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Biomedical subjects

R Levy

Publications and source records attributed to R Levy.

At least 649 records · Page 36Linked to original sources
PubMed1984

Up-regulation of opiate receptors by opiate antagonists in neuroblastoma-glioma cell culture: the possibility of interaction with guanosine triphosphate-binding proteins.

Neuroblastoma-glioma NG108-15 cells that were cultured for 48 h with the opiate antagonist, naloxone, respond to the guanosine 5'-triphosphate (GTP) analogue guanosine 5'-[beta, gamma-imido]-triphosphate (GMP-PNP) in the binding assay as the control, non-treated, cells. This was observed when the guanyl nucleotide was tested in the presence or absence of sodium chloride and also after subcellular fractionation of the membranes on a sucrose gradient which separated between two receptor-containing fractions. The findings suggest that the increase in delta type enkephalin receptors in naloxone-treated NG108-15 cells does not reflect an alteration in the interaction between the receptor and the adenylate cyclase-GTP-binding protein system.

Animals↗
PubMed1984

Biclonal B-cell lymphoma.

The cells of most tumors are considered to be genetically homogeneous because they are assumed to represent a single clone descended from one abnormal cell. We have discovered three cases of B-cell lymphoma for which this generalization is not true. In each case, the tumor was composed of two subpopulations of cells, each expressing a different immunoglobulin molecule. Antibodies directed against these immunoglobulins were used to separate the two cell subpopulations of each tumor on a fluorescence-activated cell sorter. DNA extracted from the original tumor and the two fractionated subpopulations was analyzed to determine the configuration of immunoglobulin genes. Differences were found in the arrangement of DNA in at least one immunoglobulin gene for each of the two subpopulations. Thus, biclonality of these tumors was revealed by examination of both protein markers (cell-surface immunoglobulin) and DNA markers (immunoglobulin-gene rearrangements). Our results indicate that the incidence of biclonal B-cell lymphoma may be higher than previously recognized, possibly as high as 10 per cent of all B-cell lymphomas. Furthermore, our findings may have important implications for the diagnosis and therapy of lymphoid cancers.

Adult↗
PubMed1984

Immunochemical analysis of the released Leu-2 (T8) molecule.

We recently have found that the human T cell antigen Leu-2 was specifically released from Leu-2-bearing cells. The preliminary study showed that the released Leu-2 (RLeu-2) from HPB-ALL cells was composed of a single polypeptide chain of 27,000 molecular weight (mol wt), which was smaller than the subunit of the homodimeric molecule found on the cell surface. In the present study, RLeu-2 was further characterized and compared with cellular Leu-2 (CLeu-2). Metabolically radiolabeled Leu-2 was released from HPB-ALL cells and this released Leu-2 molecule had a mol wt of 27,000. Cell surface radioiodinated HPB-ALL cells were found to release radioactive Leu-2 molecules and this antigen also had the same mol wt of 27,000. In both experiments, the CLeu-2 was reconfirmed to be composed of a 33,000-mol wt subunit under reducing conditions. These experiments establish that the 27,000-mol wt single polypeptide chain of Leu-2 released from the cell is derived directly from the homodimeric Leu-2 molecule on the cell surface, presumably by a specific proteolytic cleavage. Two-dimensional gel analysis showed that CLeu-2 exhibited extensive charge heterogeneity with predominantly basic isoelectric points, whereas RLeu-2 was a group of more acidic proteins with less charge heterogeneity. Although CLeu-2 and RLeu-2 showed several different immunochemical characteristics, the homology between these two antigens was confirmed by the following results: CLeu-2 and RLeu-2 were found to share at least three different antigenic determinants, Leu-2a and Leu-2b, and those which were detected by a polyvalent rabbit antiserum. Significant similarities between CLeu-2 and RLeu-2 were demonstrated by peptide mapping analysis of these antigens. Therefore, RLeu-2 appears to be the specific, physiological product of the CLeu-2 protein.

Animals↗
PubMed1984

Possible involvement of actin and myosin in Ca2+ transport through the plasma membrane of chromaffin cells.

The exocytosis of catecholamines by chromaffin cells following stimulation (e.g. by acetylcholine) is accompanied by a rise in the level of intracellular free Ca2+. Actually, secretion can be induced merely by making the cells leaky to Ca2+ from the external medium. We have recently demonstrated that secretion can be increased by the introduction of DNase-I, the F-actin depolymerizing agent, or of heavy meromyosin, the enzymatically active fragment of myosin. Suspecting that these changes might be associated with a higher intracellular level of Ca2+, we now have measured the influx of 45Ca2+ into chromaffin cells which have undergone fusion with DNase-I- or with heavy meromyosin-loaded liposomes. In both cases, a marked increase in Ca2+ uptake has been observed, which could be abolished by Co2+ ions (a Ca2+ channel blocker), suggesting an intimate involvement of the cellular actomyosin system in the process of Ca2+ ions transport through the Ca2+ channels of the plasma membrane.

Actins↗
PubMed1984

The erythrocyte membrane in essential hypertension. Characterization of the temperature dependence of lithium efflux.

Erythrocytes of most patients with essential hypertension are distinguished by a typical pattern of temperature-dependence of Li efflux. In the present study we have attempted to characterize this unique temperature response. Measurements of Li efflux into Na medium and Lii-Nao countertransport were conducted simultaneously at finely spaced temperature intervals with increments of 1 to 2 degrees C in the range of 10-40 degrees C. The Arrhenius plots for the efflux in Na medium and for Lii-Nao countertransport in erythrocytes of both normotensives and hypertensives were biphasic with slopes representing apparent energies of activation of about 28 and 8 kcal/mol below and above the 'break', respectively. However, the 'break' in the Arrhenius plot appeared at distinctly different temperatures: 30 degrees C for normotensives and 20 degrees C for hypertensives. The Li efflux was resolved into N-ethylmaleimide-sensitive and -insensitive components. The sensitive component exhibited a typical biphasic temperature response, with the characteristic 'break': at 30 degrees C for normotensives and at 20 degrees C for hypertensives. In contrast, the N-ethylmaleimide-insensitive component was alike in normotensives and hypertensives. It is concluded that: (a) the unique temperature dependence of Li efflux in erythrocytes of hypertensives results from a localized modification in the membrane; (b) the N-ethylmaleimide-sensitive component represents a protein moiety which distinguishes between the erythrocyte membrane of normotensives and hypertensives; (c) the expression of the temperature dependence as judged by the sharp transition in slope (within 1 to 2 degrees C), apparently reflects the cooperative involvement of membrane lipids, associated with the Li efflux system.

Biological Transport↗
PubMed1984

[Occurrence and analysis of the mycotoxin emodin].

Besides other mould species, Aspergillus wentii Wehmer is assumed to form the hydroxyanthraquinone derivative emodin which has toxic and gene mutagenic properties. As a pectinase producer this fungus is used for the industrial isolation of pectinolytic enzymes for the food industry so that a contamination of such preparations by emodin cannot be excluded. However, preliminary thin-layer chromatographic studies of extracts of the corresponding pectinolytic enzyme preparations and Aspergillus wentii Wehmer did not point to a detectable toxin formation or contamination (the limit of detection lay at 5 mg emodin/kg substrate or 0.3 mg emodin/kg enzyme).

Animals↗
PubMed1984

Selectivity in the control of opiate receptor density in the animal and in cultured fetal brain cells.

Two aspects of the mechanisms controlling down-regulation of opiate receptors were studied: 1. The possibility that morphine does not induce down-regulation of delta receptors is an observation confined to in vitro conditions was investigated by studying the regulation of receptors in neuroblastoma-glioma cells in diffusion chambers implanted in ICR mice peritonea. Injection of morphine for 9 days at a dose inducing opiate tolerance did not change the number of receptors in the chamber-implanted cells, whereas etorphine at a 1/100 dose had a profound effect. 2. Embryonic cells from rat forebrain or hindbrain were cultured with mu type opiate alkaloid (morphine) or peptide (morphiceptin) to further establish the selectivity of opiate action. A partial effect of morphiceptin but not morphine on the number of receptors in hindbrain aggregates was observed. Thus, conclusions derived from experiments with morphine may not be applicable to mu type peptides. The results suggest that the mammalian brain may contain sub-types of mu receptors. Alternatively, although interacting with a common mu receptor, morphine and mu opioid peptides may induce different regulatory mechanisms.

Animals↗
PubMed1984

Approach to quality assurance in an emergency department: a one-year review.

The Joint Commission on Accreditation of Hospitals requires that an organized quality assurance program be in place for all emergency departments under its review. The authors' institution has had a quality assurance program since 1978. The program is structured to assess medical records against pre-established standards of medical care; to review all radiologic, electrocardiographic and bacteriologic culture reports to avoid discrepancies following initial clinical intervention; and to analyze all emergency department deaths. A review of this program was undertaken for the year 1982 to assess outcome and benefit. Of 74,760 charts reviewed, 744 did not meet the pre-established standards. Seventy-seven patients were asked to return to the emergency department at once. Three hundred fourteen radiographs were initially misread by clinicians and 63 patients were called back for immediate reexamination. Seventy-four electrocardiograms were initially misinterpreted, and 21 patients required urgent call-back. One hundred eighteen patients with positive urine cultures and 35 patients with positive throat cultures were not treated or were incorrectly treated during their initial visit. These patients were notified of the need for additional therapy. There were 158 emergency department deaths, and 11 were thought to have been possibly preventable.

Emergency Service, Hospital↗
PubMed1984

A unique human B lymphocyte antigen defined by a monoclonal antibody.

We produced a hybridoma designated 4G7 from a mouse immunized with chronic lymphocytic leukemia cells. The 4G7 hybridoma secretes an IgG1 antibody that is specific for normal and malignant B lymphocytes. Using dual color immunofluorescence staining, this antibody reacted with all immunoglobulin-positive cells but no T cells in normal peripheral blood. There was no detectable 4G7 antigen on monocytes, platelets, red cells, granulocytes, or phytohemagglutinin-activated T cells. When PBL were depleted of 4G7 positive cells and stimulated with pokeweed mitogen, secreted immunoglobulin levels fell to less than 10% of control values on Day 5 and less than 1% of control on Day 7. This antibody was reactive with 155 of 176 B lineage neoplasms on which it was screened. Thirty-five cases of myeloid or T-lymphoid malignancy were negative. Our studies show that the 4G7 antigen modulates in the presence of excess antibody. Free 4G7 antigen was not found circulating in human serum. The cell surface antigen identified by 4G7 was sensitive to pronase proteolysis but resistant to trypsin and chymotrypsin digestion. A comparison of 4G7 with other known B-cell antibodies indicates that the 4G7 antigen has not been previously identified. This antibody is of use for the identification of normal B lymphocytes, the study of B-cell differentiation, and the characterization of lymphoid malignancies.

Animals↗
PubMed1984

Pan-leukocyte monoclonal antibody L3B12. Characterization and application to research and diagnostic problems.

In this report, the authors describe a murine anti-human monoclonal antibody, L3B12, which defines a pan-leukocyte cell surface antigen of approximately 180,000 m.w. Extensive screening against a variety of tissues indicates that L3B12 is sensitive and specific for leukocytes, related cells of bone marrow lineage, and their corresponding neoplasms. Unlike many lymphoid antigens that are not detectable following routine fixation and embedding, those recognized by L3B12 and related antibodies are variably preserved. L3B12 has proven useful in studying the antigen expression of normal leukocytic elements, lymphomas, and related disorders, and in enriching or depleting leukocytes from heterogeneous cell populations. From a diagnostic standpoint, L3B12 staining of tissue sections or cell suspensions is useful for distinguishing large cell lymphomas from undifferentiated carcinomas and in distinguishing lymphomas and leukemias from other small round cell tumors of childhood.

Adult↗
PubMed1984

The immunologic characterization of 95 nodal and extranodal diffuse large cell lymphomas in 89 patients.

Ninety-five diffuse large cell lymphomas in 89 patients were stained in cryostat sections with a panel of monoclonal antibodies. Lymphoma cells from 47 patients (53%) expressed either kappa or lambda light chains, usually in combination with mu heavy chains. Fifteen samples from 12 patients (14%) expressed two or more T-cell antigens and commonly expressed Ia antigens. Lymphoma cells from 10 of these patients uniformly lacked one or more pan T-cell antigens; lymphoma cells from 4 of these patients also lacked both T-subset antigens--findings which should prove useful in diagnosis. Lymphomas from 28 patients (31%) did not express immunoglobulin or T-cell antigens but commonly expressed the B-lineage antigen B1; and the remaining 9 cases generally expressed Ia antigens, common ALL antigens, or both. Our findings confirm the marked immunologic heterogeneity of diffuse large cell lymphomas; the phenotypic heterogeneity observed in T-cell cases in many instances is difficult to reconcile with current models of T-cell differentiation.

Antibodies, Monoclonal↗
PubMed1984

Clinical relevance of immunologic phenotype in diffuse large cell lymphoma.

The immunologic phenotypes of 78 diffuse large cell lymphomas were determined by an immunoperoxidase technique using a panel of monoclonal antibodies. The phenotypes were correlated with clinical and morphological parameters by univariate and multivariate analysis. Forty-one lymphomas (53%) expressed immunoglobulin (Ig+). Of the 37 cases that did not express immunoglobulin (Ig-), 9 expressed T cell antigens. Although the T cell phenotypes were antigenically heterogeneous, all cases represented mature T cell phenotypes. The majority of the remaining 28 cases expressed the B cell-associated antigen, B1. At 5 yr, actuarial survival for the Ig- patients was 63%, compared with 15% for the Ig+ patients. A significantly greater proportion of patients with Ig+ lymphomas were over the age of 65 at diagnosis. All of the 9 patients with marrow involvement were Ig+. Multiple factors were analyzed by the Cox regression procedure for their impact on survival, including antigenic profile, histologic grade, morphological classification, and numerous clinical parameters previously recognized to be of prognostic significance. In this analysis, stage, age greater than 65 yr, systemic symptoms, and marrow involvement had the greatest influence on survival. The survival difference between Ig- and Ig+ patients is explained by a higher proportion of Ig+ patients with these unfavorable prognostic factors. With our current immunologic methods, retrospective cell phenotyping analysis has not provided independent prognostic significance in diffuse large cell lymphoma. A prospective evaluation of similarly treated patients is needed to characterize the influence of phenotype fully and to determine its potential usefulness for therapy.

Adolescent↗
PubMed1984

Cellular immunoabsorption using monoclonal antibodies. Selective removal of T cells from peripheral blood and bone marrow.

T cells can be selectively removed from human peripheral blood and bone marrow by passage over a column containing monoclonal anti-T-cell antibodies covalently attached to Sepharose 6MB gel. Effective depletion of T cells from peripheral blood mononuclear cells (PBMC) resulted in the appearance of Leu-2-positive cells, most of which do not express Leu-1 or Leu-4 antigens. Using a column containing anti-Leu-1 or anti-Leu-4 attached to Sepharose 6MB gel, depletion of 98.3% and 99% of T cells from bone marrow mononuclear cells (BMMC), respectively, was demonstrated with recovery of approximately 75% of non-T cells. These columns removed 92.3-98.4% T cells from PBMC with 43.5-74.8% recovery of non-T cells. Combining anti-Leu-1 and anti-Leu-4 antibodies on the same gel removed all detectable T cells from PBMC and BMMC. Proliferative responses to the T cell mitogen, phytohemagglutinin, were abolished from both PBMC and BMMC after column treatment. Preservation of hematopoietic progenitors was observed after treatment of bone marrow, with stem cell recovery averaging 83 +/- 26% for burst-forming units (erythroid), 86 +/- 14% for granulocyte-macrophage progenitors and 94 +/- 16% for granulocyte, erythroid macrophage, and megakaryocitic elements. These results suggest that clinical application of cellular immunoabsorption techniques using monoclonal antibodies will be useful in bone marrow transplantation.

Antibodies, Monoclonal↗
PubMed1984

Li efflux in erythrocytes of pregnant women: comparison of rates and temperature dependence for detection of hypertension.

Two determinants of lithium efflux in erythrocytes were compared, in relation to pregnancy: (a) efflux rates at 37 degrees C; (b) efflux temperature dependence, expressed by the 'break' of Arrhenius plots. Eighteen women were studied both at term and after delivery. While efflux rates were changed markedly, from 0.87 +/- 0.07 to 0.56 +/- 0.05 mmol/ (IRBC h) at term and post-partum, respectively, the characteristic break temperature of each woman remained essentially constant during and after pregnancy. The property of temperature dependence is more suitable than efflux rates for differentiation of hypertension during pregnancy.

Adult↗
PubMed1984

Strategies for production of monoclonal anti-idiotype antibodies against human B cell lymphomas.

Murine monoclonal antibodies (MAB) against the idiotype (Id) of B lymphocyte malignancies are powerful reagents for the study of these diseases, and are potentially useful for treatment. Different strategies for the production of these anti-Id MAB have been compared. Initially, the Id Ig from nonsecreting B cell tumors was "rescued" by human X mouse or human X human hybridization. These somatic cell hybridizations resulted in the secretion of human Ig in 10 and 100% of the fusions, respectively. In a second step, anti-Id MAB were produced by using the "rescued" Id Ig as immunogen. A more streamlined approach is based on a one-step procedure in which the tumor cell suspension is used as immunogen. This method of immunization, coupled with a four-layer ELISA, results in the detection of anti-Id MAB in a frequency of approximately 1% of the total hybrids. By using a pool of 10 different anti-Id MAB, each reactive with the tumor of one patient, we searched for idiotypic relatedness among a panel of 50 additional tumors. No cross-reactions were found, indicating that our current strategy results in the identification of unique idiotypic determinants among human B cell tumors. Idiotypic Ig can be found in the serum of patients with B cell tumors. Among groups of patients, there is a wide spectrum of serum Id levels, ranging from less than 0.01 microgram/ml to greater than 500 micrograms/ml.

Animals↗
PubMed1984

Carcinomas of the thyroid gland invading larynx and trachea.

Twenty-nine patients with a thyroid carcinoma invading the larynx and trachea were treated over a 25-yr period. Eight patients had invasion of the walls of the trachea or larynx and 21 had invasion into the lumen. Of the 15 patients who underwent limited surgery, i.e. total thyroidectomy, tracheostomy and neck dissection, 8 had intraluminal invasion and 7 suffered from bleeding into the trachea or airway obstruction. In contrast, none of the 13 who underwent extensive surgery, i.e. thyroidectomy, laryngectomy, partial resection of the trachea and one resection of the pharynx, (12 of whom had intraluminal invasion) showed either bleeding into the trachea or airway obstruction. Although the prognosis was no better in the group undergoing extensive operation there is the feeling that in cases with intraluminal invasion extensive surgery is indicated to prevent the severe airway difficulties which often develop in such patients.

Adult↗