Showing papers in "Experimental Biology and Medicine in 1968"
TL;DR: A highly sensitive and specific radioimmunoassay for rat LH has been developed utilizing antiovine LH serum and ovine LH for iodination, and it has been possible to measure the LH in serum obtained from females throughout the estrus cycle and in serum from normal and castrated males.
Abstract: SummaryA highly sensitive and specific radioimmunoassay for rat LH has been developed utilizing antiovine LH serum and ovine LH for iodination. Estimates of the LH potency of pituitary preparations...
845 citations
TL;DR: Ingestion of acetylsalicylic acid in a divided dose 1 and 2 hours prior to testing abolished secondary aggregation, serotonin release, and platelet factor-3 activation induced by ADP, as well as aggregation and serotonin release induced by connective tissue particles, but did not affect primary ADP-induced aggregation.
Abstract: SummarySecondary aggregation of platelets was produced in 8 of 10 normal subjects by a critical concentration of adenosine diphosphate (ADP) ranging from 1.0-2.0 μM. Shortening of the Russell Viper Venom clotting time and release of serotonin-14C were also observed with the critical concentration of ADP or with higher levels, but did not occur in the two subjects who showed only primary aggregation in response to ADP. Ingestion of 1.3 gm of acetylsalicylic acid in a divided dose 1 and 2 hours prior to testing abolished secondary aggregation, serotonin release, and platelet factor-3 activation induced by ADP, as well as aggregation and serotonin release induced by connective tissue particles, but did not affect primary ADP-induced aggregation.
301 citations
TL;DR: One hundred and six isolates of Cryptococcus neoformans investigated by agglutination and absorption studies with anti-cryptococcal sera suggested the possibility of major differences in the distribution of cryptococcal serotypes.
Abstract: SummaryOne hundred and six isolates of Cryptococcus neoformans were investigated by agglutination and absorption studies with anti-cryptococcal sera. In addition to the three previously reported serotypes, a fourth serotype was distinguished and designated type D. Of the 106 isolates from man and nature, 69.8% were type A, 10.4% were type B, 6.6% were type C, and 4.7% were type D, 3.8% reacted with more than one serum, and 4.7% were untypable. The majority of type B and C strains were obtained from California, suggesting the possibility of major differences in the distribution of cryptococcal serotypes.
206 citations
TL;DR: The perfect correlation obtained between CPE, presence of virus particles, and reproduction of MD by these cells suggests a cause and effect relationship and circumstantially implicates this virus in the etiology of Marek's disease.
Abstract: SummaryDuck embryo fibroblast (DEF) monolayer cultures seeded with whole blood from birds inoculated with the JM strain of Marek's disease (MD) and which showed a cytopathic effect (CPE), also contained intranuclear herpes-like virus particles. Complete virus particles with envelope essential for infectivity of herpesviruses were not found in either the infected cells or the extracellular materials of cultures containing such cells. All cultures showing CPE contained virus particles, and when inoculated into susceptible chicks caused MD. Cytopathic effect and viral synthesis could not be induced in fresh DEF cultures with spent media from infected cultures passed through 450 mμ Millipore filters. The perfect correlation obtained between CPE, presence of virus particles, and reproduction of MD by these cells suggests a cause and effect relationship and circumstantially implicates this virus in the etiology of MD.
198 citations
TL;DR: Cerebral cortex obtained from scrapie infected mice was examined in the electron microscope and three structures of unknown origin and significance were observed, generally associated in one way or another with synaptic terminals, but on rare occasions, they were found in unidentified cell processes.
Abstract: SummaryCerebral cortex obtained from scrapie infected mice was examined in the electron microscope. Three structures of unknown origin and significance were observed: (a) enlarged cell processes containing particles and rods, (b) enlarged cell processes occupied by varicose tubules filled with moderately dense material and (c) oval bodies formed by parallel bands and fibrils which were usually but not always, in a ring-like arrangement. These structures were generally associated in one way or another with synaptic terminals, but on rare occasions, they were found in unidentified cell processes. The possible significance of the presence of these structures in scrapie infected mouse brain is discussed.
190 citations
TL;DR: Data indicate that the JM strain of Marek's disease was successfully propagated in DEF cultures and produced a characteristic CPE.
Abstract: SummaryA focal cytopathic effect (CPE) was observed in duck embryo fibroblast (DEF) cultures 11-25 days postinoculation with blood from the JM strain of Marek's disease (MD). All cell suspensions from such cultures reproduced MD when inoculated into chicks, while all of the morphologically normal DEF cultures were noninfectious. The CPE and infectivity were maintained in DEF cultures for 182 days. Both the induction of CPE in cell cultures and MD in chickens required intact cells in the inoculum. These data indicate that the JM strain of MD was successfully propagated in DEF cultures and produced a characteristic CPE.
175 citations
TL;DR: The ability of chicks to utilize glucose-U- 14C and acetate-1-14C as substrates for lipid synthesis has been studied and chick adipose tissue was found to be of minor importance as compared to liver.
Abstract: SummaryThe ability of chicks to utilize glucose-U-14C and acetate-1-14C as substrates for lipid synthesis has been studied. Chicks readily incorporated glucose and acetate carbon into fatty acids and nonsaponifiable lipids of liver and adipose tissue. Glucose-U-14C was also utilized for glyceride-glycerol formation. The relative importance of adipose tissue and liver as sites of fatty acid synthesis was estimated. Chick adipose tissue was found to be of minor importance as compared to liver, accounting for no more than 30% of total fatty acid synthesis.
159 citations
TL;DR: This report describes more fully the results of an experiment devised to distinguish between the direct effects of X-rays on leukocyte chromosomes and a possible indirect effect mediated by way of blood plasma.
Abstract: Radiation can damage human chromosomes, both in vivo (1-5) and in vitro (6-8). This report describes more fully the results of an experiment devised to distinguish between the direct effects of X-rays on leukocyte chromosomes and a possible indirect effect mediated by way of blood plasma. Blood plasma from patients who had received large doses of X-ray enhanced the degree and frequency of chromosomal aberrations of normal nonirradiated lymphocytes in short-term cell culture (9).Materials and Methods. Six patients with a variety of tumors were chosen because they had received large doses of X-rays through several different ports (see Table I). X-ray integral doses varying from 2.88 to 25.1 × 106 gR were given with a 2 meV van de Graaf generator. Six other patients with similar tumors, studied prior to X-ray, served as controls for the first group. Three of the control patients with tumors were studied before and after X-ray. None of the patients received chemotherapeutic agents or had symptoms of viral inf...
145 citations
TL;DR: An antiserum to bovine parathyroid hormone with high affinity for bovines and human parathy thyroid hormone was produced in a chicken, making possible sensitive and reproducible measurement of the hormone in normal and abnormal human sera by radioimmunoassay.
Abstract: SummaryAn antiserum to bovine parathyroid hormone with high affinity for bovine and human parathyroid hormone was produced in a chicken. It made possible sensitive and reproducible measurement of the hormone in normal and abnormal human sera by radioimmunoassay. Unequivocal separation of normal, hypoparathyroid, and hyperparathyroid sera was obtained.
136 citations
TL;DR: It is concluded that the thymic elements required for neoplastic conversion by MLV are not eliminated by ALS, which may alter the pathology of the induced tumors by a combination of immunosuppression and capacity to stimulate the proliferation of primitive lymphoid cells.
Abstract: Summary Repeated injections of rabbit antiserum against the lymphoid cells of mouse thynius (ALS) were found to increase markedly the evidence of tumors in resistant strains of mice neonatally infected with polyoma virus. In this system the effects of ALS are similar to those of early thymectomy. The BALB/c mice receiving repeated injections of ALS and infected intraperitoneally with Moloney leukemogenic virus (MLV) when 21 days old showed an increased incidence of lymphoid neoplasms as compared to that in untreated controls infected at the same age. The majority of tumors in the treated animals were reticulum cell sarcomas, type A, developing subcutaneously at the site of injection of the ALS 3-6 weeks after infection with MLV. Early thymectomy markedly decreased the incidence of leukemias in BALB/c mice infected with MLV when 3 weeks old. In this system the effects of ALS are the opposite of those produced by thymectomy. It is concluded that the thymic elements required for neoplastic conversion by MLV are not eliminated by ALS, which may alter the pathology of the induced tumors by a combination of immunosuppression and capacity to stimulate the proliferation of primitive lymphoid cells.
134 citations
TL;DR: Preliminary pathologic studies indicate a marked cytotoxic effect of the chemical on the neuroblast, and the condition is not associated with microsplanchnia and appears to be limited to the cortical hemispheres of the brain.
Abstract: SummaryAn experimental model for successful chemical induction of microencephaly is described. Methylazoxymethanol, the aglycone of cycasin, when administered to rats at a dose of 20 mg/kg of body weight on day 14 or 15 of pregnancy, uniformly produces microencephaly in all litter mates. This effect occurs independent of the strain of rats used and is highly reproducible. The condition is not associated with microsplanchnia and appears to be limited to the cortical hemispheres of the brain. Preliminary pathologic studies indicate a marked cytotoxic effect of the chemical on the neuroblast. Gliomas have occurred in about 10% of microencephalic rats permitted to live beyond 1 year.
TL;DR: It was found that female mice developed a stronger and longer lasting immune response and thatfemale mice were more responsive to small doses of antigen.
Abstract: SummaryThe immune response to a protein antigen (BSA, bovine serum albumin) was compared in male and female mice. It was found that female mice developed a stronger and longer lasting immune response and that female mice were more responsive to small doses of antigen. An explanation based on the effect estrogens have on phagocytosis is discussed.
TL;DR: It is found that the soluble fractions from the livers of female rats and four male rodent species resistant to hepatocarcinogenesis by N-hydroxy-AAF have lower capacities to transfer sulfate from PAPS to N- Hydroxy-AAF than do the soluble fraction of male rat livers.
Abstract: In comparison with the very limited or not detectable reactivity of the versatile carcinogen N-hydroxy-2-acetylaminofluorene (N-hydroxy-AAF) (1-3) with proteins and nucleic acids (4-7), its esters have shown a strong nonenzymatic reactivity at pH 7 with these tissue constituents and certain of their components (4, 8-13). The sulfonium derivatives formed by reaction of esters of N-hydroxy-AAF with methionine decompose spontaneously to yield 1- and 3-methylmercapto-AAF (0-CH3S-AAF) (8, 11), and the same compounds can be liberated by alkali at room temperature from the liver protein of rats fed N-hydroxy-AAF (11, 14). Similarly, a product obtained by enzymatic digestion of liver RNA from rats administered N-hydroxy-AAF appears to be identical with N-(guanosin-8-yl)-AAF, formed by reaction of esters of N-hydroxy-AAF with guanosine in vitro (11, 14). These findings indicate that esters of N-hydroxy-AAF are involved in the formation in vivo of protein- and nucleic acid-bound derivatives of N-hydroxy-AAF in the ...
TL;DR: Poliovirus can replicate and be passed serially in monolayer cultures of a line of hamster embryo cells subsequently fused with Sendai virus completely inactivated by low concentrations of beta propiolactone.
Abstract: SummaryPoliovirus can replicate and be passed serially in monolayer cultures of a line of hamster embryo cells subsequently fused with Sendai virus completely inactivated by low concentrations of beta propiolactone. Poliovirus fused into such a system produces a characteristic cytopathic effect.
TL;DR: Bee venom and a derived polypeptide fraction (melittin) were shown to have antibacterial activity against a penicillin-resistant strain of Staphylococcus aurens by a method similar to that used for plate sensitivity tests.
Abstract: SummaryBee venom and a derived polypeptide fraction (melittin) were shown to have antibacterial activity against a penicillin-resistant strain of Staphylococcus aurens (strain 80). This activity wa...
TL;DR: The zinc, content of serum was consistently higher than the zinc concentration in plasma by an average of 16% and zinc was determined in platelets concentrated from 10 individuals and was present in a significant amount.
Abstract: SummaryThe zinc, content of serum was consistently higher than the zinc concentration in plasma by an average of 16%. Because platelets are largely disintegrated in the clotting process, zinc was determined in platelets concentrated from 10 individuals and was present in a significant amount. It was demonstrated that 39% of the increased concentration of zinc in serum can be attributed to a slightly greater dilution in plasma, 44% being derived from platelets and 4.0% from hemolysis. This is the first known report demonstrating zinc in platelets.
TL;DR: Beta-naphthoflavone, a potent inducer of increased polycyclic hydrocarbon hydroxylase activity, was found to inhibit the occurrence of neoplastic lesions resulting from DMBA in experiments in which the beta naphth oflavone was given prior to the carcinogen.
Abstract: SummaryBeta-naphthoflavone, a potent inducer of increased polycyclic hydrocarbon hydroxylase activity, was found to inhibit the occurrence of neoplastic lesions resulting from DMBA in experiments in which the beta naphthoflavone was given prior to the carcinogen. Pulmonary adenoma formation in the A/HeJ strain mouse resulting from oral administration of DMBA and mammary tumor formation in the Sprague-Dawley rat also from oral administration of the same carcinogen were both inhibited by beta-naphthoflavone.
TL;DR: The kinetics of RNA, DNA, and protein synthesis were analyzed in normal and CLL lymphocytes stimulated by PHA in vitro and suggest that many CLLymphocytes are capable of responding to PHA but the response is distinctly delayed.
Abstract: SummaryThe kinetics of RNA, DNA, and protein synthesis were analyzed in normal and CLL lymphocytes stimulated by PHA in vitro. Normal cultures exhibited maximal increases in lymphocyte nucleic acid and protein synthesis 2 to 3 days after exposure to PHA. Under identical conditions the maximal response on the part of the lymphocytes in CLL cultures occurred between 5 to 7 days. The data suggest that many CLL lymphocytes are capable of responding to PHA but the response is distinctly delayed.
TL;DR: A regimen of small doses of the complexes elicited high titers of both types of antibodies in eight out of eight rabbits, indicating a potent immunogen for the elicitation of both anti-BSA and anti-ACTH antibodies.
Abstract: SummaryA method is described for the uniform elicitation of antibodies in rabbits to ACTH. Porcine ACTH and bovine serum albumin have been covalently cross linked with glutaraldehyde. This complex is non-steroidogenic and a potent immunogen for the elicitation of both anti-BSA and anti-ACTH antibodies. A regimen of small doses of the complexes elicited high titers of both types of antibodies in eight out of eight rabbits. These titers are still present 6 months after the last injection of antigen.
TL;DR: Diphenylhydantoin resulted in reduced fetal weight in both strains when given during late embryogenesis, and the incidence of cleft palate was significantly elevated in late, but not early, treated progeny of both strains.
Abstract: SummaryDiphenylhydantoin, 50 mg/kg, s.c., was administered to primigravid Swiss-Webster and A/J mice during early (days 7, 8, 9) and late (days 11, 12, 13) embryogenesis. Litters were delivered by caesarean section on day 18 of gestation, weighed, examined, and measured. Resorption rates were not altered in either strain treated during early embryogenesis. The A/J, but not Swiss-Webster, mice treated during late embryogenesis had a significant (p<0.05) increase in resorption. Diphenylhydantoin resulted in reduced fetal weight in both strains when given during late embryogenesis. Fetal long bone length, measured in alizarin red stained fetuses, was shortened only in late treated Swiss-Webster mice. The incidence of cleft palate was significantly elevated in late, but not early, treated progeny of both strains. Cleft palate with cleft lip occurred only in A/J mice; the rate was not different from vehicle treated controls. No other soft tissue malformations were found in either strain following Bouin's fixat...
TL;DR: Sera of patients with fogo selvagem or BPF (Brazilian pemphigus foliaceus) were found to contain antibodies reactive with the intercellular areas of stratified squamous epithelium of esophagus and skin as revealed by indirect IF (immunofluorescent) staining.
Abstract: SummarySera of patients with fogo selvagem or BPF (Brazilian pemphigus foliaceus) were found to contain antibodies reactive with the intercellular areas of stratified squamous epithelium of esophagus and skin as revealed by indirect IF (immunofluorescent) staining. These intercellular antibodies could not be distinguished histologically from those associated with nonendemic pemphigus (i.e., the forms of pemphigus which occur in rest of the world). The following observations were made on these antibodies: (1) Only sera of patients with pemphigus were found to contain these intercellular antibodies. None of 56 control sera yield such staining patterns. (2) Indirect IF staining titers of the intercellular areas could be determined reproducibly ± 1 doubling dilution in the two participating laboratories in a double blind study of 29 sera. (A 30th serum is discussed under point 5 below.) (3) The titers of intercellular antibodies appeared to be proportional to the severity of the disease process in BPF. (4) Th...
TL;DR: Interferon production and antiviral activity by L cells treated with double-stranded synthetic polynucleotide complex I:C is increased up to one hundred times by addition of DEAE-dextran.
Abstract: SummaryInterferon production and antiviral activity by L cells treated with double-stranded synthetic polynucleotide complex I:C is increased up to one hundred times by addition of DEAE-dextran. Highest interferon production (300 units) was observed when I:C (10 μg/ml) and DEAE-dx (200-400 μg/ml) were held in contact with the cells for a 12-hour period. However increased amounts of interferon were also produced when the inducer and DEAE-dx were removed 2 hours after their addition and the cultures were reincubated for 10 additional hours. The inhibitor produced was shown to have properties consistent with those of interferon.
TL;DR: The present report describes the occurrence of measles antigen and syncytia formation in cells propagated in vitro from the brain of a patient with SSPE, and the production of syncyTia in several kinds of cultured cells when exposed to these brain cells.
Abstract: Subacute sclerosing panencephalitis (SSPE) is a progressive degenerative, neurologic disease of children that begins with mental and motor deterioration. After an interval of weeks or months, a state of plastic rigidity, interrupted by myoclonic jerks, intervenes. Coma, with signs of decortication and often of hypothalamic dysfunction, occurs during the terminal stage of this fatal illness.Observation of cytoplasmic and nuclear inclusion bodies in cortical neurons of patients with SSPE led Dawson to propose a viral etiology for this disease (1). Evidence for an association between SSPE and measles virus has been reviewed and includes: a history of measles infection prior to the onset of symptoms; demonstration by electron microscopy of structures in the diseased brain that are morphologically similar to the nucleocapsids of paramyxoviruses; detection of measles, or a related antigen by immunofluorescence in the brain of patients with SSPE; and presence of exceptionally high levels of antibody against meas...
TL;DR: Model synthetic solutions were used to study cholesterol solubilization by the 6 conjugated bile salts found in human bile individually and as a mixture, and by lecithin in combination with bile salt.
Abstract: SummaryModel synthetic solutions were used to study cholesterol solubilization by the 6 conjugated bile salts found in human bile individually and as a mixture, and by lecithin in combination with bile salts. In the range of concentrations found in bile, bile salts alone solubilized only about one third as much cholesterol as might be found in comparable concentrated human gallbladder bile. Between 0.023 and 0.046 mmoles of cholesterol were solubilized per mmole of bile salts. Addition of lecithin to a bile salt solution increased the quantity of cholesterol dissolved to values observed in bile; 0.36 mmoles of cholesterol was solubilized per mmole of added lecithin. Cholesterol solubilization by lecithin was independent of the concentration and nature of the bile salt.
TL;DR: Cell lines and strains were studied with respect to possession of G-6-PD isoenzymes, using cellulose acetate strips and sucrose-agar gel electrophoretic media, which provided higher resolution of A and B bands.
Abstract: SummaryCell lines and strains were studied with respect to possession of G-6-PD isoenzymes, using cellulose acetate strips and sucrose-agar gel electrophoretic media. The latter provided higher resolution of A and B bands. The A and B types of G-6-PD were found to occur in human, diploid cultured cell populations in accordance with racial origin of the donor; while certain other heteroploid cell lines were found to possess A type G-6-PD irrespective of donor race.
TL;DR: Studying in rabbits indicates that serum muramidase activity probably is derived mostly from the degradation of granulocytes, and data suggest that serum Muramid enzyme levels may be a useful index ofgranulocyte turnover.
Abstract: SummaryStudies in rabbits indicate that serum muramidase activity probably is derived mostly from the degradation of granulocytes. The data also suggest that serum muramidase levels may be a useful index of granulocyte turnover.
TL;DR: It is concluded that most Friend virus preparations contain at least 2 viruses: one which has spleen focus-forming activity (SFFV) and which probably is responsible for inducing polycythemia when present in high titers, and another which, when active in the presence of little or no SFFV, induces anemia.
Abstract: SummarySeveral strains of Friend virus were tested for their ability to initiate focus formation in the spleens of susceptible mice. Strains which induce polycythemia had high focus-forming activity, while strains which induce anemia had little or no focus-forming activity. A positive correlation was also demonstrated between virus strains with focus-forming activity and those which initiate the resumption of erythropoiesis in plethorized mice. It is concluded that most Friend virus preparations contain at least 2 viruses: one which has spleen focus-forming activity (SFFV) and which probably is responsible for inducing polycythemia when present in high titers, and another which, when active in the presence of little or no SFFV, induces anemia. The role of either virus in initiating leukemia remains to be determined.
TL;DR: An oral hydrophilic colloid was fed for a 6-week experimental period to 2 normally active young adult males on a self-selected mixed diet, with the following results: total fecal bile acids per 24 hours obtained during the experimental period averaged 3 times the excretion level of the control period.
Abstract: SummaryAn oral hydrophilic colloid (9.6 gm/day), after a 4-week preexperimental control period, was fed for a 6-week experimental period to 2 normally active young adult males on a self-selected mixed diet, with the following results: Total fecal bile acids per 24 hours obtained during the experimental period averaged 3 times (302%) the excretion level of the control period. Serum cholesterol levels during the experimental period averaged 17% lower than during the control period. These differences were statistically highly significant by t test (p < 0.005). Total neutral sterol excretion per 24 hours in the experimental period was unchanged from the values measured during the control period. The mechanism by which the mucilloid increases fecal bile acid excretion is unknown.
TL;DR: Spiny lobsters, P. argus, immunized with living or killed bacteria, have been shown to synthesize a nondialyzable bactericidin, which was present in the hemolymph and was usually detectable within 12 hours.
Abstract: SummarySpiny lobsters, P. argus, immunized with living or killed bacteria, have been shown to synthesize a nondialyzable bactericidin. This substance was present in the hemolymph and was usually detectable within 12 hours. In the primary response, it reached a peak within 24-48 hours. The most effective antigen was a gram-negative bacillus, EMB-1, isolated from the normal intestinal flora of healthy P. argus. Varying results were obtained when specificity was tested with heterologous bacteria, but the bactericidin was less specific than mammalian antibody. Heating at 65°C for 20 min was required for complete inactivation. EDTA, dialysis, carrageenin, and freezing failed to inactivate this substance. It could be adsorbed by homologous and heterologous bacteria.
TL;DR: Aminoglutethimide was found to be a competitive inhibitor of the enzymatic conversion of cholesterol to pregnenolone by the adrenals due wholly or in part to an inhibition of the 20-hydroxylation of cholesterol.
Abstract: SummaryAminoglutethimide was found to be a competitive inhibitor of the enzymatic conversion of cholesterol to pregnenolone by the adrenals. This effect is due wholly or in part to an inhibition of the 20-hydroxylation of cholesterol.