Biomedical subjects

C J Grossman

Publications and source records attributed to C J Grossman.

At least 19 recordsLinked to original sources

PubMed1991

Antibodies to hepatitis B virus and hepatitis C virus in alcoholic hepatitis and cirrhosis: their prevalence and clinical relevance. The VA Cooperative Study Group (No. 119)

Patients with overt alcoholic liver disease who had participated in a multicenter therapeutic trial and subgroups of controls (i.e., alcoholic patients without liver disease and patients with neither alcoholism nor liver disease) were tested for hepatitis B virus and hepatitis C virus antibodies to determine the prevalence of these antibodies to determine the prevalence of these antibodies and any clinical association in the progression and outcome of alcoholic liver disease. Antibodies to hepatitis B (anti-HBs and/or anti-HBc) were found in 29.2% of patients with alcoholic liver disease, in 26.1% of hospitalized alcoholic patients without liver disease and in 24.2% of hospitalized nonalcoholic patients without liver disease; frequencies were not significantly different from one another. HBsAg was not evaluated because HBsAg+ patients had been excluded from the original trial. The presence of these antibody markers correlated with ethnic origin of and immunoglobulin levels in the patients. In contrast, antibody to hepatitis C, as detected by enzyme immunoassay, was positive in 27.1%, 4.8% and 3.0% of the three groups, respectively, the first differing significantly from the other two. Antibody to hepatitis C virus positivity correlated significantly with clinical severity of the disease and with the presence of histological features that imply chronic viral infection (periportal inflammation, cirrhosis), despite the fact that the supplementary assay for antibody to hepatitis C virus, using recombinant immunoblot assay, reduced the positive rate by 79%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Sex steroid regulation of autoimmunity.

The immune response of males and females is not identical but instead has been shown to be dimorphic in its nature, with females generally demonstrating a greater overall response than males. This dimorphism extends to both the humoral and cell mediated systems and appears to be mechanistically based on the differences in type and concentration of sex steroids in males vs females. Furthermore, growth hormone and prolactin secretions which are different in males and females may also be partly responsible for the observed dimorphism. Because autoimmune disease results from a pathological perturbation of normal immune function, it follows that expression of these diseases will also demonstrate a dimorphic pattern. Examples of this autoimmune dimorphism include (but are not limited to) lupus, rheumatoid arthritis and multiple sclerosis with the two former more prevalent in females than males and the latter more severe during pregnancy. To explain autoimmune dimorphism it therefore becomes necessary firstly to describe the cellular and hormonal interactions found in normal immune regulation and thereafter extrapolate these to autoimmune phenomena.

Autoimmune Diseases↗

PubMed1991

Alpha-fetoprotein alterations in alcoholics with liver disease. V.A. Cooperative Study Groups.

Sera on 409 male alcoholics with liver injury were assayed for alpha-fetoprotein (AFP) as part of a VA co-operative study on the natural history and therapy of alcoholic liver disease. In 78% of the patients values below normal were observed and 42% had undetectable levels. Clinically the lowest AFP concentrations were observed in the more severely ill patients with the poorest 1 year survival. Furthermore, improvement in AFP was associated with improved survival. Correlation analysis showed a relationship of AFP to (1) visceral protein concentrations (i.e. albumin, transferrin, retinal binding protein); (2) variables related to hepatic fibrogenesis (i.e. Ito cell activity, quantitative estimates of fibrosis and Kupffer cell abnormalities); and (3) changes in immunoglobulin levels particularly IgG. These findings suggest that AFP is a good index of disease prognosis.

Alcoholism↗

PubMed1990

Host response to mycobacterial infection in the alcoholic rat.

Animals, chronically treated with alcohol, were inoculated with mycobacteria (bacillus Calmette-Guérin, 10.2 x 10(6) organisms) into the spleen to produce a granulomatous hepatitis. Before infection, chronic alcohol ingestion was associated with a depressed skin test response to phytohemagglutinin, 71.7% of baseline (P = 0.009). Mycobacterial (bacillus Calmette-Guérin) infection stimulated phytohemagglutinin skin test response to 417% of baseline in controls and 299% in alcoholics (P less than 0.001). The hepatic granuloma response was altered with smaller but more numerous granulomas (mean +/- SEM, 81.2 +/- 1.5 microns2 of area with a frequency of 1.8 granulomas per field in alcoholics vs. 129.8 +/- 5.71 microns2 and 1.2 granulomas per field in controls; P less than 0.001). These changes were associated with a 10-fold increase in colony-forming units per gram of liver (54.5 +/- 18.2 in alcoholics vs. 5.6 +/- 1.83 in controls; P = 0.0006). This model offers precise parameters for host response to infection and indicates that alcohol significantly impairs the clearing capacity for mycobacteria from the liver.

Alcoholism↗

PubMed1990

Anabolic steroid effects on immune function: differences between analogues.

As an untoward effect of chronic anabolic steroid use, immunologic alterations may be induced. To evaluate this possibility five commercially available steroids with various types of structural differences were studied in male Sprague-Dawley rats. Animals were divided into five groups and treated with testosterone (Group 1), testosterone propionate (Group 2), testolactone (Group 3), oxandrolone (Group 4), and stanozolol (Group 5). Androgenic anabolic steroids were administered daily, subcutaneously dissolved in oil, at a dose of 1.1 mg/kg. Immune alterations were assessed by skin-test responses to phytohemagglutinin. After five days of treatment (1.1 mg/kg/day) a significant immuno-suppression was observed with all groups. However, by day 10, groups 3, 4, and 5 showed an immuno-stimulation. Using oxandrolone as the model stimulant, serum testosterone levels were significantly suppressed, while castration abolished the stimulatory effect. These observations indicate that immune alterations do occur with anabolic steroids which are immuno-suppressive when the steroid nucleus is intact and immuno-stimulatory with nuclear alterations. It appears that these changes are associated with altered gonadal testosterone release.

Anabolic Agents↗

PubMed1990

Nuclear progestin receptors in rat thymic tissue.

The thymus and its associated endothelial cells and lymphocytes act as an important immunological tissue. The endothelial cells of the thymus have been reported to synthesize cytoplasmic progestin receptor in response to estrogen priming. To measure nuclear progestin receptor, female rats were castrated and primed for 3 days with estradiol benzoate (30 micrograms/0.1 ml/d) and immediately before sacrifice injected subcutaneously with 0.2 mg of progesterone. By Scatchard plot analysis we found that specific progestin receptor (KA = 0.89 +/- 0.10 x 10(9) M-1) was present in the KCl-nuclear extract. The concentration of nuclear progestin receptor was found to be in the range of 312.6 +/- 49 fmole/g tissue (n = 9, 1 hour after progesterone injection) while the nuclear receptor was significantly reduced (approximately 44 fmol/g tissue) in the oil treated controls. This level verges on the limits of sensitivity for this assay. For cytoplasmic progestin receptor the concentration was 3.46 +/- 0.20 pmole/g tissue in oil treated controls (n = 14) and 3.36 +/- 0.20 pmole/g tissue in progesterone treated animals (n = 24). The KA of this thymic cytoplasmic progestin receptor was 1.35 +/- 0.06 x 10(9) M-1. By competition assay, the relative binding affinity of nuclear progestin receptor was: R5020 (a potent synthetic progestin) (100%), progesterone (9%), testosterone (0.56%), corticosterone (0.53%), estradiol-17 beta (0%). It is concluded that thymic reticuloepitheleal cells contain nuclear progestin receptor and this finding supports the hypothesis that progesterone, like other sex steroids may play a regulatory role in thymic cell function.

Animals↗

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↗