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Biomedical subjects

I Tatarsky

Publications and source records attributed to I Tatarsky.

At least 19 recordsLinked to original sources
PubMed2000

Paroxysmal nocturnal hemoglobinuria associated with in vitro inhibition of erythropoiesis by bone marrow T lymphocytes.

BACKGROUND: The etiology of bone marrow failure, a prominent feature of paroxysmal nocturnal hemoglobulinuria, is presently unknown. OBJECTIVES: To evaluate the possible influence of cellular immune mechanisms in the bone marrow failure of PNH. METHODS: We studied marrow erythroid colony formation in a patient with paroxysmal nocturnal hemoglobinuria without hypoplastic/aplastic marrow complications. RESULTS: In vitro assays revealed a pronounced inhibition of primitive erythroid (BFU-E) progenitor cell growth by marrow T lymphocytes. Removal of T cells prior to culture resulted in a 4.5-fold enhancement of BFU-E numbers. Reevaluation of in vitro erythropoiesis during steroid administration indicated a persistent, albeit less prominent, T cell inhibitory effect. CONCLUSION: Our findings provide the first direct evidence for a cellular immune inhibitory phenomenon accompanying PNH.

Adult↗
PubMed1995

Protective effect of low concentrations of oxidized low-density lipoprotein on endothelial cell integrity.

BACKGROUND: Increasing evidence suggests that oxidized low-density lipoprotein (LDL) is associated with the development of atherosclerosis in vivo. Because endothelial injury contributes to the development of the atherogenic , we investigated the efficacy of oxidized LDL on the integrity of human umbilical cord endothelial cells (HUVECs) by analyzing cytotoxicity and cell detachment. METHODS: The cellular integrity of cultured endothelial cells labeled with chromium-51. RESULTS: Low concentrations of oxidized LDL (25-50 micrograms protein/ml) induced morphological changes (cell elongation and formation of gaps in the cobblestone monolayer), decreased cellular cytotoxicity (by 13% compared with control). At higher concentrations of oxidized LDL (100 micrograms protein/ml), however, increases in cytotoxicity (by up to 70%) and cellular detachment (by up to 90%) were demonstrated. Native LDL, which was not oxidized in out cell system, did not induce any changes either in cytotoxicity or in cell detachment. The protective effect of low oxidized LDL concentrations against endothelial cell cytotoxicity and detachment was abolished by indomethacin (microM), indicating the involvement or prostaglandin synthesis in this protection. CONCLUSION: Our experiments suggest that oxidized LDL-induced alterations of endothelial cells involve a sequence of events leading from a non-cytotoxic protective stage to endothelial perturbation.

Cell Adhesion↗
PubMed1994

Low fetal morbidity in pregnancy associated with acute and chronic idiopathic thrombocytopenic purpura.

Forty-six mothers with immune thrombocytopenic purpura (ITP) gave birth to 72 babies. Sixty-two babies were delivered vaginally and 10 babies by cesarean section. There was no mortality among mothers or babies. Eighteen infants were born thrombocytopenic (PLT < 100 x 10(9)/l). Eleven infants had a platelet count of less than 50 x 10(9)/l. All the severely thrombocytopenic babies (except 1) were born to post splenectomy thrombocytopenic mothers, regardless of steroid treatment during pregnancy. Five babies had clinical manifestations of bleeding; 3 had mild purpura, 1 severe gastrointestinal bleeding, and 1 intracranial bleeding. The latter 2 babies were born prematurely to the same mother who was severely thrombocytopenic despite splenectomy in childhood. In view of very low morbidity in babies of ITP mothers, we suggest that they be delivered vaginally. Cesarean delivery should be performed in selected cases where the mother is severely thrombocytopenic despite splenectomy or where prematurity or obstetrical complications are encountered.

Acute Disease↗
PubMed1994

Respective effects of soluble interleukin-1 receptor and tumour necrosis factor receptor on IL-1 and TNF-alpha-induced DNA synthesis of common acute lymphoblastic leukaemia blasts in vitro.

This study investigates the capacity of human recombinant interleukin-1 alpha (IL-1 alpha), IL-1 beta and tumour necrosis factor-alpha (TNF-alpha) to induce DNA synthesis of highly purified blasts from nine adult common acute lymphoblastic leukaemias (cALL) in 7 d liquid culture. IL-1 alpha, IL-1 beta and TNF-alpha stimulated 3H-TdR uptake in leukaemic blasts in a dose-dependent fashion. The IL-1-induced DNA synthesis of cALL cells could not be prevented by the addition of neutralizing antibodies against IL-3, GM-CSF, IL-6 or TNF-alpha. Similarly, the TNF-alpha-stimulated 3H-TdR incorporation of leukaemic blasts was not affected by the addition of antibodies towards IL-1 alpha, IL-1 beta, IL-3, GM-CSF or IL-6. These observations suggest that IL-1 as well as TNF-alpha stimulated growth could not be attributed to the endogenous production of factors, corresponding to the antibodies used in these experiments. Both IL-1 as well as TNF-alpha mediate their action through interaction with specific cell surface receptors. Recently two distinct types of IL-1 receptors (IL-1-Rs), IL-1R(p80) and IL-1-R(p65), as well as two distinct types of TNF-receptors (TNF-Rs), TNF-R (p55) and TNF-R (p75) have been identified. Both types of TNF-Rs exist also in soluble forms (sTNF-Rs), while soluble IL-1-Rs (sIL-1-Rs) have not yet been found naturally. In this study we show that sIL-1-R as well as sTNF-R modulate the effects of their corresponding cytokine in a dose-dependent bimodal fashion; at lower concentrations they augmented while at higher concentrations they inhibited the cytokine-stimulated DNA synthesis of cALL blasts in vitro. It may therefore be concluded from this study that soluble receptors for both IL-1 and TNF, at least in vitro, are functional and interfere with their corresponding cytokine bioactivity.

Cell Division↗
PubMed1994

Effects of soluble interleukin-1 receptor and tumor-necrosis factor receptor, respectively, on the IL-1- and TNF-alpha-induced DNA synthesis of acute myeloblastic leukemia blasts in vitro.

This study demonstrates that soluble interleukin-1 receptor and tumor necrosis factor receptor modulate their corresponding cytokine-induced DNA synthesis of acute myeloblastic leukemia (AML) blasts in a dose-dependent, bimodal fashion; at lower concentrations they enhanced, while at high concentrations they inhibited, the cytokine-mediated effects. Furthermore, the concentrations of endogenously produced IL-1 beta and TNF-alpha were found to be significantly (p < 0.01) higher in supernatants of AML cells cultured in the presence of corresponding soluble receptors compared to their levels in supernatants of cells growing in the absence of these molecules. Our data might suggest that the attenuation of the spontaneous decay of IL-1 beta as well as TNF-alpha activities by soluble receptors may account for their ability to augment some of their effects.

Adolescent↗
PubMed1994

Coinfection with hepatitis viruses and human immunodeficiency virus in multiply transfused patients.

The prevalence, clinical manifestations and serological markers of hepatitis C virus (HCV), hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections were studied in 112 multiply transfused patients (49 hemophiliacs receiving either nonheat-treated factor concentrates or cryoprecipitate, 33 thalassemic, 20 refractory anemia and 10 leukemia patients). Positive serological markers for HCV, HBV and HIV were found to correlate with number of donors and duration of disease (logistic regression P = 0.0001 and 0.01 respectively). Viral infectivity was significantly correlated with type of blood product. HCV seropositivity was more common in hemophiliacs treated with nonheat-treated factor concentrates (93%) compared to those receiving cryoprecipitate (37%) or nonhemophiliacs receiving red packed cells (20%) (P < 0.001). Likewise, HBV seropositivity in patients receiving the above blood products was 83%, 61% and 26% respectively (P < 0.001), and HIV seropositivity was 35%, 6% and 0% respectively (P < 0.001). Acute or chronic liver disease was documented in 4 of 14 (28%) HCV-positive patients. Increased liver enzymes were recorded in sera of 43% HCV-positive patients and 18% HBV-positive patients compared to 22% of HBV and 20% HCV-seronegative patients (P = 0.076). Of 47 HCV-positive patients 24 were coinfected by HBV and 9 had triple infection (HCV, HBV and HIV). No solitary HIV infection was found. HIV seropositivity was always accompanied by serologic evidence for HBV with or without HCV infection.

Blood Component Transfusion↗
PubMed1993

Increased risk of cancer in patients with Gaucher disease.

BACKGROUND: An increased incidence of cancer, especially hematopoietic in origin, has long been suspected but never established in patients with Gaucher disease. METHODS: To determine whether patients with Gaucher disease have an increased risk of cancer, the authors conducted a retrospective cohort study, comparing the incidence and type of cancer in 48 patients with Gaucher disease with those of 511 control subjects without the disease. RESULTS: Among patients with Gaucher disease, 10 of 48 (20.8%) had cancer, as compared with 35 of 511 (6.8%) of the control group (P = 0.0027; relative risk, 3.6; 95% confidence interval, 1.7-7.5). As compared with the control group, patients with Gaucher disease had a 14.7-fold risk of having cancer of hematopoietic origin (10.4% [5 of 48] versus 0.78% [4 of 511], respectively; P = 0.00037; 95% confidence interval, 5.2-41.7). The mean age at cancer diagnosis in the group with Gaucher disease was 57 +/- 18 years. CONCLUSIONS: The authors conclude that patients with Gaucher disease have a significantly increased risk of cancer, occurring in late adulthood. Of all the cancers, hematologic cancers are significantly more prevalent.

Adult↗
PubMed1993

Carbamazepine (Tegretol)-induced thrombocytopenia.

A case of carbamazepine-induced thrombocytopenia is reported. The patient, a 38-year-old female, developed thrombocytopenia 10 days after receiving 400 mg carbamazepine daily. The presence of an anti-IgG carbamazepine-dependent platelet-reactive antibody was documented. Using flow cytometry, the drug-induced antibody was detected at a drug concentration as low as 10(-6) M.

Adult↗
PubMed1992

Effect of interleukin-1, tumor necrosis factor-alpha, and interferon-alpha on the blast cells of acute myeloblastic leukemia.

In this study, we further established the role of interleukin-1 alpha (IL-1 alpha), interleukin-1 beta, tumor necrosis factor-alpha (TNF-alpha), and interferon-alpha (IFN-alpha) as regulators of proliferation of acute myeloid leukemia (AML) cells. AML cells from 8 of 15 patients incorporated high levels of 3H-thymidine (3H-TdR) in the absence of exogenous growth factors. The spontaneous DNA synthesis could be abrogated with monospecific antibodies directed toward IL-1 alpha, IL-1 beta, or TNF-alpha, as well as with antigranulocyte-macrophage colony-stimulating factor (GM-CSF). Human recombinant GM-CSF reversed the inhibitory action of each of these antibodies and reinduced DNA synthesis in AML cells. Thus, in these cases, constitutively produced IL-1 or TNF-alpha had stimulated the synthesis of GM-CSF, which resulted in GM-CSF-dependent proliferation of AML blasts. Exogenous IL-1 up-regulated the endogenous production of GM-CSF, suggesting a positive regulation of autocrine growth factor production. We also present evidence that TNF-alpha may exert both stimulative as well as inhibitory effects on DNA synthesis in AML cells. The enhancing effect of TNF-alpha was mediated through the induction of GM-CSF production, as stimulation of DNA synthesis in AML blasts could be abrogated with anti-GM-CSF antibody. A concentration-dependent inhibitory effect of TNF-alpha on 3H-TdR incorporation into AML blasts was observed only when these cells were grown in the absence of GM-CSF. Finally, we show that human recombinant IFN-alpha is a potent inhibitor of AML cell proliferation in vitro.

Adolescent↗
PubMed1992

Cardiac involvement in patients with myeloproliferative disorders.

INTRODUCTION: To evaluate cardiac involvement in myeloproliferative disorders (MPD), two-dimensional and Doppler echocardiographic studies were performed in 30 patients with MPD. PATIENTS AND METHODS: There were 18 women and 12 men, with an age range from 35 to 76 years. Eighteen patients had polycythemia vera (PV), 8 had essential thrombocythemia (ET), and 4 had agnogenic myeloid metaplasia (AMM). RESULTS: Echocardiography revealed valvular lesions in 19 of 30 patients (63%) compared with only 1 of 22 patients (4.5%) in a control group of patients referred for echocardiography to exclude a cardiac source for idiopathic systemic thromboembolism (chi 2 = 13.39, p < 0.001, by chi 2 test with Yates' correction). Valvular lesions were found in 77% of patients with PV, 50% with ET, and 25% with AMM (p = NS). The aortic and mitral valves were the most commonly involved valves, and the most common echocardiographic lesion was leaflet thickening, which was found in 12 patients (40%), followed by vegetations, which were observed in 5 patients (16%). In their past history, 14 of 30 (47%) MPD patients had arterial or venous thrombosis or embolism. Twelve of 19 (63%) patients with valvular lesions had thromboembolism compared with only 2 of 11 (18%) patients without evidence of valvular lesions (chi 2 = 3.99, p < 0.05, by chi 2 test with Yates' correction). Pulmonary hypertension, unrelated to the severity of valvular disease and probably resulting from pulmonary venous occlusion, was found in four patients (13%). CONCLUSIONS: We conclude that the heart is frequently involved in patients with MPD, particularly when their past history is complicated by a thromboembolic event. Some patients have clinically significant valvular disease. Pulmonary hypertension is another relatively common finding in MPD patients. Echocardiography provides information of clinical significance in MPD patients. A larger number of patients is needed to determine whether the presence of valvular lesions is of prognostic significance and may herald future thromboembolic events.

Adult↗
PubMed1992

Comparative studies of the erythroid-potentiating effects of biosynthetic human insulin-like growth factors-I and -II.

The erythroid-potentiating effects of biosynthetic human insulin-like growth factor-I (IGF-I) and IGF-II were evaluated and compared in serum-free cultures of human marrow erythroid progenitors. IGF-I and IGF-II enhanced the in vitro growth of relatively mature (CFU-E) and primitive (BFU-E) erythroid progenitors at similar dose-dependent magnitudes. Significant elevations in erythroid colony counts were detected at 0.2-0.6 ng/mL of both peptides, with a maximal increase in CFU-E and BFU-E numbers detected at 2-6 ng/mL. Similar enhancement of erythroid progenitor cell growth by both peptides was also detected in cultures of marrow cells that had been depleted of accessory cells or in cultures of highly enriched hemopoietic progenitors. IGF-I and IGF-II enhanced erythroid progenitor cell growth at both limiting and saturating concentrations of recombinant human erythropoietin or granulocyte-macrophage colony-stimulating factor, but did not alter the sensitivity of CFU-E and BFU-E to their respective hemopoietic regulators. The erythroid-potentiating effects of IGF-I and IGF-II were completely abrogated by monoclonal antibodies directed against IGF-I membrane receptors. IGF-I and IGF-II thus appear to exert their effects on human marrow erythroid progenitors via a direct mechanism involving the type I IGF receptor.

Antibodies, Monoclonal↗
PubMed1992

High incidence of myeloproliferative disorders in Ashkenazi Jews in northern Israel.

We have analysed epidemiological parameters in 339 patients with myeloproliferative disorders (MPD) diagnosed in northern Israel between 1975 and 1989 as having polycythemia vera (191 patients), agnogenic myeloid metaplasia (AMM) (113) and essential thrombocythemia (ET) (36). Mean average annual incidence was 11.4 per 1 million residents for polycythemia vera, 6.5 for AMM and 2.1 for ET. For all three diseases the average annual incidence increased with age and was 10 times higher in patients over 65 years compared to those less under the age of 45 years. Four percent of all patients had relatives with MPD. Incidence of MPD in Jews was 10 fold higher than expected compared to Arabs and this difference was noted for all 3 diseases. The incidence in Ashkenazi Jews originating from eastern and central Europe, was 10 and 20 folds higher than in Sephardic Jews and Arabs respectively. Mean age at diagnosis of MPD in Arabs and Sephardic Jews was lower than in Ashkenazi Jews (52 and 56 years compared to 64 years P < 0.05). Likewise, mean age at diagnosis was lower in the 11.5% of MPD patients with prior exposure to biological or chemical hazards compared to unexposed individuals (58 years versus 63 years, P < 0.02). These data demonstrate a cluster of MPD in Ashkenazi Jews in northern Israel and emphasize the importance of genetic predisposition possibly interacting with acquired factors in the pathogenesis of these disorders.

Adult↗
PubMed1992

Association of lupus anticoagulant and anticardiolipin antibodies with thrombosis in patients with systemic lupus erythematosus, primary antiphospholipid syndrome and other disorders.

Lupus anticoagulant (LA) and anticardiolipin antibodies (ACA) have been associated with thrombotic events and recurrent fetal loss. In order to assess the role of LA with the thrombotic tendency in various disease states we evaluated 38 patients with confirmed LA [tissue thromboplastin index (TTI) greater than 1.3; circulating anticoagulant index (CAI) greater than 15], subgrouped as follows: a) LA associated with systemic lupus erythematosus (SLE) (n = 13); b) primary antiphospholipid syndrome (PAPS) (n = 16); and c) LA associated with other disorders (n = 9). Male/female ratio differed between the groups: 0/13, 6/10 and 4/5, respectively. Venous and arterial thrombotic events were more common in the PAPS group (87%) compared with the SLE group (61%) and the other disorders group (22%). Serum ACA antiphospholipid IgG levels by ELISA were increased in the SLE and PAPS patients, but did not differ between the groups (167 +/- 24 vs. 190 +/- 28 mu respectively). Antiphospholipid IgM levels were higher in the SLE group compared with the PAPS group (127 +/- 15 vs. 67 +/- 16 mu). Mean TTI and CAI levels did not differ between the SLE, PAPS and other disorders groups (1.8 +/- 0.19, 2.8 +/- 0.9, 2.0 +/- 0.3 for TTI; 25 +/- 4, 33 +/- 4, 32 +/- 5 for CAI). Likewise TTI, CAI and ACA levels did not differ in patients with or without thrombosis. We conclude that the prevalence of thrombotic manifestations varies among patients with similar serum intensities of LA and levels of ACA, suggesting that other factors may be involved in the pathogenesis of thrombosis in these patients.

Adult↗
PubMed1991

Impaired response of myelodysplastic marrow progenitors to stimulation with recombinant haemopoietic growth factors.

The regulation of haemopoiesis in myelodysplastic syndromes (MDS) was evaluated by measuring and comparing the in vitro response of marrow progenitors from 18 MDS patients to stimulation with recombinant haemopoietic growth factors (HGFs), granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte CSF (G-CSF) and interleukin-3 (IL-3). A similar pattern of colony growth was detected with all three HGFs in most MDS patients, exhibiting subnormal growth of GM-CFU and markedly poor to absent growth of BFU-E and CFU-GEMM. A common severe impairment in the growth of all colony types with all three HGFs was observed in five patients, four of whom presented with pancytopenia. The stimulation of MDS marrow progenitors with a five-fold higher than control saturating dose of HGFs induced a significant increase in the frequency of one, two, or all three colony types in cultures of 14 patients, whereas colony numbers in control (n = 8) marrow cell cultures were not significantly changed. All four of the non-responders were pancytopenic and three exhibited markedly impaired colony growth. Supersaturating GM-CSF, G-CSF and IL-3 increased GM-CFU numbers in six, three, and three patients, respectively. The values for BFU-E were three, six, and seven and for CFU-GEMM two, one, and five. The enhancement of MDS marrow colony numbers by supersaturating HGFs which exert their effects directly or via the action of marrow accessory cells, suggests that the progenitor cell growth abnormalities in these disorders may involve a defect in the capacity of accessory and/or progenitor cells to respond to stimulation with specific haemopoietic growth regulators.

Aged↗
PubMed1991

The prevalence and interaction of human immunodeficiency virus and hepatitis B virus infections in Israeli hemophiliacs.

The prevalence, clinical manifestations and serological markers of hepatitis B virus (HBV) and human immunodeficiency (HIV) infections were studied in 117 Israeli hemophiliacs. Positive serological markers for HBV infection (HB surface antigen, antibody to HB surface antigen or antibody to HB core antigen) were more common in patients treated with non heat-treated F-VIII concentrates (NHTC) than with cryoprecipitate (48/49 vs. 23/29, P less than 0.05), and in patients treated with greater than 10,000 factor units/year (90% vs. 62%, P less than 0.05). Of the 117 patients, 55% were HIV negative, 29% had asymptomatic HIV seropositivity and 16% had symptomatic HIV infection (lymphadenopathy syndrome, AIDS-related complex or AIDS). HIVB seropositivity was more common in patients treated with NHTC than in those treated with cryoprecipitate (83% vs. 11%, P less than 0.001), and in patients treated with greater than 100,000 compared to less than 10,000 F-VIII units/year (70% vs. 15%, P less than 0.001). Hypergammaglobulinemia correlated with HIV seropositivity, alanine aminotransferase levels and type and amount of concentrate therapy. Of 50 HIV-seropositive patients, 40 (98%) had serological markers of HBV infection compared with only 40 of 52 HIV-negative patients (77%) (P less than 0.01). Symptomatic HIV infection was more common in patients with a positive history of jaundice, 7 of 18 (38%) compared with 12 of 99 (12%) (P less than 0.005). These findings suggest that HBV and HIV infections are less prevalent in cryoprecipitate-treated patients, and that HBV seropositivity is a predictor of HIV seropositivity in hemophiliacs.

Factor VIII↗