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Showing papers in "Experimental Biology and Medicine in 1981"


Journal ArticleDOI
TL;DR: The data support the conclusion that K-562 is a multipotential leukemia cell line of human origin and demonstrates benzidine-positive material limited to the region of the Golgi apparatus.
Abstract: The K-562 leukemia cell line, originally established in our laboratory, has been characterized as an early precursor of the granulocytic series with a block for differentiation. Since K-562 blasts did not differentiate when cultured for 7-8 days in liquid media or 14-16 days in agar-gel an attempt was made to stimulate their potential for spontaneous differentiation by prolonging the time in culture. Inducers of differentiation were not added to the cultures and the cells were studied when they reached the steady state rather than during exponential growth. The cultivation of K-562 cells for 10 to 11 days in media gradually depleted of the essential nutrients needed for cell division induced their differentiation into early precursors of the monocytic, granulocytic, and erythrocytic series. Thus, the peroxidase reaction for hemoglobin demonstrates benzidine-positive material limited to the region of the Golgi apparatus. Analysis of the hemoglobin by isoelectric focusing indicated major bands in th...

253 citations


Journal ArticleDOI
TL;DR: Increased renal vascular resistance at either the afferent or efferent arteriole does not change the responses of these vessels to reductions in renal perfusion pressure, and renal nerve stimulation at frequencies which decrease urinary sodium excretion at control renal perfusions pressure does not enhance the antinatriuretic response.
Abstract: Renal nerve stimulation increases renal vascular resistance and decreases glomerular filtration rate and urinary sodium excretion. The purpose of this study was to determine whether neurally mediated changes in renal vascular resistance, glomerular filtration rate, and urinary sodium excretion at control renal perfusion pressure modified the autoregulation of renal blood flow and glomerular filtration rate and the antinatriuresis observed during reductions in renal perfusion pressure in pentobarbital-anesthetized dogs. Renal blood flow, glomerular filtration rate, and urinary sodium excretion were determined during stepwise reductions in renal perfusion pressure from 137 to 55 mm Hg (suprarenal aortic constriction) before and during electrical stimulation of the renal nerve at 0.5, 1.0, 2.0, and 4.0 Hz. In the absence of renal nerve stimulation, renal blood flow and glomerular filtration rate remained constant until renal perfusion pressure was reduced to 70 and 85 mm Hg, respectively. Urinary sodium excretion decreased linearly as renal perfusion pressure decreased. Renal nerve stimulation at 0.5, 1.0, 2.0, and 4.0 Hz increased renal vascular resistance and decreased glomerular filtration rate and urinary sodium excretion. These frequencies of renal nerve stimulation, however, did not alter the decreases in renal vascular resistance and glomerular filtration rate or the antinatriuretic response to stepwise reductions in renal perfusion pressure to 55 mm Hg. These data demonstrate that increased renal vascular resistance at either the afferent or efferent arteriole does not change the responses of these vessels to reductions in renal perfusion pressure. Renal nerve stimulation at frequencies which decrease urinary sodium excretion at control renal perfusion pressure also does not enhance the antinatriuretic response to reductions in renal perfusion pressure.

134 citations


Journal ArticleDOI
TL;DR: In vitro analysis of the mechanism of suppression using limiting dilution techniques showed that TCDD did not deplete the precursors of CTL but generated cells capable of suppressing CTL generation in vitro.
Abstract: TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), a toxic halogenated aromatic hydrocarbon, acts in the body as a cumulative poison. The chronic immunotoxic effects of TCDD were studied in C57B1/6 male mice. Total doses of 100 μg/kg or greater produced cellular depletion in thymus, spleen, and lymph nodes, and the animals appeared sick. No cellular depletion was seen following 0.4 μg/kg, and only thymus was affected by 4 and 40 μg/kg. The antibody response to SRBC and TNP-Brucella abortus was impaired following 40μg/kg TCDD, the delayed hypersensitivity response to oxazalone was impaired by 4 μg/kg and the generation of alloantigen-specific cytotoxic T cells (CTL) was sensitive to as little as 0.004 μg/kg TCDD. In vitro analysis of the mechanism of suppression using limiting dilution techniques showed that TCDD did not deplete the precursors of CTL but generated cells capable of suppressing CTL generation in vitro.

101 citations


Journal ArticleDOI
TL;DR: The data suggest that Se may be an important component of immune function, and its effect is influenced by antigen concentration, sex, and the ontogenic state, as well as nutritional and nonpharmacological levels.
Abstract: Nutritional deficiencies in vitamin E and/or selenium (Se) caused impaired immune function, as measured by the humoral response to ovine erythrocytes by young chicks, but only at low antigen doses. In the 2-week-old chick, both vitamin E and Se were required for optimum immune function; however, at 3 weeks of age, either vitamin E or Se was sufficient for optimum immune function. At this developmental stage, Se appeared to be capable of replacing vitamin E with regard to the immune system. Titrations of dietary vitamin E in the presence of adequate Se and the reciprocal experi- mental regime did not result in immune enhancement. However, the range of concentrations of each factor employed were within nutritional and nonpharmacological levels. In contrast, high dietary Se produced significant immune suppression in male but not female chicks. These data suggest that Se may be an important component of immune function, and its effect is intluenced by antigen concentration, sex, and the ontogenic state.

101 citations


Journal ArticleDOI
TL;DR: Changes in plasma levels of β-endorphin immunoreactivity may be responsible for some of the euphoria and analgesia anecdotally associated with running.
Abstract: Twenty minutes of submaximal treadmill running was associated with an elevation in plasma levels of beta-endorphin immunoreactivity (P less than 0.02). This increase was greater in men (14.9 +/- 3.4 fmole/ml) than women (2.6 +/- 1.2 fmole/ml)(P less than 0.05). Plasma levels of ACTH and growth hormone also increased after running. ACTH increased more in men (7.8 +/- 1.1 fmole/ml) than in women (1.1 +/-0.44 fmole/ml)(P less than 0.02). There was a similar growth hormone response in both sexes. No correlation can at this time be made with levels in the central nervous system. Changes in plasma levels of beta-endorphin immunoreactivity may be responsible for some of the euphoria and analgesia anecdotally associated with running.

88 citations


Journal ArticleDOI
TL;DR: Intestinal tumors were induced in Lobund strain Sprague-Dawley rats by a single administration of 1,2-dimethylhydrazine or of methylazoxymethanol acetate and the effect is interpreted as therapeutic or as antipromotional.
Abstract: Intestinal tumors were induced in Lobund strain Sprague-Dawley rats by a single administration of 1,2-dimethylhydrazine (DMH) or of methylazoxymethanol acetate (MAM). At 34 days later (DMH), or at 7 and 35 days later (MAM), groups of rats were administered indomethacin (20 mg/liter) in the drinking water. When examined at Week 20, in those that consumed indomethacin there was a significant reduction in numbers of rats with intestinal tumors, compared to the control rats. In view of the interval between exposure to the carcinogen and treatment with indomethacin, the effect is interpreted as therapeutic or as antipromotional.

65 citations


Journal ArticleDOI
TL;DR: The patients receiving IVH had significantly lower mean selenium levels in erythro-cytes and plasma and mean glutathione-peroxidase activities than the values from the university population, and these chronic IVH patients appear to be at risk for seenium deficiency.
Abstract: The purpose of this study was to determine selenium concentration in erythro-cytes and plasma and to compare these values to the measured erythrocyte glutathione-peroxidase activity for a university and a long-term intravenous hyperalimentation (IVH) population. In addition, we wished to determine if these chronic IVH patients were at risk for selenium deficiency. There was a positive correlation (r = 0.67) between erythrocyte selenium levels and erythrocyte glutathione-peroxidase activities in the university population. The patients receiving IVH had significantly lower mean selenium levels in erythro-cytes and plasma and mean glutathione-peroxidase activities than the values from the university population. No correlation existed between erythrocyte selenium levels and erythrocyte glutathione-peroxidase activities in this IVH patient population. These chronic IVH patients when compared with the university population appear to be at risk for selenium deficiency.

61 citations


Journal ArticleDOI
TL;DR: It is suggested that elevated plasma-free cortisol as well as depressed plasma insulin in protein-energy malnourished infants is partially responsible for the depressed plasma somatomedin and reduced protein synthesis and growth in children.
Abstract: Plasma insulin, growth hormone, somatomedin, free and bound cortisol, and serum albumin were measured in human infants with protein-energy malnutrition and in age-matched control subjects. Insulin and somatomedin were reduced, growth hormone and free and total cortisol were elevated in malnourished infants. Free cortisol and somatomedin were negatively correlated (r = −0.78) and somatomedin and percentage weight deficit were negatively correlated in marasmus (r = −0.62) and kwashiorkor (r = −0.68). It is suggested that elevated plasma-free cortisol as well as depressed plasma insulin in protein-energy malnourished infants is partially responsible for the depressed plasma somatomedin and reduced protein synthesis and growth in children.

60 citations


Journal ArticleDOI
TL;DR: It is demonstrated that the regulation of hepatic zinc metabolism has multihormonal components and changes in hepatic metallothionein-bound zinc involve synergistic effects of glucagon and glucocorticoids which act through two separate, yet related mechanisms.
Abstract: Abstract Recent evidence suggests glucocorticoids alter hepatic zinc metabolism. The induction of metallothionein synthesis seems to be one of the key regulatory steps involved. The experiments reported here were designed to examine the influence of glucagon on liver metallothionein-bound zinc. Glucagon (1.0 mg/kg) and/or dexamethasone (2.0 mg/kg) was administered to 175-225 g male rats. An independent, synergistic effect of glucagon which increased the binding of zinc to liver metallothionein induced by glucocorticoids was identified. The glucagon response was short lived with a maximum 7 hr after administration and a return to initial levels 7 hr thereafter. A maximal increase in metallothionein-bound zinc in response to dexamethasone, a synthetic glucocorticoid, increased steadily to 21 hr after administration. Administration of both the glucocorticoid and glucagon resulted in a significant, but short-lived, augmentation of the action of either hormone alone. Actinomycin D blocked the dexamethasone effect but had no effect on glucagon action, suggesting the latter does not involve de novo RNA synthesis. These results suggest that changes in hepatic metallothionein-bound zinc involve synergistic effects of glucagon and glucocorticoids which act through two separate, yet related mechanisms. These findings expand our view of the widespread role of glucagon and glucocorticoids in liver function and demonstrate that the regulation of hepatic zinc metabolism has multihormonal components.

59 citations


Journal ArticleDOI
TL;DR: Data on resin and fiber sequestration of micellar fatty acids and monoglycerides compare favorably with the binding of other micellars components including phospholipid, bile salt, and cholesterol.
Abstract: Mixed micelles were prepared containing sodium taurocholate, monolein dioleyl lecithin, cholesterol, and an equimolar mixture of palmitic, oleic, and linoleic acids. These were incubated with commercial bile acid-sequestering resins, cholestyramine and DEAE-Sephadex, or various dietary fibers and fiber components including wheat bran, cellulose, alfalfa, lignin, and two viscosity grades of guar gum. Binding of monolein and fatty acids was determined as the difference between the radioactivity of the added micellar component, and that recovered in the centrifugal supernatant after incubation. In general, the extent of monoglyceride or fatty acid sequestration was characteristic and reproducible for each binding agent. Cholestyramine and DEAE-Sephadex essentially quantitatively bound monoglycerides and all three fatty acids from micellar medium. Low- and high-viscosity grades of guar gum sequestered 15-23% of the monolein and 32-33% of the fatty acids, showing a significant preference for linoleic a...

59 citations


Journal ArticleDOI
TL;DR: Balb/c mouse cells were persistently infected with RS virus and continued passage of the virus produced in these Balb/ c cells resulted in a 10-fold increase in the amount of infectious virus produced.
Abstract: Balb/c mouse cells were persistently infected with RS virus. Continued passage of the virus produced in these Balb/c cells resulted in a 10-fold increase in the amount of infectious virus produced. Approximately 80% of the BCH4 cells expressed RNP and “spike” antigen intracellularly and associated with the cell surface.

Journal ArticleDOI
TL;DR: It is found that blood drawn from the portal vein of normal rabbits contains twice the concentration of GABA as that drawn simultaneously from the abdominal aorta, and human-derived colonic bacteria grown anaerobically secreted a large amount of GABA equivalents into culture media when measured by a radioreceptor technique.
Abstract: Blood contains more of the major inhibitory neurotransmitter, γ-aminobutyric acid (GABA), than does cerebrospinal fluid. However, the source and physiologic importance of this compound in the peripheral circulation are unknown. We have found that blood drawn from the portal vein of normal rabbits contains twice the concentration of GABA as that drawn simultaneously from the abdominal aorta. Also, human-derived colonic bacteria grown anaerobically secreted a large amount of GABA equivalents into culture media when measured by a radioreceptor technique. The production of inhibitory neuroactive substances, such as GABA, by colonic bacteria may play a role in the pathogenesis of certain disease states, for example, hepatic encephalopathy.

Journal ArticleDOI
TL;DR: Cultured endothelial cells from bovine aorta and umbilical vein induced retraction of a fibrin clot formed by addition of thrombin to cell-free plasma showed many characteristics in common with platelet- and fibroblast-induced clot retraction, suggesting that confluency inhibits the cell contractile capacity.
Abstract: Cultured endothelial cells (EC) from bovine aorta and umbilical vein induced retraction of a fibrin clot formed by addition of thrombin to cell-free plasma. Fibrin clot retractile (FCR) activity increased with time (1-24 hr) and with the number of cells in the system (1-4 × 106/ml, final concentration), and was inhibited at 22° or in the presence of Na2-EDTA; moreover, no retraction occurred when batroxobin was used as a clotting agent instead of thrombin. FCR of EC thus showed many characteristics in common with platelet- and fibroblast-induced clot retraction. FCR activity of bovine EC increased with the number of subcultures, being very low in cells harvested from primary cultures. In contrast, human EC had high activity in primary cultures. Like fibroblasts, EC with a higher density in culture showed lower FCR, suggesting that confluency inhibits the cell contractile capacity. FCR could thus represent a simple in vitro test to further characterize the biology of EC and to evaluate their role i...

Journal ArticleDOI
M. I. Castro1, J. C. Rose1, W. Green1, Noel D.M. Lehner1, D. Peterson1, D. Taub1 
TL;DR: The studies indicate that ketamine-HCl does not perturb these particular hormonal systems in M. fascicularis monkeys, and ketamine anesthesia produced no significant changes in plasma insulin, glucose, or cortisol concentrations.
Abstract: Ketamine-HCl has been reported, depending on experimental conditions and dosage given, to have significant cardiovascular and endocrine effects in some species. However, previous studies in primates have inadequately distinguished between animal handling and ketamine effects. We, therefore, examined the effects of various doses of ketamine (0, 5, 10, 15, and 20 mg/kg) on mean arterial blood pressure and on plasma insulin, glucose, and cortisol concentrations in 10 chronically cannulated Macaca fascicularis monkeys which had been acclimated to restraining chairs. Each monkey received three different doses of ketamine according to a balanced incomplete block design. Ketamine anesthesia produced no significant changes in plasma insulin, glucose, or cortisol concentrations nor did it affect mean arterial blood pressure. In addition, the effects of ketamine-HCl on endocrine responses to insulin-induced hypoglycemia were examined in four animals according to a cross-over design. These animals also had c...

Journal ArticleDOI
TL;DR: From these rates of amino acid and nitrogen accretion the adequacy of the exogenous supply of amino acids and nitrogen to the fetus via the umbilical uptake can be assessed.
Abstract: Total body water and nitrogen concentrations were determined for whole body homogenates of 18 fetal lambs. Nitrogen concentration averaged 10.5 ± 0.1 mg nitrogen/100 mg dry tissue. Amino acid represented approximately 82% of the total nitrogen and 55% of the total carbon content of the fetus. The carbon/nitrogen ratio attributable to amino acids decreased from 3.42 at 66 days to 3.06 at term. Total amino acid concentrations in the whole body homogenates were also determined for 20 amino acids. Cystine and hydroxy-proline concentrations increased significantly (correl. coeff. = 0.78) and markedly with gestation. The branch chain amino acids, leucine, isoleucine, and valine, along with phenylalanine, showed a significant decline in concentration (correl. coeff. ≧ −0.79). From these rates of amino acid and nitrogen accretion the adequacy of the exogenous supply of amino acids and nitrogen to the fetus via the umbilical uptake can be assessed. Calculations of the excess supply of amino acids to the fe...

Journal ArticleDOI
TL;DR: It is concluded that the presence of such a substance supports the concept of local regulation of bone metabolism and is consistent with this substance being a small polypeptide without the exposed amino acids, lysine or arginine
Abstract: A substance recovered from the medium of embryonic chick bones growing in organ culture inhibits the proliferation of chick calvarial bone cells in vitro. This inhibition of proliferation occurs within 3 hr after exposure of the cells to the inhibitory substance (IS) in a manner which does not appear to affect the protein synthesis or the gross morphology of the cells. The medium from which IS is obtained can be diluted 500-fold and still retain significant inhibitory activity. Cells in culture spontaneously escape the inhibition of a single dose of IS within 24 hr of exposure, however, upon further addition of IS to these cells inhibition of proliferation is again observed. Cells derived from chick bone as well as rat and human bone are more sensitive to the inhibition than are chick dermal fibroblasts and chick liver and muscle cells. IS is not destroyed after treatment of the conditioned medium with trypsin, phospholipase A2, RNase, neuraminidase, or heat. IS is also not a commonly produced pro...

Journal ArticleDOI
TL;DR: Significant decreases in the dietary protein level were associated with concomitant reductions in growth rate and there was also evidence for some progressive increase in plasma concentrations of GH as dietary protein levels were decreased.
Abstract: Two- to three-week-old broiler chicks were fed isocaloric purified diets with varying levels of protein (soy protein supplemented with glycine and methionine). The growth rates of the birds were monitored throughout the period of 14 days on the purified diets, while the circulating concentrations of growth hormone (GH) were determined at the end of this period. As expected, decreases in the dietary protein level were associated with concomitant reductions in growth rate. While this decrease in growth rate was observed with chicks fed 12 and 18% protein (compared with 24%), circulating concentrations of GH were observed to be only elevated with severe protein restriction (10% and lower). There was also evidence for some progressive increase in plasma concentrations of GH as dietary protein levels were decreased.

Journal ArticleDOI
TL;DR: These results correlate with laboratory and clinical investigations which have suggested that gut sutures have the highest frequency of association with surgical wound infection, followed by silk and nylon in descending order of frequency.
Abstract: Sutures were incubated in suspensions of radiolabeled Enterobacteriaceae or Staphylococcus aureus and nonadherent bacteria were removed by washing. Adherence of bacteria to gut was up to 100 times greater than to nylon; adherence to polyglycolic acid or silk was intermediate. These results correlate with laboratory and clinical investigations which have suggested that gut sutures have the highest frequency of association with surgical wound infection, followed by silk and nylon in descending order of frequency. Braided materials had increased adherence compared to nonbraided materials, probably due to increased surface area. Adherence of Enterobacteriaceae to suture material was saturable and time dependent and was blocked by addition of unlabeled bacteria. Adherence of bacteria to sutures may be an integral part of the pathogenesis of certain surgical infections.

Journal ArticleDOI
TL;DR: The immune response to vaccination was accompanied by protection against natural challenge and antibody induced by vaccine virus persisted for at least 3.5 years, the longest period observed.
Abstract: Small-scale studies were carried out to test the KMcC strain varicella virus at various passage levels for clinical and serologic responses in order to find an optimal level of attenuation for vaccine purpose. Virus at passage 50 induced antibody responses, caused only minimal clinical reactions, and will be studied further. The clinical reactions to vaccine virus were very mild at all virus passage levels and were limited to mild transient fever and papular rash that became vesicular in a small proportion of individuals. The immune response to vaccination was accompanied by protection against natural challenge and antibody induced by vaccine virus persisted for at least 3.5 years, the longest period observed. Attenuation of virus appeared to be accompanied by alteration in the proportion of incomplete virus particles formed and by the degree of spontaneous release of virus from infected cells.

Journal ArticleDOI
TL;DR: Exposure to PBB resulted in a disruption of the normal homeostasis of the pituitary-thyroid axis and was associated with accumulation and retention of PBB in thyroid and liver and acute administration of P BB had little effect on intrathyroidal radioiodine accumulation and incorporation into iodoamino acids.
Abstract: The effects of polybrominated biphenyls (PBB) on the pituitary-thyroid axis were investigated in male rats. PBB was administered by gavage for 20 days at 1, 3, or 6 mg/kg/day; controls were gavaged with vehicle alone. PBB treatment had no effect on body weight. There was a definite time- and dose-dependent reduction in plasma thyroxine (T4) levels after 10 and 20 days of PBB administration. Reduced plasma T4 levels were correlated with increased plasma TSH levels at 20 days. In rats treated with 6 mg/kg PBB, an increase in 5-hr thyroidal 131I uptake was seen, with a decrease in 131I incorporation into monoiodotyrosine and an increase in intrathyroidal iodine. In contrast to propylthiouracil, acute administration of PBB had little effect on intrathyroidal radioiodine accumulation and incorporation into iodoamino acids. Liver and thyroid weights remained elevated at 2 and 5 months after the last 1 and 3 mg/kg PBB administration, respectively, and plasma T4 levels were significantly lower than contro...

Journal ArticleDOI
TL;DR: The results suggest that carbenoxolone, like prostaglandins, is cytoprotective to the rat gastric mucosa, and similarities in the time response for cy toprotection by these two compounds suggest that they exert their effect by a common mechanism.
Abstract: Gastric necrosis was induced in the rat by oral administration of absolute ethanol. Carbenoxolone sodium, administered orally, but not intravenously, reduced the severity of ethanol-induced lesions in a dose-responsive manner. Maximum inhibition of lesion formation occurred when carbenoxolone was administered 15 min before ethanol. Our results suggest that carbenoxolone, like prostaglandins, is cytoprotective to the rat gastric mucosa. Similarities in the time response for cytoprotection by these two compounds suggest that they exert their effect by a common mechanism.

Journal ArticleDOI
TL;DR: This finding suggests that the endothelium may be stimulated by proteolytic enzymes to ingest large particles or complexes, and that even without Fc receptors, the endotchelium can remove potentially harmful materials from circulation by phagocytosis.
Abstract: Human endothelial cells in culture and in tissue sections were examined for Fc receptors by several different methods, including the binding of FITC- and ferritin-labeled antibodies to IgG, rosette formation with sensitized sheep erythrocytes, and binding of opsonized latex particles. Although human polymorphonuclear leukocytes reacted positively in all of these tests, endothelial cells freshly isolated or cultured from umbilical cord veins were consistently negative. A small number of cells cultured from umbilical arteries formed rosettes with sheep erythrocytes, but cells from pulmonary arteries did not. Fc receptors could not be found in vessels of the umbilical cord or in lung tissue sections, but vessels in the placenta contained prominent Fc receptors. Cultured endothelial cells that were suspended by trypsin took up latex beads and immune complexes by endocytosis. Undisturbed monolayers of cells were much less active. This finding suggests that the endothelium may be stimulated by proteolyt...

Journal ArticleDOI
TL;DR: It is demonstrated that A and E series prostaglandin analogs inhibit DNA synthesis in two unrelated tumor types and thus may be potent inhibitors of tumor growth.
Abstract: Analogs of the A and E series prostaglandins were screened in vitro for their chemotherapeutic potential against Lewis lung carcinoma and B16 amelanotic melanoma cells, since in vivo studies had demonstrated that PGA1 and an analog of PGE2 inhibited tumor growth. DNA synthesis by collagenase-dispersed tumor cells was evaluated at timed intervals after exposure to the 16, 16-dimethyl analogs of PGA1, PGA2, PGE1, and PGE2. In general, the PGA derivatives were more potent than the PGE analogs. However, the maximum effect was achieved with combined PGA and PGE treatment. These findings demonstrate that A and E series prostaglandin analogs inhibit DNA synthesis in two unrelated tumor types and thus may be potent inhibitors of tumor growth. These effects were not due to tumor cell cytotoxicity. These results suggest that these compounds may prove useful as cancer chemotherapeutic agents.

Journal ArticleDOI
TL;DR: Dietary-induced zinc deficiency results in an impaired cell-mediated immune response to non-H2 allogenic tumor cells in mice, which suggests that either a deficiency or toxic level of zinc impairs theimmune response to allogeneic tumor cells.
Abstract: Dietary-induced zinc deficiency results in an impaired cell-mediated immune response to non-H2 allogenic tumor cells in mice. Animals maintained on a zinc-deficient diet for as little as 2 weeks develop a severe impairment in their ability to generate a cytotoxic response in the face of tumor challenge. This impairment is totally reversible by returning zinc-deficient mice to normal dietary zinc intake. Such animals now demonstrate a normal cytotoxic response to tumor challenge. If mice are treated with toxic doses of dietary zinc, a similar impairment of the cell-mediated cytotoxic response occurs. This suggests that either a deficiency or toxic level of zinc impairs the immune response to allogeneic tumor cells.

Journal ArticleDOI
TL;DR: The data suggest that the stimulatory factor acts to increase cell proliferation by promoting entry of cells into the S phase of mitosis, probably acting via an increased proliferation in osteoblast precursor cells.
Abstract: Embryonic chick bones growing in organ culture release a substance into the culture medium which stimulates bone formation in previously untreated bones. This “conditioned” medium also enhances proliferation of monolayer cultures of chick calvaria cells in serum-free medium. The active principle is nondialyzable, indicating a molecular weight greater than 12,000 daltons. Dialysis also separates the mitogenic activity from a low-molecular-weight inhibitor. The amount of the mitogen found in conditioned medium increases as the rate of bone resorption increases in response to treatment with parathyroid hormone or 1,25-dihydroxyvitamin D3. Maximal stimulation of DNA synthesis in calvaria cells is evident with conditioned medium obtained 3 to 5 days after treatment of bone cultures with parathyroid hormone. The cells must be treated with the conditioned medium continuously for 20 hr in order to obtain peak enhancement of DNA synthesis; there is no detectable effect in the first 8 hr. In contrast, the i...

Journal ArticleDOI
TL;DR: It is found that interferon affects cardiac cell function in vitro, may have relevance to clinical application and none of the interferons used produced morphological effects on the heart cells and with rat Interferon the beating rate effect was reversible.
Abstract: Interferon which has been shown to exert important effects on cellular function was utilized to investigate its effect on cardiac cell beating in vitro. When steadily pulsating rat cardiac cultures were continuously exposed to rat interferon for 24 hr, a decrease in the beating rate was observed. Mouse interferon which also exerted antiviral activity on rat heart nonmuscle cells also decreased the beating rate of rat cardiac cultures. Human leukocyte interferon when tested at the same dose at which rat interferon was active, exhibited no antiviral activity in rat heart nonmuscle cells and did not exert beating rate effects. When mouse interferon was incubated with antiserum prepared against mouse interferon both antiviral and beating activity were neutralized to the same extent. None of the interferons used produced morphological effects on the heart cells and with rat interferon the beating rate effect was reversible. This finding, that interferon affects cardiac cell function in vitro, may have ...

Journal ArticleDOI
TL;DR: Subnormal assimilation of cobalamin from the fish with normal absorption of crystalline radio-B12 was noted in subjects with simple gastric achlorhydria and in patients who had undergone partial gastrectomy, as well as in patients with pernicious anemia.
Abstract: The main purpose of this investigation was to study the assimilation of cyanocobalamin from fish. For this reason rainbow trout were injected with 57Co-vitamin B12 and sacrificed 2 to 3 weeks later. The radioactivity was found to be evenly distributed in the muscle mass. In contrast to findings in birds and mammals the liver contained on the average less radioactivity than did the kidneys, head, skin, and muscle mass. The radiolabeled fish was ingested by three healthy subjects in 50- to 300-g portions and the absorption measured by the stool excretion method. The study shows that from an average of 2.07 μg of vitamin B12 (50 g of fish), 4.05 μg (100 g), 9.2 μg (200 g), and 13.3 μg (300 g) the assimilation of cobalamin averaged 0.87, 1.55. 3.90, and 3.98 μg, respectively. In two of the subjects, an upper limit of absorption was reached, while in one it was still climbing. A standard urinary excretion test using 100 g of fish, eaten by healthy subjects and by patients who presented with low serum v...

Journal ArticleDOI
TL;DR: The maximal artery response to each of the hydroperoxy fatty acids was almost 1.4 times stronger than that obtained with serotonin, LA, or AA, and the cumulative dose–response contraction was approximately 400 times that of serotonin.
Abstract: The contractile activity of linoleic acid (LA), arachidonic acid (AA), 13l-hydroperoxy-cis-9-trans-11-octadecadienoic acid (13HPLA), or 15l-hydroperoxy-cis-5-cis-8-cis-11-trans-13-eicosatetraenoic acid (15HPAA) was tested on canine basilar artery segments in a small chamber, using serotonin as the reference vasoconstrictor. The cumulative dose–response contraction was approximately 400 times that of serotonin. On the other hand, either 15HPAA or 13HPLA at 10-6M induced a contraction almost equal to the maximum attained with serotonin (1 × 10-6M) contraction. The maximal artery response to each of the hydroperoxy fatty acids was almost 1.4 times stronger than that obtained with serotonin, LA, or AA.

Journal ArticleDOI
TL;DR: The results suggest that the stimulus provided by penile intromission can account for the induction and persistence of daily prolactin surges independently of ovarian support and that this physiological stimulus can be simulated by electrical or mechanical stimulation of the uterine cervix at appropriate intervals.
Abstract: Ahstract. In rats, the induction of pregnancy or pseudopregnancy is dependent upon the number of penile intromissions as well as the interintromission interval. The mating-induced stimulation of the uterine cervix is “stored” within the brain and repetitively expressed as two daily surges of prolactin for at least 10 days. It has been reported that the prolactin surges persist for only 6 days if the uterine cervices of ovariectomized (OVX) rats are stimulated artificially (CS). The present study demonstrates the effects of different methods of CS on prolongation of nocturnal (N) and diurnal (D) surges of prolactin secretion through Day 10 in OVX rats. Female rats were permitted to mate with males from proestrus through estrus, or received a mechanical (glass rod) or electrical stimulus of the uterine cervix at 1700 hr proestrus. All animals were OVX on the morning of estrus and blood was sampled by decapitation 10 days later. Both N and D surges of prolactin were present on Day 10 in mated rats or rats receiving a mechanical CS on proestrus. However, rats stimulated electrically on proestrus had neither N nor D surges of prolactin on Day 10. On the other hand, a second electrical stimulus on the morning of estrus prior to OVX induced prolactin surges which persisted through Day 10. Similar results were obtained in rats whose uterine cervices were artificially stimulated 14 days after OVX. However, N surges, when significantly elevated, were smaller than those of acutely OVX rats and D surges were present in only a small proportion of the animals sampled on Day 10. These results suggest that the stimulus provided by penile intromission can account for the induction and persistence of daily prolactin surges independently of ovarian support and that this physiological stimulus can be simulated by electrical or mechanical stimulation of the uterine cervix at appropriate intervals.

Journal ArticleDOI
TL;DR: It is concluded that PB blockade of preovulatory gonadotropin surges may be via its suppression of hypothalamic NE release during the afternoon of proestrus.
Abstract: In previous studies we observed that LHRH concentrations increase in the preoptic-suprachiasmatic tuberoinfundibular system (PSTS) during the morning hours of proestrus when norepinephrine (NE) and dopamine (DA) turnover rates are low. Concomitant with the preovulatory surge in gonadotropins, NE turnover rates increase, DA turnovers decrease, and LHRH declines in PSTS. The present studies examine the effects of phenobarbital (PB) on these proestrous events. PB, when given at 0900 hr proestrus, does not prevent the rise in median eminence (ME) LHRH which occurs between 0900 and 1200 hr. When the barbiturate is administered at 1200 hr, LH, FSH, and prolactin proestrous surges are blocked. While PB (given at 1200 hr) does not affect the increase in turnover rates of NE and DA which occur between 1200 and 1400 hr proestrus it markedly suppressed NE turnover rates in ME and suprachiasmatic nuclei but not in the medial preoptic nuclei between 1500 and 1700 hr. The decline in ME-DA which occurs between 1...