Mapping of transcription sites of simian virus 40-specific late 16S and 19S mRNA by electron microscopy. Simian virus 40 (SV40) late 19S and 16S mRNAs were annealed to complementary regions of partially melted viral double-stranded SV40(LHpa II) DNA or SV40(LBam HI) DNA. The RNA-DNA hybrid regions within the DNA molecules were visualized as loops [with SV40(LBam HI) DNA] in the electron microscope. The data confirm the previous localizations of the 3' and 5' ends of 16S SV40 mRNA and of the 3' end of late 19S SV40 mRNA. The 5' end of the major stable SV40 late 19S mRNA has been positioned at 0.755 map unit. Thus, the sequences of viral DNA from 0.655 to 0.755 map unit, including the replication origin, are not converted into major stable species of late viral mRNA.


Bovine papilloma virus: presence of virus-specific DNA sequences in naturally occurring equine tumors. Four of five spontaneous benign equine connective tissue tumors of unknown etiology and a bovine papilloma virus (BPV)-induced equine tumor contained BPV-specific DNA sequences as determined by DNA-DNA hybridization of DNA from tumors with BPV DNA labeled in vitro. Analysis of the kinetics of reassociation indicated that 20-75% of the BPV genome was present in the various tumors. The number of partial BPV genome equivalents ranged from 60 to 500 copies per diploid quantity of cellular DNA. Thermal denaturation profiles of duplexes formed between labeled BPV DNA and DNA from tumor cells indicated two tumors contained viral DNA with base sequences identical to BPV DNA. Three tumors (including DNA from the BPV-induced tumor) contained BPV-related DNA sequences that were less thermally stable. The decrease in thermal denaturation temperature may be due to the presence of (adenine + thymine)-rich regions of the BPV genome in the tumor cells.


Specific changes in the pattern of protein synthesis during meiotic maturation of mammalian oocytes in vitro. High resolution two-dimensional electrophoresis has been used to examine the pattern of protein synthesis during meiotic maturation of mouse oocytes in vitro. Fluorograms of [35S]methionine-labeled oocyte proteins have revealed that meiotic progression from dictyate to metaphase II (meiotic maturation) is accompanied by marked changes in the pattern of proteins synthesized by oocytes. Virtually all of the changes observed take place subsequent to the breakdown of the oocyte's germinal vesicle, but are not dependent upon the occurrence of other morphological events, such as spindle formation or polar body emission. These changes in protein synthesis do not take place in oocytes that fail to undergo breakdown of germinal vesicles spontaneously or in oocytes arrested at the germinal vesicle stage by dibutyryl 3':5'-cyclic AMP. These data suggest that mixing of the oocyte's nucleoplasm and cytoplasm may trigger many of the changes in protein synthesis that accompany meiotic maturation of mouse oocytes in vitro.


Surface localization of sites of reduction of nitroxide spin-labeled molecules in mitochondria. The relative rates of reduction of several spin-labeled molecules that partition differently across the hy-drophobic-interface of inner membranes from rat liver mitochondria were investigated. Spin labels localized either deep in the hydrophobic region or in the aqueous phase are only slowly reduced; however a spin-labeled analogue of the cationic detergent cetyltrimethylammonium bromide that partitions at the interface is rapidly reduced by coupled electron transport. Chemical studies on the reduction and oxidation of the spin label show that loss of signal is due to reduction and not destruction of the label. No evidence was found for flip-flop of the label in submitochondrial preparations. Spin reduction of respiring mitochondria, mitoplasts, or inverted submitochondrial preparations is inhibited by rotenone but is relatively insensitive to antimycin A and KCN. Because the midpoint potentials of the spin labels were found to be similar to that of ubiquinone, it is concluded that reducing equivalents of mitochondrial electron transport from this region of the chain are channeled to either membrane interface.


Gonadotropin-induced regulation of luteinizing hormone receptors and desensitization of testicular 3':5'-cyclic AMP and testosterone responses. Administration of human chorionic gonadotropin (hCG) to male rats was followed by dose-related changes in luteinizing hormone (LH) receptors in the testis. After treatment with a low dose of hCG (10international units), the number of LH receptors increased slightly over the first 24 hr, then fell to about 30% of the control value. These changes occurred with occupancy of only 8% of the available receptors, and were initially accompanied by increased basal testosterone production in vitro with no change in basal 3'5'-cyclic AMP production. During stimulation with hCG in vitro, such testes showed a transient decrease in cyclic AMP response on the first day after gonadotropin treatment and no change in testosterone response. By contrast, a 20-fold higher dose of hCG caused more rapid and complete loss of LH receptors, with major and transient occupancy of receptors at 24 hr and marked elevations of basal cyclic AMP and testosterone production in vitro. The initial occupancy of receptors was accompanied by a rapid fall in the cyclic AMP response to hCG in vitro, and was followed by marked receptor loss and inhibition of the cyclic AMP response for up to 5 days. The testosterone response to hCG in vitro was completely inhibited for about 3 days, then rose to the control level at 5 days, when only a small proportion of the original receptor sites and cyclic AMP response had begun to return. Such complete recovery of the steroidogenic response when only a fraction of the receptor population had returned was consistent with the presence of receptor reserve or "spare" receptors in the testis. These studies have demonstrated that negative regulation of LH receptors by exogenous gonadotropin is accompanied by consequent changes in cyclic AMP and testosterone responses to hCG in vitro. Hormone induced desensitization of interstitial cell responses was initially related to occupancy of LH receptors and later to a protracted loss of receptor sites.


Binding and internalization of thrombin by normal and transformed chick cells. Thrombin stimulates cell proliferation in cultures of normal chick embryo fibroblasts but not in cells transformed with Rous sarcoma virus. Analysis of medium conditioned by Rous-sarcoma-virus-transformed cultures demonstrates that these cells do not secrete molecules that can inhibit or inactivate thrombin. The interaction of thrombin with these cells was investigated with enzymatically active 125I-thrombin. The amount of cell-associated 125I-thrombin was found to be three times greater with normal cells than with transformed cells. In both types of cell, greater than 50% of the total cell-associated 125I-thrombin was found as a component that was not dissociated from the cells by trypsin treatment, an observation suggesting that a significant portion was not on the cell surface. The amount of the trypsin-insensitive fraction increases with time up to 12 hr, whereas the trypsin-sensitive fraction is saturated after 1-4 hr. Autoradiography of thin sections of 125I-thrombin-treated cells observed by electron microscopy reveals that after 10 hr incubation greater than 70% of the label is localized in the cytoplasm of both normal and transformed cells. Autoradiograms of sodium dodecyl sulfate/polyacrylamide slab gels demonstrate that 40% of the intracellular label is the size of native thrombin with the remainder in two large fragments of 22,000 and 19,500 daltons.


The number of receptors for beta-melanocyte stimulating hormone in Cloudman melanoma cells is increased by dibutyryl adenosine 3':5'-cyclic monophosphate or cholera toxin. Cultured Cloudman melanoma cells exposed either to dibutyryl 3':5'-cyclic AMP and theophylline or to cholera toxin bind significantly more 125I-labeled beta-melanocyte stimulating hormone (MSH) and fluorescein-labeled MSH than untreated cells. MSH binds to melanoma cells in the G2 phase of the cell cycle. The stimulation of MSH binding by dibutyryl cyclic AMP results from an increase in the number of MSH receptors per G2 cell and, to a lesser extent, from an increase in the number of G2 cells. The affinity of the receptors for MSH is not influenced by dibutyryl cyclic AMP.


A transplantable insulinoma in the rat.

A transplantable insulinoma in the rat. A transplantable insulinoma was developed in inbred albino rats of the NEDH strain. The original tumor, 1 cm in diameter, was removed from the pancreas of a male parabiont 566 days folowing 1000 rads (10J/kg) of total body x-irradiation. The time required for implanted fragments to grow to 0.5-1.5 cm in diameter decreased from 5-8 months in the first generation to 2-5 months in the seventh generation. Successful transplantation in male animals followed for 4 or more months after transplantation was significantly greater than in female animals followed for a similar period of time (96% versus 69%). Light and electron microscopy revealed that the tumors consisted predominantly of well-granulated beta cells. Ultrastructural studies also showed small numbers of D-cells. Tumor extracts contained an average of 223 units of immunoreactive insulin and 25.9 mug of immunoreactive somato-statin per gram wet weight of tissue. Tumors generally produced increasingly profound hypoglycemia within 2-4 months following transplantation, with plasma glucose levels frequently falling to 40 mg/100 ml or lower prior to death. Removal of tumors from chronically hypoglycemic animals resulted in transient rebound hyperglycemia with plasma glucose levels above 300mg/100 ml within the first 24 hr and a gradual decline to normal levels of 129 mg/100ml in 2-4 days. These observations correlated with findings of marked atropy and degranulation of the beta cells in the pancreata of tumor-bearing animals, and with gradual return of normal light microscopic morphology following tumor removal.


Presence of corticotropin in brain of normal and hypophysectomized rats. Immunoreactive and bioreactive corticotropin (ACTH-like) activities have been detected in the median eminence and remaining medial basal hypothalamus of both normal and hypophysectomized adult male rats: bioreactive ACTH (pg/100 mug of protein) 1028 in median eminence and 1289 in medial basal hypothalamus; immunoreactive ACTH (midportion ACTH antibody), 1554 in median eminence and 1887 in medial basal hypothalamus. By use of appropriate antibodies and bioassay, it was demonstrated that immunoreactivity was not due solely to alpha-melanotropin, which has previously been reported to be present in the brain of hypophysectomized animals. The Sephadex G-50 gel filtration patterns determined by immunoassay of column eluates obtained from hypothalamic extracts of normal or hypophysectomized animals were similar but were not identical to the pattern derived from whole pituitary. Immunoreactive (midportion ACTH antibody) ACTH concentrations (pg/100 mug of protein) of other central nervous system areas in normal animals were: cerebellum 34.3, cortex 46.3, thalamus 23.8, and hippocampus 116.3. The total amount of bioreactive ACTH present in the median eminence and medial basal hypothalamus is approximately 1% of that present in the pituitary. The present data suggest that such ACTH may have a diencephalic rather than pituitary origin and raise the question of the functional significance of such ACTH.


Dissociation of increases in levels of 3':5'-cyclic AMP and 3':5'-cyclic GMP from induction of ornithine decarboxylase by the tumor promoter 12-O-tetradecanoyl phorbol-13-acetate in mouse epidermis in vivo. A single application of 17 nmol of 12-O-tetradecanoyl phorbol-13-acetate (TPA) to mouse skin caused a marked (200- to 400-fold) induction of ornithine decarboxylase (EC 4.1.1.17, L-ornithine carboxy-lyase) activity in mouse epidermal and epidermal-dermal preparations. No change in the basal level of 3':5'-cyclic AMP occurred in epidermal-dermal preparations within 30 min of TPA application. Intraperitoneal injection of the beta-agonist isoproterenol resulted in a dose-dependent accumulation of 3':5'-cyclic AMP occurred in epidermal-dermal preparations within 30 min of TPA application. Intraperitoneal injection of the beta-agonist isoproterenol resulted in a dose-dependent accumulation of 3':5'-cyclic AMP 10 min after injection, but caused no induction of ornithine decarboxylase. When isoproterenol was injected 10 min prior to an application of either 1.7 or 17 nmol of TPA, the magnitude of the ornithine decarboxylase induction was the same as induction with TPA alone. Topical application of 17 nmol of TPA caused no increase in the level of 3':5'-cyclic GMP present in the mouse epidermal-dermal preparations 2-20 min after application. Intraperitoneal injection of 1.75 mumol of dibutyryl 3':5'-cyclic GMP and/or butyryl derivatives of cyclic GMP caused a 6-fold increase in the level of cyclic GMP and/or butyryl derivatives of cyclic GMP in epidermal-dermal preparations within 5 min of injection, and the level remained elevated for at least 20-30 min. This dose of dibutyryl 3':5'-cyclic GMP was incapable of inducing ornithine decarboxylase. Injection of dibutyryl 3':5'-cyclic GMP 5 min before application of 1.7 nmol of TPA or 30 min before application of 17 nmol of TPA did not alter the magnitude of the ornithine decarboxylase induction produced by TPA alone. These results suggest that early increases in the total intracellular levels of either 3':5'-cyclic AMP or 3':5'-cyclic GMP are not part of the mechanism by which TPA induces ornithine decarboxylase in the epidermis.


Role of surface modulating assemblies in growth control of normal and transformed fibroblasts. Cellular microtubules, microfilaments, and surface receptors have been postulated to form a surface modulating assembly that regulates surface receptor mobility and cell growth. To test this hypothesis, we examined three agents known to affect cell growth [colchicine, concanavalin A (Con A), and the src gene product of Rous sarcoma virus] for their effects on chick embryo fibroblasts. Individual cells from serum-starved normal fibroblast populations became committed to enter S phase at various times over a 12 hr period after exposure to serum. Colchicine and other microtubule-disrupting agents blocked entry into S phase at a point close to the commitment point for each cell. The lectin Con A also blocked entry into the S phase when present in doses sufficient to modulate surface receptor mobility. In contrast, succinyl-Con A, which does not induce surface modulation, had no effect. Both Con A and colchicine blocked the appearance of cytoplasmic factors capable of stimulating DNA replication in a cell-free system. To study endogenous effects on the surface modulating assembly, we infected fibroblasts with a Rous sarcoma virus (tsNY68) having a temperature-sensitive mutation in the transforming (src) gene. We have previously shown that microtubular and microfilamentous structures of the surface modulating assembly are direct or indirect targets of the src gene product with consequent reduction in the capacity of Con A to induce surface modulation. TsNY68-infected fibroblasts shifted to the non-permissive temperature acquired normal microtubular morphology more rapidly (2 hr) than cells grown at the permissive temperature in the presence of protein synthesis inhibitors (7.5 hr). This suggests that the src gene product acts directly on the surface modulating assembly rather than via the nucleus or at the level of protein synthesis. Furthermore, "transformation" of the surface modulating assembly was partly blocked by treatment of the infected cells with Con A but not succinyl-Con A. Both Con A and colchicine inhibited entry into the S phase following a shift from nonpermissive to permissive growth conditions. All of these observations are in accord with the hypothesis that the surface modulating assembly acts as a signal regulator in growth control.


Mutagenesis in S49 mouse lymphoma cells: induction of resistance to ouabain, 6-thioguanine, and dibutyryl cyclic AMP. The effects of mutagens on three genetic markers--resistance to ouabain, 6-thioguanine, and dibutyryl cyclic AMP (Bt2cAMP), were investigated in a mouse lymphoma cell line, S49. Nitrosoguanidine, ethyl methanesulfonate, ICR 191, and x-rays were used. Mutagen-specific responses were seen. Ouabain resistance was induced by nitrosoguanidine, but not by ICR 191. ICR 191 induced resistance to 6-thioguanine more efficiently than did nitrosoguanidine; the converse was true of resistance to Bt2cAMP. The relative frequency of biochemically distinguishable subtypes of mutants resistant to Bt2cAMP was characteristic of the mutagen used to generate them. The results can be interpreted as follows: nitrosoguanidine and ethyl methanesulfonate frequently, but ICR 191 and x-rays rarely, give rise to DNA base sequence changes that result in structurally altered but functional proteins. This type of change is required for induction of mutants resistant to ouabain and of certain classes of mutants resistant to Bt2cAMP. Resistance to 6-thioguanine and other classes of mutants resistant to Bt2cAMP can result from DNA base sequence changes that lead to extensive alteration of protein structure or expression; these changes are induced by ICR 191 or x-rays.


Host-determined differences in expression of surface marker characteristics on human and simian lymphoblastoid cell lines transformed by Epstein-Barr virus. In an attempt to account for differences in the biologic behavior of Epstein-Barr virus in different primate species, we studied lymphocyte surface markers on primary and transformed cells. Among primary leukocytes, the distribution of cells with characteristics of bone-marrow-derived cells (B cells) was similar in humans, wooly monkeys, and cotton-top marmosets. However, after transformation by Epstein-Barr virus, cells from each species were characterically different. Transformed human umbilical cord cells expressed the complement receptor; monkey cells exhibited both this receptor and the receptor for IgG Fc (EA7S); and marmoset cells did not have either surface marker. We measured the transformation efficiency of human and marmoset leukocyte subpopulations enriched or depeleted in cells with the complement receptor. In both species the highest efficiencies of transformation were found in populations with the greatest numbers of cells with the receptor. The data therefore suggest that, in all species, a cell with the complement receptor is susceptible to transformation but that this receptor is not expressed on transformed marmoset cells. Thus, in Epstein-Barr virus-induced transformation it is necessary to distinguish between transformation of growth properties (immortalization) and transformation of cell surface properties.


Reduction of collagen biosynthesis in blood vessels and other tissues by reserpine and hypophysectomy. Synthesis of collagen in the vasculature and other tissues of normotensive rats is markedly reduced by reserpine. Hypophysectomy produces similar effects. The effects of reserpine on collagen biosynthesis may be mediated through the hypothalamus.


A new class of murine leukemia virus associated with development of spontaneous lymphomas. A new type of murine leukemia virus has been detected in thymuses of leukemic and late preleukemic AKR mice, in lymphomas developing in NIH Swiss mice carrying the AKR ectopic virus-inducing loci Akv-I or Akv-2, and in the thymus of a preleukemic C58 mouse. The viruses induce focal areas of morphologic alteration in a mink lung cell line and are tentatively referred to as "mink cell focus-inducing" (MCF) strains. They have the host range of both xenotropic and N-tropic ecotropic murine leukemia viruses, are neutralized by antisera to both ecotropic and xenotropic viruses, and are interfered with by both viruses. They may represent a particular type of genetic recombinant which emerges during the preleukemic period in high-ecotropic-virus mouse strains, and they may play a significant role in the etiology of spontaneous lymphomas.


Structure of human plasma low-density lipoproteins: molecular organization of the central core. Human plasma low density lipoprotein (LDL) exhibits a thermal transition over the temperature range 20-40 degrees. This transition is associated with a structural change within the lipoprotein particle and is reflected in the small-angle x-ray scattering profiles from LDL. The scattering profile of the quasispherical LDL particle at 10 degrees shows a relatively intense maximum at 1/36 A-1 which is absent from the scattering of LDL at 45 degrees. Theoretical calculations, using model electron density distributions, have been carried out to describe the packing of arrangement of the cholesterol esters, based on perturbations of the molecular packing of crystalline cholesteryl myristate, adequately reproduces the high relative intensity of the x-ray scattering maximum at 1/36 A-1. The perturbations of the packing in the crystal structure of cholesteryl myristate involve "melting" of the hydrocarbon chains of the esters together with translations of pairs of molecules parallel to the molecular long axis. The interaction of opposing steroid moieties, with C18 and C19 angular methyl groups interlocked, exhibited in the crystal structure is retained in the perturbed arrangement. At 45 degrees, thermally induced disorder of this arrangement averages the electron density of the central core. The x-ray scattering profiles of particles with a homogeneous electron density in the core region do not show a high relative intensity of the subsidiary maxima in the 1/36 A-1 region, in agreement with experimental observation. The results of these calculations support the concept that the thermal transition observed for LDL is due to a smectic leads to disordered transition of the cholesterol esters in the core of the LDL particle.


Cell-surface glycosyltransferases in cultured fibroblasts: increased activity and release during serum stimulation of growth. Cell-surface galactosyltransferase was studied in suspensions of intact baby hamster kidney fibroblasts with both endogenous and exogenous glycoprotein acceptors. The cell-surface location of galactosyltransferase was demonstrated in experiments with the enzyme modifier alpha-lactalbumin, which does not enter the cell. The addition of alpha-lactalbumin to the assay medium for galactosyltransferase resulted in accumulation of lactose in the medium but not in the cells. There was no detectable hydrolysis of UDP-galactose to free galactose by these cells, nor did a 100-fold molar excess of free galactose inhibit cell-surface galactosyltransferase. There was a marked increase in specific activity of cell-surface exogenous galactosyltransferase in serum-stimulated as compared to resting fibroblasts. Dividing but not resting fibroblasts released galactosyltransferase, but not sialyl- or fucosyltransferase, in soluble form into the tissue culture medium. The release of galactosyltransferase was greater from virally transformed than from nontransformed fibroblasts.


Incorporation of N-acetylglucosamine into endogenous acceptors of rough microsomes from rat liver: stimulation by GTP after treatment with pyrophosphate. Upon incubation of UDP-N-acetyl[14C]glucosamine and GDP-mannose with rough microsomes from rat liver, GlcNAc incorporation occurred mostly into acid-labile products extractable by chloroform/methanol that were presumed to be dolichol pyrophosphate GlcNAc and, for a small part, dolichol pyrophosphate N,N'-diacetylchitobiose. The production of this latter glycolipid was greatly enhanced when rough microsomes, previously treated with pyrophosphate, were incubated in the presence of GTP. Furthermore, under these particular conditions, high levels of radioactivity were obtained in products precipitated by trichloroacetic acid and not extracted by chloroform/methanol. The label appeared in acid-labile and in acid-resistant products, presumed to be dolichol pyrophosphate mannosylated oligosaccharides, and glycoproteins, respectively. From these results, dolichol pyrophosphate N,N'-diacetylchitobiose appears to be an obligate metabolic intermediate in protein glycosylation by this system. Whether or not dolichol pyrophosphate N,N'-diacetylchitobiose must be mannosylated prior to transfer of the N,N'-diacetylchitobiose moiety to protein is an open matter, because GlcNAc was also incorporated into acid-resistant products when the reaction was carried out in absence of GDP-mannose.


Tumorigenicity of simian virus 40-transformed human cells and mouse--human hybrids in nude mice. Four different human cell lines transformed by simian virus 40 (SV40) were tested for their tumorigenicity in athymic nude mice. Two of these lines, W18Va2 and GM52VA, were found to be tumorigenic when inoculated at a concentration of 1 x 10(7) cells per mouse. The other two cell lines, LN-SV and GM54VA, were found to induce very small tumors only after the injection of approximately 1 x 10(8) cells per mouse. Somatic cell hybrids between either LN-SV or GM54VA SV40-transformed human cells and normal mouse peritoneal macrophages, which have retained the human chromosomes carrying the SV40 genome, were found to be much more tumorigenic than the SV40-transformed human cell parents. These experiments suggest that the genetic background in which the human chromosomes carrying the SV40 genome are present plays a role in the modulation of the expiration of malignancy.


Subunit interaction in cyclic AMP-dependent protein kinase of mutant lymphoma cells. We have previously selected and characterized mutant S49 mouse lymphoma cells that possess an adenosine 3':5'-cyclic monophosphate (cAMP)-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37) with an increased apparent affinity constant (Ka) for activation by cAMP. The Ka lesion in one such mutant clone has been shown to result from a structural mutation involving the kinase holoenzyme's regulatory (R) subunit. The present report examines the interaction of R and catalytic (C) subunits of the kinases in extracts of the mutant cells and the normal "wild type" (WT) parental line. Subunit recombination experiments were performed, by using purified WT and mutant R subunits, and C subunits purified from WT cells. As compared to WT R subunits, only 1/6 as much mutant R subunit was required to reassociate with and suppress 50% of C subunit activity, at equilibrium. NaSCN activates cAMP-dependent kinase of both cell types by causing the holoenzyme to dissociate. In comparison with WT, a 2-fold higher concentration of NaSCN is required to maximally activate the kinase in mutant extracts. Both the reassociation result and the increased resistance of the mutant enzyme to a nonspecific dissociating agent strongly suggest that the mutant R subunit binds C subunit more tightly than does the WT R subunit. This interpretation raises the possibility that increased R-C subunit binding affinity in the mutant cell is responsible for the increased Ka for activation by cAMP of the mutant holoenzyme, and thus for the decreased potency of cAMP in regulating intact mutant cells.


Feline oncornavirus-associated cell-membrane antigen (FOCMA): distinction between FOCMA and the major virion glycoprotein. The humoral antibody response of feline leukemia virus (FeLV)-exposed cats to the feline oncornavirus-associated tumor cell-membrane antigen (FOCMA) is directly correlated with immunosurveillance against tumor development under natural conditions. By means of membrane immunofluorescence and radioimmunoprecipitation, the antibody response to FOCMA was found to be independent of the antibody response to the major envelope and core proteins of FeLV, gp70 and p30. This was especially true for healthy viremic cats, where antigenemia with circulating FeLV gp70 and p30 apparently binds any free antibody to these proteins, but high levels of FOCMA antibody are often concurrently present. Exhaustive in vitro absorption of highly immune nonviremic serum with gp70 and p30 also failed to remove FOCMA antibody activity. These results indicate that FOCMA is not one of these major FeLV structural proteins.


Natural human antibodies reactive with primate type-C viral antigens. A survey of human sera from healthy individuals revealed the presence of naturally occurring antibodies that react in radioimmunoprecipitation assays with proteins of mammalian type-C viruses. Of 39 sera tested, 100% showed reactivity against baboon endogenous virus, whereas only 49% showed reactivity against simian sarcoma-associated virus. Polyacrylamide gel electrophoresis of immune precipitates revealed one to three bands that comigrate with the virus structural proteins. There were low, but detectable, levels of antibody to the major internal protein of murine leukemia virus, but no activity against the structural proteins of avian sarcoma virus.


Characterization of polyoma virus T antigen. High-titer antiserum raised in rats against the tumor (T) antigen of polyoma virus was used to purify the T antigen by the Staphylococcus protein A antibody adsorbent technique. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis allowed the identification of a protein with an apparent molecular weight of 100,000-108,000 as a major component induced in lytically infected mouse cells. In cells infected by ts A mutants this component was temperature sensitive. Several minor components were also observed. In pulse and chase experiments there was a slight decrease in electrophoretic mobility of T antigen during the chase period at the permissive temperature, suggesting that the T antigen is a modified protein. In two lines of transformed cells, the amount of T antigen seemed to be considerably less than in lytically infected cells, but the size of the antigen appeared to be equal.


Structure of a large segment of the genome of simian virus 40 that does not encode known proteins. The nucleotide sequence of the region of DNA of simian virus 40 extending from 0.595 to 0.790 map unit has been derived. The sequence includes the DNA complementary to the 5' end of early mRNA and to the 5' end of some of the forms of late RNA. Because there are termination codons in all three phases in early and late RNA, there is a sequence of almost 800 nucleotides of simian virus 40 DNA that probably does not code for known viral proteins. The sequence spans the 5' end of the early mRNA at 0.67 map unit and overlaps a species of late RNA whose 5' end is at 0.65 map unit and whose 3' end is at 0.77 map unit. This RNA is retained on oligo(dT)-cellulose columns in high salt concentrations. Analysis of the sequence of late strand RNA suggests that this RNA is not covalently linked to the mRNA that encodes structural proteins. There is another species of late RNA of simian virus 40 whose 5' end is at 0.775 map unit. The nucleotide sequence of this region of simian virus 40 DNA contains several examples of repeated sequences, most of which are located in DNA that does not encode known peptides. These may be analogous to the reiterated sequences that have been described in animal cell DNA.


Mapping of closed circular DNAs  by cleavage with restriction endonucleases and calibration by agarose gel electrophoresis. The cleavage of DNA by restriction endonucleases can be limited by the addition of ethidium bromide. When closed circular DNA is used as a substrate, DNA with one-site cleavages of one or both strands can be made by adding appropriate amounts of dye. The singly cleaved DNA is a complete set of full-length permuted linear molecules. Fractionation of the products of a digestion of the permuted linears with a single-hitting restriction endonuclease by gel electrophoresis yields a series of bands that can be used to determine relative molecular weights of the DNA fragments in the gel without the introduction of standards. It is possible to determine the relative molecular weight of a fragment to within +/-2.5%. These molecular weights immediately allow the determination of the HindIII and Hpa I maps of simian virus 40. The HindIII map of bacteriophage PM2 was determined by this method with one ambiguity that was resolved by using traditional techniques.


Induction of functional beta-adrenergic receptors in HeLa cells. HeLa cells contain beta-adrenergic receptors that are characterized by specific binding of I[3H]dihydroalprenolol, increased 3':5'-cyclic AMP production in intact cells after incubation with l-isoproterenol, and increased adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activity in the presence of l-isoproterenol. After cells were cultured with butyrate, the number of beta-adrenergic receptors, cyclic AMP production in intact cells, and adenylate cyclase activation by l-isoproterenol were increased severalfold over those of untreated cells. The increase involved the induction of synthesis of new receptor molecules with identical affinities for l-[3H]-dihydroalprenolol; all three processes were blocked by cycloheximide and actinomycin D. This induction was relatively specific for butyric acid and only the closely related short-chain fatty acids, propionic and valeric acids, were capable of partially inducing the same effect. In contrast to induction of beta-adrenergic binding sites, there was no increase in basal or fluoride-activated adenylate cyclase activity, indicating that the beta-adrenergic receptor and adenylate cyclase and different molecules that may be controlled separately.


Histaminase (diamine oxidase) activity in human tumors: an expression of a mature genome. High histaminase [amine:oxygen oxidoreductase (deaminating) (pyridoxal-containing), EC 1.4.3.6] activity is found in certain human tumors and in the placenta of most mammals. The present study explores the relationship of tumor histaminase to histaminases found in placenta and other human, pig, and rat tissues. The electrophoretic mobility and Michaelis constants for the deamination of histimine and putrescine were identical for histaminases from human placenta and from medullary thyroid carcinoma. An antibody was raised in rabbits against human placental histaminase that was highly purified by a new affinity procedure. In separate studies, using inhibitory concentrations of antibody and a second antibody precipitation technique, identical patterns of immunoreactivity were found for histaminases from human placenta, kidney, medullary thyroid carcinoma, and small cell lung carcinoma; human intestinal histaminase crossreacted well but less strongly than did enzymes from these other tissues. Histaminases from pig kidney, pig intestine, and rat intestine showed no crossreaction; histaminases from rat thymus and adrenal gland showed minimal crossreactivity. The findings suggest that placental histaminase activity is not a unique product of a fetal or trophoblastic genome. The presence of histaminase in malignancies does not appear to be an example of ectopic tumor production of a placental trophoblastic protein.


Granulocyte collagenase: selective digestion of type I relative to type III collagen. Collagenases produced by human polymorphonuclear leukocytes, human lung fibroblasts, and rabbit pulmonary alveolar macrophages were compared in their ability to digest soluble native type I and type III collagens. While the fibroblast and macrophage collagenases attacked the two substrates at approximately equal rates, the leukocyte collagenase attacked type I collagen preferentially (15:1) in comparison to type III collagen. This was true with human or rabbit collagen substrates. Thus, proteolysis of collagen, particularly in acute inflammation, may have a significant role in controlling the types of collagen present in connective tissue.


Cleavage of Rous sarcoma viral polypeptide precursor into internal structural proteins in vitro involves viral protein p15. The polypeptide precursor pr76 to the internal viral group specific (gs) antigen proteins of Rous sarcoma virus, synthesized in a cell-free system of ascites cells, has been processed in vitro into the viral proteins by purified viral protein p15 as well as by disrupted Rous sarcoma virus. Disrupted Rauscher murine leukemia virus does not stimulate the cleavage process in vitro. Autocatalytic cleavage of the polypeptide precursor pr76 or Rous sarcoma virus, which contains the peptide sequence of p15, is not observed.


Covalent linkage of a protein to a defined nucleotide sequence at the 5'-terminus of virion and replicative intermediate RNAs of poliovirus. The 5'-terminus of poliovirus polyribosomal RNA is pUp. A candidate for the 5'-terminus of poliovirion RNA was recovered as a compound migrating toward the cathode when 32P-labeled virion RNA was completely digested with ribonucleases T1, T2 and A and analyzed by paper ionophoresis at pH 3.5. Treatment with proteinase K reversed its direction of migration, indicating the presence of protein. Treatment with venom phosphodiesterase liberated all of the radioactivity as pUp, suggesting that poliovirion RNA has a protein-pUp 5'-terminus. Treatment of virion RNA with T1 ribonuclease alone generated a proteinase K-sensitive oligoribonucleotide. Analysis of the oligoribonucleotide using ribonucleases A and U2 showed its structure to be protein-pU-U-A-A-A-A-C-A-G. Digests of replicative intermediate RNA contained sufficient protein-pUp to suggest that this structure is at the 5'-end of most nascent poliovirus RNA molecules. We suggest that a protein-nucleotide structure acts as a primer for initiating synthesis of poliovirus RNA.


Evidence that the preoptic region is a receptive site for the dipsogenic effects of angiotensin II. Drinking elicited by administering angiotensin II (ANG II) to the preoptic region with cannulae passing through the lateral ventricles was attenuated significantly when the ventricles or subfornical organ were pretreated with saralasin acetate (Sar1-Ala8-angiotensin II). If the cannulae in the preoptice region were angled to bypass the lateral ventricles water intake elicited by ANG II was less and pretreating the cerebral ventricles with saralasin acetate did not reduce the drinking response. The results suggest that the preoptic region may be a receptive site for ANG II in addition to the subfornical organ and/or cerebral ventricles.


Protein synthesis and amnesia: studies with emetine and pactamycin. Two antibiotic inhibitors of protein synthesis, emetine and pactamycin, have been tested for their effects on cerebral and peripheral protein synthesis and amnesia. Peripherally administered emetine but not pactamycin inhibited cerebral protein synthesis, although this inhibition was lower than that observed with cycloheximide or anisomycin. Pactamycin had a lesser effect on adrenal protein synthesis than emetine. This was reflected in the ability of emetine but not pactamycin to block ACTH-induced corticosteroidogenesis. Anisomycin and cycloheximide caused amnesia in a passive avoidance task, whereas pactamycin and emetine did not. These results are inconsistent with the amnesia being due to inhibition of protein synthesis in a peripheral organ. They are also inconsistent with the amnesia being due to the suppression of an adrenocortical response as previously suggested. No obvious correlation between amnesia and the mechanism of protein synthesis was observed. The most parsimonious explanation is that inhibition of cerebral protein synthesis is necessary for amnesia.


The influence of alpha-receptors on lordosis in the female rat. The alpha-adrenergic agonist clonidine suppressed lordotic responding in spayed female rats brought into heat by estrogen and progesterone. The suppression was blocked by the alpha-antagonist yohimbine, but not by phenoxybenzamine or pimozide. The suppression was blocked by the alpha-antagonist yohimbine, but not by phenoxybenzamine or pimozide. Phenoxybenzamine itself had no suppressive effect on lordosis, though yohimbine did under some conditions. These results argue against an important facilitatory influence of norepinephrine on lordosis in the rat. Further, in comparison with the quite different findings recently reported from the guinea pig, they offer support for the presence of two different kinds of alpha-adrenergic receptors in the brain with different physiological functions.


Plasma corticosterone and brain catecholamines in stress: effect of psychotropic drugs. In nonstressed rats, subcutaneous administration of haloperidol (HAL) and large doses of diazepam (DZ) increased plasma corticosterone (CS). Hypothalamic norepinephrine (NE) was lowered significantly by desmethylimipramine (DMI), HAL and, to a lesser extent, by DZ and phenobarbital (PHB). In rats pretreated with either DZ, DMI, HAL or PHB the restraint-induced rise of CS was diminished, DZ being most potent. CPZ had a variable effect, slightly increasing or decreasing the CS response. Pretreatment (16 hr) with pargyline (PA) did not affect the CS rise to stress. The reduction of hypothalamic NE evoked by restraint was attenuated by DZ, and to a lesser extent, by PHB and HAL. Restraint of PA-treated rats did not lower the PA-elevated hypothalamic NE. The stress-induced increase in hypothalamic dopamine was prevented by CPZ and, partially, by PHB. It is emphasized that the net plasma CS and brain catecholamine changes in response to stress are dependent on the drug-induced neuroendocrine feedback state prevalent immediately before commencement of the stress procedure.


Anticonvulsant activity and selective inhibition of NAD-dependent oxidations by 1,4-disubstituted piperazines. Several 1-(1-aryl-3-ethylthiocarbamido)-4-(arylaminothiocarbonyl)piperazines were synthesized, characterized by their sharp melting points and elemental analyses and evaluated for anticonvulsant activity. All disubstituted piperazines at a dose of 100 mg/kg i.p. provided 10-90% protection against pentylenetetrazol-induced convulsions in mice. These disubstituted piperazines selectively inhibited the in vitro oxidation of nicotinamide adenine dinucleotide (NAD)-dependent oxidation of pyruvate, alpha-ketoglutarate, beta-hydroxybutyrate and NADH by rat brain homogenates. The NAD-independent oxidation of succinate remained unaltered. The anticonvulsant activity possessed by disubstituted piperazines was unrelated with their ability to selectively inhibit respiratory activity of rat brain homogenates. Amongst 1-(substituted benzyl)-4-(substituted benzoyl)piperazines exhibiting central nervous system (1, 2) depressant activity it was found that 1-(2-chlorobenzyl)-4-(2-chlorobenzoyl)piperazine possessed maximum activity (2). The ability of piperazine carbamides (3) and piperazinothiocarbamides to possess anticonvulsant activity (4) prompted synthesis of 1-(1-aryl-3-ethylthiocarbamido)-4-(arylaminothiocarbonyl)piperazines and evaluation of their anticonvulsant activity. The effects of these disubstituted piperazines were also investigated on the in vitro respiratory activity of rat brain homogenates in an attempt to elucidate the biochemical mechanism of action for their anticonvulsant activity.


Spasticity: its physiology and management. Part III. Identifying and assessing the mechanisms underlying spasticity. Patients with spasticity may have similar motor signs and yet have completely different underlying neural mechanisms. This paper reviews some experimental tests which have been developed to detect and analyze excitatory excesses and inhibitory deficits giving rise to the abnormal motor signs of spasticity. Although at the present time these tests may not lend themselves to routine clinical application, their results are creating a body of knowledge which will become the foundation for diagnosis and treatment of spasticity in the future.


Functional characteristics of the intraspinal spread of viscerosomatic activity. The functional characteristics of the intraspinal spread of the dual-component viscerosomatic reflex response were studied in chloralose-anaesthetized cats. In the region of the direct inputs of splanchnic afferents into the spinal cord, the initial part of the early (propriospinal) component is evoked by afflux from the extraspinal pathway in the sympathetic chain and has the shortest latent period. At segment Th8 to Th12 level this was 5.2--8.1 msec; cranially and caudally from this level it was longer. Activity spreading from the adjacent segments via intraspinal longitudinal systems also participates in the origin and course of the early component of the efferent discharge. The rate of ascending intraspinal irradiation in the thoracic region was 3.2--12 m/sec (6.6 +/- 2.4 m/sec). The rate of the descending spread of propriospinal activity in the thoracic region via intraspinal pathways was 3.6--18.3 m/sec (12.5 +/- 4.5 m/sec); in the lumbar region it was significantly lower -- 2.9--19.3 m/sec (7 +/- 4.5 m/sec). The latent period of the later component varied from 20 to 30 msec and displayed a cranio-caudal increase in length. The rate of the descending spread of the later component in the thoracic and lumbar cord did not differ significantly (20 +/- 10 m/sec and 22 +/- 13 m/sec respectively). The continuous splanchnic discharge in the lumbosacral region is correlated to the different rate of the intraspinal spread of the early and the late response and to their overlapping.


Effect of various adaptational temperatures on oxidative capacity of the brown adipose tissue. Changes in total weight, protein content and activity of cytochrome oxidase have been followed in the brown adipose tissue (BAT) of golden hamsters, white mice and white rats adapted to various temperatures. Important interspecies differences have been detected. The weight and the cytochrome oxidase activity of the BAT of the white mouse changes little under the influence of different adaptational temperatures, whereas in the white rat and in the golden hamster a decrease of adaptational temperature considerably increases the total weight, protein content and cytochrome oxidase activity of this organ. Different adaptational temperatures induce variable effects on the BAT of the golden hamster. Mild cold stimuli favour the accumulation of proteins and of oxidative enzymes, in particular. Severe cold stress also induces growth processes, so that the weight of the BAT increases proportionally to the total body weight of animals. The metabolic capacity of the BAT, measured as total cytochrome oxidase activity, changes substantially with decreasing temperature of adaptation in all species studied, increasing twice, six times and almost twelve times in the mouse, rat and golden hamster, respectively.


Dermal cylindroma (turban tumor). Case report. We present an unusual case of massive dermal cylindroma (turban tumor), occupying the entire scalpand forehead. It was treated by a total scalping procedure and skin grafting in two stages. Additional tumors of the face, neck, chest, shoulders, and back were excised and closed. The nose was treated by shoving and dermabrasion, similar to a rhinophyma. The lip was treated by dermabrasion. There has been no evidence of recurrence in the scalp which was treated by excision and grafting. There is now a papular quality of the skin over the nose and on the uppler lip, indicating that regrowth may occur. The etiology, pathology, and a review of the literature are presented.


Surgical treatment of hemifacial microsomia. (First and second branchial arch syndrome). A review of 17 patients operated upon for unilateral hemifacial microsomia, and followed for up to 18 years, clarifies several principles of management. The management is facilitated by dysplasia predominance grouping, with the major functional deformity dictating the sequence of repair. Our surgical goals are: (1) provision of adequate upper airway; (2) preservation of normal teeth and adequate alveolar bone to achieve proper dental occlusion; (3) restoration of binaural hearing; (4) external ear construction; (5) acceptable facial symmetry; (6) balanced facial animation; and (7) a child with an acceptable self-image.


Malignant fibrous histiocytoma of the parapharyngeal space. Case report. Of the large variety of tumors that may occur in the parapharyngeal space, malignant fibrous histiocytoma is one of the most rare. We present such a case and discuss the diagnosis, classification, and treatment.


[Effect of chlorimipramine on the so-called ponto-geniculo-occipitalactivity (PGO) in a primate, Papio hamadryas (author's transl)]. Three hamadryas adult baboons (female) received 24 daily injections of Chlorimipramine (1.7 mg/kg). The effects on sleep were nearly identical with the effects observed in man. PGO activity, recorded in the lateral geniculate nucleus, was much disturbed. The total number of PGO fell downward from the first recording. The number of PGO/min during paradoxial sleep was even more decreased. This fact suggests a selective influence of CL I on the mechanisms of PGO activity. Is the particular effect of importance to the treatment of depression symptoms?


Ultrasonography of the genitourinary tract in children. The author discusses the utility of ultrasound in investigating the genitourinary tract in neonates, infants, and children, and emphasizes the inter-dependence of ultrasonography and uroradiology.


Renal parenchymal infections in children. The excretion urogram-nephrotomogram is the most important imaging study in the diagnosis of renal parenchymal infection in children. If renal parenchymal infections are discovered before significant necrosis has occurred, vigorous treatment with appropriate parenteral antibiotics may result in resolution without the need for surgical drainage.


Sleep-waking changes in cardiac arrhythmia in a coronary care patient. A single case is reported in whom ventricular cardiac arrhythmias were related to the occurrence of polygraphically verified sleep. A strong relationship was found to exist between the heart rate in any one minute and the number of premature ventricular contractions, with higher rates associated with a greater number of these ectopic beats.


Esophageal complications in the treatment of oat cell carcinoma with combined irradiation and chemotherapy. A case of esophageal stenosis was noted in a patient treated with a combination of irradiation and chemotherapy for oat cell carcinoma. Review of the entire series of 22 patients revealed an unusually high rate (8/22) of esophagitis. These complications are discussed in relation to timing radiation dose and multidrug chemotherapy


Angiographic assessment of gross anatomy of hepatocellular cardinoma: comparison of celiac angiograms and liver pathology in 100 cases. Of 190 sets selective celiac and/or hepatic angiograms obtained in patients with hepatocellular carcinoma (HCC), comparison with gross anatomy of the liver was subsequently made by autopsy in 77 and by surgery in 23. It was found that the gross anatomy of HCC can be assessed with certain accuracy by careful interpretation of the angiograms, because tumor vasculature and vascular alterations in the noncancerous parenchyma are closely related to the mode of tumor growth, size of tumor nodules and their distribution. Even a fibrous capsule of the tumor may be discerned as a radiolucent zone around the tumor contour. Diagnosis of the gross anatomical type of HCC is important to the selection of therapeutic measure and assessment of prognosis.


Ultrasonography and computed tomography in the diagnosis of homogeneous masses. Ultrasonography can demonstrate the homogeneity, while CT can demonstrate the density of a mass lesion. If a mass appears echo-free at ultrasonography, but is denser than water at CT, a solid tumor with grossly uniform cellular structure (usually a lymphoma or sarcoma), or a hematoma or hemorrhagic cyst is likely. However, if the mass has water density at CT, a cystic lesion is confirmed. One case for each category is presented.


Hydrocortisone inhibition of the bradykinin activation of human synovial fibroblasts. Human synovial fibroblasts in culture respond to bradykinin with a 20-fold increment in intracellular cyclic AMP concentrations, however bradykinin does not directly activate adenylate cyclase activity in a particulate fraction derived from these cells. Bradykinin evokes a release of labeled arachidonic acid and prostaglandins E and F from synovial fibroblasts pre-labeled with 3H-arachidonic acid. Hydrocortisone inhibits the bradykinin induced increment in cyclic AMP and the release of arachidonic acid and prostaglandins E and F from synovial fibroblasts. Indomethacin, which also inhibits the cyclic AMP response to bradykinin, has no effect on the release of arachidonic acid from synovial fibroblasts. Indomethacin does, however, inhibit the quantity of prostaglandins released into the medium. These studies support the hypothesis that bradykinin does not activate human synovial fibroblast adenylate cyclase, but presumably activates a phospholipase whose products in turn result in the synthesis of prostaglandins. These and other investigations also suggest that a product(s) of the prostaglandin pathway causes the increment in cyclic AMP.


Modulation of human platelet adenylate cyclase by prostacyclin (PGX). Prostacyclin (PGX) (57)-9-deoxy-6,9alpha-epoxy-delta5-PGF1alpha has been found to be a potent stimulator of cAMP accumulation in platelets than PGE1. The prostacyclin stimulation of platelet cAMP accumulation can be antagonized by the prostaglandin endoperoxide PGH2, and a PGH2-induced platelet aggregation is antagonized by prostacyclin. A model of platelet homeostasis is proposed that suggests platelet aggregation is controlled by a balance between the adenylate cyclase stimulating activity of prostacyclin, and the cAMP lowering activity of PGH2.


Effects of prostacyclin (PGX) on cyclic AMP concentrations in human platelets. Prostacyclin (PGX) strikingly increases cyclic AMP concentrations in human platelets. Prostacyclin is approximately 10 times more active than PGD2, 30 times more active than PGE1 and more than 1000 times more active than its stable end product, 6-oxo-PGF1alpha. These results correlate well with the anti-aggregating activity of prostacyclin, compared with PGE1 and PGD2.


Effect of papaverine on cyclic AMP, calcium uptake and force of contraction in isolated guinea-pig auricles. The effects of papaverine on cyclic AMP (c-AMP), 45 calcium uptake and force of contraction were studied in electrically stimulated left guinea-pig auricles. Papaverine (2 x 10(-6) - 2 x 10(-5)M produced a concentration-dependent positive inotropic effect which was not affected by 10(-7) M propranolol. Papaverine (10(-5)M increased cyclic AMP; this effect developed faster than the increase in twitch tension. Papaverine (10(-5)M) enhanced 45calcium uptake. These results are taken to support the idea of a causative series of interactions between a papaverine induced increase in c-AMP, calcium uptake and force of contraction.


[Herpetic etiology of gastric and duodenal ulcer. II. Study in humans]. By inducing experimental ulcers in the rabbit with the type 1 Herpes simplex strain, isolated from the herpes vesicles from a vagotomized patient, the authors demonstrate the protective role of vagotomy, the ulcerogenic capacity of the virus, which can be considered as an etiological factor of human gastroduodenal ulceration. They also discuss the possibilities for a new medical therapy of this disturbance.


[The risk of grave evolution of tuberculosis in  young children (under 2 years of age)]. Between 1971 and 1972, 22% of all children under two years with tuberculosis presented with severe forms of the disease (meningitis, miliaria, caseous forms). In the period 1974-1975, although the number of cases in the group was reduced by half, the severe forms still represented 20,4% of the total. The risk of severe evolution of tuberculosis decreases rapidly, from 55--66% in the first months of life. to 14,2--15,5% at 1--2 years. The risk of death in children aged between 0 and 2 years with tuberculosis (all forms) was of 26,6--58,3% between 0 and 5 months but only 4,5--9,3% in the second year of life. The risk of death in young children with severe forms of tuberculosis was as high as 70--76,7% in those under the age of 6 months. The source of infection was identified in 72,4--76,4% of the severe cases. At the onset of the disease only 57,1% of the sources were known, while 42,9% were discovered later, by epidemiologic investigations. An analysis of cause for a severe evolution of tuberculosis in young children led to the conclusion that BCG vaccination should be performed systematically at birth, and that tuberculin skin test be carried out in all hospitalized children, regardless the diagnosis. They also recommend the use of anamnestic data concerning the possible existence of tuberculosis cases in the families of patients, performing of radiologic controls in young mothers etc. In the case of infants that come into a close contact at a very early age with parents, or other relatives suffering with tuberculosis, chemoprophylaxis with two associated tuberculostatics is indicated.


[Immunological aspects of workers exposed to the risk of silicogenesis]. Comparative studies were performed, of changes of serum proteins and IgG, IgA and IgM immunoglobulins in workers exposed to silicogenic dust. Depending on their response to tuberculin testing (2 U of PPD) these subjects were classified in negative and hyperergic. In both groups there was found a decreased albumin concentration in the serum and high alpha-2 globulin. In hyperergic subjects there was noted a slight increase of beta globulins and a significant rise in the titer of gammaglobulins. Immunoglobulins G showed a significant rise in hyperallergic subjects and slightly decreased in tuberculin negative ones, without attaining a level of immunologic deficiency. In both groups IgM immunoglobulins were significantly lowered, while IgA immunoglobulins were occasionally increased, although there was no positive correlation with tuberculin allergy. In three cases there was a slight IgA deficiency.


[Immediate results of strictly supervised, intermittent treatment with rifampicin and ethambutol in patients with chronic pulmonary tuberculosis]. Of the 118 patients suffering from chronic pulmonary tuberculosis, living within the district of the Tîrgu Mureş Tuberculosis Dispensary, 100 accepted a strictly surveyed treatment and of these 90 continued for at least 6 months. The present paper reports on the immediate radiologic and bacteriological results and the factors influencing them. The following conclusions were drawn: 1) A 2/7 Rifampicin/Etambutol strictly supervised treatment is the most efficient method for neutralizing chronic bacillary sources. 2) The age and origin of the patients, the duration and extent of the pulmonary process, duration of the treatment and associated diseases are the factors that furnish the prognosis of the expected results. 3) Apart from the very good results obtained the method cannot solve all chronic cases and the classical antiepidemic measures must be applied in continuation.


[Frequency of isolation of tuberculous bacilli as a function of some mechanical factors in patients with pulmonary tuberculosis]. A series of mechanical factors, such as postural changes and every day movements, favour mobilization of bronchoalveolar secretions and, hence, offer greater chanses of detecting the tuberculosis bacillus. It is recommended to collect, in out-patient units, two sputum samples, one in the morning and the second several hours later, after beginning the day's work.


[Value of methods used in the etiological diagnosis of pleural exudates]. A study was carried out on 64 cases of pleural exsudates, i.e. 23 of neoplastic origin, 13 tuberculous, 10 with various etiologies and 8 the cause of which could not be determined. In all cases pleural biopsy puncture was performed, once or several times, the histologic examination confirming 80% of the cases of tuberculosis and 40% of the cancer cases. Biochemical methods are orientative, their significance increasing when the other probability tests give convergent results.


[Changes in time of the microbial flora in bronchopulmonary infections]. The authors carried out a study on 100 cases with broncho-pulmonary infections in two different periods: 1963--1964 and 1973--1974. Changes in the microbial flora were investigated, as well as the sensitivity of germs to antibiotics. An increase was noted in the number of chronic bronchitis and a decrease in the number of pneumonia cases. In the microbial flora there was a constant proportion of staphylococcus, streptococcus and coli strains. The proportion of micrococci decreased with time and pneumococci practically disappeared, being replaced by klebsiella germs. Sensitivity to penicilin remained almost identical while that to chloramphenicol decreased significantly, as well as sensitivity to tetracycline and neomycine. The practical conclusion is that in some cases the application of penicilin treatment, before the results of the antibiogram are available appears to be justified.


[Histochemical and histoenzymatic studies of chick-embryo tibial rudiments cultured in vitro in the presence of bovine growth hormones]. The AA. have studied the effect of the bovine GH on the cellular and intercellular components of the chick embryo tibias cultured organotypically. They have observed a strong increase of the proliferative activity of the chondroblasts such as showed by a stronger uptake of the tritiated timidine by traited tibias in comparison with the control tibias. The chondroblasts of the traited tibias show an increase of some enzymatic activities connected with the aerobic cycle and of the UDPG-DH, connected with the uronic acids cycle. In the amorphous matrix of the traited tibias they have showed a greater polimerisation and sulfation of the condroitinesulfate A and C, which, almost exclusively, constitute the mucopolisaccharidic component of the matrix.


[Correlations of ventilation measurements with alpha 1-antitrypsin deficiency chronic suppurative bronchopneumopathies]. The corrleations of ventilometry and alpha-1-antitrypsin deficiency were studied in a lot of 105 patients with chronic obstructive bronchopneumopathy associated with various forms of chronic pulmonary suppuration. Alpha-1-antitripsin deficiency was determined by Erikson's gelatin film test, simplified by Keith et al. Ventilation dysfunctions were found in 79% of the cases, predominantly obstructive, mixed, advanced or severe. Alpha-1-antitrypsin deficiency was detected in 11.4% of the patients as against 4.1% in the controls, the deficiency being more accentuated in the mixed (75%) and obstructive (25%) ventilation dysfunctions. Determination of alpha-1-antitrypsin deficiency, corroborated with other investigations may supply useful information for detecting a predisposition and for the evolutive prognosis of these respiratory diseases.


[Active-evolutive pulmonary tuberculosis with negative tuberculin reaction]. In a lot of 452 patients with various forms of tuberculosis, in various locations, the authors have investigated the efficiency of tests currently employed in detecting tuberculin sensitivity (intradermoreaction to PPD, the test to sensitines and the Ustvedt test), in relation with several immunologic tests performed in vitro (index of lymphoblastogenesis to PPD and/or phytohaemagglutinin, leucocyte migration inhibition test, and the rosette test). It was noted that the two groups of investigations give similar results when tuberculin reactions are positive and intense. Under the conventionally admitted threshold of tuberculinic allergy the test of blastic transformation of lymphocytes, and especially the leucocyte migration inhibition tests are still positive and may be considered as a valuable means for measuring infra-tuberculinic allergy, as well as for the diagnosis of latent tuberculous infections.


[Antagonism between focal epilepsy and taurine administered by cortical perfusion]. The therapeutic action of taurine cortical perfusion was tested in cats affected with Premarin and cobalt cortical epileptogenic foci. In all animals taurine provoked the disappearance of EEG epileptic abnormalities. In the case of Premarin focus the effect appeared more quickly than in the cobalt one. This different time-course, according to previous reports on the antiepileptic action of the parenteral administration of the amino acid, suggests the hypothesis of a taurine direct inhibitory action against Premarin focus and, on the contrary, a mediated action towards the cobalt's. The latter might be related to the metabolic production of some taurine derivative.


Importance of associated viral and bacterial infections in the production of acute pneumonias. Bacteriologic and virologic investigations carried out in a group of 85 patients with acute pneumonia have allowed the determination of the etiologic agent in 52.9% of the cases. Of these, 40% showed combined viral and bacterial infections. Mixovirus infections were frequently associated with staphylococcic ones (7 out of 8 cases) and adenovirus infections with the pneumococcic ones (6 out of 7 cases). The most severe and longdrawn clinical pictures with frequent pleuropulmonary complications (in 22.24% of the cases) had a biphasic evolution in only 6 of the 18 pneumonias of mixed etiology. For their high frequency and their clinical peculiarities, mixed etiology pneumonias might be considered as distinct clinical entities.


[Biochemistry of collagen and locomotor apparatus. Hereditary diseases of the connective tissue and rheumatic diseases (3)]. In inflammatory granuloma, synovial sclerosis or inflammation and in Dupuytren's contracture, the neocollagen contains chains and/or transverse links that are characteristic of rapidly growing immature tissues. In arthrosis, a conversion of collagen synthesis towards a cutaneous type may occur. The destruction of cartilage in rheumatoid arthritis is brought about by a specific collagenase that originates from the inflamed synovial membrane. Finally, certain forms of osteoporosis may be due to alterations of the osseous collagen which impair the mechanism of calcification.


[Bronchial adenoma].

[Bronchial adenoma]. Twenty-four patients with bronchial adenoma seen over a 20-year period are reviewed. Follow-up data was available in all patients. They included 19 with carcinoid, 2 with adenoid-cystic carcinoma, and 3 with muco-epidermoid carcinoma. Recurrent pulmonary infection, cough and hemoptysis were the most common clinical manifestations. Surgical resection was performed in all but one patient, who was treated by irradiation; bronchoplastic and conservative resectional procedures were used in 5 patients with carcinoid adenoma. Carcinoid tumors are considered to be very slowly-growing malignant neoplasms that sometimes give rise to metastases to regional lymph nodes. Such metastases were present in only one patient. All patients are alive and well. Adenoid-cystic carcinoma is a more aggressive tumor with a tendency to recur. Much of the difficulty in its treatment is due to its close proximity to the bifurcation of the trachea. One patient was operated upon three times for local recurrences and ultimately died from respiratory failure after the third operation. The other patient received radiation therapy with cobalt and is well, without recurrence, 3 years after the treatment. The 3 muco-epidermoid carcinomas were histologically similar to such tumors of salivary glands but behaved clinically like highly malignant tumors, no patients surviving 8 months after resection. The term bronchial adenoma is a misnomer. The neoplasms grouped under this heading should be called carcinoid adenoma, adenoid-cystic carcinoma, and muco-epidermoid carcinoma and considered as separate entities, since the ultimate course and prognosis is definitely different.


Hybridization in situ of SV40 plaques: detection of recombinant SV40 virus carrying specific sequences of nonviral DNA. The detection and recovery of SV40 genomes containing foreign DNA sequences can be facilitated, and the risk of accidental dispersal reduced, by in situ hybridization and radioautography.


Design of specific inhibitors of angiotensin-converting enzyme: new class of orally active antihypertensive agents. A hypothetical model of the active site of angiotensin-converting enzyme, based on known chemical and kinetic properties of the enzyme, has enabled us to design a new class of potent and specific inhibitors. These compounds, carboxyalkanoyl and mercaptoalkanoyl derivatives of proline, inhibit the contractile response of guinea pig ileal strip to angiotensin I and augment its response to bradykinin. When administered orally to rats, these agents inhibit the pressor effect of angiotensin I, augment the vasodepressor effect of bradykinin, and lower blood pressure in a model of renovascular hypertension.


Sesquiterpene antitumor agents: inhibitors of cellular metabolism. Helenalin and tenulin injected into CF1 male mice bearing Ehrlich ascites tumors inhibit DNA synthesis and DNA polymerase enzymatic activity in the tumor cells. Helenalin inhibited protein synthesis. Both drugs increased the concentration of adenosine 3',5'-monophosphate, and interfered with glycolytic and mitochondrial energy processes. Cholesterol synthesis was also inhibited, resulting in lower serum cholesterol levels in tumor-bearing animals. Data obtained in vitro indicate that the cyclopentenone-bearing sesquiterpene lactone and related compounds do not alkylate puring bases of nucleic acids but rather undergo a Michael-type addition reaction with the sulfhydryl groups of reduced glutathione and l-cysteine. Thus, the inhibition of cellular enzyme activities and metabolism that has been observed with these drugs might be explained by the occurrence of a Michael-type teaction.


A phospholipid derivative of cytosine arabinoside and its conversion to phosphatidylinositol by animal tissue. We have synthesized an analog (ara-CDP-DL-dipalmitin) of cytidine diphosphate diglyceride (CDP-diglyceride) in which the antitumor drug, cytosine arabinoside, is substituted for the cytidine moiety. Enzymes in rat and human liver convert this analog to phosphatidylinositol, thereby releasing cytosine arabinoside-5'-monophosphate, an obligatory intermediate in the activation of cytosine arabinoside. Unlike cytidine diphosphate diglyceride, however, ara-CDP-DL-diapalmitin is not an efficient substrate for phosphatidylglycerophosphate synthesis in liver or phosphatidylserine in Escherichia coli. The antitumor activity of ara-CDP-DL-dipalmitin in mice bearing L5178Y leukemia is described.


Antigen-antibody reactions in rat brain sites induce transient changes in drinking behavior. The septum or hypothalamus of rat brain was injected through implanted cannulas with antibody against membrane antigens in the rat brain or with antibody against exogenous soluble antigens (such as ovalbumin) followed by the specific antigen. Both immunological systems produced a moderate but highly significant decrease in drinking by thirsty rats. This phenomenon is suggested as an experimental model for behavioral disorders resulting from nondegenerative, immunological processes in the brain.


[Changes in Achilles tendon reflex under influence of non endocrine factors]. Numerous physiopathological processes such as diurnal variations sex, age, pregnancy, muscular effort, diseases and drugs modify the Achilles reflexogram. Their multiplicity explains the difficulty of general interpretation of changes in the reflexogram which bring into play the energy reserves of the muscle cell and its potassium content.


[Topographic diagnosis of hypertensive pheochromocytoma]. In a series of 9 cases of hypertensive pheochromocytoma, the author noted in five of them abolition of the lower abdominal skin reflex on the same side as the tumour. They were in four cases suprarenal pheochromocytomas and in the fifth case an ectopic paraganglioma of Zuckerland's organ. In 3 cases, the abolished reflex became normal and equal to that on the opposite side after removal of the tumour. In two others, it remained abolished. In 4 patients, most of the other abdominal skin reflexes, expecially those, on the opposite side, very brisk before the operation, became normal afterwards. The author concludes that in cases of hypertensive pheochromocytoma, careful study of the abdominal skin reflexes may provide a useful contribution to topographic diagnosis.


[Phreno-celiac disease and merycism in adults]. In this paper are described two new examples of a peculiar semiological association of which the authors have already reported a case, and in which occured simultaneously a phreno-coeliac disease and merycism since childhood. Strong epigastric pains accompained the merycism. In these two cases, the compression of the coeliac trunk by the median arcuate ligament of the diaphragm was important; in one case existed besides a compressive stenosis of the superior mesenteric artery. After the surgical liberation of the coeliac artery and the peri-coeliac neurectomy in one case, all symptoms relieved. This good result persists after twelve months. Because of the rarity of the phreno-coeliac disease and of this type of merycism, the authors think that this association is not accidental, but the result of a new nosological association.


[Severe hemolytic jaundice and Wilson's disease]. The onset of spontaneous hemolytic jaundice in a young subject should lead to the search for Wilson's disease when clinical examination reveals cirrhosis. This hemolysis may evolve in the form of severe jaundice to a stage where the cirrhosis remains usually latent or well tolerated. The intervention of a toxic, allergic of infective factor liable to produce a hepatic lesion which frees a dose of copper sufficient to trigger off hemolysis, is discussed. The mechanism of the latter, that of the coagulation disorders observed, liver cell failure and widespread intravascular coagulation, are analysed in this paper and compared with data in the literature. The dramatic character of the case indicates that it is necessary to treat as a routine with penicillamine all homozygous forms of Wilson's disease.


[Endomyocardial biopsy by venous route. Our initial results]. The authors report their experience of right ventricular endomyocardial biopsy by the technic of Caves and Schulz. The instrument which consists of a spiral metallic catheter covered with synthetic material, includes at one end a hand lever and at the other end a biopsy forceps 3 mm in diameter. It is introduced through the skin into the right internal jugular vein then pushed under direct vision with an image intensifier upto the tip of the right ventricle. The angle of the distal part of the bioptome may be freely modified before use. Passage across the tricuspid orifice from the right atrium is usually easy. 30 good quality samples were thus taken from 10 patients with various forms of heart disease. There were no complications. The simplicity, rapidity and benign nature of this technic are emphasised together with its use in the diagnosis of myocardiopathies.


[Criteria of identification of schistosomiasis caused by Schistosoma hamatobium and S. mansoni (486 patients: 275 case of schistosomiasis)]. Out of a total of 486 patients who originated from French Equatorial Africa, from the West Indies or from the Indian Ocean, the authors identified 275 cases of schistosomiasis of which 230 were due to S. Hematobium and 45 to S. Mansoni. The diagnostic methods were biopsy of the rectal mucosa, immunofluorescence, in the West Indians, examination of the stools, in the Africans examination of the urine, intravenous urography and less often cystoscopy. The value of these investigations was studied in each case, then by comparison with one another and with data in the literature. The most valuable investigation was biopsy of the rectum, better in Africans than examination of the urine, immunofluorescence and better than cystoscopy when this was possible.


[Value of bone marrow biopsy in solid tumors. Apropos of 96 cases]. This study of 96 bone biopsies carried out in 84 patients with various malignant solid tumours showed 27 normal bone marrows, 21 hypoplastic marrows, 34 irritant marrows and 14 metastatic marrows. All the patients in the last group and 75% of those with signs of irritation already had other metastases. Tolerance to chemotherapy was better in the normal marrows than in the other cases. There was a significant relationship between the irritant or metastatic or metastatic aspect and the existence of peripheral leucoerythroblastosis (metastatic marrows) or increased platelets (irritant appearances). A significant difference existed during the first five months of survival between these cases with a metastatic marrow and those with an iritant marrow. Bone biopsy should, in our opinion, form part of the routine investigation of cancer patients. It may identify metasine investigation of cancer patients. It may identify metastases where radiography and bone scans have failed.


[10 cases of multiple malignant tumors]. The authors report ten cases of multiple malignant tumours noted on a general medical unit : 4 cases of chronic lymphatic leukemia associated with one visceral carcinoma. One case of polycythemia associated with a bifocal colonic carcinoma and a skin carcinoma. 5 double carcinomas mainly bronchial and digestive. They recall the general characteristics of these multiple carcinomas and discuss their pathogenesis with special reference to factors of immunodepression and genetic factors.


The FTA-ABS test: a diagnostic help or hindrance? The fluorescent treponemal antibody absorption (FTA-ABS) test, an excellent confirmatory treponemal test, has been used increasingly for syphilis screening and case detection. To evaluate its performance as an initial test, we did Venereal Disease Research Laboratory (VDRL) slide and FTA-ABS tests on 1,043 patients suspected of having syphilis. When retested in both a local and a reference laboratory, sera from 226 patients with borderline or reactive results demonstrated interlaboratory consistency for the VDRL but not the FTA-ABS. Borderline FTA-ABS results correlated poorly with the diagnosis of syphilis in both laboratories; a reactive FTA-ABS test correlated well only in the reference laboratory. Performance of the test appeared to be diminished by its use in a low-prevalence population and by seemingly minor alterations in the test procedure at the local laboratory.


Studies of serum testosterone and its reduction products. Levels of serum testosterone (T) and its metabolites dihydrotestosterone (D) and androstanediol (A) measured by a competitive protein binding method were as follows, respectively: in adult males (mean +/- 1 SD), 435 +/- 114, 41 +/- 11, 43 +/- 12 ng/100 ml; in adult females, 30 +/- 14, 18 +/- 8, 18 +/-9; in prepubertal males, 14 +/- 7, 10 +/- 4, 10 +/- 5; and in prepubertal females, 15 +/- 4, 9 +/- 4, 12 +/- 7. These studies are presented to establish relative normal values for these metabolites in various age groups. To help elucidate the role of testosterone metabolites in certain androgenic disorders, patients with idiopathic hirsutism and gonadal disorders were subjected to short-term stimulation with HCG or ACTH and suppression with dexamethasone. Most patients with idiopathic hirsutism showed suppression of all three androgens (particularly androstanediol). Further comparisons of these androgens may aid in elucidating the problem in idiopathic hirsutism.


Predictors of the duration of infectious mononucleosis. The clinical course of infectious mononucleosis was monitored in 122 patients to determine predictors of duration of illness. Gastrointestinal symptoms and palatal petechiae were associated with a prolonged recovery period. Multiple regression analysis of quantitative data identified the number of days from onset of symptoms to diagnosis as the only statistically significant indicator. Liver enzymes, white blood cell count, percentage atypical lymphocytes and heterophil titer had no prognostic value for the length of illness.


Anorexia nervosa: a combined therapeutic approach. Ten female patients with a diagnosis of anorexia nervosa were treated with a combination of behavior modification and psychotherapy and, when appropriate, psychotropic medication. All patients had favorable weight gain and improvement in adjustment during hospitalization. Later crises for each patient thus far have not significantly affected their weight. Three case histories illustrate the method used. The interrelationship between weight gain and the process in psychotherapy is illustrated and the psychopathologic features typical of this patient population are discussed. We conclude that the combined therapeutic method described is an effective and appropriate approach to the treatment of patients with anorexia nervosa.


Benign tumors of the esophagus: experience with 20 cases. Benign tumors of the esophagus are rare and require an alert suspicion for early diagnosis. These tumors may not cause symtoms before attaining large size, yet they may prove fatal when small. Because of the possibility of malignancy and their tendency to obstruct, benign tumors of the esophagus should be resected when diagnosed. This report details our experience in 20 patients with benign esophageal tumors seen at Emory University Hospital between 1955 and 1975. There were 15 men and five women in the group, ranging in age from 17 to 75 years. The tumor series included 13 leiomyomas, four cysts, two cases of multiple polyps, and one case of granular cell myoblastoma. Six of the tumors were asymptomatic; the remaining 14 had symptoms of dysphagia, pain, and hematemesis. In one instance, episodic hematemesis and melena were so severe that they produced hemorrhagic shock. Characteristic radiologic features helped in making the preoperative diagnosis in 18 of the 20 cases. Two patients had coexisting disease masking the presence of the esophageal tumor. Seventeen patients had surgical resection. There were no operative deaths and follow-up results have been satisfactory.


Intracranial meningioma containing metastatic foci. A case of a woman with carcinoma of the lung who died as the result of an expanding fluid mass over the right cerebral hemisphere is presented. Adjacent to this fluid mass was a small meningioma containing a metastatic focus. This was one of many metastases from the primary bronchiolar carcinoma. Photomicrographs are presented and comments regarding tumor collison are given.


Nephroblastoma in the Black child: a review of treatment in the Johannesburg Paediatric Tumour Clinic. Twenty-five Black children with nephroblastoma who were referred to the Paediatric Tumour Clinic during the preceding 4 years, are reviewed. Results indicate that in the case of a locally advanced, fixed, primary tumour, initial surgery, even if it is combined with chemotherapy, may be a factor in the rapid postoperative development of multiple pulmonary metastases. Pre-operative irradiation appeared to be advantageous for these patients. Long-term chemotherapy holds no advantage over short-term chemotherapy.


Paget's disease of the vulva: a case report. A patient with Paget's disease of the vulva is described. A brief review of some recent literature underlines the controversy regarding the histogenesis of the disease, and stresses the use of simple vulvectomy in its treatment. The importance of ruling out concomitant carcinoma is also stressed.


Parasitic infections in Black children in an endemic schistosomiasis area in Natal. Urine and stool specimens from 856 school children aged from 7 to 20 years, and from 80 preschool children, were examined for Schistosoma haematobium and intestinal helminths and protozoa. S. haematobium was present in 57% with a peak of 81% in 13-14-year-old children. Peak intensity preceded peak incidence and egg loads gradually decreased with age. There was no clear-cut difference between boys and girls with regard to intestinal parasites, nor was there a close correlation between the incidence of Schistosoma spp. and that of the intestinal parasites. There was a considerable reduction in the incidence of Ascaris lumbricoides and Trichuris trichiura infestation with age.


Kidney transplantation for the uremic diabetic patient. Although the diabetic patient is at high risk for transplantation and the progression of cardiovascular disease continues, results of our experience indicate that kidney transplantation can be performed with only slightly less favorable results than in the nondiabetic patients. We have found that the survival rate achieved by diabetics who receive a kidney graft is superior to that achieved by diabetic patients who receive dialysis. We also believe that some of the secondary complications of diabetes, which are aggravated by uremia, will be improved and that successful vocational rehabilitation is possible in the majority of diabetic patients.


Radiation-induced fibrosarcoma following treatment for breast cancer. A patient with radiation-induced fibrosarcoma following mastectomy and postoperative radiation for bilateral breast carcinoma is described. Only six such cases have been reported in the literature. In this patient erosion of the axillary artery produced massive hemorrhage, and emergency transthoracic ligation of the subclavian artery caused gangrene of the extremity and empyema and sepsis. Interscapulothoracic amputation not only was life-saving but offered the patient a reasonable chance for long-term survival. Only aggressive surgical management can salvage a patient with radiation-induced sarcoma.


Viral infections in renal transplant donors and their recipients: a prospective study. The majority of renal allograft recipients develop viral infections, usually with cytomegalovirus (CMV). Their source if virus has not been defined clearly; one possibility if the transplanted kidney itself. To explore this, prospective viral studies were performed on 28 living related donor-recipient pairs. Donors did not have clinical illnesses and viruses were not recovered from throat, urine, or renal tissue, but five (18%) had fourfold rises in antibody titers to herpes group viruses. During the 6 months after transplantation, 24 recipients (86%) had viral infections, 18 of which were associated with CMV. There was no correlation between specific titer rises in the donors and infections in the recipients. Recipients with dual viral infections had more severe clinical courses than those with single infections or with no infection. Recipients with complement-fixing (CF) antibodies to CMV pretransplant had a higher incidence of CMV infections than recipients without pretransplant antibody. Three of seven recipients who lacked CF antibody to CMV and whose donors were seropositive developed clinical illnesses associated with CMV. Latent virus might have been transmitted with the transplanted kidney in these instances, but since lack of CF antibody does not rule out previous CMV infection, the CMV could have been of recipient origin. We conclude that the donor organ is a source of virus for few renal transplant recipients.


Experience with regional vaccination against swine fever in enzootic areas for limited periods using C-strain virus. In three areas of the Netherlands with a high incidence of swine fever all pigs over two weeks old were vaccinated with the so-called "Chinese" (C)-strain of vaccine virus. The mass vaccination at the start of each compaign was supplemented thereafter by vaccination of young stock at the age of 6 to 8 weeks and of all pigs introduced from outside. In one area vaccination was pursed for three years, and in two areas for one year. Vaccination was compulsory and supported by stamping out of affected herds and the application of the usual veterinary police measures. The number of outbreaks in the vaccinated areas declined from two weeks after the start of the campaign and clinical disease had diappeared after five months. During this period outbreaks related to vaccination were diagnosed in each area. Some outbreaks were due to vaccination procedures which probably caused the spread of virus from congenitally infected litters to susceptible piglets, which had lost maternal antibodies. Only one "vaccine break" was diagnosed. Outbreaks of swine fever, due to the presence of residual virus in the designated areas, have not been reported up to two years after vaccination was discontinued. The campaigns have shown that swine fever can be eradicated from enzootic areas by a strict vaccination regime pursued for one year.


[An atypical form of Aujezky's disease after vaccination (author's transl]. Four atypical case of Aujezky's disease in dogs are described. Two weeks before the outbreak of the disease, the dogs had been vaccinated with a live tissue culture vaccin, based on the Bartha strain. By culturevirus (cytopathogenic effect) the Bartha vaccin was identified and a vaccination reaction was proved. Vaccination with this must be discouraged.


[Aujeszky's disease in goats (authors transl)]. The small number of cases of Aujeszky's disease in goats referred to in the literature is stressed, and an outbreak in goats causing many deaths is reported. The flock of goats concerned was occasionally housed in a barn during the night in which there also were fattening pigs. The first deaths occurred without previous symptoms, the animals being found dead in the morning. In subsequent cases, symptoms were observed which continued for a few or several hours and consisted in agitation, lying down and rising, screaming plaintively, profuse sweating and, in the terminal stage, spasms and paralysis. Pruritus was not observed in any of the animals. Of the fifteen goats which had been housed in the pig-sty, thirteen died during ten days. In the same period, only one out of forty pigs died, and the others showed anorexia and somnolence for a couple of days but soon recovered. In two goats studied, the virus of Aujeszky's disease was isolated from the central nervous system. It is suggested that, in cases of disease or death in ruminants occurring in the proximity of pigs, there should primarily be a strong suspicion of Aujeszky's disease, regardless of the symptoms observed.


Stomach cancer of a 14-year-old boy with ataxia-telangiectasia. A 14-year-old boy with ataxia-telangiectasis died of pneumonia, stomach cancer and its diffuse metastasis. The onset of walding gait was noticed from 3 years of age. Immune globulin including IgA was normal or slightly increased. Main autopsy findings were: old cancerous ulcer of 1.4 X 2.3 cm at the lesser curvature, and diffuse cancer infiltration over ulcer surface to serous membrane. The tumor was diagnosed histologically as adenocarcinoma tabulare mucocellulare.


Determination of hydroxylysine in urine. A new method for colorimetric determination of urinary hydroxylysine is described. Approximately one-hundredth of human urine collected for 24 hr was diluted to 25 ml and titrated to pH 2.0 with 2  hcl, and then subjected to column chromatography on Dowex 50 X 4 (H+ form). Amino acids were eluted from the column with 1.5 N NH4OH. Hydroxylysine in the elute with 1.5 N NH4OH was separated from the other amino acids, especially from serine and threonine, by preparative paper chromatography. The paper corresponding to hydroxylysine was cut and eluted with water. An aliquot of the eluate with water was oxidized by sodium metaperiodate, and formaldehyde liberated from hydroxylysine was assayed by chromotropic acid reagents, after removing periodate and iodate with Dowex 1 X 8 (formate form). Excretion rate of hydroxylysine in urine of adults was shown to be approximately 110 mumoles per day.


Serum angiotensin converting enzyme activity in human bronchial asthma. Using hippuryl-L-histidyl-L-leucine as a substrate analog, serum angiotensin converting enzyme (ACE) was spectrophotometrically estimated in patients with bronchial asthma. There were significantly low activities of serum ACE in 115 patients with bronchial asthma irrespective of the presence or absence of acute attack. The activity of serum ACE was reduced more markedly in the chronic type of bronchial asthma than in the paroxysmal type.


[2 pools of mitochondria in a single mechanoreceptor neuron]. The microspectrofluorimetric technique was applied to measure the intracellular ratio of oxidized flavoproteins and NADH in isolated neuron preparation from the stretch receptor organ of the crayfish Astacus leptodactilus. Two pools of mitochondria were detected differing from each other in their functional activity in the single cell at the same time. The mitochondria of the pool are localized near the nucleus, those of the other one being placed along the cell membrane. Physiological treatments (stretch, calcium deficient media) produce different changes in the activity of mitochondria belonging to the different pools. It is suggested that these pools of mitochondria furnish with energy different functional mechanisms within the same cell.


Direct evidence for absence of beta-adrenergic receptors in rat cerebral vessels histochemical study with a fluorescent beta-blocker. A fluorescent marker for beta-adrenergic receptor sites, 9-amino-acridin propranolol (9-AAP), was administered intravenously to rats. In contrast to other tissues which are known to contain beta-adrenergic receptors, 9-AAP fluorescence was not observed in the walls of the pial as well as parenchymal cerebral vessels. These negative findings strongly suggest that in the rat, beta-adrenergic receptors are not present in the cerebral vasculature. The role of the alpha-adrenergic receptors needs more study.


Lower motor neuron disease in wild mice caused by indigenous type C virus and search for a similar etiology in human amyotrophic lateral sclerosis. In certain genetically susceptible populations of wild mice a progressive motor neuron disease with a long latent period is caused by indigenous type C leukemia virus. Neuronal damage appears to be due primarily to a direct neurotropic effect of the virus and not to an immunogenic mechanism. The disease can be prevented by antiviral genetic means. Search for a similar virus in humans with ALS has been negative.


[Cholesterol synthesis in the skin of rats with rickets]. The rachitogenic diet causes an inhibition of cholesterol synthesis in rat skin. Intensity of 2-14S-acetate incorporation into cholesterol precursors (matastenol, lathosterol, 7-dehydrocholesterol) and cholesterol drops considerably. UV-irradiation of animals suffering from rachitis intensifies cholesterol synthesis in skin. Simulteneously an increase is detected in the metabolic fund of cholesterol synthesis precursors, including 7-dehydrocholesterol, which is necessary to form antirachitic compounds in the organism.


[Effect of glucocorticoid hormones on nuclear RNA-polymerase activity and RNA metabolizability in rat skeletal muscles]. It has been found that in hypercorticism induced by a prolonged ACTH administration when protein synthesis is inhibited in the skeletal muscles the incorporation of Na2HP32O4 into muscle RNA intensifies by 30% and the RNA-polymerase activity of muscle nuclei is approximately twice as high. In the adrenalectomized rats 3 hours after a single hydrocortisone administration a sharp rise in the RNA-polymerase activity of the skeletal muscle nuclei is observed as well. Such an increase in RNA synthesis is suggested to be a response to the inhibition of protein synthesis through feedback mechanisms.


[Neurochemical mechanisms of the action of tricyclic antidepressants of the imipramine group]. The main role in determination of the pharmacologic effects of the imipramine groups antidepressants is given to their influence on neurotransmitters metabolism in synapses, the activity of enzymic systems regulating the transport of ions, as well as on the system of cyclic AMP metabolism. Interaction of tricyclic antidepressants with membrane and, as the result, distrubance in reuptake of transmitters (epinephrine and 5-hydroxytryptamine) in neurons is supposed to be one of the mechanisms of synaptic transmission regulation. The possible role in inhibition of biological amines deamination, in particular of phenylethylamine, in antidepressive effect of tricyclic antidepressants is discussed. It is supposed that the thymoanaleptic effects of the imipramine group antidepressants are due to activation of central serotoninergic processes, and their psychoanaleptic effect due to activation of the adrenergic system. Inhibition of the Na+, K+-ATPase activity quilizing effect of tricyclic antidepressants.


[The effect of newer anthelmintics on Fasciola hepatica in experimentally infected rats]. The reports deals with the results of testing seven new antihelminthics for Fasciola hepatica in the experimentally invaded Wistar rat. The greatest influence on juvenile flukes (2 and 4 weeks of age) was exerted by diamphenetid (Coriban) applied in a single dose of 100 mg kg-1. Hexachlorophene applied in the dose of 50 mg kg-1 showed the highest effect on sexually mature flukes. All the tested antihelminthics of the halogenated salicylanilide group were ineffective on juvenile stages and only slightly effective on mature F. hepatica flukes. It follows from the results that the effectiveness of some antifasciolics on laboratory animals need not always be in correlation with their effect in ruminants - hence it is necessary to verify the results obtained in laboratory animals and to check them on natural F. hepatica hosts.