differentiation of slightly toxigenic strains of Clostridium perfringens isolated from food products proved inappropriate. The production of dry toxin and the application of cross toxinneutralization proved to be most suitable in the typing of such strains. The type differentiation carried out as described above showed that the studied strain belonged to type A.


[Study of the immunity in swine vaccinated with type C anti-foot-and-mouth disease vaccine]. Experiments were carried out to adapt a cell culture strain of the foot-and-mouth disease virus, type C, to the organism of susceptible pigs. It was established that 4 to 5 passages are needed to adapt the virus, all treated animals showing the symptoms of the disease from the 24 hour following infection which assumed a generalized course. In determining the index of protection (P) of a given F.M.D. vaccine through challenging immunized pigs its value proves to be 4.5. It is stressed that this is a suitable and economic method to evaluate the immunogenic properties of F.M.D. vaccines for pigs.


[Participation of Aujeszky's disease virus in the respiratory diseases of swine]. Clinical, virologic and seroligic investigations on vaccinated and unvaccinated pigs fattened on two farms with a record of a stationary Aujeszky's disease infection were carried out. Aujeszky's virus was isolated from the lungs of all pigs and partially of other viscera of some of the animals. The serologic studies revealed the dynamics of the antibody titer reise which spoke of the development of an infectious process. The clinical signs observed along with the morphologic changes characteristic of pneumonia, coupled with the advancement of the Aujeszky's disease infection demonstrated that on stationary fattening pig farms Aujeszky's disease assumed the course of a respiratory affection. The discripancy between the results obtained with vaccinated and unvaccinated animals, which were negligible on one of the farms and considerable on the other, was due to variations in the intensity of the infection as well as to the level of passive immunity.


[Ultrastructure of liver damage in chronic vinyl chloride intoxication (author's transl)]. Liver biopsies taken from 15 workers at a PVC-producing factory were examined by electron microscopy. The hepatocytes showed focal hydropic swelling, disseminated toxic steatosis, peculiar para-crystalline inclusions in enlarged mitochondria, focal cytoplasmic degradations, and occasional single cell necroses. These regressive changes were more prominent in cases with a shorter interval of non-exposure prior to the biopsy. Further, a focal compensatory hyperplasia of the smooth endoplasmatic reticulum was found. With increase of the non-exposure time interval, a regression of the degree of steatosis as well as an age-independent excessive lipofuscin deposition was seen in the hepatocytes. Apparently, these are sequelae of increased autophagia of lipids and increased lipid oxidation by the vinylchloride. In the sinusoids, activation, enlargement and proliferation of Kupffer cells was noted. The tendency of these cells to proliferate is apparently caused by the cancerogenic stimulation by vinylchloride. The prominent hyperplasia of lipocytes is probably connected with the deposition of collagen and the peculiar perisinusoidal fibrosis.


[Iron containing nuclear inclusions in human pigmentary cirrhosis (author's transl)]. In human pigmentary cirrhosis nuclear (pseudo-)inclusions of cytoplasmic material, containing less or more degenerated and therefore faintly stained hemosiderin granules, are to be observed. But sometimes there are also finely fibrillar or granular proteinaceous materials, stainable by the Prussian-blue reaction, lying between the chromatin-strands or occupying the whole nucleus and displacing the chromatin to the nuclear envelope (margination of chromatin). Such uncoloured substances may condense into homogeneous masses and nearly hexagonal (0r related) crystals with a diameter up to 14 micron and a yellow-brownish colour, giving a strongly positive PERL's reaction. In contrast to the preceding stages intranuclear crystals of this kind have been observed in one case only. After destruction of the nuclear envelope and the marginated chromatin the crystals are lying free in the cytoplasm and later on, the cytoplasm being destroyed too, they may be ingested by von Kupffer cells. All the iron containing crystals, to be found in the cytoplasm, derive from former intranuclear inclusions. The intranuclear deposits of iron containing protein are interpreted as ferritin-aggregates. It is supposed that ferritin molecules, built up in the cytoplasm, do enter the nucleus via the pores of the nuclear envelope. Such an event not only signalizes a cytopathologic reaction but in turn may give rise to such additional cytopathologic lesions as cell shrinking and cell death.


The endocrine cells of the pancreas and related tumours. Ultrastructural study and classification. Up to seven endocrine cell types have been identified ultrastructurally in the pancreas, including glucagon A cells, insulin B cells, somatostatin D cells, pancreatic peptide F cells and 5-hydroxytryptamine EC cells. In addition, D1 cells, which have been proposed as the cell type producing VIP and possible P cells of unknown function are seen. Various patterns of endocrine cell differentiation have been found in 20 endocrine pancreatic tumours. Well and poorly differentiated B cells have been identified in 6 insulinomas, diagnostic G cells in 3 out of 7 gastrinomas, D1 and/or F cells in 7 diarrheogenic tumours. Moreover, cells apparently unrelated to the prevalent clinical syndrome have been noted in 8 of the 20 tumours. Granular non diagnostic cells (poorly diagnostic gastrin cells? D1 cells?) were particularly frequent in gastrinomas; agranular or poorly granular cells, either by "active" or "Stem cell" type, were present in nearly all tumours, particularly in diarrheogenic tumours, gastrinomas and malignant insulinomas. A cytological classification of pancreatic endocrine tumours is proposed.


Effects of galactoflavin-induced riboflavin deficiency upon rat hepatic cell ultrastructure. The primary cytoplasmic effect of galactoflavin-induced riboflavin deficiency upon rat liver cells involved focal sites of degradation which were manifested by the formation of membranous whorls. The nuclear effect of riboflavin deficiency concerned fluctuations in the total number of perichromatin granules per nucleus. These granules increased in number during the deficiency reaching a peak at three weeks. Nucleoli appeared compact with no evidence for segregation of nucleolar components. The possible correlation between increased synthesis of perichromatin granules and altered protein synthesis is discussed.


Complementation between temperature-sensitive (ts) and host range nontransforming (hr-t) mutants of polyoma virus. Two major classes of polyoma mutants are defective in cell transformation: early temperature-sensitive mutants of the tsA type which are defective in viral DNA synthesis and transformation at 39 degrees, but not at 32 degrees; and host range nontransforming (hr-t) mutants which fail to transform at either temperature. Mixed infection of mouse 3T3 cells by hr-t mutants and early tsA-type mutants results in enhanced growth of the tsA-type mutants at 39 degrees, indicating that the hr-t mutants can supply the early viral function required for viral DNA synthesis. The hr-t mutants also complement late is mutants which fail to produce infectious progeny at 39 degrees because of alterations in the 45,000-dalton major virion protein. Mixed infection of hamster BHK or rat Y1 cells by hr-t and tsA-type mutants results in efficient transformation at 39 degrees, indicating that the two classes of mutants can complement for transformation. No complementation is observed in pair-wise crosses among the early tsA-type mutants alone. The tsA-type mutants are located in the distal portion of the early region of the polyoma genome [Miller, L. K., and Fried, M. (1976) J. Virol. 18, 824-832]. The hr-t mutants are located in the proximal portion [Feunteun, J., Sompayrac, L., Fluck, M., and Benjamin, T. (1976) Proc. Nat. Acad. Sci. USA]. These results suggest that the early region of the polyoma genome is divided into two functional regions which can complement for transformation. The ts3 mutant of polyoma is located in the proximal portion of the late region.


[Presence of iron in the composition of prolyl hydroxylase]. Binding of iron with the molecule of prolyl hydroxylase was studied using 59Fe. The label was administered into one-day-old rats and within 36 hours the enzyme was isolated from skin. After the final step of purification (DEAE cellulose) 59Fe was not found in fractions of prolyl hydroxylase. The purity of the enzyme preparations was controlled by polyacrylamide gel disc electrophoresis. The data obtained suggest that Fe ions are not inherent in the enzyme molecule.


[Hypoxia and tissue permeability for non-electrolytes]. The activity of cytochrome oxidase in tissues was decreased in short-term adaptation to reduce pO2 and administration of KCN in small doses. In the former case the activities of peroxidase and catalase were increased in blood. These effects as well as administration of Na2ATP into rats led to an increase in water content in tissues, to soption of acidic vital stain (phenol red) and to decrease in the ether-soluble fraction of lipids. The alterations were accompanied by decreased permeability of cells to n-hexane (estimation by gas-liquid chromatography). The decrease in cell permeability for nonelectrolytes was apparently due to conformational alterations in protein molecule of cytoplasmic membranes.


[Possible significance of hexokinase binding to mitochondrial membranes]. A magnitude of the Pasteur's effect and content of bound hexokinase were studied in various malignant and normal tissues. In all cases studied these two values were practically the same. Dynamics of changes in subcellular localization of hexokinase and the Pasteur's effect were similarly altered in liver tissue during ontogenesis. Binding hexokinase with mitochondrial membranes was assumed to be the cytophysiological mechanism for regulation of glycolytic activity by respiration.


[Activity and stability of NAD.H-oxidase, succinate oxidase and cytochrome oxidase of rat liver and pancreatic mitochondria in chronic allergic colitis]. A comparative study of thermostability of NADH-, succinate- and cytochrome oxidases was carried out in liver mitochondria and pancreas of rats in normal state and in chronic allergic colitis. In the pathology degradative alterations occurred in mitochondria, which were manifested as a decrease in the stability of mitochondrial mutinzyme systems of tissues studies. The results suggested occurrence of latent impairments in structure of mitochondria.


[Effect of carboxycathepsin on biological activity of bradykinin]. An effect of carboxycathepsin (peptidyl-dipeptidase EC 3.4.15.1) from bovine kidney on bradikinine was studied. The bradikinine activity was determined by monitoring the rat uterine horn retraction. Carboxycathepsin caused rapid inactivation of bradikinine (440-500 mcg of bradikinine/mg/min). The rate of bradikinine inactivation depended on the incubation time, content of the enzyme and substrate in the samples. In presence of EDTA carboxycathepsin did not inactivate bradikinine.


[Hexokinase activity in blood serum during carcinogenesis]. During carcinogenesis, induced by diethylnitrosamine in rats Wistar (in doses of 2.5 mg per Kg of weight daily with drinking water), the hexokinase (HK) activity in blood serum was observed with the appearance of the first morphological symptoms of tumor growth. It is observed mainly starting from the first months. At the end of the experimental period (8-9th month), when hepatomas develop in the liver, the HK activity in blood serum was noted almost in all cases. No serum HK activity was found in control rats.


[Molecular aspects of the action of insulin]. Molecular aspects of the insulin action in an organism are discussed. The following mechanisms of the hormone effect are considered: induction of the synthesis of glycolytic enzymes in cell-targets under effect of insulin; mechanisms of the insulin reception in cell-enzymes in cell-targets; the possible role of cyclic nucleotides as mediators in the effect of insulin in cell targets.


[Role of cyclic adenosine-3',5'-monophosphate in the regulation of histidase in the skin in the process of ontogeny]. In rat skin the histidase activity was observed 2--3 days before delivery; it was increased at the first days of postnatal development, achieving a maximal level at the 5th day and then it was decreased (within 2--3 weeks of postnatal development) to the level activity, which was found in adult animals. Concentration of urocaninic acid in skin correlated with the histidase activity. Content of urocaninic acid in skin and the histidase activity were altered under effect of administration of cylic-3',5'-AMP, dibutyryl cyclic-3',5'-AMP, glucagon, sodium fluoride, theophylline, actinomycin D and cycloheximide.


[Growth and the cellular transformation of undifferentiated nephroblastoma in tissue culture]. Cultivated undifferentiated malignant nephroblastoma would produce fibroblastoid zones of growth. The tumor cells differed from normal renal fibroblasts by an abundance of mitochondria; cell boundaries were not distinguished. No differentiations in tumor cells cultures absent in the primary material were noted.