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Biomedical subjects

A Winkelstein

Publications and source records attributed to A Winkelstein.

At least 73 records · Page 4Linked to original sources
PubMed1980

Depressed T cell colony growth in systemic lupus erythematosus.

Phytohemagglutinin-stimulated peripheral blood T lymphocytes, plated in agar, are capable of forming discrete lymphoid colonies. In 35 normal subjects, the average number of colonies was 6,020 +/- 351 (SEM). By contrast, in 39 patients with systemic lupus erythematosus (SLE), the mean colony number was 2,774 +/- 384, a value significantly less than controls (P less than 0.001). Normal responses were measured in 5 patients with progressive systemic sclerosis and in 7 of 8 patients with rheumatoid arthritis. Colony growth in SLE showed a strong correlation with disease activity but did not correlate with responses of blood lymphocytes to phytohemagglutinin in suspension cultures, the number of circulating T cells, or serologic abnormalities.

Adult↗
PubMed1980

The pharmacologic effects of PGE1 on murine lymphocytes.

Although PGE1, in pharmacologic quantities, possesses significant in vivo immune-modulating activities, its effects on different lymphoid populations have not been defined. In the present study, lymphocyte numbers, turnover rates, and functional activities were assessed in Swiss-Webster mice receiving PGE1, 200 microgram twice daily, for up to 14 days. The most pronounced cellular alterations were observed in the thymus. After 2 wk, the number of theta-positive cells decreased by 81%. Total splenic cellularity was concomitantly reduced by 28%. This was primarily due to a loss of B lymphocytes; the number of these cells decreased by 40%. Bone marrow lymphocytes were also decreased by PGE1 administration. By contrast, peripheral blood lymphocytes and splenic T cells were not significantly altered. Similar changes in lymphocyte numbers were observed in adrenalectomized mice, indicating that depletion was not due to a corticosteroid effect. In normal mice, PGE1 reduced the in vivo incorporation of 3HTdr in both the thymus and the spleen by approximately 50%; this finding, in conjunction with histologic and cytologic observations, suggests a decrease in intrinsic rates of lymphopoiesis. Residual splenocytes were not impaired in their in vitro responses to three polyclonal mitogens: PHA, Con-A, and endotoxin. Studies in cortisol-treated mice showed that PGE1 caused a decrease in both steroid-sensitive and steroid-resistant thymocytes and splenocytes.

Adrenalectomy↗
PubMed1979

The effects of cyclophosphamide on mitogen-induced and antibody-dependent cellular cytotoxicity in guinea pigs.

Lymph node cells from normal guinea pigs, when stimulated with the non-specific mitogen PHA, were transformed to activated killer cells, capable of lysing 51Cr labeled mouse fibroblasts. Similarly, these lymphoid cells effected lysis of antibody coated chicken red cells in an antibody-dependent cellular cytotoxicity assay. Following cyclophosphamide, 150 mg/kg IP, the reactivity of an aliquot of lymph node cells to effect either cytotoxic reaction was not diminished. These results indicate that this immunosuppressant does not promote a selective decrease in either lymphoid effector. Rather, they are diminished in parallel with the generalized lympholysis resulting from drug administratioin. During the recovery phase, lymph node cells showed increased ability to lyse target cells, suggesting a rebound phase of heightened activity. Thymic cells from normal and cyclophosphamide treated animals were poor effectors in either cytotoxic assay. The addition of an equal number of thymocytes to lymph node cells resulted in decreased mitogen-induced cytotoxicity. Thymic inhibitory activity was mediated only by viable cells and the phenomenon did not represent an altered shift in PHA sensitivity. This suppressive activity persisted when thymic cells from cyclophosphamide treated-animals were employed, indicating that inhibitory cells were also not selectively depleted by this drug. In antibody-dependent cellular cytotoxicity assays, thymocytes from normal or cyclophosphamide-treated animals did not alter the cytotoxicity capacity of lymph node cells.

Animals↗
PubMed1979

The effects of azathioprine and 6 MP on immunity.

The thiopurines, azathioprine and 6 MP are potent inhibitors of both experimental and clinical immune responses. The primary pharmacological activities are mediated by competitive inhibition of enzymes concerned with de novo purine base synthesis; Immunosuppressive activities appear to result from cytotoxic activities directed against antigen-responsive lymphocytes; this inhibition is maximal when the treatment course coincides with the proliferative expansion phase of the response. By contrast, thiopurines are comparatively ineffective if used during an effector phase of an immune response. Furthermore, administration prior to antigenic challenge does not lead to immune inhibition; in fact, it may lead to augmentation of selected immune responses. Treatment with thiopurines does not result in acute lymphopenia; prolonged courses will cause a moderate decrease in circulating lymphocytes. The drug does not selectively deplete peripheral T or B cells but can acutely reduce K (killer) cells, which are effectors in ADCC responses. In addition, short-lived thymocytes and marrow lymphocytes are rapidly depleted by these anti-metabolites. Many in vitro functions of lymphocytes, from treated animals remain normal. Recent studies indicate that, in vitro, azathioprine is specifically able to bind murine T lymphocytes; this can be shown by their ability to inhibit their capacity to rosette with sheep erythrocytes. Azathioprine is also a potent inhibitor of mixed lymphocyte culture responses and can readily suppress the in vitro generation of cytotoxic T cells. These observations suggest that drugs exert preferential toxicities for murine T cells. B lymphocytes for mice appear to vary in their susceptibility for thiopurines. By contrast, the activity of human B cells can be readily suppressed with this drug whereas T helper function is comparatively resistant. In addition to immunosuppressive properties, thiopurines are capable of exerting anti-inflammatory activities, primarily by inhibiting the replication of hematopoietic precursors.

Animals↗
PubMed1979

Use of quantitative bacteriologic techniques to diagnose catheter-related sepsis.

A case of polymicrobial sepsis occurred in a patient who had a permanent indwelling hyperalimentation catheter. Because it was undesirable to remove the catheter, quantitative bacteriologic techniques were used to determine whether the catheter was the source of sepsis. Blood drawn from a peripheral vein had 25 colonies per milliliter whereas blood drawn through the catheter had more than 10,000 colonies per milliliter. On the basis of these results, the catheter was removed. The catheter tip was found to be infected with the same organisms that were present in the blood. Quantitative bacteriologic techniques may prove useful in diagnosing catheter-related sepsis when it is undesirable to remove the catheter.

Adult↗
PubMed1979

Effect of prostaglandin E on immune complex nephritis in NZB/W mice.

Pharmacologic quantities of prostaglandin alter the immune complex nephritis of NZB/W mice. To study the mechanism of this change, NZB/W mice received 200 micrograms. of prostaglandin E1 or E2 twice daily starting at 2, 4, or 6 months of age. Mice were sacrificed at bimonthy intervals, renal function and serologic parameters were evaluated, and renal tissue was examined by light, fluorescence, and electron microscopy. Therapy decreased the incidence of proteinuria, lessened renal pathology, and prolonged survival. Maximal beneficial effects occurred when treatment began at 2 months of age. The most striking change was a decrease in the rate of immune complexes depositing in the mesangium and their absence from peripheral loops. Accompanying this change was a reduction in glomerular hypercellularity and a decrease in renal perivascular and interstitial mononuclear infiltrates. By contrast, treatment did not alter serum levels of immunoglobulins, antinuclear antibodies, and antisingle or double-stranded DNA. These results indicate that prostaglandin E is capable of prolonging survival in NZB/W mice by decreasing the rate of immune complexes depositing in glomeruli.

Animals↗
PubMed1979

Aplastic anemia following infectious mononucleosis: possible immune etiology.

A 17-year-old female developed severe aplastic anemia following serologically proven infectious mononucleosis. In vitro studies, using the granulocyte colony forming technique, suggested that the aplasia may have resulted from an immune mechanism. The patient's marrow grew no granulocyte colonies and caused inhibition of colony formation when mixed with normal marrows. The patient recovered fully after therapy with antithymocyte globulin and marrow cultures showed disappearance of the inhibitory effect. These observations suggest that the severe aplasia may have resulted from an aberrant immune response which followed infection by EB virus.

Adolescent↗
PubMed1978

Red-cell hypoplasia and increased bone marrow reticulin in systemic lupus erythematosus: reversal with corticosteroid therapy.

A 29-year-old Chinese male developed severe aregenerative anemia. The bone marrow was diffusely hypercellular with increased marrow reticulin and a persistent failure of erythroid differentiation beyond the pronormoblast stage. Although he did not manifest classic features of systemic lupus erythematosus, multiple serologic studies were in accord with this diagnosis. The patient's defect in erythropoiesis was studied by an in vitro technique for the growth of erythroid colonies. Despite the severe erythroid hypoplasia, the patient's marrow yielded abundant large erythroid colonies. Serum erythropoietin activity was high as judged by use of this in vitro assay. Although the patient's native serum did not affect colony formation, a separated IgG fraction was markedly inhibitory to colony growth. This suggests that the erythroid hypoplasia may have resulted from a unique autoantibody. The patient's hematologic abnormalities completely reversed following treatment with corticosteroids.

Adrenal Cortex Hormones↗
PubMed1977

Immunologic characterization of chronic lymphocytic leukemia cells.

Immunologic characterization of the neoplastic cells in the circulation of patients with CLL suggests these cells show significant differences in membrane characteristics from normal B lymphocytes. Although the leukemic cells bear a homogenous membrane-associated immunoglobulin, they also react with an anti-human T cell serum. In all patients studied, 60-90% of the cells, were stained by this antiserum. This suggests that the leukemic cells share antigenic determinants with T lymphocytes. CLL cells, unlike normal B cells, showed a marked increase in mouse-complement receptors. No increase in receptors for guinea pig complement was observed in the leukemic cells. The population of SIg-bearing lymphocytes was significantly greater than that of complement-receptor bearing lymphocytes. The total number of E-rosetting cells was increased in all CLL patients. Mitogenic responses of the leukemic cells were depressed and delayed. These results suggest that neoplastic lymphocytes cannot be classified as T- or B-derived on the basis of criteria used to define normal lymphocytes.

Antilymphocyte Serum↗
PubMed1977

Observations on the anemia and neutropenia of human copper deficiency.

Following extensive bowel resection, a young woman experienced severe malnutrition; subsequent administration of parenteral nutrition precipitated the copper deficiency syndrome. This consisted of hypocupremia, subnormal ceruloplasmin levels, anemia, and severe neutropenia. The bone marrow was megaloblastic, vacuolated, and sideroblastic; granulocytic maturation was not observed beyond the myelocyte stage. Copper sulfate therapy was followed by a marked reticulocytosis, increase in hematocrit, and recovery of neutrophils. Additional studies indicated that both serum and urinary erythropoietin values were low; serum activity increased after copper supplementation. Abnormal granulopoiesis was demonstrated using the in vitro granulocyte colony assay. The patient's granulcoytic stem cells were normal on two occasions; however, mixing studies showed that culture of the patient's copper-deficient marrow with her copper-deficient serum yielded significantly reduced numbers of granulocyte colonies. Thus, copper appears to be a necessary element for normal hematopoiesis; lack of this trace element may result in ineffective erythropoiesis and granulopoiesis.

Adult↗