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Biomedical subjects

C J Grossman

Publications and source records attributed to C J Grossman.

At least 37 records · Page 2Linked to original sources
PubMed1989

Antagonist profile of 6,7-dichloro-3-hydroxy-2-quinoxalinecarboxylate at excitatory amino acid receptors in the neonatal rat spinal cord.

In the neonatal rat spinal cord, 6,7-dichloro-3-hydroxy-2- quinoxalinecarboxylate antagonised responses mediated at both N-methyl-D-aspartate (NMDA) and non-NMDA receptors. The antagonism of responses to NMDA was unsurmountable and mediated via an antagonist action at the allosterically-linked strychnine-insensitive glycine site. At non-NMDA receptors, 6,7-dichloro-3-hydroxy-2-quinoxalinecarboxylate appeared to act as a competitive antagonist at low concentrations and a non-competitive antagonist at higher concentrations. In contrast to published data, this antagonist did not distinguish between the responses mediated by DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) and kainate.

Animals↗
PubMed1989

The interactions of insulin-like growth factor I(IGF-I) with protein-calorie malnutrition in patients with alcoholic liver disease: V.A. Cooperative Study on Alcoholic Hepatitis VI.

Plasma concentrations of insulin-like growth factor I (IGF-I) were measured in 95 alcoholic men with a spectrum of alcoholic liver injury and protein-calorie malnutrition (PCM). Circulating levels of IGF-I were depressed in the alcoholic patients (0.23 +/- 0.02 U/ml; mean +/- S.E.M.) compared to controls (1.0 +/- 0.07, P less than 0.0001). Plasma IGF-I levels declined progressively with falling indices of PCM (P less than 0.001) and correlated especially with the parameters relating to protein deficiency. While the severity of liver dysfunction and histopathologic alterations in the liver also related to plasma IGF-I concentration, partial correlation analysis showed that only PCM correlated significantly with IGF-I levels independent of the other factors. These findings indicate that IGF-I levels reflect nutritional status even in the presence of alcoholic liver disease.

Adult↗
PubMed1989

Cell-mediated immune responses associated with short term alcohol intake: time course and dose dependency.

Using a rat model, we report here the duration of heavy drinking necessary to produce immunosuppression, the recovery time after such alcohol-induced immunosuppression, and the variations in immune response associated with varied amounts of alcohol consumption. Immune status was evaluated by means of delayed cutaneous hypersensitivity (DCH)-like responses to phytohemagglutinin. The daily consumption of 5 g of ethanol/kg body weight/d resulted in a prompt reduction in DCH-like responses which was significant by Day 3 (p = 0.03) and maximal by Day 11 (45% of baseline). These data were consistent with a similar reduction of migration inhibitory factor activity in spleen cells from ethanol fed rats. Cessation of ethanol resulted in a return to baseline within 4 days. In a second experiment ethanol was administered daily in doses ranging from 0.5 to 6.0 g/kg. Early (Day 5) low dose ethanol (0.5-2 g/kg) stimulated immune response (153-188% of baseline) while high dose (6.0 g/kg) suppressed (79% of baseline). Continued treatments resulted in a loss of stimulation at low dose and increased suppression at higher doses. The relationship of these animal studies to human binge drinking and the possible risk for infection in the alcoholic remains to be established.

Animals↗
PubMed1989

Ethanol and soluble mediators of host response.

Lymphokines serve to modulate host inflammatory response by providing a communication link among cells involved in resistance to infection. In the alcoholic, this system may be impaired due to a combination of the direct effects of ethanol on immunocompetent cells and the soluble factors involved in cell-cell interactions. In this paper, we review the literature on this subject, describe an ethanol-related impairment of migration inhibitory factor activity in the rat, and present a possible mechanism for this alteration.

Alcoholism↗
PubMed1989

Phytohemagglutinin skin test responses to evaluate in vivo cellular immune function in rats.

It is often necessary to have a small animal model which permits the sequential evaluation of functional immune status over a period of time. We report here the in vivo, intradermal response to phytohemagglutinin which produces an area of induration that is histologically similar to a typical delayed cutaneous hypersensitivity response, and that provides fast, quantitative, reproducible results similar to those observed with standard but more laborious and variable in vitro tests of immune function. For small animal studies this has the advantage of permitting longitudinal evaluations over time without sacrificing the animal. Using phytohemagglutinin-microprotein (0.2 mg/0.1 ml), injected intradermally, a delayed cutaneous hypersensitivity-like response is induced which is maximal at 24 hr. When immune function was altered either by treatment with a chemical immunosuppressant (ethanol) or by hormonal manipulations (hypophysectomy and rat growth hormone), the delayed cutaneous hypersensitivity-like response (area of induration) correlated closely with both macrophage migration inhibitory factor changes (r = 0.98; P less than 0.001) and mixed lymphocyte reaction changes (r = 0.99; P less than 0.05). These observations suggest that this technique correlates well with standard in vitro measures of immune response and may thus permit an in vivo estimation of immune reactivity.

Animals↗
PubMed1989

Age dependent alterations of host immune response in the ethanol-fed rat.

The interaction between ethanol and aging with respect to cellular immune response is unclear. For our studies, Sprague-Dawley rats were pair fed using a synthetic liquid control diet (LCD) or a diet in which ethanol was substituted for carbohydrate (LED). The special diets were started when the rats' age varied from 1-18 months and were continued for one, two, or three months. In a second set of experiments, rats were treated continuously with these diets for 24 months. At each study period blood was drawn for serum and the spleen cells removed. Immune response was assessed by the lymphocyte transformation test using combinations of cells and serum from each of the rat groups. When LCD or LED were started in aged rats (18 months), after three months, there was a significant decrease in the Concanavalin A induced lymphocyte transformation test using the serum from LCD rats compared to serum from LED rats with either cells from LCD (1,273 +/- 831 (DPM +/- SD) vs 302 +/- 139; p less than 0.04) or cells from LED animals (984 +/- 338 vs 420 +/- 196; p less than 0.02). When the diet started at younger age or for less than three months these effects were not seen. In the continuously LCD or LED fed rats, the blastogenic response peaked at three months of treatment (four months of age) and decreased at six months and remained constant over the remainder of the 24 month period. There was no difference in lymphocyte DNA synthesis comparing any of the serum or cell groups with respect to diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1989

Longevity among ethnic groups in alcoholic liver disease.

As part of a multicenter V.A. Cooperative Study, 437 male veterans with varying stages of alcoholic liver injury were followed over a 4.5 year period. Their ethnic distribution consisted of 256 Caucasians, 109 black Afro-Americans, 63 Puerto Rican Hispanics, and 9 Native American Indians. Survival analyses revealed significant differences between groups (P = 0.0002): 66% of Afro-Americans were still living at 42 months; Caucasians were intermediate with 40% survival; and only 28% of Hispanics were alive. The number of Native American Indians enrolled was too small to draw conclusions but none of those enrolled survived beyond 24 months. Survival regression analysis of 30 clinical, laboratory, histologic and nutritional parameters, revealed the following significant risk factors: clinical severity (P less than 0.0001), histologic severity (P less than 0.0001), race (P = 0.001), age (P = 0.002), BUN (P = 0.01) and ALT (P = 0.02). These analyses indicated that ethnicity, independent of other variables, is significantly associated with outcome from the disease.

Adult↗
PubMed1988

6,7-Dinitro-quinoxaline-2,3-dion and 6-nitro,7-cyano-quinoxaline-2,3-dion antagonise responses to NMDA in the rat spinal cord via an action at the strychnine-insensitive glycine receptor.

6,7-Dinitro-quinoxaline-2,3-dion (DNQX) and 6-nitro,7-cyano-quinoxaline-2,3-dion (CNQX) produce an unsurmountable antagonism of responses to N-methyl-D-aspartate (NMDA) in the baby rat hemisected spinal cord. These effects of DNQX and CNQX can be prevented in a dose-dependent manner by co-superfusion with D-serine or glycine (in the presence of strychnine). The results suggest that the unsurmountable blockade of NMDA responses by DNQX and CNQX reflects an antagonist effect mediated at the allosterically linked strychnine-insensitive glycine receptor.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1988

Kynurenic acid antagonises responses to NMDA via an action at the strychnine-insensitive glycine receptor.

Kynurenate produces an unsurmountable antagonism of the response to N-methyl-D-aspartate (NMDA) in the baby rat hemisected spinal cord. This effect is completely reversible and prevented by co-superfusion with D-serine or glycine in the presence of strychnine. In the presence of D-serine kynurenate acts as a weak competitive antagonist. The results suggest that one of the actions of kynurenate is to antagonise NMDA responses via an action at the strychnine-insensitive glycine receptor.

Animals↗
PubMed1988

Kynurenate and FG9041 have both competitive and non-competitive antagonist actions at excitatory amino acid receptors.

The antagonist profile of kynurenate and FG9041 have been characterised in a modified preparation of the baby rat hemisected spinal cord. Both kynurenate and FG9041 were competitive antagonists of responses to kainate and AMPA, although neither antagonist was selective for kainate versus AMPA. In contrast, both antagonists produced an apparent unsurmountable antagonism of responses to NMDA, indicating a different mode of action at the NMDA receptor.

Animals↗
PubMed1988

Hepatitis B vaccination. Response of alcoholic with and without liver injury.

Alcoholics are at risk to develop hepatitis B infections, chronic active hepatitis, and even hepatoma. Hence, immunization with hepatitis B vaccine is recommended. However, immune abnormalities may coexist which alter their responsiveness to vaccination. This study compares the immune response to this vaccine in controls (group I), alcoholics without overt liver disease (group II), and alcoholics with clinical liver disease (group III). By the seventh month after the initial vaccination, 89% in group I, 70% in group II, and 18% in group III had a response greater than 36 RIA units. The magnitude of the response was significantly different in groups I, II, and III (19,456 vs 8,326 vs 153 RIA units, respectively; P less than 0.05, group I vs III). In those who did not respond, a significant (P less than 0.02) lower helper/inducer (T4) class of lymphocytes was observed as compared to patients who exhibited an adequate response. These observations suggest: (1) that the response to hepatitis B vaccine is a T-cell-dependent event and (2) that in this population, using the existing vaccine, postvaccination evaluations of antibody concentrations are needed before protection against hepatitis B infection can be assumed.

Adult↗
PubMed1988

Alcohol and immune regulation. I. In vivo effects of ethanol on concanavalin A sensitive thymic lymphocyte function.

Alcohol is known to suppress the immune response, but the underlying mechanism to account for this immune suppression is still not clearly elucidated. In an attempt to clarify such mechanisms, experimental rats were fed for 50 days on a 36% ethanol, Lieber diet (LED) while control (LCD) rats were fed a similar diet supplying the same amount of calories but lacking ethanol. It was found that both LCD and LED animals grew at a linear rate (LCD: r = 0.981, LED: r = 0.961) but that LCD animals grew more rapidly. While thymic weights in the LED group were significantly smaller (P less than 0.05) than in the LCD group, the ratios of thymic weight/body weight between these groups were not significantly different. To identify the effects of ethanol on immune response, thymic (Th) or splenic (S) cells were prepared and incubated in culture with the mitogen, Con A and rat serum prepared from LCD or LED groups. It was found that lymphocytes prepared from thymus of LED animals appeared to be depressed in mitogen-driven blastogenic transformation when incubated in LCD serum but not LED serum. Furthermore, lymphocytes prepared from the spleen of LED animals appeared to be depressed in mitogen driven blastogenic transformation when incubated in LED serum but not LCD serum. Since lymphocytes of the thymus and spleen are undergoing maturation and replication this implies that ethanol may alter these processes.

Animals↗
PubMed1988

Lymphocyte subset alterations in patients with alcoholic hepatitis.

Twenty-three patients with alcoholic hepatitis (AH) were entered into a study to evaluate the relationship between alcoholic hepatitis, malnutrition, and immune status. In order to quantify these variables, objective parameters of nutritional status and lymphocyte phenotype and function were used. On admission to hospital, the mean number of CD4 helper/inducer cells, CD8 suppressor/cytotoxic cells, and CD3 lymphocytes were significantly reduced compared to age matched, non-hospitalized laboratory controls. In order to ascertain whether this abnormality was reversible, 12 patients, who were willing to remain in the hospital for 30 days, were treated for this entire period with oral nutritional supplementation using a commercially available preparation high in calories, protein, and branch chain amino acids. After 30 days of this therapy and abstinence, the number of CD4 cells increased from a mean (+/- SD) of 658 +/- 428 to 815 +/- 599/mm3. There was no difference in results of the lymphocyte transformation test comparing pre- and post-therapy values using either fetal calf or autologous serum. For all groups tested, cells cultured in autologous serum exhibited a significantly decreased response to mitogen compared to cells cultured in fetal calf serum. Both the total nutritional and the protein depletion (kwashiorkor) scores improved significantly during the 30 days of nutritional supplementation (p less than 0.0009 and p less than 0.0004, respectively). Therefore, we have observed an alteration in the numbers of helper lymphocytes in patients admitted with AH. This abnormality was modifiable by abstinence and nutritional supplementation over a brief period of hospitalization.

Hepatitis, Alcoholic↗
PubMed1987

Effects of mixed bacterial toxins on immune response.

Mixed bacterial toxin (MBT) is an experimental substance for treatment of certain forms of cancer. To ascertain if the cancer regression affects reported for MBT might be mediated via immunoendocrine interactions, MBT was tested in vivo in male Wistar rats or in vitro on Thymic (Tc) or Splenic (S) lymphocytes prepared from these same animals. In order to evaluate gonadal steroid effects on this process, certain groups of these rats were also castrated before treatment. Tc or S lymphocytes were prepared from these groups and cell responsiveness was monitored by in vitro blastogenic assays. Certain assay wells also contained Concanavalin A as a mitogen. The addition of MBT in vitro significantly stimulated Tc-cell responses (p less than 0.05) for all experimental groups except for certain groups of castrate MBT injected rats. Furthermore, S cells did not respond in the presence of MBT added in vitro except after castration and pretreatment with MBT where in vitro addition of MBT to cultures significantly stimulated blastogenic responses (p less than 0.02). The results of these assays are consistent with the hypothesis that the anticancer effects attributed to MBT result from the ability of MBT to act as a nonspecific mitogen-like stimulator of immature Tc-cells and mature S-cells. These results also suggest that MBT may modulate a serum factor under the control of gonadal steroids and possibly of thymic origin which can effect T-cell responsiveness.

Animals↗
PubMed1985

Interactions between the gonadal steroids and the immune system.

The immune system is regulated by the gonadal steroids estrogen, androgen, and progesterone, but the circulating levels of these steroids can also be affected by immune system function. Such interactions appear to be mediated through the hypothalamic-pituitary-gonadal-thymic axis and depend on pituitary luteinizing hormone released by thymic factors under the control of the gonadal steroids.

Androgens↗
PubMed1985

Studies on the cytosolic estrogen receptor from rat thymus.

The estrogen receptor present in rat thymus cytosol was characterized by its association constant, KA, the number of binding sites present, Bmax, and by the effect of added estradiol on the binding parameters. The binding parameters were determined by fitting the raw binding data directly to the hyperbolic binding function, and the Lineweaver-Burk, Scatchard, and Woolf linear transforms of the hyperbolic function. The binding parameters were also determined using the direct linear plot method of Eisenthal and Cornish-Bowden. The Woolf plot and the direct linear plot gave results that indicated that added estradiol caused both competitive and noncompetitive inhibition of the receptor. The Scatchard and Lineweaver-Burk methods were not capable of showing a systematic trend. The parameters derived from the hyperbolic binding equation were in agreement with the Woolf and direct linear plot methods. The results of this study show that the cytosolic estrogen receptor from rat thymus is both competitively and noncompetitive inhibited by estradiol.

Animals↗