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M Menon

Publications and source records attributed to M Menon.

At least 127 records · Page 7Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

The role of plasma lipoproteins in steroidogenic response of rat luteal cells during gonadotropin-induced refractory states.

Administration of human chorionic gonadotropin (hCG) to pregnant mare's serum gonadotropin--hCG primed rats results in the loss of in vitro responsiveness of the ovaries to exogenous gonadotropins for progesterone production. This state is associated with a loss of membrane receptors for hCG and a concomitant increase in lipoprotein receptors. Although lipoproteins potentiated gonadotropin response in ovaries from saline-injected rats, no stimulation was observed in hCG-desensitized ovarian cells. Examination of the time course for the loss of lipoprotein response after hCG injection revealed that injection with 50 IU of hCG results in a loss of gonadotropin response as early as 1 h after injection, but exogenous cholesterol-carrying lipoprotein fractions, LDL and HDL, were capable of stimulating progesterone production up to 4 h after hormone injection. Measurement of endogenous cholesteryl ester content showed that there was a 72% decline during this period with a concomitant increase in the basal progesterone production. One hour after hCG injection there was no stimulation of steroidogenesis by hCG in the presence or absence of exogenous lipoproteins. The refractoriness to exogenous hCG appeared only 4 h later when the hCG dose was reduced to 10 IU, whereas with 25 IU of hCG, the effect was similar to that observed using 50 IU of hCG. Such diverse steroidogenic stimuli as hCG, LH, LDL, cAMP, and cholera enterotoxin failed to stimulate progesterone synthesis in vitro in luteal cells of rats injected with 50 IU of hCG 48 h prior to sacrifice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

"Pan-myeloid" reagent: the monoclonal antibody MCS-2 in the routine immunodiagnostic service of leukemia phenotyping.

This retrospective analysis describes the reactivity of several monoclonal antibodies (MoAbs) which detect myelomonocytic antigens of the cells of 182 leukemias. These leukemias were assigned to definite subtypes of lymphocytic and myelo(mono)-cytic leukemias on the basis of standard leukemia phenotyping using morphological, cytochemical, isoenzymatic and mainly immunological criteria. The MoAb MCS-2 was negative in all cases of lymphocytic leukemia, whereas two of the three other commonly used "myeloid MoAbs" MCS-1, OKM-1 and 1/12/13 showed positivity in B-chronic lymphocytic leukemia (B-CLL), B-lymphoma (MCS-1), T-acute lymphoblastic leukemia (T-ALL) and Sézary syndrome (OKM-1). MCS-2 was positive in all samples of acute myelomonoblastic leukemia (AMMoL), chronic myelocytic leukemia (CML) and CML-myeloid blast crisis, which was not the case for MCS-1, OKM-1, or 1/12/13. In 14 cases (11 acute myeloblastic leukemia (AML), 3 CML-myeloid blast crisis) where MCS-2 was positive and one or all of the three other MoAbs were negative, the cells were mainly Ia-positive and peroxidase-negative. MCS-2 is a diagnostically important MoAb in the routine leukemia phenotyping of myelomonocytic leukemias. After having tested a large number of normal and malignant specimens, we would like to term MCS-2 a "pan-myeloid MoAb" reacting with the myelomonocytic cell lineage from the earliest myeloblast to granulocytes and monocytes.

Antibodies, Monoclonal↗

Sterilization failures with bipolar tubal cautery.

From a consecutive series of 105 patients undergoing bipolar tubal sterilization (BPS), ten pregnancies were reported, and a tubal patency rate of 16% was found at hysterosalpingography. There were no significant clinical variables separating the BPS failure patients from those with successful sterilization. Ninety percent of the BPS failures were intrauterine, and 90% occurred within three cycles of BPS. The results of this investigation suggest that (1) BPS tubal occlusion may be associated with an increased failure (pregnancy and tubal patency) rate; (2) the majority of BPS failures are intrauterine gestations; (3) delayed fibrosis, rather than immediate tubal destruction, may be the mechanism of BPS tubal occlusion; (4) for maximum effectiveness, patients undergoing BPS should use alternative contraception for two to three cycles; and (5) surgeons employing BPS require precise training in the application of this modality of female sterilization.

Cautery↗

Effect of orchiectomy and ovariectomy on oxalate production, transport and excretion in rats.

The role of sex hormones on oxalate synthesis by liver, transport by renal cortical mitochondria and urinary excretion was studied in adult male and female Sprague-Dawley rats. Orchiectomy decreased the hepatic synthesis of oxalate whereas ovariectomy increased it by 10 per cent. Castration inhibited oxalate transport by the renal mitochondria uncompetitively in both sexes. Urinary levels of oxalate were unaffected after orchiectomy whereas ovariectomy resulted in an initial elevation in the urinary oxalate levels which returned to control values by 21 days. The results are discussed in light of recent data.

Animals↗