Search PubMed⌕ Search

Biomedical subjects

A Winkelstein

Publications and source records attributed to A Winkelstein.

122 records · Page 7Linked to original sources
PubMedDate not supplied

Uromodulin: a specific inhibitor of IL-1-initiated human T cell colony formation.

Uromodulin, an 85 kDa naturally occurring immunosuppressant, was found to selectively and specifically inhibit the ability of IL-1 to induce colony responses by highly enriched suspensions of PHA-stimulated T lymphocytes. Dilutions of 1 x 10(-8) M completely blocked the colony growth of T lymphocytes cultured with 50 U/ml IL-1; 1 x 10(-9) M dilutions reduced scores by 83%. By contrast, uromodulin did not inhibit the responses of unseparated mononuclear cells, isolated T lymphocytes cultured with irradiated adherent cells, or stimulated T cells whose growth was initiated by either IL-2 or a soluble factor derived from Raji cells.

Colony-Forming Units Assay↗
PubMedDate not supplied

Inhibition of human lymphoproliferative responses and altered lymphocyte membrane phenotype by succinylacetone.

Succinylacetone (SA) proved to be a potent inhibitor of in vitro lymphoproliferative responses. This compound (3.0 mM) reduced the incorporation of 3HTdr by > 90% in mononuclear cell cultures stimulated with PHA, anti-CD3, IL-2 or phorbol dibutyrate-Ca2+ ionomycin. Furthermore, SA caused profound reduction in isotope uptake even if added to 3-day PHA-stimulated cultures as late as 6 h prior to harvest. Cells exposed to SA prior to mitogenic challenge and washed were not impaired in their proliferative activities. The addition of hematin to SA-containing cultures did not reverse the proliferative block. Phenotypic studies of stimulated cells suggested that SA does not preferentially affect one functional group of lymphocytes. However, it appeared that SA may act selectively to inhibit expression of transferrin receptors (CD71), a T-cell activation antigen. These data suggest that SA acts as a noncytotoxic immune inhibitor; this activity may be mediated, in part, by blocking cell activation and subsequent progress through the mitotic cycle.

Animals↗
PubMedDate not supplied

Changes in coagulation factors, complement, immunoglobulins, and immune complex concentrations with plasma exchange.

Seventeen patients with a spectrum of immunologically-related disorders were studied before and immediately after plasma exchange (PE) for changes in coagulation factors, complement, immunoglobulins, and immune complex levels. Each PE replaced 50 per cent of the plasma volume with 5% albumin and saline. With PE, coagulation profiles indicated a decrease of 23 to 55 per cent in the levels of fibrinogen, Factors II, V, VII, VIII, IX, X, XI, XII, and Fletcher factor. Only minimal changes were noted in the prothrombin time and activated partial thromboplastin time. Most coagulation factors, except fibrinogen, returned to baseline by 48 hours. Following three PE/week, fibrinogen was reduced by 51 per cent; other factors were not significantly altered. C3 and C4 fell by 35 to 40 per cent with each PE; these approached baseline by 24 hours. Immunoglobulins (G,A,M) were reduced by 34 +/- 3,37 +/- 3 and 34 +/- 3 per cent, respectively. After three PE, the total immunoglobulins were decreased by 50 to 55 per cent. Five of eight patients who had three or more PE developed hypogammaglobulinemia (IgG less than 450 mg/dl). Immune complexes were reduced by 50 +/- 4 per cent with each PE. Multiple exchanges in five patients led to a greater reduction (80 +/- 6%). Thus PE was an effective means of reducing immune complexes but led to hypogammaglobulinemia and hypofibrinogenemia.

Antigen-Antibody Complex↗
PubMedDate not supplied

Plasma exchange in rheumatoid vasculitis.

Vasculitis is an uncommon, extremely debilitating complication of severe, chronic rheumatoid arthritis. High levels of circulating immune complexes along with vascular deposition of immunoglobulins and complement indicate an immune complex mediated disease. No pharmacologic therapy has been completely effective and the incidence of mortality is exceptionally high. This study shows clinical improvement with combination of plasma exchange and cytoxan therapy. We report an association in the conspicuous decline of immune complexes with objective clinical remission in 2 patients who underwent combination therapy. This adjunctive combination therapeutic modality is recommended in the treatment of rheumatoid vasculitis.

Aged↗
PubMedDate not supplied

The effects of pharmacologic agents on mitogen-induced cellular cytotoxicity in guinea pigs.

Using pharmacologic agents as probes, three aspects of the mitogen-induced cellular cytotoxicity reaction (MICC) were evaluated. These included the requirement for a concomitant lymphoid DNA synthetic response, the role of microtubules and microfilaments in effecting target cell lysis, and the potential inhibitory activity of hydrocortisone. Results, using both PHA and Con A stimulated guinea pig lymph node cells, indicate that this form of cytotoxicity occurs as a phenomenon independent of 3H-Tdr incorporation. Animals treated with cyclophosphamide showed cytotoxic reactions equivalent to untreated controls whereas mitogen-induced proliferative responses were greatly impaired. Further studies indicated that the in vitro exposure of lymph node cells to either mitomycin or cytosine arabinoside markedly reduced DNA synthesis but did not depress the ability of mitogen-stimulated lymphocytes to effect target cell lysis. The microtubular antagonists, vincristine, vinblastine and colchicine, inhibited cytotoxic reactions if the agents were present at the time that lymphocyte-target cell interaction was established. However, the antimicrofilament agent cytochalasin B was not inhibitory; this contrasts to this agent's ability to suppress antigen-induced cell-mediated cytotoxic reactions. In a third series of experiments, hydrocortisone showed a dose-related inhibition of MICC responses. The action of the steroid was apparent only if the drug was present at the onset of the culture; no suppression was observed if it was added after an initial one day incubation.

Animals↗
PubMedDate not supplied

Experimental evaluation of nonspecific immunostimulation and chemotherapy in the intracranial tumor-bearing Fisher rat.

One hundred sixty rats bearing intracranial tumors were divided into groups of 10 to evaluate C-I interval +, effect of chemotherapy alone (BCNU), chemotherapy and C. parvum, and C. parvum alone in the rat tumor model. All therapy was administered intraperitoneally: BCNU -5.2 mg/kg (40% of LD10) on the 9th and 16th post tumor implant day, and C. parvum-1.4 mg regardless of the body weight and the 6th or 23rd day and 6th and 23rd post tumor implant day. An additional group received BCNU on the 9th and 16th day and C. parvum every 3rd day beginning with the 11th post implant day. It is concluded that C. parvum given before BCNU yields the greatest increase in survival in this animal system. Two or more injections were detrimental and injections after BCNU were of less value. C. parvum alone was minimally effective. If nonspecific immunostimulation is contemplated in this animal tumor system, it would appear to be best given before chemotherapy. This may relate to the brain as a "privileged immune site", or a peculiarity of the blood brain barrier in an intracranial lesion as it related to combined therapy.

Animals↗
PubMedDate not supplied

Bleomycin-induced scleroderma.

Two men are reported who developed cutaneous fibrosis indistinguishable from that encountered in progressive systemic sclerosis (PSS, scleroderma) after treatment with the antitumor agent, bleomycin. In vitro study of the dermal fibroblasts of 1 patient showed that these cells synthesized increased quantities of collagen and therefore resembled cells derived from individuals with naturally occurring PSS. Bleomycin was shown to stimulate collagen production by cultured normal skin fibroblasts. Also, in 1 of the patients, bleomycin stimulated a lymphoproliferative response in vitro. These effects of bleomycin may be responsible for certain toxic reactions to this drug in the skin and lung.

Adult↗