Biomedical subjects

I Tatarsky

Publications and source records attributed to I Tatarsky.

At least 55 records · Page 3Linked to original sources

PubMed1988

Spontaneous intracranial hemorrhage in immune thrombocytopenic purpura.

Spontaneous intracranial hemorrhage (ICH) is a rare but devastating complication in patients with chronic immune thrombocytopenic purpura (ITP). We report four patients with chronic ITP unresponsive to steroid treatment who developed ICH. One patient had systemic lupus erythematosus; in another patient, the ICH originated from an arteriovenous malformation. High dose steroids, platelet concentrates, emergency splenectomy, and subsequent evacuation of intracranial hematoma, if necessary, can lead to a reasonable outcome of ICH in patients with chronic ITP.

Adolescent↗

PubMed1988

Splenectomy in agnogenic myeloid metaplasia and postpolycythemic myeloid metaplasia. A study of 34 cases.

A retrospective analysis of 34 successive splenectomies in 137 patients with myelofibrosis was carried out. Indications, complications, and response to splenectomy were compared between 22 patients with agnogenic myeloid metaplasia (AMM) and 12 patients with postpolycythemic myeloid metaplasia (PPMM). Painful splenomegaly, refractory hemolytic anemia, and refractory thrombocytopenia were the common indications for surgery. The best results were obtained for painful splenomegaly. For the other indications, half to three fourths of the patients improved with splenectomy. An increased incidence of excessive hemorrhage, infected hematoma, and early mortality was more common in the PPMM group and was found to be connected with large spleens, prolonged bleeding time, and prominent thrombocytopenia. Persistent thrombocytosis after surgery was more common in the AMM group. Leukemic transformation seemed to be related to thrombocytosis and to prior therapy with alkylating agents. Median survival following splenectomy was 43 months in the AMM group and 32 months in the PPMM group. We conclude that splenectomy has a role in improving the quality of life by ameliorating mechanical discomfort and decreasing transfusion requirement in the late phase of AMM. However, in patients with PPMM, because of the high complication rate, splenectomy should be carefully considered for specific indications on an individual basis.

Adult↗

PubMed1987

Prognostic significance of plasma cell morphology in multiple myeloma.

The effect of bone marrow plasma cell morphology at diagnosis on survival time was evaluated in 139 patients with multiple myeloma. According to the morphological classification scheme the patients were categorized as mature (30 patients), immature (76 patients) or plasmablastic (33 patients). The plasmablastic group had an estimated median survival (Kaplan-Meier method) of 10.9 months, compared with 32.2 months for immature and 60 months for mature types (P = 0.0000). The prognostic value of a morphologic classification in multiple myeloma was further demonstrated by means of a multivariate linear regression analysis of survival data. Expected survival was calculated using clinical features and morphologic subtypes. The estimated survival time for plasmablastic myeloma was shorter by 51.4 months and for immature myeloma patients by 35 months, compared with mature myeloma patients with similar clinical characteristics. Plasma cell morphology at diagnosis is an important predictor of survival duration in patients with multiple myeloma.

Bone Marrow↗

PubMed1987

Additional variant of type I von Willebrand disease.

We introduce a family with a von Willebrand subgroup that has not been described before. All of the eight subjects examined had normal levels of factor VIII coagulant activity (FVIII:C), a moderate reduction in the level of von Willebrand factor antigen (VWF:Ag), which resulted in a high FVIII:C/VWF:Ag ratio, and normal crossed immunoelectrophoresis, with normal multimeric pattern. The ristocetin cofactor in plasma and platelets was very low. Bleeding time was prolonged in two subjects without clearcut linkage to laboratory findings. In addition, an abnormality of platelet aggregation in response to ADP was observed: a decreased initial response was followed by marked disaggregation.

Adenosine Diphosphate↗

PubMed1987

Immunoglobulin synthesis in myelodysplastic syndromes: normal B-cell and immunoregulatory T-cell functions.

Peripheral blood cells from patients with myelodysplastic syndromes were assayed for B-cell and immunoregulatory T-cell functions. The B/T cell ratio in myelodysplastic patients (n = 11) was significantly higher than in controls (n = 12). These patients had a reduction in total T-cell (OKT3+) frequency and in T-cell subset (OKT4+/OKT8+) ratios. The response of patients' cells to both pokeweed mitogen (PWM) and phytohemagglutinin (PHA) was reduced, but patients' B cells responded normally to stimulation with Staphylococcus aureus Cowan (SAC). The levels of IgG and IgM detected in 7-day culture supernatants of PWM-stimulated patient and control cells were similar. Normal B-cell and immunoregulatory T-cell functions were subsequently demonstrated in allogeneic co-culture combinations of enriched T and B cells from patients and controls. The data presented indicate that the frequent infections of myelodysplastic patients are not causally related to impaired humoral mechanisms. The data also favor the possibility that the stem cell disorder in these syndromes is functionally expressed at a subsequent stage to the lymphoid differentiation pathway.

Antibody Formation↗

PubMed1987

Production of human pluripotent progenitor cell colony stimulating activity (CFU-GEMMCSA) in patients with myelodysplastic syndromes.

The present study was aimed at assessing the possible relationship between the T-lymphocyte abnormalities and the stem cell dysfunction in myelodysplastic syndromes (MDS), by investigating the production of specific stimulators of stem cell differentiation in such patients. Conditioned media from peripheral blood mononuclear cells (PBMNC) of MDS patients and healthy controls, prepared with or without phytohaemagglutinin (PHA), were assayed for their capacity to stimulate the in-vitro formation of multilineage colonies (CFU-GEMM) in target marrow cell cultures of healthy donors. Both PHA-induced DNA synthesis and T-cell subpopulation ratios (T4/T8) in patient cells were significantly lower than in controls. However, no impaired production of pluripotent progenitor cell colony stimulating activity (CFU-GEMMCSA) by PHA-stimulated and unstimulated PBMNC, could be found. Normal levels of activity were also produced by isolated T lymphocytes of MDS patients. Autologous serum neither enhanced nor suppressed the production of CFU-GEMMCSA. Our observations demonstrate that PHA-induced production of CFU-GEMMCSA is not directly correlated with DNA synthesis. Furthermore, we have found that both major T-cell subsets, defined by OKT4 and OKT8 monoclonal antibodies, are equally capable of producing CFU-GEMMCSA. The normal production of CFU-GEMMCSA by T cells of MDS patients suggests that this T-cell function is not an etiological factor in the stem cell disorder of myelodysplastic syndromes.

Anemia, Sideroblastic↗

PubMed1987

The effect of low dose ARA-C on in-vitro haemopoiesis of marrow cells from myelodysplastic patients.

The effect of low dose (10(-12)-10(-7) M) ARA-C on differentiation and proliferation in liquid and semisolid culture of marrow cells from 13 patients with myelodysplastic syndrome (MDS) were studied following incubation in liquid culture with low dose ARA-C. In six of ten patients an increasing number of myeloid cells acquired the morphologic appearance of mature monocyte-macrophages. Increasing number of cells reacted positively to fluoride sensitive naphthyl acetate esterase and specifically bound MY4 monoclonal antibody. Phagocytosis and killing of Candida albicans by monocyte-macrophages incubated with low dose ARA-C was normal and similar to that of the untreated cells. All MDS patients showed reduced myeloid colony and increased cluster formation. Low dose ARA-C had slight but non-significant inhibitory effects on myeloid colony growth. The results indicated that the differentiation pattern of myeloid precursor cells form a subset of MDS patients was altered by exposure to low dose ARA-C in vitro.

Bone Marrow↗

PubMed1987

Myeloid progenitors from the bone marrow of patients with vitamin D resistant rickets (type II) fail to respond to 1,25(OH)2D3.

The active metabolite of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), has been shown to enhance the growth of human granulocyte/macrophage haemopoietic progenitors in vitro and to induce these cells to differentiate along the monocyte/macrophage pathway. In order to evaluate the relationship between specific receptors for 1,25(OH)2D3 and the role of 1,25(OH2D3 in the regulation of haemopoietic cell differentiation, we examined the effect of haemopoietic cell differentiation, we examined the effect of 1,25(OH)2D3 on the in vitro growth and differentiation patterns of marrow myeloid progenitor cells from two patients with 1,25(OH)2D3 resistant rickets, resulting from defective receptors to vitamin D. A significant rise in the frequency of myeloid colonies in control marrow cell cultures was induced by 2 X 10(-9) to 2 X 10(-7)M 1,25(OH)2D3. This rise reached a plateau at 2 X 10(-9)_2 X 10(-8) M 1,25(OH)2D3, resulting in a maximal 54 +/- 9% increase in colony numbers. In contrast, no stimulatory effect could be detected when 1,25(OH)2D3 was added to cultured marrow cells from the patients with 1,25(OH)2D3 resistance. Analysis of colony composition revealed that 2 X 10(-8) and 2 X 10(-7) M, 1,25(OH)2D3 induced a 50 +/- 26% increase in the frequency of colonies composed only of monocytes/macrophages in control, but not in the patients' marrow cell cultures. The effect of 2 X 10(-8) and 2 X 10(-7) M 1,25(OH)2D3 on progenitor cell differentiation towards monocytes/macrophages was also observed in marrow cell suspension cultures. Whereas 1,25(OH)2D3 induced a 81-136% increase in the frequency of monocytes in control marrow cells, no effect could be detected on the generation of mature monocytes in marrow cells of the 1,25(OH)2D3 resistant patients. Our results show that marrow granulocyte/macrophage progenitor cells from patients with 1,25(OH)2D3 resistance fail to respond to 1,25(OH)2D3. We thus demonstrate that the effect of 1,25(OH)2D3 on the proliferation and differentiation of haemopoietic progenitor cells is mediated through its binding to specific cytoplasmic receptors.

Bone Marrow↗

PubMed1987

Influence of splenectomy on hemostasis in agnogenic myeloid metaplasia.

The effect of splenectomy on hemostatic tests was studied in 10 patients with agnogenic myeloid metaplasia. Prolonged partial thromboplastin time and abnormal prothrombin consumption were found before splenectomy and were normalized postoperatively in the majority of patients. Prolonged bleeding time and prothrombin time were normalized in some patients. While platelet counts and fibrinogen levels rose significantly following splenectomy, platelet aggregation remained impaired. Thrombocytosis and increased fibrinogen level after splenectomy in patients with agnogenic myeloid metaplasia can enhance a thromboembolic tendency.

Adult↗

PubMed1987

Mycoplasma-induced in vitro production of interleukin-2 and colony-stimulating activity.

Mitogenic doses of membranes purified from Mycoplasma pneumoniae as well as concanavalin A (ConA) were tested for their ability to induce production of interleukin-2 (IL-2) and granulocyte-macrophage colony-stimulating activity (GM-CSA) by human peripheral blood mononuclear cells. Unlike ConA, M. pneumoniae exhibited a significantly lower mitogenic effect and lacked the ability to induce production of IL-2. On the other hand, peak levels of GM-CSA produced in the presence of M. pneumoniae and detected in colony assays of human target marrow cells were approximately 80% of those produced in the presence of ConA. Whereas ConA induced a similar time-related effect upon [3H]thymidine uptake and GM-CSA production, maximal GM-CSA production preceded the peak proliferative response to M. pneumoniae, thereby indicating that M. pneumoniae-induced production of GM-CSA is not quantitatively correlated with DNA synthesis. These findings may contribute to the understanding of the inflammatory manifestations induced by this organism.

Cell Membrane↗

PubMed1987

Immune basis for cimetidine-induced pancytopenia.

We report a case of a female patient with chronic myelogenous leukemia who presented, 8 yr after initial diagnosis, with pancytopenia, encephalopathy, and myalgia. The tentative diagnosis was accelerated phase of chronic myelogenous leukemia. However, because the patient had been treated with cimetidine for 7 months we first omitted this drug. When cimetidine was stopped, bone marrow recovered, and myalgia and encephalopathy subsided. Immunological studies showed stimulation of the patient's lymphocyte blastogenesis by cimetidine and a marked increase in the proportion of cytotoxic/suppressor T lymphocytes after incubation of peripheral blood lymphocytes with cimetidine for 6 days. These findings indicate a role for cell-mediated immunity in the pathogenesis of cimetidine-induced pancytopenia in this patient.

Aged↗

PubMed1987

Effect of 1,25-dihydroxyvitamin D3 and 13-cis-retinoic acid on in vitro hematopoiesis in the myelodysplastic syndromes.

The effect of 2 X 10(-10) to 2 X 10(-7) mol/L 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) and 10(-9) to 10(-6) mol/L 13-cis-retinoic acid on in vitro differentiation and proliferation of marrow cells from patients with myelodysplastic syndrome (MDS) was assessed. Cells from 17 patients were studied by the semisolid technique, and cells from seven patients by both liquid and semisolid cultures. After incubation in liquid culture with 1,25(OH)2D3, in six of seven patients evaluated an increasing number of myeloid cells (185% to 470%) acquired the morphologic appearance of mature monocyte-macrophages, and a decrease in the number of immature myeloid cells (26% to 75%) was observed. Phagocytosis and killing of Candida albicans by monocyte-macrophages incubated with 1,25(OH)2D3 were normal and similar to those processes in untreated cells. 1,25(OH)2D3 increased the percentage of monocytes that phagocytosed C. albicans in three patients. Thirteen of 17 patients showed reduced myeloid cloning, and eight showed increased cluster formation. Cloning efficiency was significantly lower in patients with refractory anemia with excess of blasts and chronic myelomonocytic leukemia. Concentrations of 2 X 10(-9) to 2 X 10(-8) mol/L 1,25(OH)2D3 and 10(-8) to 10(-7) mol/L retinoic acid had a stimulatory effect on myeloid colony growth in five of the six patients with sideroblastic and refractory anemia, but in only two of the 11 patients with refractory anemia with excess of blasts and chronic myelomonocytic leukemia. The results indicate that the differentiation pattern of myeloid precursor cells from a subset of patients with MDS was altered by exposure to 1,25(OH)2D3.

Adolescent↗

PubMed1987

Human stem cell colony-stimulating activity (CFU-GEMMCSA) in medium conditioned by leukemic B-lymphocytes.

Media conditioned by B-lymphocytes of patients with chronic lymphocytic leukemia (B-CLL) induced the formation of multilineage colonies (CFU-GEMM) in cultures of human target marrow cells. Maximum levels of stem cell colony-stimulating activity (CFU-GEMMCSA) were detected by day 3 of leukemic B-cell cultures, remaining constant thereafter. Stimulation of leukemic B-lymphocytes with B-cell mitogens such as Cowan strain Staphylococcus aureus (SAC) and anti-mu enhanced the production of CFU-GEMMCSA by these cells. 3H-thymidine uptake in response to these mitogens was detected only in SAC-stimulated cultures, thereby demonstrating that mitogen-induced enhancement of CFU-GEMMCSA production by leukemic B-lymphocytes is independent of DNA synthesis. Conditioned media of leukemic B-lymphocytes stimulated the formation of human marrow granulocyte-macrophage (GM-CFU) and early erythroid (BFU-E) colonies as well. These observations indicate a role for B-lymphocytes in the regulation of hemopoietic stem cell and progenitor cell growth in vitro.

B-Lymphocytes↗

PubMed1987

Effect of plasmacytoma cells on the production of granulocyte-macrophage colony-stimulating activity (GM-CSA) in the spleen of tumor-bearing mice.

Mice bearing syngeneic plasma cell tumors are characterized by elevated numbers of granulocyte-macrophage progenitors (GM-CFU) in the spleen. We investigated the role of syngeneic plasmacytomas in the hematologic response to tumor cell transplantation by assaying the production of granulocyte-macrophage colony-stimulating activity (GM-CSA) by cultured spleen cells of tumor-bearing mice and by plasmacytoma cells, alone and in coculture with spleen cells. Elevated levels of GM-CSA were detected in 7-day culture supernatants of spleen cells from Balb/c mice transplanted 2 weeks previously with syngeneic 4T00.1 plasmacytoma cells. Colony assays of spleen cells from tumor-bearing mice demonstrated the presence of both granulocyte-macrophage and tumor cell colonies. A high frequency of GM-CFU was detected in cultures which had not been supplemented with an exogenous source of GM-CSA. Significant levels of GM-CSA were detected in media conditioned by 4T00.1 plasmacytoma cells. 4T00.1-conditioned medium did not stimulate the growth of primative erythroid (BFU-E) and multilineage (CFU-GEMM) colonies, but stimulated the growth of FDC-P1 cells, thereby establishing the activity produced by 4T00.1 cells as GM-CSF. The levels of GM-CSA in media conditioned by coculturing control spleen and 4T00.1 cells were significantly higher than those detected in media conditioned by spleen cells alone. The colony frequency induced by the coculture supernatants, however, did not exceed the sum of the colonies detected in marrow cell cultures stimulated with media conditioned by control spleen and 4T00.1 cells alone. Our findings demonstrate that murine plasmacytoma cells are capable of secreting GM-CSF. They further suggest a key role for GM-CSA production by tumor cells in the hemopoietic response of mice bearing syngeneic plasma cell tumors.

Animals↗

PubMed1986

Treatment of polycythemia vera with hydroxyurea.

Thirty-six patients with polycythemia vera were treated with hydroxyurea for 12 to 67 months. Nineteen patients were previously treated with other drugs. In the vast majority of patients, an average dose of 1 g/day was sufficient to control hematocrit value and platelet count. Half of the patients experienced relief of pruritus, and two thirds experienced regression of splenomegaly. None of the patients had either thrombotic complications or leukemia. Four patients suffered from mild side effects, which included fever, hyperbilirubinemia, and stomatitis, and were relieved of their symptoms when treatment was stopped. However, two patients experienced renal failure, a possible major complication not described previously.

Aged↗

PubMed1986

Impaired immunoglobulin synthesis in multiple myeloma: a B-cell dysfunction.

Peripheral blood samples collected from normal individuals and patients with benign monoclonal gammopathy and multiple myeloma were separated and assayed for their T- and B-cell subpopulations as well as immunoglobulin (IgG, IgM) synthesis in vitro. To rule out any functional or quantitative alterations related to therapy, only newly diagnosed multiple myeloma patients and subjects with benign monoclonal gammopathy were included in our study. Multiple myeloma patients were further subdivided into two groups. Group A consisted of patients with low and intermediate tumor burdens, while group B included patients with high tumor mass. B- and T-cell subset analysis revealed an abnormal ratio between B/T and OKT4+/OKT8+ lymphocytes compared to healthy controls. These alterations were especially prominent in group B multiple myeloma. Immunoglobulin synthesis was studied in pokeweed-mitogen-stimulated lymphocyte cultures. The results indicate that the failure to synthesize and secrete immunoglobulin resides within the B-cell lineage and is probably due to a functional B-cell defect. T-cell immunoregulatory functions seem to be unaffected in both multiple myleoma and benign monoclonal gammopathy patients.

B-Lymphocytes↗

PubMed1986

Sialic acid of platelets and granulocytes in polycythemia vera.

Previous studies have shown that erythrocytes of polycythemia vera (PV) patients have an increased content of sialic acid on their membrane compared with normal erythrocytes. This has been attributed to the presence of an abnormal clone known to proliferate in this disease. Since granulocytes and platelets originate from the same stem cell that is involved in this disease, it was of interest to see whether these cells also bear increased amounts of sialic acid compared with their normal counterparts. While normal values were found for granulocyte populations, elevated values were found for the platelet populations of PV patients.

Blood Platelets↗

PubMed1986

Eosinophilic fibrohistiocytic lesion of bone marrow associated with monoclonal gammopathy and osteolytic lesions.

We describe a 63-year-old male patient with severe osteoporosis, multiple lytic bone lesions, and monoclonal gammopathy (IgG lambda). Whereas the tentative diagnosis in this case was multiple myeloma, bone marrow trephine biopsies of the iliac crest and from an osteolytic lesion of the tibia both showed a peculiar infiltrate consisting of numerous elongated mast cells, eosinophils, and some plasma cells and lymphocytes. The bone marrow lesions fit the diagnosis of eosinophilic fibrohistiocytic lesion of bone marrow (EFHBM). The patient had no abnormality that could be related to a known allergic disease, and no relationship to drug hypersensitivity could be established. The features of the bone marrow infiltrate and its association with monoclonal gammopathy may suggest a linkage between EFHBM and the monoclonal gammopathy.

Bone Marrow Diseases↗