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Biomedical subjects

Y Naparstek

Publications and source records attributed to Y Naparstek.

At least 55 records · Page 3Linked to original sources

Nodular vasculitis associated with propylthiouracil therapy.

Cutaneous vasculitis is a rare complication of propylthiouracil therapy. We describe a patient who presented with lower extremity subcutaneous nodules, hemorrhagic bullae, and necrotic ulcers during treatment with this agent. Examination of a skin biopsy specimen revealed nodular vasculitis. This type of vasculitis has not been described in association with propylthiouracil therapy before. Nodular vasculitis not associated with the drug is characterized by a chronic protracted course, whereas in the patient reported the lesions rapidly regressed when use of the drug was discontinued.

Aged↗

The infrequent association of systemic lupus erythematosus and solid tumors.

The authors describe the clinical course of two patients with long-standing, indolent systemic lupus erythematous (SLE) who developed, respectively, a breast carcinoma and a malignant melanoma 8 and 15 years after the diagnosis of lupus; both patients died with evidence of widespread, rapidly progressive metastatic disease at a time when the SLE was minimally active and did not require immunosuppressive therapy. The association of SLE and solid tumors in the same patient is reviewed. The frequency of this association appears to be low and the most often described tumors are of uterine and bladder origin. The clinical course of the solid malignancy in these patients is not always described in detail. Careful epidemiologic studies on the true incidence of solid tumors in patients with SLE are required to better understand this association.

Adult↗

A variant of HLA-DR4 determines susceptibility to rheumatoid arthritis in a subset of Israeli Jews.

HLA-DR4 is associated with risk for developing rheumatoid arthritis (RA) in most populations. In Israeli Jews, in whom the Dw10 subtype of DR4 predominates, no association of RA with DR4 has been found. The inability to detect an association could be due to the high frequency of DR4-Dw10. We used DNA typing with amplification by the polymerase chain reaction and dot-blotting with allele-specific oligonucleotides to determine DR4 variants in 131 Jewish RA patients living in Israel and 134 controls. In both Ashkenazi Jews and non-Ashkenazi Jews, the rare variant Dw15 (previously identified in Japanese populations and in Japanese patients with RA) was found to be the main allele associated with the risk of developing RA (relative risk = 9.2, corrected P less than 0.001). However, this low-frequency allele could be responsible for susceptibility in only 11.5% of the patients. Susceptibility for rheumatoid factor-positive RA was associated with Dw4 and Dw15; the risk for rheumatoid factor-negative RA was associated only with Dw14. The distribution of the HLA-DQ alleles associated with DR4 showed that more than half of the RA patients with Dw15 also had HLA-DQw2. The frequencies of DQw7 and DQw8 were not different in RA patients compared with controls. The results suggest that, as in other populations, susceptibility for the development of RA in Israeli Jews is associated with DRB1 locus alleles of the DR4 group.

Alleles↗

Schönlein-Henoch syndrome in adults and children.

Sixty-one patients (15 adults and 46 children) with Schönlein-Henoch syndrome (SHS) were seen at the Hadassah University Hospital over the last 20 years. The presentation, clinical course, and prognosis of these patients were studied. The disease course was generally similar in children and adults, except for the epidemiological background and the pattern of skin and joint involvement. In these nonselected patients, the disease was self-limited, and progressive renal failure was not found. The long-term prognosis was excellent for both adults and children.

Adolescent↗

Lupus refractory pleural effusion: transient response to intravenous immunoglobulins.

A patient with systemic lupus erythematosus complicated by refractory bilateral pleural effusions is described. High dose corticosteroids with azathioprine, as well as intrapleural instillation of corticosteroids, proved ineffective in management. As our patient remained severely symptomatic and required repeated thoracocentesis, a therapeutic trial of intravenous immunoglobulins (IVIG) was attempted. IVIG had a beneficial effect, although of a transient and partial nature. Despite the results achieved, it seems that IVIG has limited value in treating lupus pleural effusion.

Adult↗

Inhibition of T lymphocyte heparanase by heparin prevents T cell migration and T cell-mediated immunity.

Previously we reported that activated T lymphocytes express a heparanase enzyme that degrades the heparan sulfate moiety of the proteoglycan of the extracellular matrix (ECM). Expression of the heparanase enzyme was found to be associated with the ability of activated T lymphocytes to penetrate blood vessel walls and accumulate in target organs. We recently found that relatively low doses of heparin administered to mice or rats inhibited T cell-mediated immune reactions. In the present study we investigated the effects in vitro and in vivo of the heparanase inhibitor, heparin, on the expression of T lymphocyte heparanase and on the ability of T lymphocytes to mediate a delayed-type hypersensitivity (DTH) reaction. We found that heparanase was induced by immunizing mice with antigen in vivo or by activating T lymphocytes with concanavalin A in vitro. Relatively low doses of heparin administered once daily in vivo (5 micrograms) or present in vitro (0.1 microgram/ml) inhibited the expression of heparanase induced by immunization or by concanavalin A incubation. Higher or lower doses of heparin did not have these effects. The same doses of heparin that inhibited expression of heparanase also inhibited the ability of the lymph node cells to migrate to a site of antigen and adoptively produce a DTH reaction. These findings suggest that modulation of cell-mediated immune reactions may be achieved by relatively low doses of heparin which inhibit expression of T lymphocyte heparanase.

Animals↗

Sequential anti-idiotypes define reciprocal idiotopes on the same anti-DNA antibody.

Sequential anti-idiotypes have defined a pair of idiotypes with an idiotype-anti-idiotype relationship to each other in the variable region of the monoclonal anti-DNA antibody 16/6. A rabbit immunized with 16/6 made an antibody-1 (anti-Id-16/6R) and an antibody-2 (anti-anti-Id-16/6 or anti-anti-Id 16/6M). The latter bound to M-2, a monoclonal mouse anti-Id-16/6. M-2 was used to immunize a second mouse, which produced M-16. The variable region of M-16 mimics an antigenic surface on Id-16/6 and binds to a peptide contained within the first hypervariable region of the light chain of 16/6. The complementary idiotypes of 16/6 represent a reciprotope, an idiotype/anti-idiotype pair within the variable region of the same immunoglobulin molecule which may have functional importance.

Animals↗

Suppression of experimental autoimmune diseases and prolongation of allograft survival by treatment of animals with low doses of heparins.

The ability of activated T lymphocytes to penetrate the extracellular matrix and migrate to target tissues was found to be related to expression of a heparanase enzyme (Naparstek, Y., I. R. Cohen, Z. Fuks, and I. Vlodavsky. 1984. Nature (Lond.). 310:241-243; Savion, N., Z. Fuks, and I. Vlodavsky. 1984. J. Cell. Physiol. 118:169-176; Fridman, R., O. Lider, Y. Naparstek, Z. Fuks, I. Vlodavsky, and I. R. Cohen. 1987. J. Cell. Physiol. 130:85-92; Lider, O., J. Mekori, I. Vlodavsky, E. Baharav, Y. Naparstek, and I. R. Cohen, manuscript submitted for publication). We found previously that heparin molecules inhibited expression of T lymphocyte heparanase activity in vitro and in vivo, and administration of a low dose of heparin in mice inhibited lymphocyte traffic and delayed-type hypersensitivity reactions (Lider, O., J. Mekori, I. Vlodavsky, E. Baharav, Y. Naparstek, and I. R. Cohen, manuscript submitted for publication). We now report that treatment with commercial or chemically modified heparins at relatively low doses once daily (5 micrograms for mice and 20 micrograms for rats) led to inhibition of allograft rejection and the experimental autoimmune diseases adjuvant arthritis and experimental autoimmune encephalomyelitis. Higher doses of the heparins were less effective. The ability of chemically modified heparins to inhibit these immune reactions was associated with their ability to inhibit expression of T lymphocyte heparanase. There was no relationship to anticoagulant activity. Thus heparins devoid of anticoagulant activity can be effective in regulating immune reactions when used at appropriate doses.

Acetylation↗

Autoreactive T cells with atypical MHC restriction from MRL-lpr/lpr mice: forbidden clones revisited.

MRL-lpr/lpr mice spontaneously develop a lethal form of systemic lupus erythematosus associated with massive lymphadenopathy, polyclonal B-cell activity, autoantibody production and antibody-dependent tissue injury. The sequence of events leading to B-cell proliferation and pathogenic autoantibody production are not clearly defined--abnormalities of both B and T cells have been observed. Isolation of individual T-cell clones would facilitate analysis of the cellular events involving both B and T cells that lead to autoantibody production. For this purpose, an autoreactive T-cell line (ARTC-1) was derived from the splenocytes of an unimmunized MRL-lpr/lpr mouse and maintained in culture by stimulation with syngeneic antigen presenting cells, without exogenous antigens. By T-cell receptor analysis it was demonstrated that ARTC-1 cells developed as a clone even through no attempt was made to clone them in vitro: Southern blot analysis of ARTC-1 revealed a single rearrangement of the TcR beta chain locus with the other TcR beta chain gene remaining in the germline configuration. Northern blot analysis confirmed these findings and demonstrated that ARTC-1 utilized C beta 1 J beta 1.3 exclusively. ARTC-1 had atypical MHC requirements for activation: antigen-presenting cells bearing both I-Ak and I-Ek major histocompatibility complex class II antigens were required for maximal proliferation of the ARTC-l clone. Activated ARTC-l secreted soluble factors that induced B-cell proliferation, immunoglobulin secretion, and anti-DNA antibody production. Unregulated cells of the AR-TC1 type could, therefore, lead to polyclonal B-cell activation and autoantibody production in vivo in the absence of exogenous antigenic stimulation.

Animals↗

Soluble antigen induces T lymphocytes to secrete an endoglycosidase that degrades the heparan sulfate moiety of subendothelial extracellular matrix.

The antigen-mediated induction of heparanase, an endoglycosidase capable of degrading heparan sulfate from the subendothelial extracellular matrix (ECM), was investigated in a rat T lymphocyte cell line reactive against the basic protein (BP) of myelin. We found that nonactivated T lymphocytes could be induced to express heparanase activity following exposure to soluble but not to ECM-bound BP. The induction of heparanase was immunologically specific and independent of the presence of syngeneic or allogeneic antigen presenting cells (APC). However, anti-IA antibodies inhibited heparanase expression. Soluble BP induced secretion of heparanase into the culture medium within minutes, despite inhibition of protein synthesis. Cell lysates of T lymphocytes contained heparanase activity. Thus, T lymphocytes secrete a preformed heparanase following exposure to specific antigen.

Animals↗