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Biomedical subjects

M Menon

Publications and source records attributed to M Menon.

At least 127 records · Page 7Linked to original sources
PubMed1986

Phenotyping of malignant hematopoietic cells. Analysis of 1200 cases of leukemia-lymphoma.

1255 cases of leukemia-lymphoma were tested between 1972 and 1984 by multiple marker analysis. Routine leukemia phenotyping was performed using standard morphological and cytochemical techniques in combination with clinical and histo-pathological information; the main emphasis was put on immunological surface marker analysis using erythrocyte rosette assays, TdT and a large panel of poly- and monoclonal antibody tests. The 1255 cases were divided into these major types and subtypes: 349 cases of ALL and related immature T- and Burkitt-lymphomas (cALL, pre B-ALL, B-ALL and Burkitt-lymphomas, T-ALL and immature, mostly leukemic T-lymphomas, Null-ALL), 454 cases of mature T- and B-cell malignancies (T-CLL, mycosis fungoides, Sezary-syndrome, T-lymphomas, B-CLL, hairy cell leukemia, multiple myeloma, B-lymphomas), 263 cases of acute myeloid leukemias (AML, AMMoL/AMoL), 182 cases of chronic myeloid leukemias (CML in chronic phase, CMoL, CML in blast crisis), 6 cases of erythroleukemia and 1 case of megakaryoblastic leukemia. A simplified classification scheme which has been used in our laboratories is presented. Phenotyping is of diagnostic, prognostic and therapeutic relevance, most evidently for patients with ALL. Routine leukemia phenotyping should be performed with highly standardized techniques and reagents and by combining information from several fields in the multiple marker analysis. New areas of leukemia research might become very useful for the routine procedure of phenotyping.

Adult↗
PubMed1986

Inhibition of gonadotropin-releasing hormone receptors in rat anterior pituitary monolayer cell cultures by danazol.

To study possible cellular antigonadotropic effects of danazol, monolayer cultures of anterior pituitary cells from immature female rats were treated with danazol. Measurements of luteinizing hormone release in response to 10(-8) mol/L gonadotropin-releasing hormone challenge and iodine 125-labeled gonadotropin-releasing hormone binding activity were done after exposure to increasing concentrations of danazol and for increasing lengths of time. It was found that luteinizing hormone secreted by pituitary cells in response to gonadotropin-releasing hormone was inhibited after danazol treatment in a dose- and time-dependent manner when compared to controls. Also, a 45% decrease in gonadotropin-releasing hormone receptor binding capacity was observed in pituitary cells cultured in the presence of increasing concentrations of danazol in the range of 10(-8) to 10(-4) mol/L when compared to controls. Furthermore, exposure to danazol for 25 to 96 hours caused a marked decrease in gonadotropin-releasing hormone binding activity (p less than 0.005). Under these experimental conditions danazol treatment decreased the pituitary receptors for gonadotropin-releasing hormone in a dose- and time-dependent manner. Scatchard analysis of saturation curves for the binding of gonadotropin-releasing hormone to cellular gonadotropin-releasing hormone receptors indicated that the observed decrease in gonadotropin-releasing hormone binding in the danazol-treated group was due to a change in the number of gonadotropin-releasing hormone binding sites rather than a change in the affinity. It is therefore concluded that the antigonadotropic activity of danazol appears to be related to a decrease in gonadotropin-releasing hormone receptors in the pituitary.

Animals↗
PubMed1986

Reactivity pattern of 'myeloid monoclonal antibodies' with emphasis on MCS-2.

The reactivity pattern of the murine monoclonal antibody (MoAb) MCS-2 was tested on a panel of 724 cases of leukemia-lymphoma. MCS-2 was positive in 178/185 (96%) cases of AML (FAB M1-3), 10/10 cases of AMMol/AMoL (FAB M4/5), 42/45 (93%) cases of CML, 1/1 case of CMoL, 37/38 (97%) cases of CML-myeloid blast crisis, 0/9 cases of CML-lymphoid blast crisis. No positive staining was seen in 238 cases of T-CLL, mycosis fungoides, Sèzary-syndrome, B-CLL, hairy cell leukemia, multiple myeloma and T- and B-lymphoma nor in 32 cases of B-ALL, Burkitt-lymphoma, Null-ALL and immature T-lymphoma. A positive expression was found in 8/110 cases of cALL, 1/6 cases of pre B-ALL and 1/35 cases of T-ALL. Fifteen other MoAbs (MCS-1, OKM1, My-1, Leu-M1, Leu-M3, CA-2-38, MY4, MY7, MY8, MY9, VIM-D2, VIM-D5, Mol, Mo2, 63D3) which are associated with the myelomonocytic cell lineages were tested by indirect immunofluorescence on 60 or more patients (62-149 cases). A wide variability in the frequency of positivity was seen for the panel of cases studied and for the blast cell populations per individual samples: 21-96% of the AML cases (FAB M1-3) and 31-100% of the AMMoL/AMoL cases (FAB M4/5) were positive for the various MoAbs. None of the analysed MoAbs stained only myelocytic or only monocytic leukemias, but a certain degree of preference for the monocytic variants was noted for Leu-M3, CA-2-38, MY4, VIM-D2, Mo2 and 63D3. The detection of MCS-2 on immature ALL blast cells might indicate a coexpression of lymphoid and myeloid markers on very immature cells, or an abnormal gene expression by malignant cells, or the identification of a so far undetected subclass of acute leukemias.

Adult↗
PubMed1986

Heterogeneity of marker expression in B-cell leukemias and its diagnostic significance.

Lymphoproliferative disorders of B-cell origin are identified by surface immunoglobulin markers. Clinically, these include several types of leukemias and lymphomas. We have attempted to further characterize B-cell leukemias immunologically using monoclonal antibodies Leu-1 and FMC-7. While cases of classical B-CLL have been shown to react with Leu-1 monoclonal, most other B-cell leukemias often do not react with Leu-1. Our results show that use of an additional monoclonal FMC-7 does not contribute towards diagnostic reliability.

Antibodies, Monoclonal↗
PubMed1986

Binding of oxalate to mitochondrial inner membranes of rat and human kidney.

Oxalate bound specifically to homogenates of rat kidney and liver but not to homogenates prepared from heart, lung, skeletal muscle, spleen, stomach, small or large intestine. In the renal cortex, binding was localized to the inner mitochondrial membrane where it was enriched fourfold when compared to homogenate. Binding of the oxalate reached equilibrium in two minutes at 23C. Analysis of the binding sites by Scatchard plot indicated that the maximum binding capacity was 49 pmol./mg. protein and the apparent dissociation constant (Kd) was 43 nM. The IC50 of oxalate was 0.25 microM. Among the inhibitors studied the IC50 was in the following order: oxalate less than oxamate less than parabanate less than glyoxalate less than oxaloacetate less than malate less than citrate = glycollate. Heat and treatment with lubrol abolished the binding completely. Binding was not enhanced by the presence of calcium in the incubation medium; neither was it inhibited by the presence of calcium together with its transport inhibitors. A binding substance with some characteristics similar to the rat mitochondrial binding factor was also found in the human renal cortex.

Animals↗
PubMed1986

A case of TdT-positive B-cell acute lymphoblastic leukemia.

The phenotypic marker profile of a patient with B-cell acute lymphoblastic leukemia (B-ALL) is described. The blast cells showed typical FAB L3 morphology, had the characteristic t(8;14) chromosomal abnormality, and were monoclonal in the expression of surface immunoglobulins. The clinical course of this patient is consistent with the poor prognosis described for B-ALL cases. Surface marker analysis identified cells positive for surface immunoglobulins, Ia-like antigen, common ALL-antigen, and terminal deoxynucleotidyl transferase. This marker profile shows immunologic characteristics of the two B-cell leukemia subtypes, pre-B-ALL and B-ALL. This "intermediate" immunologic phenotype might either be the result of an uncoupling of the sequential immunologic maturation processes or of an arrest of the cells at an intermediate stage between the two otherwise clearly defined leukemia subtypes, but closer to the typical B-ALL stage. This latter observation is supported by isoenzyme marker analysis, as the cells were negative for the hexosaminidase I isoenzyme, which is positive in pre-B-ALL but negative in B-ALL.

Acute Disease↗
PubMed1986

Monocyte-associated acid phosphatase isoenzyme profiles as determined in acute myeloid leukaemia cells.

The acid phosphatase (acP) isoenzymes from the blast cells of 102 cases of acute myeloid leukaemia were separated by isoelectric focusing on horizontal polyacrylamide gels. The cases were classified on the basis of the FAB cooperative group criteria. Several single bands were combined into groups (I-IV). An increase in the number of acP isoenzymes was noted which paralleled the assumed maturation along the granulocytic cell lineage from FAB M1 to FAB M3 and along the monocytic cell lineage from FAB M4 to FAB M5. One isoenzyme which was resistant to tartrate inhibition was found in 40% of the monocytic variants FAB M4 and M5, but not in the nonmonocytic cases FAB M1-M3 and M6. This particular isoenzyme, which has been described as being characteristic for hairy cell leukaemia, also appears to be a marker of the monocyte/macrophage system and the respective neoplastic counterparts. The FAB M4 and M5 patients expressed a characteristic profile of group I isoenzymes which allows for the discrimination between monocytic and nonmonocytic cells.

Acid Phosphatase↗
PubMed1986

Diagnostic value of immunological leukemia phenotyping.

The diagnostic value of immunological leukemia phenotyping using a panel of reagents in immunofluorescence assays was assessed in 309 consecutive patients. The cells from 307 patients could be clearly phenotyped and assigned to one of the subgroups with a definite immunophenotype. Each phenotype was characterized by a distinct marker profile. A simplified classification scheme based on surface antigen expression is presented. A combination of complementary reagents ('first panel') was used for the first-line screening. The application of selected reagents from the 'second panel' allowed for further subtyping and confirmation of the primary diagnosis. The contribution of different key reagents to the identification of distinct immunophenotypes is discussed. Multiple marker analysis, i.e. the combination of information from several disciplines, is a necessary and very useful tool in the routine investigation of patients with hematopoietic malignancies.

Antigens, Neoplasm↗
PubMed1986

Incidence of TdT positivity in cases of leukemia and lymphoma.

The expression of the enzyme marker terminal deoxynucleotidyl transferase (TdT) was examined by immunofluorescence assay in the cells from 333 cases with various types and subtypes of leukemia or lymphoma. More than 90% of cALL and T-ALL, 70% of Null-ALL and 80% of pre-B-ALL were TdT-positive. One case in the commonly TdT-negative group of B-ALL showed TdT-positive cells. All cases of mature B-cell malignancies (B-CLL, hairy cell leukemia, B-cell lymphoma) have been TdT-negative. In the group of mature T-cell malignancies, T-CLL and mycosis fungoides were negative and 2 out of 6 mature T-cell lymphomas were TdT-positive. 13% of acute myeloid leukemias and 36% of CML in blast crisis expressed TdT. Therefore, these TdT-positive cases of CML in blast crisis also carrying the common ALL-antigen belong to the lymphoid subtype. CML and erythroleukemia were invariably TdT-negative. TdT has become an indispensable indicator of immature lymphoid leukemia cells and is particularly valuable as part of the panel of markers used in leukemia phenotyping.

B-Lymphocytes↗
PubMed1986

Correlation of surface marker expression with morphologically and immunologically defined subclasses of acute myeloid leukaemias.

The expression of myeloid-associated cell surface antigens detected by monoclonal antibodies (MoAb: MCS-2, MCS-1, MY7, MY9, Leu-M1, OKM1, VIM-D5, Mol, My-1, MY8, MY4, Leu-M3, VIM-D2, Mo2) of the HLA-DR/Ia-like antigen and of the Fc-receptor was determined on the blast cells from 91 patients with acute myeloid leukaemias classified as M1-M5 in the French-American-British (FAB) system. The surface antigen analysis revealed a highly heterogeneous reaction profile. Nevertheless, distinctive patterns of marker expression referring to morphologically defined subgroups were delineated. Several MoAb (especially MCS-2 and MY7 which were positive in most cases of the five FAB subgroups) appear to be useful for the recognition of myelomonocytic cells regardless of the commitment to either the granulocytic or monocytic cell lineage whereas other Mo Ab (especially MY4, Leu-M3, VIM-D2, Mo2) react predominantly with the monocytic variants and are helpful in the identification of monocytic commitment. The 91 cases could be divided into three immunologically defined phenotypes (Types I-III) corresponding to sequential differentiation levels. Correlations of these MoAb-defined phenotypes with the FAB subtyping showed that immunological and morphological classifications are not completely concordant and that only the parameters Type I and FAB M1 were significantly related. A scheme of early myeloid differentiation sequences based on the expression of surface antigens is presented.

Adult↗
PubMed1985

Estradiol potentiation of gonadotropin-releasing hormone responsiveness in the anterior pituitary is mediated by an increase in gonadotropin-releasing hormone receptors.

In order to investigate the mechanism by which 17 beta-estradiol potentiates the action of gonadotropin-releasing hormone on the anterior pituitary in vitro, cultured pituitary cells from immature female rats were used as the model system. Cultures exposed to estradiol at concentrations ranging from 10(-10) to 10(-6) mol/L exhibited a significant augmentation of luteinizing hormone release in response to a 4-hour gonadotropin-releasing hormone (10 mumol/L) challenge at a dose of 10(-9) mol/L compared to that of control cultures. The estradiol augmentation of luteinizing hormone release was also dependent on the duration of estradiol exposure. When these cultures were incubated with tritium-labeled L-leucine, an increase in incorporation of radiolabeled amino acid into total proteins greater than that in controls was observed. A parallel stimulatory effect of estradiol on iodine 125-labeled D-Ala6 gonadotropin-releasing hormone binding was observed. Cultures incubated with estradiol at different concentrations and various lengths of time showed a significant increase in gonadotropin-releasing hormone binding capacity and this increase was abrogated by cycloheximide. Analysis of the binding data showed that the increase in gonadotropin-releasing hormone binding activity was due to a change in the number of gonadotropin-releasing hormone binding sites rather than a change in the affinity. These results suggest that (1) estradiol treatment increases the number of pituitary receptors for gonadotropin-releasing hormone, (2) the augmentary effect of estradiol on luteinizing hormone release at the pituitary level might be mediated, at least in part, by the increase in the number of binding sites of gonadotropin-releasing hormone, and (3) new protein synthesis may be involved in estradiol-mediated gonadotropin-releasing hormone receptor induction.

Animals↗
PubMed1985

High concordance between marker profiles of 22 human leukemia-lymphoma cell lines tested with the same monoclonal antibodies before and during the second international workshop on human differentiation antigens.

Our laboratory participated in the Second International Workshop and Conference on Human Leucocyte Differentiation Antigens. In this international study the reactivity profiles of monoclonal antibodies were analyzed on normal and malignant hematopoietic cells. The Workshop was divided into three categories: the T-cell, B-cell and myelomonocytic cell studies. We blindly tested 159 coded monoclonal antibodies of the panel for the T-cell study on 22 permanently established leukemia cell lines. The monoclonal antibodies were provided by the Workshop Committee and their reactivity with the target cells was visualized by standardized indirect immunofluorescence. After decoding it was recognized that 11 monoclonal antibodies had been examined on these cell lines prior to the Workshop. The reactivity of these 11 monoclonal antibodies was analyzed and compared with the earlier results. From a total of 217 paired tests done blindly in the Workshop study and prior to the Workshop, 191 tests (88%) did not show significantly different data. The possible reasons for discrepancies include nonspecific Fc-receptor-binding on some cell lines and a relatively nonspecific reactivity of some monoclonal antibodies. This analysis demonstrates the stability of the antigen expression on human leukemia-lymphoma cell lines grown at consistently optimal conditions, for the tests, using the same monoclonal antibodies as in the Workshop, had been performed 0.5-5 years prior to the Workshop study. On the other hand, nonspecific Fc-binding, wide "specificity" of monoclonal antibodies and a shift in antigen expression of the cells (due to poor growth conditions, involuntary induction of differentiation and other factors) must be taken into consideration upon immunological analysis.

Antibodies, Monoclonal↗
PubMed1985

Association of decreased natural and antibody-dependent cellular cytotoxicity and production of natural killer cytotoxic factor and interferon in neonates.

Cord blood lymphocytes (CBL) were compared with adult peripheral blood lymphocytes (a-PBL) for their: (i) natural killer (NK) and antibody-dependent cellular cytotoxic (ADCC) activities, (ii) target-binding capacity, (iii) ability to induce soluble natural killer cytotoxic factor (NKCF), (iv) interferon (IFN)-, interleukin 2 (IL-2)-, and lectin-induced augmentation of NK activity, and (v) ability to produce IFN against tumor targets in vitro. CBL depleted of adherent cells and Percoll-separated, NK-enriched subpopulations demonstrated significantly lower NK, ADCC, and target-binding activities compared to a-PBL. CBL produced significantly lower levels of NKCF directed against K562 tumor targets in comparison with a-PBL. Although the NK activity of CBL was not stimulated by either IFN or IL-2 to the same levels shown by a-PBL, the percentage enhancement of cytotoxicity of CBL by IFN and IL-2 was greater than that of a-PBL. Lectin-induced enhancement of cytotoxicity was significantly greater for CBL in comparison with a-PBL. Further, the ability of CBL lymphocytes to produce IFN-gamma in vitro against K562 target cells was significantly lower than that of adult PBL. These studies suggest an association between decreased NK, ADCC, and target-binding activities, induction of NKCF and IFN production by CBL, and increased susceptibility of neonates to infection.

Adult↗
PubMed1985

Lipoprotein augmentation of human chorionic gonadotropin and prolactin stimulated progesterone synthesis by rat luteal cells.

A collagenase dispersed cell suspension from PMSG-hCG primed immature rats responded to exogenously added hCG, cholera enteroxin, prolactin, and 8-Bromocyclic-AMP with increase in progesterone production in a dose dependent manner, and this stimulation was augmented by the plasma lipoprotein fractions hHDL and hLDL. The responsiveness to low doses of prolactin was not apparent when lipoprotein fractions were not included in the assay mixture. When the incubation mixture contained either LDL or HDL, the stimulatory effect of prolactin on progesterone production was evident at 5 and 10 micrograms prolactin/ml of the incubation mixture. Progesterone production, both basal and hormone stimulated, was maximum on day 7 of pseudopregnancy. Although the extent of hCG and prolactin stimulation of progesterone production and its potentiation by lipoprotein fractions was observed to be higher on days 3 and 5 than that seen on day 7, the net amount of progesterone produced was highest on day 7. The basal as well as hormone and lipoprotein stimulated progesterone production started to decline after day 7, reaching a nadir on day 14. These experiments show that prolactin is effective in stimulating progesterone production by rat luteal cells in vitro and that lipoprotein fractions, LDL and HDL further potentiate this response. This study further suggests that it is important to include LDL or HDL as a source of cholesterol for in vitro experiments in which the steroidogenic response of luteal cells to exogenous stimuli is tested.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1985

Expression of a monocyte-specific esterase isoenzyme in cases of acute myeloid leukemias.

The carboxylic esterase (E.C. 3.1.1.1) isoenzymes from cases of acute myeloid leukemias were separated by analytical isoelectric focusing on horizontal thin-layer gels. One isoenzyme consisting of one or two components (bands) could be completely and selectively inhibited by addition of 40 mM sodium fluoride (NaF) to the staining bath. The 105 cases were classified into the groups M1-M6 according to the FAB proposals. The NaF-sensitive isoenzyme was not detected in cases of FAB groups M1/2 (acute myeloblastic leukemia without or with maturation), group M3 (acute promyelocytic leukemia) or group M6 (erythroleukemia). Thirty-one out of 33 cases in the FAB group M4 (acute myelomonocytic leukemia) and 9/9 cases in FAB group M5 (acute monocytic leukemia) expressed the NaF-sensitive isoenzyme. The NaF-sensitive isoenzyme was found at different staining intensities; all M5 cases showed the isoenzyme at strong or very strong intensity, whereas most of the M4 cases displayed the isoenzyme at weak, medium or strong staining intensity. The data presented are further evidence that the presence of the NaF-sensitive esterase isoenzyme indicates monocytic involvement or differentiation in cases of myeloid leukemias. The easy and fast to perform method of isoelectric focusing can be used to distinguish the monocytic variants among the acute myeloid leukemias and can supplement the morphological analysis of these cases.

Carboxylic Ester Hydrolases↗
PubMed1985

Effects of 2-deoxy-D-glucose on glycolysis, proliferation kinetics and radiation response of human cancer cells.

The effects of 2-deoxy-D-glucose (2-DG) on energy metabolism, cell proliferation kinetics, radiation-induced DNA repair, and micronuclei formation in HeLa cells have been studied. Results show that the 2-DG induced modifications of the radiation effects are biphasic: at high 2-DG concentrations (greater than 2.5 mM), DNA repair is inhibited and manifestation of radiation damage is enhanced as observed by an increase in the radiation (X ray) induced micronuclei formation; lower concentrations of 2-DG (less than 2.5 mM) do not inhibit DNA repair and a decrease in the frequency of micronuclei formation is observed. These data, in correlation with the effects of 2-DG on glycolysis and cell proliferation kinetics, can be explained by the hypothesis that 2-DG induced modifications of radiation effects arise as a result of energy linked differential inhibitions of pathways of repair and fixation of DNA damage. Implications for cancer therapy are discussed.

Cell Division↗