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Biomedical subjects

E Merler

Publications and source records attributed to E Merler.

At least 55 records · Page 3Linked to original sources

A cytogenetic study on workers exposed to low concentrations of benzene.

A cytogenetic study was performed on 22 healthy workers engaged in benzene production and exposed to low concentrations of benzene, ranging from 0.2 to 12.4 p.p.m. (threshold limit value 10 p.p.m.). Workers were divided into two groups according to the different levels of exposure, inferrable also from the concentration of benzene in the alveolar air and the levels of urinary phenols. Each exposed subject was paired with a suitable control, living in the same area and of similar smoking habits and age. No statistically significant increase of sister chromatid exchange (SCE) frequency was observed in the exposed groups. In controls, SCE frequency was positively correlated with age and smoking habits. Among structural chromosomal aberrations, only the chromosome-type ones were significantly higher in exposed than in control subjects, and their increase was still significant when gaps were discarded.

Adult↗

[Mortality from malignant tumors in residents of the city of Verona in 1980].

Malignant tumours mortality among residents of the city of Verona (267,703 at 31-12-1980) during the year 1980 is assessed from the ISTAT individual death cards and/or municipal death certificates (especially in the case of deaths outside the municipality). The figures are broken down by site, apparatus or system (in accordance with the VIII-ICD), sex, age at death, and compared with the Italian mortality figures for 1976 (indirectly standardised) and those for the province of Verona for 1976-77 (directly standardised). Tumour mortality per site was generally higher than the Italian level. This is line with the differences noted between geographical areas and the similarity of the rates in more industrialised areas. A salient finding was that lung tumour mortality exceeded that for the province of Varese, which is among the highest in Italy entered on the Register of Tumours. Genital and breast tumours were responsible for the highest number of deaths in women, while stomach cancer was the second cause of death in both sexes. The study will be completed with an analysis of tumour deaths during 1980 and 1981 in the province of Verona as a whole.

Epidemiologic Methods↗

Mechanisms for the removal of senescent human erythrocytes from circulation: specificity of the membrane-bound immunoglobulin G.

Direct antiglobulin (Coombs') tests of erythrocyte (RBC) subpopulations confirmed the presence of membrane-bound immunoglobulin G (IgG) on old (density greater than 1.110) human RBCs but not on the young (density less than 1.110) RBCs. After thermal elution of the bound IgG, this Coombs' reaction was negative, but incubation of thermally eluted IgG (He-IgG) with heat-treated RBCs induced a positive antiglobulin test. A positive direct antiglobulin reaction was also obtained after incubation of heat-treated RBCs with anti-T antibody. Similar results were obtained when young RBCs treated with Vibrio cholerae neuraminidase (VCN) were incubated with anti-T or with IgG eluted by heat from old RBCs. Nevertheless, pre-absorption of heat-eluted IgG with T and/or Tn antigen, did not prevent it from binding to either heat-treated old or VCN-treated young RBCs as assessed by the antiglobulin consumption assay. Pre-treatment of either VCN-treated young or heat-treated old RBCs with anti-T and/or anti-Tn antibodies had no significant effect on the binding of radiolabeled He-IgG (eluted from old RBCs). The results indicate that even though desialylation of the erythrocyte membrane is required for binding of both anti-T-Tn and He-IgG, the specificity and consequently the RBC binding sites for He-IgG and anti-T seem to be different.

Antigens, Tumor-Associated, Carbohydrate↗

Is schizophrenia an immunologic receptor disorder?

A model is proposed for an autoimmune etiology for schizophrenia. We propose that schizophrenia is a syndrome (not a disease). We suggest that autoantibodies (and/or cell-mediated immunity) directed against autologous neurotransmitter receptors are responsible for the ebb and flow of psychotic symptomatology. The hypothesis is predicated on autoimmune models in other known receptor diseases as well as on the newly emerging recognition that general immune dysfunction exists in certain schizophreniform psychoses.

Antibody Formation↗

In vitro humoral immune response of human peripheral blood lymphocytes to tetanus toxoid sepharose 4B.

The in vitro immune response of unfractionated human peripheral blood lymphocytes (PBL) from immune donors who had not been re-immunized with tetanus toxoid (TT) prior to donation was investigated. In this study we were able to stimulate PBL with tetanus toxoid coupled to Sepharose 4B (STT) for production of anti-tetanus toxoid antibody (Ab). Soluble tetanus toxoid or STT alone did not stimulate production of specific Ab. Pokeweed mitogen (PWM) and STT were required for optimal production of IgG and IgM antibodies specific to tetanus toxoid. Specific Ab responses were reduced in low and high concentrations of STT. Depletion of monocytes had no effect on either total IgG or specific IgG synthesis, but decreased the synthesis of both total and specific IgM. Depletion of E-rosette-forming cells decreased the production of specific Ab, suggesting T-dependency of the immune response to STT. Simultaneous production of total immunoglobulin and specific Ab by Sepharose 4B was negligible in the absence of PWM. In the presence of PWM, total immunoglobulin production was optimal, and specific anti-TT Ab production was undetectable. The specificity of the anti-TT Ab was studied by absorption of the culture supernates with an STT column which removed all measurable specific Ab.

Antibody Formation↗

Altered heterogeneity of monocytes in acute myelomonocytic leukemia.

Human peripheral blood monocytes isolated from normal donors and patients with acute myelomonocytic leukemia (AMML) were separated on a discontinuous density gradient of bovine serum albumin (BSA) into five fractions. Cells from each fraction were assayed for cell surface markers, prostaglandin E2 (PGE2) production, ability to affect proliferation in response to antigen by autologous peripheral blood lymphocytes previously depleted of monocytes, and ability to regulate immunoglobulin (Ig) synthesis by allogeneic B-lymphocytes. Fractions 1-5 from normal donors contained 11, 10, 23, 34, and 22%, respectively, of the total number of monocytes. In contrast, in 6 patients with AMML fraction 3 was considerably larger (52%) than any other fraction, in 1 patient comprising 87% of her monocytes. Cells from each fraction differed markedly in accessory function. In general, cells from fraction 3 were poorer as helper cells than cells from other fractions. They also produced after stimulation larger amounts of PGE2 than did cells from other fractions of the gradient. These data show that PBL contain a subpopulation of monocytes, which either helps poorly or suppresses in vitro immunologic function of T-cells (proliferation) and B-cells (lg synthesis), and that this subpopulation is increased in the blood of patients with AMML.

B-Lymphocytes↗

Modulation of human monocyte functions by Fc fragments of IgG: a comparison to other monocyte 'activators'.

Human monocytes were maintained in tissue culture and the effect of various stimuli on their morphology and capacity to synthesize and secrete total protein, lysozyme, acid phosphatase, prostaglandin E and the second component of complement were determined. Human monomeric IgG, Fab fragments and albumin had no effect on the secretion of these products. However, addition of Fc fragments significantly decreased the synthesis of both lysosomal enzymes and the second component of complement and increased production of prostaglandin E. The addition of Con A to the monocyte monolayers resulted in a similar response. Latex particles slightly increased the secretion of acid phosphatase and C2, but had no effect on lysozyme secretion. Fc fragments also stimulated protein synthesis by monocyte monolayers cultured in serum-free medium. These 'activators' and endotoxin- or antigen-activated mononuclear cell supernatants (AMNS) resulted in varying degrees of increased spreading and adherence of the monocytes. The results of these studies suggest that the molecular species inducing the 'activated state' qualitatively and quantitatively determines the characteristics of the secretory response.

Acid Phosphatase↗

Role of lipids in the immune response. I. Localization to a lipid-containing fraction of the active moiety of an inhibitor (SIF) of lymphocyte proliferation.

By further study, a previously described inhibitor of lymphocyte proliferation and immunoglobulin synthesis, soluble inhibitory factor (SIF), has been shown to comprise two moieties; a nondialyzable protein, apparently inert with regard to inhibition of proliferation, and a polar lipid bound to the protein fraction, presumably by hydrophobic interaction. The lipid contained the activity responsible for inhibition of PHA-induced DNA synthesis. It was tentatively identified as a lipid with an as yet unidentified polar group, on the basis of mobility on thin layer chromatographic plates and behavior on silicic acid.

Amino Acids↗

Purification and biochemical characterization of human lymphocyte mitogenic factor (LMF).

Supernatants of human T lymphocytes stimulated by TT antigen release two factors that induce mitogenesis in autologous and allogeneic B lymphocytes. These factors are precipitated by 60% ammonium sulfate and 50% ethanol, and are both destroyed by heating to 70 degrees C for 5 min. By equilibrium ultracentrifugation there was a peak of mitogenic activity in the fraction with a specific gravity of 1.3147 corresponding to a partial specific volume of 0.761. After ultrafiltration through an Amicon XM50 membrane, the concentrate was chromatographed on a Sephadex G-200 column. Mitogenic activity was found only in the post-albumin fraction. When the post-albumin fraction was run on an isoelectrofocusing column, two distinct mitogenic factors were identified. The major peak of mitogenic activity (LMF) had a pI of 6.68 +/- 0.05 and the minor peak (MMF) had a pI OF 7.27 +/- 0.05. Amino acid analysis of LMF identified it as a protein and PAGE showed that LMF probably was a tetramer with a m.w. of 80,000.

Amino Acids↗

Role of lipids in the immune response. II. An enhancer of antibody production (APS) that is a lipid closely associated with lymphocyte mitogenic factor (LMF).

Lymphocyte mitogenic factor (LMF) is a lymphokine produced by dividing T cells. An activity coeluting with LMF from a Sephadex resin is extractable from LMF with chloroform-methanol. It enhances but does not initiate antibody formation measured by generation of plaque-forming cells (PFC). It does not cause proliferation of B cells. This activity elutes from a silicic acid column and produces a pattern on thin layer chromatography that suggests that the compound(s) responsible for the activity is a polar lipid.

Antibody Formation↗

Increased prostaglandin production by human monocytes after membrane receptor activation.

Human monocytes in culture release small amounts of prostaglandin E (PGE) into the medium. Addition of Fc fragments of IgG to human monocyte monolayer cultures results in a marked increase in PGE release; Fab fragments, monomeric IgG, and human serum albumin have no effect. An IgG1 myeloma has no effect on PGE levels but addition of the heat aggreagted protein results in a marked increase of PGE secretion. Exposure of the cells to Con A, which binds to a specific monocyte plasma membrane receptor, also results in a large increase in PGE release. The magnitude of the increase in PGE secretion produced by exposure of the monocytes to these ligands greatly exceeds the stimulation observed after the addition of antigen-activated mononuclear cell supernatants, zymosan, Sephadex beads, or endotoxin, to monocyte cultures. Prostaglandin E2 (PGE2) accounts for approximately 70% of the total prostaglandins released by stimulated cells. After addition of Indomethacin to monocyte cultures, the stimulatory effects of the ligands on PGE release are inhibited. Addition of Con A to monocyte cultures results in an increased incorporation of [3H]-arachidonic acid into PGE2. These results suggest that this ligand stimulates synthesis as well as release of this prostaglandin.

Binding Sites↗

Human erythroid burst-forming unit: T-cell requirement for proliferation in vitro.

Human mononuclear leukocytes were fractionated into populations of null, T and B cells by immunoabsorbent column chromatography followed by E-rosette formation and purification of T cells by differential centrifugation and osmotic lysis. The unfractionated and fractionated cell populations were first separately cultured for 14 days in plasma clots in the presence of two international units erythropoietin. Typical erythroid burst-forming unit (BFU-E)-derived colonies grew in the unfractionated cell cultures but not from T- or B-cell cultures. BFU-E colonies grew in null cell cultures but most of the colonies were small and variably hemoglobinized with less than three subcolonies. When intact T cells were added to null cells and cocultured, many typical large BFU-E colonies with more than 10 well homogenized subcolonies appeared. Increasing numbers of large BFU-E colonies in null cell cultures were induced by stepwise addition of T cells but not by the addition of B cells. A conditioned medium in which T cells had been induced to divide by tetanus toxoid substituted for intact T cells in this T-cell-dependent BFU-E colony formation observed in null cells. These findings demonstrate that the BFU-E, a committeded erythroid stem cell, resides in the null cell fraction of peripheral blood, but its proliferative capacity and differentiation in vitro requires a soluble product of T cells. Such experiments now permit a new approach to the assessment of various disorders of erythropoiesis. Erythroid hypoplasia in a particular case may be due to dysfunction of the committed precursor cell or to a failure of a helper effect induced by T cells.

B-Lymphocytes↗

Cellular requirements for the formation of EA rosettes by human monocytes.

The binding of sensitized red cells to Fc receptors in human monocytes was studied by evaluating the effects of various pharmacological reagents and other treatments on EA rosette formation. Cytochalasin B and 2-deoxyglucose inhibited rosette formation in a dose-dependent manner. Sodium azide and incubation at 4 degrees also inhibited rosette formation, while at 37 degrees increased numbers of RBCs bound to the monocytes. The microtubular poisons, vinblastine and colchicine at high concentrations resulted in decreased adherence of monocytes and inhibition of rosette formation, while at low concentrations of colchicine, enhanced rosette formation was sometimes observed. Contrary to the effects on rosette formation, binding of [125I] IgG to monocyte monolayers was not altered by treatment of the monocytes with drugs. Magnesium ions were required to promote monocyte adherence, but both magnesium and calcium were needed for the best rosette formation. We conclude that the formation of EA rosettes is dependent not merely on binding of IgG to the Fc receptor but requires metabolically active monocytes, an intact cytostructure and suitable environmental conditions (temperature and cation concentration).

Antimetabolites↗

The necessity for T cell help for human tonsil B cell responses to pokeweed mitogens: induction of DNA synthesis, immunoglobulin, and specific antibody production with a T cell helper factor produced with pokeweed mitogen.

Human B lymphocytes obtained from tonsils do not proliferate when stimulated with pokeweed mitogen. A soluble factor produced from T cells cultured with pokeweed mitogen stimulates B cells to synthesize DNA and differentiate into immunoglobulin producing cells. This PWM produced supernatant induced a PFC response to SRBC. The T cell supernatant activity is produced within 12 hr of stimulation in the presence of serum and without a requirement for T cell division. Optimal stimulation of B cells occurred at 7 to 9 days of culture. This helper factor activity eluted postalbumin from a column of Sephadex G-200. Insolubilized pokeweed mitogen was not mitogenic for B cells. The continuous presence of the lectin in culture was not required for B cell proliferation or for immunoglobulin synthesis.

Antibody Specificity↗