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Biomedical subjects

M G Mutchnick

Publications and source records attributed to M G Mutchnick.

53 records · Page 3Linked to original sources

In vitro thymosin effect on T lymphocytes in ankylosing spondylitis.

Peripheral blood "total" and "avid" T-cell rosettes (ER) were enumerated in 35 patients with ankylosing spondylitis (AS). The in vitro effect of thymosin fraction 5 on "avid" ER formation was also determined. "Total" ER numbers, but not proportions, were lower in patients with AS as compared to matched controls, Both the proportion and number of "avid" ER were lower in the patient group. Thymosin induced a significant increase in "avid" ER proportions and numbers in the patient group with no such effect observed in the controls. It is suggested that there are increased numbers of circulating T lymphocytes in patients with AS that can respond to exogenous thymic factors and acquire the capability to form "avid"ER.

Adult↗

In vitro synthesis of antibody to specific bacterial lipopolysaccharide by peripheral blood mononuclear cells from patients with alcoholic cirrhosis.

An enzyme-linked immunosorbent assay was used to detect antibody to specific bacterial lipopolysaccharide (LPS) in serum and in pokeweed mitogen (PWM) stimulated culture supernatants of peripheral blood mononuclear cells from four patients with alcoholic cirrhosis (AC). Antibody to LPS (derived from a single strain of Escherichia coli isolated from each patient's stool), was detected in the sera of each patient to a 10(-4) dilution. Only one of four control sera was positive at the 10(-4) dilution, with the others positive at 10(-3) dilution. Antibody to LPS was detected in the culture supernatants in three of the four patients and in none of the control subjects. Supernatants from patient cultures pretreated with mitomycin C or harvested after 1 day of incubation did not have detectable antibody. These results indicate that we can expand, in vitro, the population of peripheral blood B lymphocytes obtained from patients with AC and cause them to synthesize antibody against specific LPS from their own gut flora.

Antibody Formation↗

Effect of portacaval anastomosis on hypersplenism.

Leukopenia, thrombocytopenia, and hemolytic anemia occur commonly in advanced cirrhosis. Some investigators have reported that portacaval anastomosis (PCA) abolished hypersplenism while others have not found PCA to be uniformly beneficial. We compared the frequency of hypersplenism before and after admission to a controlled investigation of the effects of PCA in 52 unoperated control subjects and 38 patients with patent PCA. The two groups were followed for an average period of 5 1/2 years. On admission to the study leukopenia was present in about 2% of patients, thrombocytopenia in 6%, and hemolytic anemia in 4%. Splenomegaly was present in 48% and hypersplenism in 11%. After randomization splenomegaly disappeared more frequently in the shunted group. In addition, fewer patients with PCA developed splenomegaly for the first time after inclusion into the study than did unoperated control subjects. Leukopenia, thrombocytopenia, and hemolytic anemia, when present at inclusion into the study, disappeared with equal frequency in the shunted and unshunted patients, and appeared with equal frequency in both groups after randomization in previously unaffected patients. In no instance was hypersplenism clinically significant nor was splenectomy considered or carried out in any of these 90 patients. In additional uncontrolled studies we observed that therapeutic PCA did not affect hypersplenism differently from prophylactic PCA. We conclude that PCA has neither clinically nor statistically significant effects on hypersplenism.

Anemia, Hemolytic↗

Thymosin-dependent T-lymphocyte response in inflammatory bowel disease.

Peripheral blood "total" and "avid" thymus-dependent (T) lymphocytes were enumerated in 45 patients with Crohn's disease (CD) and in 23 patients with ulcerative patients (UC) by using the spontaneous rosette technique (ER). The in vitro effect of thymosin fraction 5, a polypeptide extract of the thymus gland, on avid ER formatin was also determined in these patients. The proportion and number of "total" ER were lower in patients with CD (P < 0.02), but not with UC, when compared with controls. More impressive differences were observed when "avid" ER were determined in patients with CD (P < 0.001) and UC (P < 0.05). Incubation with thymosin resulted in a significant increase in "avid" ER in patients with CD and UC, with no such effect observed in the controls. These results indicate that the determination of "avid" rather than "total" ER provides a more sensitive method for detecting alterations in T-cell immune competence. In addition, it is suggested that there is an increased number of circulating T-lymphocytes in CD and UC capable of responding to exogenous thymic factors. This may indicate the presence of a thymosin-responsive immunodeficiency state in these diseases.

Adult↗

Adrenocorticosteroid therapy in alcoholic hepatitis. A prospective, double-blind randomized study.

In a prospective, randomized, double-blind study of prednisolone therapy of acute alcoholic hepatitis, 39% of the total group of 28 patients died. Mortality and cumulative survival were similar in steroid- and placebo-treated patients. After 14 days of therapy, the serum albumin concentration and white blood count were significantly higher in the steroid group, but all other parameters were similar. An increased risk of fungal infection appeared to be associated with steroid therapy.

Acute Disease↗

Influence of SRBC/lymphocyte ratio on T-cell rosettes in alcoholic liver disease and inflammatory bowel disease.

Thymus-derived (T) rosette-forming cells were enumerated in patients with alcoholic liver disease and in patients with inflammatory bowel disease using variable sheep red blood cell (SRBC)/lymphocyte ratios. SRBC/lymphocyte ratios of 60:1 and 32:1 did not reveal significant differences from controls in Crohn's disease. The percentage, but not absolute count, of T cells was significantly reduced in alcoholic hepatitis at the 60:1 ratio. Both the percentage and absolute count of T cells were reduced in alcoholic hepatitis and Crohn's disease with the 8:1 ratio. No significant reduction in T cells was seen at any ratio in patients with compensated alcoholic cirrhosis or ulcerative colitis. Use of a SRBC/lymphocyte ratio of 8:1 indentifies T cells which demonstrate an avidity for SRBC. This avidity may be related to the density of SRBC receptors on the surface of T cells and/or the affinity of these receptor sites for SRBC. Use of the 8:1 ratio may provide a more sensitive means by which to monitor changes in T-cell rosettes in patients suspected of having an altered cellular immune state.

Colitis, Ulcerative↗

Ankylosing spondylitis with selective IgA deficiency and a circulating anticoagulant.

A patient with ankylosing spondylitis was found to have selective IgA deficiency and a non-heparin, immediate-acting antithrombin (antithrombin V). T cells were decreased, and serum IgG was increased. In vitro synthesis of IgG by peripheral blood lymphocytes was very high. This association of ankylosing spondylitis with the T cell and protein abnormalities is probably fortuitous but does demonstrate that severe spondylitis may evolve in the absence of IgA.

Antithrombins↗

Intraarterial vasopressin in the treatment of upper gastrointestinal hemorrhage: a prospective, controlled clinical trial.

Intraarterial vasopressin has been reported to be effective in the treatment of massive upper gastrointestinal hemorrhage. A prospective, controlled clinical trial comparing conventional treatment with conventional therapy plus intraarterial vasopressin was undertaken. Sixty episodes of upper gastrointestinal hemorrhage were evaluated during a 40-month period; 32 received conventional and 28 conventional plus vasopressin therapy. The two groups of patients were similar in type and severity of their bleeding lesions and in their underlying diseases. Vasopressin was more effective in controlling hemorrhage from nonvariceal lesions (P less than 0.05) and from varices (P less than 0.01) than conventional therapy. Transfusion requirements were significantly reduced in those patients who received vasopressin. Paradoxically, survival was not affected by vasopressin administration. The failure of cessation of hemorrhage to improve survival is thought to be due to the degree of advancement of the underlying disease, to the torrential nature of the hemorrhage, to the frequency of recurrent hemorrhage, and to the use of intraarterial vasopressin in some patients in the conventional treatment group in whom conventional therapy had failed.

Adult↗

Thymosin alpha 1 and thymosin beta 4 modulate human colonic lamina propria lymphocyte function.

Thymosin alpha 1 and thymosin beta 4 are two thymosin fraction 5-derived peptides with the capacity to alter a variety of immune functions in human and animal models. In this study we investigated the effect of both thymosin alpha 1 and thymosin beta 4 on human colonic lamina propria lymphocyte (LPL) proliferation and ornithine decarboxylase (ODC) activity. LPL from eighteen human colon specimens were cultured in the presence or absence of thymosin alpha 1 and thymosin beta 4. We found that both peptides suppressed thymidine incorporation into LPL. However, thymosin alpha 1 and thymosin beta 4 did not alter thymidine incorporation into phorbol ester (PDB) and calcium ionophore (ionomycin)-stimulated LPL. Furthermore, thymosin alpha 1 and thymosin beta 4 also did not alter ODC activity in Con A-stimulated LPL. These results suggest that both peptides alter LPL proliferation, and that the mechanism for this inhibition may not involve the calcium fluxes or the ODC pathway but may involve protein kinase C. We postulate that thymosin alpha 1 and thymosin beta 4 may participate in the modulation of the human mucosal immune system.

Colon↗

Thymus-derived peptides in the treatment of viral chronic hepatitis.

The immune system plays a crucial role in the control and eventual clearance of hepatitis B virus (HBV) infection. Immune mechanisms are now believed to participate in the pathogenesis of the hepatitis C virus (HCV) and to account perhaps for the high frequency of progression from acute to chronic disease. Although IFN-alpha has been proven effective in the treatment of viral chronic hepatitis B and C, response rates are low, reactivation of disease is appreciable and side effects of treatment are frequent. Both antiviral and immune modulatory activity have been ascribed to IFN-alpha and are believed to account for its therapeutic effect. Immune-active peptides including those derived from the thymus have also been evaluated over the past 15 years for the treatment of viral chronic hepatitis. This review summarizes clinical studies and experimental observations which provide the rationale for the use of these agents in the treatment of chronic hepatitis associated with HBV and HCV. Primary attention is focused on thymosin-alpha (T alpha 1), a synthetic peptide, which has been evaluated in clinical trials. T alpha 1 has in vivo and in vitro immune-modulatory activity on lymphoid populations as well as the potential of more direct antiviral activity. Preliminary results of clinical trials utilizing combinations of T alpha 1 with various IFN preparations are also reviewed.

Antiviral Agents↗

Thymic humoral factor effect on intracellular lymphocyte cAMP in patients with ankylosing spondylitis.

Intracellular cAMP was measured in peripheral blood mononuclear cells from patients with ankylosing spondylitis and from controls. The effect of thymic humoral factor (THF) on T lymphocyte cAMP content was monitored in both groups to determine if there were any differences in immature T cell proportions. Equivalent cAMP levels were found in patients and controls in the absence of THF and again after stimulation with this immune modulator.

Adult↗