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Biomedical subjects

A Winkelstein

Publications and source records attributed to A Winkelstein.

At least 91 records · Page 5Linked to original sources
PubMed1977

Hairy cell leukaemia: seven cases with probable B-lymphocytic origin.

Mononuclear cells from seven patients with hairy cells leukaemia were examined for features suggestive of either a lymphocytic or monocytic origin. Immunofluorescent staining of both methanol fixed and incubated cells, using monospecific antisera, revealed a predominant cell-associated immunoglobulin in each case. Three were positive for mu and kappa chains, two for gamma and kappa chains, one for delta and kappa chain determinants and one reacted only with antigamma chain serum. Formation of EAC rosettes, a feature of both B lymphocytes and monocytes, was variable. T cells, as judged by E rosettes, were not elevated in any patient. Phytohaemagglutinin reactivity was normal in six and depressed in one case. With the exception of minimal activity in assays for glass adherence and latex particle phagocytosis, none of the cells showed features typical of monocytes. Hairy cells were negative by peroxidase stain and lacked the electron microscopic characteristics of monocytes. They did not react in either rosette or phagocytic assays with anti-A or anti-D coated erythrocytes nor did they elaborate granulocyte colony stimulating factor, a monocyte-derived in vitro granulopoietin. Although unequivocal classification of these abnormal cells is not possible, the data storngly suggests that this represents a variant of a B lymphocytic neoplasm.

Adult↗
PubMed1976

Acute myeloblastic leukemia and hypercalcemia. A case of probable ectopic parathyroid hormone production.

We studied a patient with acute myeloblastic leukemia, hypercalcemia, hypophosphatemia and inappropriately elevated serum parathyroid hormone levels to define the mechanism of the hypercalcemia. On six occasions during two years, hypercalcemia occurred in conjunction with relapses of leukmia. Each time, serum calcium decreased to normal levels in parallel with reduction of the leukemic mass. During two periods of hypercalcemia, immunoreactive parathyroid hormone values were abnormally high. In addition, hormone was detected in vitro after short-term incubation of the leukemic cells (after 24 hours, the patient's cells produced 129 pg of PTH per milliliter, whereas myeloblasts from a normocalcemic patient with leukemia produced only 33 pg). In freeze-thawing experiments, 39 pg of parathyroid hormone was released form 1 x 108 of the patient's myeloblasts; no hormone was released from the normocalcemia cells. These findings suggest that the hypercalcemia resulted from ectopic parathyroid hormone production by leukemic cells.

Adult↗
PubMed1976

Absence of imune deficiencies in a case of progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a rare disease related to a slow virus infection of the central nervous system; it is usually seen in patients who have impaired immunologic function. The present patient with biopsy-proved PML was found to have no demonstrable defects in either cellular or humoral immunity as assessed by multiple parameters. Thus, it appears that PML may occur in the presence of intact immune responses.

Biopsy↗
PubMed1975

Disseminated intravascular coagulation in heat stroke. Response to heparin therapy.

A 14-year-old patient with heat stroke, disseminated intravascular coagulation, central nervous system dysfunction, and renal failure was treated, in addition to conventional therapy, with heparin sodium for seven days. Despite very poor prognostic signs on addmission, the patient survived the acute episode and ultimately progressed to a complete recovery.

Acute Kidney Injury↗
PubMed1975

Diphenylhydantoin-induced serum sickness with fibrin-platelet thrombi in lymph node microvasculature.

In this 16 year old boy a syndrome, characterized by high fever, generalized lymphadenopathy, splenomegaly, diffuse skin rash, facial and periorbital edema, neutropenia, thrombocytopenia, elevated serum glutamic oxaloacetic transaminase (SGOT) levels and transient electrocardiographic changes, appeared 2 weeks after the institution of diphenylhydantoin therapy. Lymph node biopsy, performed at the height of the illness, revealed widespread subendothelial fibrin exudation and fibrin-platelet thrombi in the lymph node microvasculature, a finding most consistent with thrombotic thrombocytopenic purpura. Although many types of abnormal lymph node histology have been described with diphenylhydantoin, this appears to be the first instance of this histologic picture. This syndrome may be related to a serum sickness-like illness which triggered an episode of localized coagulopathy.

Acute Disease↗
PubMed1975

Effects of cytotoxic immunosuppressants on tuberculin-sensitive lymphocytes in guinea pigs.

The immunosuppressive activities of two phase-specific drugs, 6-mercaptopurine (6-MP) and methotrexate, and a cycle-specific agent, cyclophosphamide, were evaluated on the lymphocytic component of established tuberculin hypersensitivity in guinea pigs. In these animals, purified protein derivative (PPD)-sensitive lymphocytes are in an intermitotic phase of their proliferative cycle. Neither phase-specific drug significantly altered either the number or functional activities of these lymphocytes. By two in vitro criteria, PPD-induced lymphoproliferation and elaboration of migration inhibition factor (MIF), the responses of lymph node cells were equivalent to sensitized controls. In addition, these agents did not deplete pools of T lymphocytes, impair responses to phytohemagglutinin (PHA), nor inhibit cutaneous reactivity if employed before sensitization. In contrast, cyclophosphamide showed broader immunosuppressive effects including significant toxicities for intermitotic lymphocytes. This drug depleted pools of T cells and markedly impaired the in vitro proliferative responses of residual lymphocytes. The latter occurred with both PHA and PPD. Suppression of PHA reactivity was a dose-dependent phenomenon but was evident even with small quantities of this alkylating agent. The suppression of antigen-induced responses was independent of the proliferative status of target lymphocytes in vivo, after a single large dose, it persisted for more than 3 wk. In total, these results indicate that the effective use of cytotoxic drugs as immunosuppressants must include consideration of both the cycle specificities of the agent and the proliferative activities of the target lymphoid population.

Animals↗
PubMed1975

In utero sensitization with influenza virus in man.

Following a community-wide epidemic of influenza A/England virus infection, 64 cord blood samples were evaluated for their fetal serum and lymphocyte responses to this virus. Cord sera were tested for HI antibody vs. A/England with and without 2-ME. A fourfold or greater reduction in titer was observed in four, indicating fetal IgM antibody responses. In addition, lymphocyte samples from three of 16 tested showed proliferative responses to influenza A suggesting fetal lymphocyte sensitization with influenza virus. These data suggest that, in some pregnancies, influenza virus is capable of transplacental sensitization of the fetus.

Female↗
PubMed1974

Immunological responsiveness of tuberculosis patients receiving rifampin.

Rifampin has been shown to impair both humoral and cell-mediated immune responses in animal models. In order to detect a similar effect in man, 11 patients with active tuberculosis were evaluated before, 2 weeks after, and 12 to 16 weeks after initiating rifampin. Several parameters were serially measured including blood lymphocytes, intradermal response to intermediate strength tuberculin (PPD), and in vitro proliferative responses to phytohemagglutinin (PHA), a nonspecific mitogen, and to the specific antigens, PPD and influenza A. No changes in lymphocyte counts were noted. No changes in response were noted 2 weeks after beginning treatment with rifampin. However, compared with initial and 2-week responses, the PHA response was reduced by 47%, the PPD by 68%, and the influenza by 75%, and 6 of 11 patients showed no induration after tuberculin skin testing at the 12- to 16-week point. These results indicate that in doses employed for the treatment of tuberculosis, rifampin has an immunosuppressive effect in man that develops gradually.

Adult↗
PubMed1973

Differential effects of immunosuppressants on lymphocyte function.

In vitro and in vivo parameters of T lymphocyte function were evaluated in guinea pigs following treatment with the "cycle-active" drugs, 6-mercaptopurine (6MP) and methotrexate, and the "non-cycle-active" alkylating agent, cyclophosphamide. Commencing at the time of sensitization to tuberculin protein, animals were treated with an 8 day course of one of the cytotoxic drugs. This regimen either reduced or abolished the cutaneous response to PPD. The two cycle-active drugs inhibited the in vitro lymphoproliferative response to PPD and suppressed the elaboration of migration inhibition factor (MIF) by lymph node cells. However, these agents did not reduce blood lymphocytes, deplete the cellularity of the thymic dependent areas of peripheral tissues, or alter the in vitro response of lymph node cells to the nonspecific mitogen PHA. In contrast, treatment with cyclophosphamide was associated with a reduction in peripheral blood and tissue lymphocytes and impaired responses to PHA by residual lymph node cells. In vitro proliferative responses to PPD were inhibited but the capacity of lymph node cells to elaborate MIF was not suppressed. In addition to their effects on antigen-reactive lymphocytes, all three drugs significantly reduced the number of macrophages in induced peritoneal exudates. With respect to immunosuppressive activities, results of these investigations suggest that the noncycle-active agents affect both intermitotic and dividing T lymphocytes without impairing certain intermitotic functions of residual cells. The cycle-active drugs have a more restricted toxicity limited to those T lymphocytes which have been stimulated to undergo active DNA synthesis by antigenic challenge.

Animals↗