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Biomedical subjects

D B Kaufman

Publications and source records attributed to D B Kaufman.

At least 91 records · Page 5Linked to original sources

Induction of T-cell proliferation and enhancement of NK activity by supernatants from Con A-stimulated human peripheral blood mononuclear cells: a new lymphokine.

Supernatants from human peripheral blood mononuclear cells activated by Con A contain a factor(s) that stimulates blastogenic activity of normal human peripheral blood mononuclear cells. This Con A supernatant (CAS) contains stimulatory activity for E-rosette positive lymphocytes (T cells) and requires adherent cells for stimulation of T-cell proliferation. CAS does not contain detectable amounts of IL-2 as determined by its inability to support CTLL cell growth. Nor does it contain IL-1 or interferon. Examination of functional activity of lymphocytes stimulated for 3 days by CAS revealed that NK activity is augmented. This supernate does not appear to have any direct effect on B-cell function, although it induces suppression of polyclonal PWM stimulation of immunoglobulins. Thus, CAS appears to contain a new cytokine with immunomodulating potential.

Cell Division↗

Inhibition of suppressor cell function by cimetidine in a murine model.

Immunomodulatory effects of cimetidine, an H2 histamine receptor antagonist, have been reported in humans and animals. To define these effects more clearly, the action of cimetidine on suppressor cell function was studied utilizing a murine model of contact hypersensitivity. Intravenous inoculation of BALB/c mice with DNP-coupled syngeneic spleen cells induced the production of DNP-specific suppressor cells which could easily be demonstrated by a reduction in ear swelling after contact sensitization with 1-fluoro-2,4-dinitrobenzene (DNFB) following transfer of spleen and lymph node cells to naive syngeneic recipients. Cimetidine treatment of animals in which suppressor cells were induced resulted in an inability of these mice to transfer cellular suppression as measured by development of a normal immunologic response in the recipient mice. The effect of cimetidine was both dose and time related. While all groups receiving cimetidine showed some loss of suppressor cell function, the maximum effect (up to 100% inhibition) was seen when 50 mg/kg of cimetidine was administered intraperitoneally 2 days before or on the day of suppressor cell induction. Some restoration also occurred when cimetidine was given after the day of induction. It has been shown that suppressor cells possess histamine receptors which may be involved in suppressor cell activation. The results indicate that cimetidine may inhibit the functioning of these receptors.

Animals↗

Complications of heparin administration in normal individuals.

The incidence, severity, and pathogenic mechanism of heparin-associated thrombocytopenia with both bovine and porcine heparin administration were studied in forty normal males randomized to one of four treatment groups: beef lung heparin #1, beef lung heparin #2, porcine gut heparin, and saline control. All of the subjects receiving heparin developed a reversible increase in serum transaminases (SGOT, SGPT). However, other measurements of liver function were normal. Thirty-three percent of these heparinized normals had decreased platelet counts. The incidence of platelet count decrease was similar for both bovine and porcine heparins, but 4 of the 20 normals receiving bovine heparin had platelet counts less than 150,000/microliters. Immune pathogenesis was investigated by analyzing plasma from the volunteers for both platelet antibody and immune complexes. None of the men had increased platelet-associated IgG. Among the ten subjects with decreased platelet counts, IgG immune complexes were detected in three and C1q in seven. The heparin-associated thrombocytopenia appears not to be mediated by a platelet antibody. More probably it reflects a direct effect of the heparin on platelets.

Adult↗

Natural killer augmentation in systemic lupus erythematosus via a soluble mediator derived from human lymphocytes.

Seventeen patients with diagnosed systemic lupus erythematosus were studied for natural killer activity and the ability of a human soluble immune-response factor to modify this activity. Defective natural killer activity was found in patients with systemic lupus erythematosus regardless of the stage of disease, medication, or organ system involvement (24.6% versus 47.8% cytotoxicity). After treatment with the immune-response factor, the natural killer activity increased in all patients, with a mean of 47.3% compared with 24.6% before treatment. This product has other immunologic activities and was shown to be free of interferon. The mechanism of action is not yet known, but such an immune-response factor has potential use in the treatment of systemic lupus erythematosus.

Adolescent↗

Diphtheria-tetanus skin testing. Its clinical value for delayed hypersensitivity.

Skin testing as an in vivo means of evaluating cell-mediated immune function is extremely valuable. However, problems lie in selecting the appropriate antigens and interpreting the results. The suggestion that diphtheria-tetanus would provide a good antigen in infants and children was evaluated by comparing skin test observations with results of skin biopsy examinations. Thirteen subjects, seven of whom were immunodeficient, were evaluated by skin reactions and dermal biopsy specimens. Fifty percent of the immunodeficient patients had positive skin test reactions but had biopsy specimens that were not consistent with delayed-type hypersensitivity (DTH). Although all normal controls on whom biopsies were done had histologic DTH reactions, two had negative or equivocal skin reactions. Our data suggest, on the contrary, that delayed hypersensitivity testing with this antigen is not a good screening test for disorders of immunity or inflammation.

Adolescent↗

Maturational effects of thymic hormones on human helper and suppressor T cells: effects of FTS ('Facteur Thymique Sérique') and thymosin.

Human peripheral blood lymphocytes were isolated from healthy donors and pre-incubated with two thymic factors, FTS, a new synthetic polypeptide originally isolated and purified from serum, and thymosin Fraction V. After 24 hr of pre-incubation, the cells were washed and added to an allogeneic MLR and assayed for their ability to induce a suppressor or helper response. It was found that both factots were capable of inducing both helper and suppressor T cells and that the response was unpredictable. In both instances, more than 50% of the subjects studied responded with a helper effect. The addition of Con A augmented these effects. Since both helper and suppressor T cells can be induced by the factors studied herein, one must be aware of the potential effects on T-T and T-B balances of manipulation in clinical situations such as SLE or cellular immune deficiency states.

Cells, Cultured↗

The influence of thymosin on affinity binding in the E-rosette assay.

Human peripheral blood lymphocytes (PBL) were analyzed in the E rosette assay with respect to (1) the effect of SRBC/lymphocyte ratio on rosette number; (2) the effect of this ratio on the presence of lymphocytes with multiple binding sites for SRBC; and (3) the influence of thymosin on increasing the number of lymphocyte receptors for SRBC. An increase in the SRBC/lymphocyte ratio was associated with an increase in rosette number. The number of multiple binding rosettes was also dependent on the SRBC/lymphocyte ratio. At saturing SRBC concentrations, greater than 30% of the rosettes were in the morula form. Treatment of PBL with thymosin was associated with a slight increase in the number of total rosettes and a large increase in number of morulas. It is suggested that the morula represents a mature form of T cell in contrast to the 2 - 3 SRBC rosette, which may be induced by thymosin to become a morula form.

Animals↗

Acute and chronic effects of chemically induced unilateral renal disease in rats.

Chemically induced unilateral renal disease was associated with a high incidence of proteinuria, diuresis, a morphological spectrum ranging from perinephritis to acute tubular or cortical necrosis, and unilateral or bilateral glomerular fibrinogen deposition during the first 2 wk after induction. Later, a decrease in proteinuria and return to normal urine output was not infrequently followed by recurrent proteinuria, hypergammaglobulinemia, morphological alterations, and deposition of IgG and beta1C on the glomerular basement membranes and mesangium of the contralateral kidney and the treated kidney. Intercapillary deposition of fibrinogen in association with IgG and beta1C was occasionally observed in one or both kidneys. The morphologic, immunohistologic, serologic, and chemical findings suggest that this model may be useful for further defining the course and prognosis of unilateral renal disease produced by vascular insufficiency.

Animals↗

Cryoglobulins. III. Further studies on the nature, incidence, clinical, diagnostic, prognostic, and immunopathologic significance of cryoproteins in renal disease.

Serial serum samples from a large number of patients with immunologic renal disease, normal healthy controls, acute infections as well as non-immunological renal disease were studied for the presence, nature and properties of cryoproteins, and these correlated with serial renal functional, morphologic, immunohistologic and clinical fingings as well as serologic observations. A high incidence of cryoproteins were found in renal disease thought to be mediated by immune complexes. Cryoprecipitates were not detected in the other patients. The presence of fibrinogen in a serum cryoprecipitate was always associated with rapidly progressive disease and poor prognosis. An association between the detection of cryoproteins and the clinical and morphological activity of disease was observed. Persistence of cryoproteinemia was associated with progression and apparent disappearance with resolution or progression to end stage renal disease. In patients with hematuria or proteinuria of questionable significance cryoprotein detection was always associated with immune complex nephritis. Renal transplantation in the presence of cryoproteinemia was associated with recurrent nephritis in the graft. Cryoproteins were found to have biologic properties attributable to antigen-antibody complexes, to contain immune complexes of antigen and antibody and to have serologic factors concentrated. The detection of serum cryoglobulins was found to be a better index of clinical and morphologic activity of immune complex renal disease than was serum complement. As in our previous studies, these proteins appear to be of diagnostic and prognostic value in renal disease and provide a method of antigen identification in these disorders.

Animals↗