Showing papers in "Experimental Biology and Medicine in 1967"
TL;DR: While the B-cytotoxic effects of streptozotocin resemble those of alloxan, their specificity is very much greater, as demonstrated by the wide margin between diabetogenic dose and general toxicity.
Abstract: SummaryStreptozotocin is a highly effective cytotoxic agent for pancreatic B-cells. After intravenous administration of 65 mg streptozotocin per kg, damage to B-cells is apparent as early as one hour after intravenous administration of the drug. Frank necrosis associated with phagocytosis is best seen after 7 hours, when pancreatic insulin release and hypoglycemia are also noted. By 24 hours, pancreatic insulin content is reduced to 5% of normal or less. While the B-cytotoxic effects of streptozotocin resemble those of alloxan, their specificity is very much greater, as demonstrated by the wide margin between diabetogenic dose and general toxicity.
566 citations
TL;DR: A cell line derived from a myeloma patient was found to produce only λ−type light chains of immunoglobulin which were secreted into the culture medium.
Abstract: SummaryA cell line derived from a myeloma patient was found to produce only λ−type light chains of immunoglobulin which were secreted into the culture medium. There appears to be no formation of γ−, α−, or μ−heavy chains or of intact immunoglobulins. The light chains produced gave a reaction of identity with the Bence-Jones protein of the original patient's urine upon immunodiffusion and showed a similar molecular size upon gel filtration. The cells produced about 15 μg λ−chain per day per 106 cells (45 × 107 chain molecules per day per cell) under the culture conditions used.
296 citations
TL;DR: The simplicity of the technique permits an experienced operator to immobilize an animal in approximately 30 to 45 seconds, and use of the plastic box permits immobilization in a relatively uniform volume.
Abstract: Discussion and conclusionThis method offers several significant advantages over those described previously. The simplicity of the technique permits an experienced operator to immobilize an animal in approximately 30 to 45 seconds. Only 2 hours are required to produce lesions, offering further saving of time. Apparently this rapid production of lesions represents a synergistic effect of the dual stresses employed. We believe that the mode of restraint also contributes to the improved results obtained. This method obviates additional environmental variables that may be difficult to control, e.g., increased temperature, as with plaster of paris immobilization (5); pain, as with nailing the paws to a board (1); or ingestion of sharp metal fragments, as with wire screen immobilization(3). Furthermore, use of the plastic box permits immobilization in a relatively uniform volume. Bonfils and Lambling, on the basis of studies in a large series of animals, described a linear inverse relationship between incidence ...
264 citations
TL;DR: The inhibition of hemagglutination was found to be a sensitive technique for detection of small amounts of antigen in sheep erythrocytes by brief treatment with glutaraldehyde.
Abstract: SummaryMethods have been described for the preservation of sheep erythrocytes by brief treatment with glutaraldehyde. These cells could be conjugated to proteins in the presence or absence of coupl...
216 citations
TL;DR: Single cell clones derived from 4 lines of human leukemia and Burkitt lymphoma cells in long-term culture by a semi-solid agar procedure showed some clonally derived cell strains were shown to produce only one component of heavy chain immunoglobulins and others produced 2 components as determined by immunofluorescence.
Abstract: SummarySingle cell clones were derived from 4 lines of human leukemia and Burkitt lymphoma cells in long-term culture by a semi-solid agar procedure. Some clonally derived cell strains were shown to produce only one component of heavy chain immunoglobulins and others produced 2 components as determined by immunofluorescence. One of 4 cell lines tested contained 2 different types of cells. One cell type produced only Ig M. The other cell type produced both Ig M and Ig G. All of the clones derived from 3 other cell lines produced the same immunoglobulins as their parent cultures.We thank Mr. Donald Wudarski for excellent technical assistance and Dr. M. Konn for assistance with the immunofluorescent studies.
209 citations
TL;DR: It is demonstrated that “normal” propulsive activity is determined to a significant degree by the presence of the normal flora, and this function of the flora has important implications for host defense.
Abstract: SummaryThe rate of propulsion of gastrointestinal contents was compared in germfree and conventional mice using a non-absorbable radioactive substance, yttrium 91. Following intragastric administration, the marker was propelled much more rapidly through the gastrointestinal tract of conventional as compared to germfree animals, demonstrating that “normal” propulsive activity is determined to a significant degree by the presence of the normal flora. This function of the flora has important implications for host defense. The precise mechanism of action of the flora is obscure.
207 citations
TL;DR: Histamine could not be detected in the arterial or gastric venous blood of anesthetized dogs when the stomach was filled with 8 or 14% ethanol and the damaging effect of ethanol depends upon the concentration in contact with the mucosa and not upon the quantity absorbed.
Abstract: SummaryThe effect of ethanol upon the barrier function of the stomach was studied by irrigating pouches of the canine oxyntic glandular mucosa with solutions of ethanol ranging from 0.5 to 27% w/v. Solutions of 8% or less did not damage the mucosal barrier as judged by the fluxes of Na+, K+ and H+. Solutions of 14 and 27% broke the barrier, for fluxes of the ions across the mucosa were greatly increased during and following ethanol application. In contrast to acetylsalicylic acid which is much more damaging in acid than in neutral solution, ethanol has essentially the same effect upon the barrier when applied in 100 mM HCl or in 30 mM phosphate buffer, pH 7.5. The rate of absorption of ethanol is a linear function of its concentration. The damaging effect of ethanol depends upon the concentration in contact with the mucosa and not upon the quantity absorbed. Low concentrations of ethanol (8% or less) stimulate acid secretion. Histamine could not be detected in the arterial or gastric venous blood of anest...
190 citations
TL;DR: The method was shown to give reliable measurement of VEE virus antibodies in sera from humans with naturally acquired infections, and to be able to determine the optimum conditions for various agents to produce plaques.
Abstract: SummaryA method for production of plaques by arboviruses in small wells of disposable plastic trays is described. Each of 19 viruses from Central or South America produced plaques in MA-111 and VERO cell lines. Optimum conditions for various agents were determined. The method was shown to give reliable measurement of VEE virus antibodies in sera from humans with naturally acquired infections.
168 citations
TL;DR: Intradermal, intraperitoneal and intravenous injections of horseradish peroxidase solutions induce increased vascular permeability in rats and this phenomenon occurs also in the guinea pig but is minimal or non-existent in the mouse.
Abstract: SummaryIntradermal, intraperitoneal and intravenous injections of horseradish peroxidase solutions induce increased vascular permeability in rats. The vascular leakage is confined to venules, is of short duration, can be inhibited by a combination of histamine and serotonin antagonists and is associated with mast cell degranulation. This phenomenon occurs also in the guinea pig but is minimal or non-existent in the mouse.
148 citations
TL;DR: In this paper, a tissue culture cell strain of foreskin nbroblasts obtained from 5 neonates with Down's Syndrome (trisomy 21-22) were shown to be at least twice as susceptible and, on the average, 3 times more susceptible to transformation by the SV40 virus as diploid foreskin from normal neonates.
Abstract: SummaryTissue culture cell strains of foreskin nbroblasts obtained from 5 neonates with Down's Syndrome (trisomy 21-22) were shown to be at least twice as susceptible and, the average, 3 times as susceptible to transformation by the SV40 virus as diploid foreskin nbroblasts from normal neonates. An even greater susceptibility to in vitro SV40 transformation was found in a strain of trisomy 18 nbroblasts. It is suggested that one reason for the increased incidence of neoplasia in Down's Syndrome is a heightened intrinsic susceptibility of the trisomic cells to carcinogenic agents.We thank C. Sprague and E. Deutsch for excellent technical assistance.
145 citations
TL;DR: In this article, removal of G immunoglobulin from infectious serum of affected mink with Aleutian disease has been shown to significantly reduce the virus titer in the serum.
Abstract: SummaryMink affected with Aleutian disease have viremia which persists until death. Removal of G immunoglobulin from infectious serum of affected mink markedly reduces the virus titer. The virus in the serum exists as a complex with immunoglobulin, in which in vivo infectivity is still present.
TL;DR: Mammalian prolactin inhibits thyroxin-induced resorption of the tail in Rana catesbeiana tadpoles, and the possible importance of prolACTin as a larval growth hormone in amphibians is emphasized.
Abstract: SummaryMammalian prolactin inhibits thyroxin-induced resorption of the tail in Rana catesbeiana tadpoles. Mammalian growth hormone does not show this effect. The possible importance of prolactin as a larval growth hormone in amphibians is emphasized.
TL;DR: The results suggest that theitamin D-dependent binding activity is due to the presence of a specific calcium binding protein in the supernatant fraction of duodenal mucosal homogenates from vitamin D-treated rachitic rats.
Abstract: SummaryOral administration of 500 IU of vitamin D2 or vitamin D3 to rachitic rats resulted in the elaboration of a Ca-binding factor which could be detected in the supernatant fraction of duodenal mucosal homogenates at 72 hours after administration of the vitamin. This factor was found to be associated with the initial or protein containing portion of the supernatants after percolation through Sephadex G-25; this indicates that the factor is a macromolecule, presumably a protein. Further separation of the supernatants by Sephadex G-100 gel filtration showed that the increased binding activity seen after vitamin D administration was mainly associated with only one of the protein peaks present in the Sephadex G-100 fractions. This particular peak was much less prominent in the fractionated supernatant of the mucosal homogenates from rachitic rats. The results suggest that the vitamin D-dependent binding activity is due to the presence of a specific calcium binding protein in the supernatant fraction of duo...
TL;DR: In vitro exposure of erythrocytes to ozone resulted in an increased osmotic fragility associated with the formation of TBA reactants, which suggests that lipid peroxidation may be involved in the mechanism of ozone toxicity.
Abstract: SummaryIn vitro exposure of erythrocytes to ozone resulted in an increased osmotic fragility associated with the formation of TBA reactants. This suggests that lipid peroxidation may be involved in the mechanism of ozone toxicity.
TL;DR: Electrolyte composition and flow rate have been characterized in rat submaxillary saliva evoked by electrical stimulation of the sympathetic innervation and β-adrenergic receptors are involved in regulation of electrolyte composition by sympathetic nerves and by the adrenergic component of the action of pilocarpine.
Abstract: SummaryElectrolyte composition ([K], [Na], [Cl], [HCO3]) and flow rate have been characterized in rat submaxillary saliva evoked by electrical stimulation of the sympathetic innervation. [K] and [H...
TL;DR: Hemagglutinin titration using eryth-rocytes from 1- to 3-day-old chicks included a low temperature and a pH of 6.2, and the hemagglu-tinin was used to detect rises in HI antibody in paired serum specimens.
Abstract: SummaryRubella hemagglutinin of high titer was prepared by alkaline extraction of infected BHK-21/13S cells grown in suspension culture. After this treatment, soni-cation or tween-ether extraction increased hemagglutinin titer 4-16-fold. Optimal conditions for hemagglutinin titration using eryth-rocytes from 1- to 3-day-old chicks included a low temperature and a pH of 6.2. A limited number of stability tests indicated that alkaline extracted hemagglutinin was stable at — 70°C and +4°C. The hemagglu-tinin was used to detect rises in HI antibody in paired serum specimens. Hemagglutination inhibition antibodies were present in titers of 1:40′ to 1:320, 2 to 3 years after rubella infection.The supervision of all tissue culture preparation by Mrs. Anna Hall and the excellent technical assistance of Miss Marianne Davis and Miss Ludie Holland are gratefully acknowledged.
TL;DR: Experimental techniques commonly employed in maximum biliary excretion studies were shown to significantly alter normal thermoregulatory mechanisms and a decrease in body temperature significantly decreased the bilirubin transport maximum in both rats and mice.
Abstract: SummaryThe influence of temperature on the maximum biliary excretion of bilirubin and sulfobromophthalein was studied in anesthetized rats and mice. Experimental techniques commonly employed in maximum biliary excretion studies were shown to significantly alter normal thermoregulatory mechanisms. A decrease in body temperature significantly decreased the bilirubin transport maximum in both rats and mice. A loss of body temperature in the rat also produced a significant decrease in the BSP transport maximum. In both rats and mice bile flow showed a diminution corresponding with the decrease in rectal temperature. The results emphasize the importance of monitoring body temperature during the course of experiments employing maximum biliary excretion as an endpoint.The authors wish to acknowledge with gratitude the excellent assistance of Mrs. Sharon Shriver.
TL;DR: The results of these studies show that lipogenesis is enhanced in liver and adipose tissue of intact rats as a consequence of meal-feeding, and that in the nibbling rat 50-90% of the fatty acids are synthesized in adipOSE tissue whereas when fatty acid synthesis is stimulated by meal- feeding, adiposes tissue apparently accounts for about 95% ofthe total fatty acids synthesized.
Abstract: SummaryThe results of these studies show that lipogenesis is enhanced in liver and adipose tissue of intact rats as a consequence of meal-feeding. Fatty acid synthesis was approximately 200-fold higher in adipose tissue and 9-fold higher in liver of meal-fed as compared to nibbling rats. Increases in fatty acid radioactivity in adipose tissue, liver and serum were observed between 6 and 9 hours after the initiation of the meal. A possible explanation for these changes is proposed. Serum glucose and serum liver total lipid and cholesterol levels were also determined and no significant alterations due to meal-feeding were noted. From the observed rates of glucose-U-14C incorporation into liver and adipose tissue fatty acids an estimate was made of the relative importance of these tissues as sites of fatty acid synthesis. These calculations suggest that in the nibbling rat 50-90% of the fatty acids are synthesized in adipose tissue whereas when fatty acid synthesis is stimulated by meal-feeding, adipose tiss...
TL;DR: Hemagglutination inhibition experiments demonstrated that the antibodies produced in rats by repeated intraperitoneal injections with newborn rabbit colon in Freund's complete adjuvant were specific for gastrointestinal antigen and represented autoantibodies in a true sense.
Abstract: SummaryAutoantibodies to germ free rat colon were produced in rats by repeated intraperitoneal injections with newborn rabbit colon in Freund's complete adjuvant. Antibodies were assayed by means of indirect hemagglutination of sheep erythrocytes sensitized with a heat stable phenol-water extract of germ free rat colon or by fluorescent antibody staining of rat colon sections. The response of rat colon injected rats was less intense. A few of the rats injected with adjuvant alone also developed an anti-colon titer. Hemagglutination inhibition experiments demonstrated that the antibodies were specific for gastrointestinal antigen and represented autoantibodies in a true sense. They were found to be specific for at least three different colon determinants: one unique for germ free rat colon, one common for rat and rabbit colon, and one common for both colons and a polysaccharide from Eschericria coli O:14, grown on synthetic medium. No or only very weak cross reactions appeared with similar antigens extract...
TL;DR: Viruses were recovered from throat specimens of 21 of 53 dogs with respiratory disease and from the post-mortem tissues of 7 of 10 dogs, and were specific to the isolated virus and SV-5 and not to other members of the parainfluenza group.
Abstract: SummaryViruses were recovered from throat specimens of 21 of 53 dogs with respiratory disease and from the post-mortem tissues of 7 of 10 dogs. Many of these dogs were infected with more than one agent. The agents were 2 canine adenoviruses, a canine herpes virus and a SV-5-like virus. Rises in antibody titer to the isolated viruses were demonstrated in dogs which survived. The antibody response to the SV-5-like virus was specific to the isolated virus and SV-5 and not to other members of the parainfluenza group.
TL;DR: The role of intestinal bacteria in converting the naturally occurring glucoside cycasin to its hepatotoxic and carcinogenic aglycone (methylazoxymethanol) has been studied and variations in the intestinal flora probably have a role in determining the toxicity of ingested Cycasin.
Abstract: SummaryThe role of intestinal bacteria in converting the naturally occurring glucoside cycasin to its hepatotoxic and carcinogenic aglycone (methylazoxymethanol) has been studied. Germfree rats, in which cycasin is nontoxic, were monocontaminated with several strains of bacteria prior to being given cycasin. Levels of glucosidase activity in the bacteria were determined by the assay of cell free extracts, using cycasin as a substrate. The toxicity of cycasin in rats given the various bacteria and the amounts of unchanged cycasin excreted were consistent with the glucosidase assays. Intestinal microorganisms therefore convert cycasin to the toxic aglycone, and variations in the intestinal flora probably have a role in determining the toxicity of ingested cycasin.
TL;DR: An attachment was designed which made it possible to use the Allo-Kramer shear press to determine the breaking strength of the tibia of 4-week old chicks, and it was found to be highly correlated with tibia ash.
Abstract: SummaryAn attachment was designed which made it possible to use the Allo-Kramer shear press to determine the breaking strength of the tibia of 4-week old chicks. Breaking strength determined in this manner was found to be highly correlated with tibia ash. It is suggested that the breaking strength is as good a measure of dietary calcium and phosphorus levels as is tibia ash. Also the breaking strength of bones as determined in this manner may be useful in evaluating factors influencing fragility of bones.
TL;DR: The concept that insulin in the fluids surrounding Islet tissue can inhibit secretion of insulin by the β-cells is discussed in the light of these results.
Abstract: SummaryIsolated Islets of Langerhans from the rat's pancreas were incubated in media containing varying combinations of glucose, rat insulin, and guinea pig anti-insulin serum (GPAIS). Neither insulin nor GPAIS modified the rate at which insulin was secreted in response to glucose. The concept that insulin in the fluids surrounding Islet tissue can inhibit secretion of insulin by the β-cells is discussed in the light of these results.
TL;DR: Assays for N- and ring-hydroxylation of 2-acetylaminorluorene by hepatic microsomes from normal and 3-methylchloranthrene -treated rats, hamsters, mice, rabbits, and guinea pigs showed marked differences in these enzyme activities in normal animals of the different species and in the effects of MC-treatment.
Abstract: Summary1. Assays for N- and ring-hydroxylation of 2-acetylaminorluorene (AAF) by hepatic microsomes from normal and 3-methylchloranthrene (MC) -treated rats, hamsters, mice, rabbits, and guinea pigs showed marked differences in these enzyme activities in normal animals of the different species and in the effects of MC-treatment. The microsomes of all species, except the guinea pig in which A′-hydroxylation could not be detected, showed increases in N-hy-droxylation on MC-treatment; the largest increase was observed with hamster liver microsomes. Only rat and mouse liver microsomes showed large increases in ring-hydroxylation activity on MC-treatment. Increases in N-hy-droxylation activity of hamster liver microsomes and in ring-hydroxylation activity by rat liver microsomes after MC treatment were inhibited by administration of actinomycin D or puromycin. 2. MC-treatment of rats or hamsters did not affect the reduction of N-hy-droxy-AAF by liver homogenates. 3. MC administration caused a decrease in urina...
TL;DR: Aerosols of adenovirus types 4 and 7 and parainfluenza 3 were tested for biological stability as a function of relative humidity and exhibited maximum stability at 80% RH and a minimum biological decay rate at 20% RH.
Abstract: SummaryAerosols of adenovirus types 4 and 7 and parainfluenza 3 were tested for biological stability as a function of relative humidity. The levels tested were 20%, 50%, and 80%. Both adenoviruses exhibited maximum stability at 80% RH. Parainfluenza on the other hand exhibited a minimum biological decay rate at 20% RH. Studies were carried out with aerosols having mass median diameters of about 2 μ.The authors wish to cite the excellent technical assistance of Joseph W. Dominik and John F. Brewer of Fort Detrick and of Martin Schneider of Walter Reed Army Inst. of Research. The statistical analyses by Dr. N. Bohidar of Fort Detrick are also acknowledged.
TL;DR: Individual follicles, with their enclosed oocytes, were dissected from the ovary of the leopard frog, Rana pipiens, and their response to steroid hormones studied, and steroids appear to act directly on the oocyte and calcium ions appear to be important for the biological action of the steroids.
Abstract: SummaryIndividual follicles, with their enclosed oocytes, were dissected from the ovary of the leopard frog, Rana pipiens, and their response to steroid hormones studied. Biologically and chemically related substance, progesterone, pregnenolone and 11-deoxycorticosterone, were most effective in producing germinal vesicle breakdown. Removal of the follicular tissue did not prevent the action of the steroid progesterone on the germinal vesicle. Steroids appear to act directly on the oocyte and calcium ions appear to be important for the biological action of the steroids.The author wishes to express his sincere appreciation to The Upjohn Co. for the support which greatly aided this study. The efforts of Dr. Albert Notation in preparation of sulfated steroids are also acknowledged.
TL;DR: Alteration of a delicate balance between collagen synthesis and collagen breakdown in remodeling tissues has been hypothesized as the mechanism by which some pathological conditions characterized by abnormal amounts of collagen may be produced.
Abstract: Summary and conclusions1. Collagenolytic activity in normal and pathological human tissue has been demonstrated by culturing tissue specimens on reconstituted bovine collagen substrate. 2. Collagenolysis appears to be associated primarily with epithelium and not with deep connective tissue elements. 3. Alteration of a delicate balance between collagen synthesis and collagen breakdown in remodeling tissues has been hypothesized as the mechanism by which some pathological conditions characterized by abnormal amounts of collagen may be produced.
TL;DR: In prepuberal female rats melatonin retards puberty and decreases pituitary weight as well as the weights of the ovaries and the uteri, confirming that melatonin reduces LH secretion.
Abstract: Summary1. Pinealectomy when performed in male rats results in a significant increase in weight of the testes, the prostates and the seminal vesicles. This suggests that the pineal gland usually inhibits the secretion of LH and of FSH. 2. Melatonin administered to male rats diminishes the weights of prostates and of seminal vesicles, but does not change testicular weight, indicating that exogenous melatonin suppresses the secretion of LH, but does not interfere with FSH release. 3. In prepuberal female rats melatonin retards puberty and decreases pituitary weight as well as the weights of the ovaries and the uteri, confirming that melatonin reduces LH secretion. 4. It is suggested that the pineal gland exerts an anti-FSH effect through compounds different from melatonin.
TL;DR: The changes observed in plasma suggest that acute pituitary-adrenal responses to the types of stress used are not altered by marked diurnal variation in plasma corticosterone levels.
Abstract: SummaryAdult female rats were subjected to 3-minute ether or immobilization stress during the trough (08:30) or peak (16:30) of the circadian rhythm in adrenocortical function. Two samples of perip...
TL;DR: Administration of concentrated preparations of interferon of high titer inhibited the development of splenomegaly induced by Friend virus in Swiss and DBA2 mice.
Abstract: SummaryAdministration of concentrated preparations of interferon of high titer (extracted from either mouse brain or serum and spleen) inhibited the development of splenomegaly induced by Friend virus in Swiss and DBA2 mice. Interferon was effective only when treatment was continued daily throughout the duration of the experiment, and when inoculated mtraperitoneally (rather than intravenously).We acknowledge with gratitude the excellent assistance of Mile. Chantal Bourali and Mile. Marie-The rese Thomas. Dr. Raymond Latarjet kindly supplied us with the Friend virus and with a large number of Swiss mice which permitted us to start a colony of these mice. We are indebted to Dr. Charles Chany and to Dr. Rebecca Falcoff for discussion and help in preparation of this report, and to Mr. Philippe Lazar and Mrs. Suzanne Gue guen for analyzing our experimental results and aiding us in their presentation. We should like to thank Dr. John F. Enders for reviewing this manuscript and Dr. Sidney Farber for constant en...