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Biomedical subjects

G P Schechter

Publications and source records attributed to G P Schechter.

At least 55 records · Page 3Linked to original sources
PubMed1982

Molecular and cellular pathogenesis of hemoglobin SC disease.

Solution and cell studies were performed to ascertain why individuals with hemoglobin (Hb) SC have disease whereas those with Hb AS do not. The polymerization of deoxygenated mixtures containing sickle cell Hb (Hb S; alpha 2 beta 2(6)Glu leads to Val) and Hb C (alpha 2 beta 2(6)Glu leads to Lys) was investigated by measurements of delay times and solubilities. In mixtures containing more than 40% Hb S, polymerization takes place by the same mechanism as in solutions of Hb S alone, with no evidence for independent crystallization of Hb C. A detailed comparison of Hb S/Hb C and Hb S/Hb A mixtures with identical concentrations and proportions of Hb S show that there is no significant difference in the tendency of Hb C and Hb A to copolymerize with Hb S. In 50:50 Hb S/Hb C mixtures, polymerization is about 15 times more rapid than in 40:60 Hb S/Hb A mixtures at the same total Hb concentration. Measurements on density-fractionated erythrocytes show that SC cells contain a higher total Hb concentration and a more uniform distribution of reticulocytes compared to normal (AA) or sickle trait (AS) cells. The concentration distribution for C trait (AC) cells is much closer to that of SC cells than to AS or AA cells. It appears, therefore, that the presence of Hb C results in the SC cell beginning its life with an abnormally high Hb concentration. From these findings we conclude that both the larger proportion of Hb S and the higher intracellular Hb concentration contribute to the pathogenesis of Hb SC disease.

Anemia, Sickle Cell↗
PubMed1982

Fc receptor-defined T-lymphocyte subpopulations in patients with cutaneous T-cell lymphoma.

The distribution of peripheral blood T cells bearing Fc receptors for IgG (T gamma) and IgM (T mu) was determined in 18 patients with cutaneous T-cell lymphoma (Sézary syndrome, mycosis fungoides) and 15 normal controls. The mean percent of T mu and T gamma cells in the patients with morphologically normal lymphocytes was similar to that of the control subjects. In 13 patients with circulating malignant cells representing 30-100% of their peripheral blood lymphocytes, the mean percentages of T mu and T gamma were low. In 9 patients the majority of the malignant T cells did not exhibit Fc receptors for IgG or IgM. In some patients, however, high blood lymphocyte counts resulted in normal or high concentrations of all the T-cell subsets. Further, in 4 patients, lymphocytes with the characteristic nuclear abnormalities of "Sézary/mycosis" cells were found in both the T mu and T gamma, as well as the Tnon gamma non mu, subpopulations. The heterogeneity of the Fc receptors on cutaneous T-cell lymphoma lymphocytes suggests that these receptors are not useful as clonal markers in these disorders.

Adult↗
PubMed1982

Expression of glucagon receptors on T- and B- lymphoblasts: comparison with insulin receptors.

Activation of T- and B-lymphocytes by a variety of immunological stimuli has been reported to induce specific insulin receptors. The purpose of the present work was to determine whether glucagon receptors are also induced in activated cells. Studies of glucagon and insulin receptors were carried out using normal human mononuclear cells activated by phytohemagglutinin or T-cell growth factor (TCGF), as well as established B- and T-lymphoblastoid cell lines. With phytohemagglutinin, glucagon and insulin binding increased 15- and 36-fold, respectively, and peaked after 5 days in parallel with the rise in thymidine incorporation. Increased binding was associated with an increase in the number of receptors, most marked for insulin, though affinity for the insulin receptor was decreased. Normal human mononuclear cells cultured with TCGF showed an early modest rise in insulin binding due to increased receptor number, without a change in affinity, and a striking and progressive rise up to 50-fold in glucagon binding due to both increased receptor number and affinity. The differences in receptor response to these T-cell mitogens suggest that TCGF selects out a T-lymphoblast subset with very high glucagon receptors. B- and T-lymphoblastoid cells showed patterns of glucagon and insulin receptors that appear to be characteristic for each cell type. Glucagon binding was 7-fold higher (P less than 0.01), while inulin binding was 7-fold lower (P less than 0.01) in T- vs. B-lymphoblastoid cells. T-Cell lines had twice the number of glucagon receptors, whereas B-lines had 4-fold the number of insulin receptors, with much greater affinity for insulin compared with T-line insulin receptors. Induction of both insulin and glucagon receptors on activated lymphoblasts suggests that these receptors may play a significant role in cell function.

B-Lymphocytes↗
PubMed1982

Flow cytometric analysis of DNA content of bone marrow cells in patients with plasma cell myeloma: clinical implications.

DNA content analysis by flow cytometry was performed in 32 patients with plasma cell myeloma and 3 patients with Waldenstrom's macroglobulinemia to determine the biologic and potential clinical usefulness of this technique. Hyperdiploid tumor DNA content was found in 23 myeloma patients (72%) during the course of illness, including 16/28 at presentation, but in none of 3 patients with Waldenstrom's macroglobulinemia. There was no significant association of aneuploidy in myeloma patients with age, sex, race, or M-protein class. Myeloma patients with aneuploid tumor cells were more likely to have advanced stage (p = 0.032) than patients with diploid plasma cells, and all patients with renal failure had aneuploid tumors. Pretreatment factors significantly associated with survival included stage (p = 0.01), serum creatinine (p = 0.003), and tumor DNA content (p = 0.005). Multivariate analysis using the Cox life table regression procedure indicated that the significant relation of tumor DNA content with survival remained after adjusting for stage (p less than 0.005). Myeloma patients with diploid tumors at diagnosis frequently had aneuploid plasma cells at the time of relapse, indicating a possible relationship of chromosomal alterations in the tumor to clinical drug resistance. We conclude that aneuploid tumor cells at the time of diagnosis of myeloma are of independent prognostic significance, and the development of aneuploidy is a frequent occurrence at clinical relapse, suggesting the change in DNA content are of biologic and clinical significance.

Adult↗
PubMed1982

Skeletal manifestations in cutaneous T-cell lymphomas.

The clinical course of three patients with cutaneous T-cell lymphoma (CTCL) in whom skeletal disease developed is presented and the literature on skeletal involvement in these disorders is reviewed. Three separate types of skeletal manifestations occurred: (1) osteolytic lesions, (2) osteoblastic lesions, and (3) diffuse osteoporosis. Hypercalcemia was present in two cases. Tumor cells from two patients in short-term culture secreted osteoclast-activating factor(s). Both of these patients had pathologic evidence of osteoclast activation in bone sections. Thus, the tumor cells in certain patients with CTCL may derive from a monoclonal proliferation of a T-cell subset capable of producing humoral bone-resorbing factor(s) similar to those demonstrated in cultures of mitogen- and antigen-activated normal lymphocytes. Since skeletal lesions are unusual, it would follow that other T-cell subsets account for pathologic cell proliferation in most patients with CTCL.

Adult↗
PubMed1981

Hairy cell leukemia: association with disseminated atypical mycobacterial infection.

The cases of four patients with hairy cell leukemia and disseminated atypical mycobacterial infection (three with M. kansasii and one with M. intracellulare) are reported. These four patients were from a population of 38 patients with hairy cell leukemia evaluated at three institutions; there was an incidence figure of 10.5%. Despite infection with very drug-resistant strains, two patients showed marked clinical improvement following aggressive multiple drug therapy. Such infection should be suspected in a patient with hairy cell leukemia who has persistent fever without an obvious source. Tissue biopsy usually led to diagnosis; urine cultures were also positive in two patients.

Aged↗
PubMed1981

The effect of zinc on cellular immunity in chronic uremia.

Delayed hypersensitivity to mumps was examined in 25 apparently well-nourished men receiving regular hemodialysis, each of whom had a history of mumps. A positive reaction was observed in eight of nine patients already under therapy with zinc added to the dialysis bath. In contrast, 11 of 16 untreated patients were anergic. Four of the anergic patients were subsequently treated with zinc resulting in restoration of sensitivity in three patients. There were no significant differences in lymphocyte, monocyte, or T-cell counts between the two groups of patients. Consequently, zinc probably acts by improving the function of one or more of these cell types. Protracted zinc deficiency may be a major cause of impaired cellular immunity in chronic renal failure.

Adult↗
PubMed1981

Hypercalcemia associated with T-cell lymphoma-leukemia.

Two adults who had T-cell lymphoma-leukemia and recurrent hypercalcemia in the absence of radiographic evidence of bone disease are described. Bone histopathology showed marked osteoclastic activation. Bone resorbing factors, including both prostaglandin E and a material produced in the presence of a prostaglandin synthetase inhibitor, were detected in the in-vitro culture fluids of malignant cells of one of the patients. Serum levels of parathyroid hormone were not elevated. These findings suggest that hypercalcemia resulted from in-vitro osteoclast activation by tumor cell product(s), one of which may be similar, if not identical, to the lymphocyte product osteoclast-activating factor. Two other patients having T-cell lymphoma-leukemia and hypercalcemia have been identified in the literature: the malignant cells of one of these patients also released a calcium-mobilizing factor in vitro.

Adult↗
PubMed1981

Identification of human mononuclear leukocytes bearing receptors for somatostatin and glucagon.

Mononuclear leukocytes (MNL) were isolated from human blood by Ficoll-Hypaque. These cells were further separated into lymphocyte (L) and monocyte (M) enriched fractions. L contained 99% lymphocytes and M contained 74% monocytes, a threefold enrichment over MNL. Specific binding to somatostatin, glucagon, and insulin was measured in the three fractions. Binding of all three hormones in the M fraction was increased by a factor of 3 compared with MNL and was linear with cell number. Binding of glucagon and insulin to the L fraction was very low while, in contrast, somatostatin binding was substantial and linear with lymphocyte number. Autoradiography confirmed the binding of glucagon to monocytes and of somatostatin to both monocytes and lymphocytes. Somatostatin is the first of the peptide hormones shown to bind to both types of circulating mononuclear cells, perhaps complicating quantification of somatostatin binding in disease states in which differential alteration of binding of lymphocytes or monocytes might occur.

Autoradiography↗
PubMed1981

Prolymphocytic leukemia. Response to asparaginase.

A 69-year-old woman previously diagnosed as having chronic lymphocytic leukemia had a lymphocyte count of 1,500 X 10(9)/L develop. Bone marrow and peripheral blood lymphocyte morphology and lymphocyte surface markers were consistent with the diagnosis of prolymphocytic leukemia of the null cell type. The leukemia was resistant to management with alkylating agents, combination chemotherapy including doxorubicin hydrochloride, or leukapheresis. The addition of asparaginase to the previously ineffective prednisone and vincristine sulfate therapy produced a dramatic response during a two-week period with a decrease in the peripheral lymphocyte count from 980 X 10(9) to 20 X 10(9)/L and a return toward normal of the concentration of polymorphonuclear leukocytes. Previously, there has been only infrequent or transient benefit from treatment provided these patients from regimens including chemotherapy, splenectomy, irradiation, and leukopheresis. It is suggested that asparaginase be considered as initial induction therapy for this disease process.

Aged↗
PubMed1980

Lymphocyte transformation in patients with cutaneous T-cell lymphomas.

The proliferative responses of peripheral blood mononuclear cells from ten patients with cutaneous T-cell lymphoma were tested after stimulation with a variety of mitogens, including phytohemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM), staphylococcal protein A (SPA), and lymphocyte-conditioned medium (LyCM). Responses were measured by the incorporation of tritiated thymidine and by flow microfluorometry (FMF). In general, responses were depressed, although a broad range of responses were observed ranging from very poor to near normal responses. SPA and PWM were the most potent mitogens in the CTCL patients, unlike controls in whom PHA and SPA were the optimum mitogens and PWM was weakly mitogenic. FMF studies in two patients clearly demonstrated that aneuploid Sezary cells and not admixed normal lymphocytes were proliferating in response to SPA and PWM stimulation. The unusual pattern of mitogen responses found in these CTCL patients suggests Sezary cells may be derived from T-cell subpopulations with special affinity for SPA and PWM. The ability of FMF to demonstrate that aneuploid cells respond to mitogen stimulation makes it a useful additional technique in the evaluation of lymphocyte blastogenesis in patients with malignant lymphoproliferative disorders.

Adult↗
PubMed1980

Myeloproliferative syndrome with sideroblastic anemia and acquired hemoglobin H disease.

Hemoglobin H disease usually occurs as a result of inheritance of the genes for alpha thalassemia; however, occasionally patients acquire hemoglobin H in association with hematologic malignancy. This report concerns a 63-year-old Filipino man with a myeloproliferative syndrome with marked thrombocytosis and apparently acquired hemoglobulin H disease. The patient had hemolytic anemia, dimorphic red blood cells (RBC) and abundant ringed sideroblasts in the marrow. The peripheral blood contained 27% hemoglobin H and about two-thirds of his RBC had hemoglobin H inclusion bodies. There was no previous history of anemia or evidence of thalassemia in two siblings or nine adult children of the patient. In vitro studies of globin chain synthesis documented markedly decreased production of alpha globin with alpha/beta biosynthetic ratios of 0.05 in peripheral blood reticulocytes and 0.10 in bone marrow cells. The relative concentration of mRNA for alpha globin was approximately 20-fold less than that of beta globin, apparently accounting for the deficiency in alpha globin synthesis.

Anemia, Sideroblastic↗
PubMed1980

Prospective staging evaluation of patients with cutaneous T-cell lymphomas. Demonstration of a high frequency of extracutaneous dissemination.

A prospective pretreatment staging evaluation was done on 49 consecutive patients with mycosis fungoides or the Sézary syndrome to study patterns of disease spread and prognostic factors. Routine staging procedures included complete blood count, blood chemistries, chest roentgenogram, lymphangiogram, radionuclide scans, bone marrow aspiration and biopsy, liver biopsy, and lymph node biopsy. Special evaluations included cytogenetic analysis, electron microscopy, and T-cell cytology. Extracutaneous lymphoma was documented by light microscopy in 51% of patients and by the three special procedures in 88%. Extracutaneous lymphoma was most frequent in blood and lymph nodes; 18% of patients had visceral involvement. Patients with generalized erythroderma had a higher frequency of extracutaneous disease than did patients with cutaneous plaques and tumors by both light microscopy and special studies. Survival was directly related to the type of skin involvement and the presence or absence of extracutaneous disease. Systemic dissemination of cutaneous T-cell lymphoma is frequent, generally asymptomatic, and develops early via the circulation. These findings may explain why cutaneous therapies are associated with a high frequency of relapse.

Adult↗
PubMed1979

Periostitis associated with myelofibrosis.

Two patients with myelofibrosis developed fever, leg pain and periostitis. The first patient had myelofibrosis with myeloid metaplasia and was symptomatic for months before x-rays showed periosteal new bone formation in the lower extremities. He subsequently developed periostitis of both upper extremities. Radiation of the lower extremities resulted in significant pain relief. The second patient had a past history of polycythemia vera and experienced painful periostitis of the tibiae and fibulae. 99mTechnetium pyrophosphate bone scans showed increased uptake in the involved bones in both patients. Asymptomatic or painful periostitis may be related to the increased bone blood flow associated with myelofibrosis. Radiation can afford successful palliation in the severely symptomatic patient.

Diagnosis, Differential↗
PubMed1979

Suppressor monocytes in human disease: a review.

Suppressor monocytes have been found in a number of human diseases most of which are associated with lymphopenia and deficiences in cell mediated immunity. In our studies both quantitative and qualitative differences in monocytes were detected in certain patients with advanced Hodgkin's disease or tuberculosis. In certain patients lymphocyte activating factor production by monocytes was severely depressed in part secondary to decreased activation by suppressed T cells, although at times primary impairment of macrophage function was also probably contributory. Mononuclear cell cultures from patients with advanced Hodgkin's disease also manifested excessive prostaglandin secretion; however, the association of this with monocyte suppression and deficient LAF production was inconstant. Furthermore, reversibility of monocyte suppression could not regularly be achieved by inhibition of prostaglandin synthetase with indomethacin suggesting that excessive production of prostaglandins is unlikely to be the sole mechanism of monocyte inhibition of lymphoproliferation. It also remains to be established whether the inhibition of lymphoproliferation in vitro is important to in vivo delayed hypersensitivity or whether the mechanism is related to other macrophage effects such as tumor cytostasis and cytolysis.

Cell Communication↗