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Biomedical subjects

M C Jacob

Publications and source records attributed to M C Jacob.

54 records · Page 3Linked to original sources

T lymphocytes from invaded lymph nodes in patients with B-cell-derived non-Hodgkin's lymphoma: reactivity toward the malignant clone.

Tumor-infiltrating T lymphocytes (TIL-T) are always present in B-cell-derived non-Hodgkin's lymphoma (NHL). In this investigation, we explored the possibility that collaboration might exist between these cells. TIL-T were isolated from 39 lymph nodes of patients with NHL. In most of the cases, few of them (less than 10%) possessed surface activation receptors CD25 or OKT9. In 80% of the cases, they proliferated in response to recombinant interleukin-2 (rIL-2), but the degree of proliferation was often low as compared with control populations. The influence of irradiated autologous malignant cells on the TIL-T proliferation in response to rIL-2 (40 U/mL) was also investigated: in 38% of the cases, this proliferation was not modified (group O), and in 41% it was higher (group +) and in 21% it was lower (group -). The mechanism of this immune response (specific or not) is not elucidated at present. The definition of these groups was statistically correlated with different parameters of the disease: (1) percentage of TIL-T was higher in group + (44% +/- 17%) than in group O (31% +/- 18%) and group - (24% +/- 15%); (2) B-cell proliferation in centrofollicular lymphomas was more frequently nodular or nodular and diffuse in group + (83%) and O (55%) than in group - (0%); (3) low-grade malignancies in the Working Formulation were more frequent in group + (75%) than in group O (60%) or group - (12%); (4) favorable prognosis evaluated with the Grenoble cytologic classification was more frequent in group + and O (87%) than in group - (12%); (5) actuarial survival curves showed a significantly better prognosis for patients in group +.

Adult↗

Production of granulopoiesis-stimulating and -inhibiting activities by T cells associated with malignant cells in lymphomas.

The possible role of T lymphocytes in the formation of granulomatous reactions seen in certain malignant lymphoid tumours was investigated by measuring the granulopoietic colony-stimulating activity (CSA) and granulopoietic-inhibiting activity (IA) produced by stimulated T-lymphocytes isolated from peripheral blood, spleen and lymph nodes of patients and normal subjects. Lymph-node T-cells from patients with benign lymphoid hyperplasia, B-cell non-Hodgkin's lymphoma (B-NHL), and non-granulomatous Hodgkin's disease (HD) showed no CSA, but the cells produced IA of 40 +/- 23%, 40 +/- 24% and 50.5 +/- 22.5% respectively. The corresponding cells from patients with HD accompanied by granulomatous reactions produced CSA of 6.85 +/- 6.5 u/microliters and IA of 23.5 +/- 21%. The presence of a granulomatous reaction in malignant lymphoma was correlated with the stimulation of granulopoiesis in vitro by T lymphocytes associated with malignant cells. A correlation was demonstrated between neutrophilic and eosinophilic colonies obtained in vitro under the influence of CSA-producing T cells isolated from malignant lymphomas and the neutrophils and eosinophils present in the granuloma. These results showed that tumour-infiltrating T cells play a role in the presence of granulomatous reactions seen in lymphomas. Peripheral-blood T cells from healthy subjects, and from patients with B-NHL, or with HD unaccompanied by granulocytic reactions produced CSAs of, respectively, 5 +/- 0.5 u/microliter, 4.8 +/- 2.2 u/microliters and 5.3 +/- 0.4 u/microliters, and IAs of 45 +/- 18%. 50 +/- 5.5% and 50.5 +/- 7% respectively. The corresponding values for HD patients with granulocytic reactions were CSA. 17 +/- 15.5 u/microliters, and IA, 9.5 +/- 9%. No correlation was demonstrated between neutrophilic colonies obtained in vitro under the influence of HD blood T cells and neutrophils present in blood. Only one correlation was found: between the percentage of eosinophilic colonies and the number of blood eosinophils. HD blood T cells did not seem to explain completely granulocytic reactions seen in blood.

B-Lymphocytes↗

A human monoclonal IgM with autoantibody activities against heparan sulphate and the mitotic spindle.

A monoclonal IgM kappa from a patient with Waldenström's macroglobulinaemia (IgM-Rod) was found to react at temperatures below 28 degrees C with all tissue basement membranes and the cell coat of non-haematopoietic cells. IgM-Rod antibody was directed against heparan sulphate side chains of heparan sulphate proteoglycans as shown by binding in a solid-phase ELISA to heparan sulphate glycosaminoglycans but not to other purified subcomponents of the extracellular matrix; and by specific inhibition of the observed reactivity by heparitinase treatment. IgM-Rod showed cross-reactivity by indirect immunofluorescence with an as yet unidentified structure expressed in the nucleus during cell division and becoming associated with the mitotic spindle apparatus. The co-existence of both binding activities for heparan sulphate and nuclei determinants in the same IgM molecule was deduced from adsorption-elution experiments and from the inhibitory effect of a mouse monoclonal anti-idiotypic antibody directed against the paratope of IgM-Rod.

Antibodies, Anti-Idiotypic↗

Limiting dilution analysis of the frequency of IL2 responsive T cells in lymph nodes involved by B-cell non-Hodgkin's lymphomas.

Total T lymphocytes separated from twelve lymph nodes involved by B-NHL were studied in limiting dilution experiments for their ability to proliferate in the presence of both R-IL2 used at a final concentration of 40 U/ml and irradiated autologous malignant B cells as feeders. The number of proliferating T-lymphocyte precursors (PTL-P) thus estimated was low in each case (mean: 1/4503; range, 1/200 to 1/11013). Once expanded, proliferation of the IL2 responsive T cells in the presence of autologous malignant B cells remained strictly dependent on the addition of exogenous IL2. Control cases consisted of T lymphocytes separated from peripheral blood of six healthy subjects and cultured in the presence of both R-IL2 (40 U/ml) and irradiated autologous total mononuclear cells as feeders; the mean frequency of PTL-P thus obtained (1/173; range, 1/49 to 1/457) was significantly higher than in malignant lymph nodes (p less than 0.01). These findings do not support the hypothesis that, in this series of patients, expansion of malignant B cells may lead to the activation and growth of T cells sensitized against the tumour.

Antigens, Differentiation, T-Lymphocyte↗

Role of autologous lymph node T cells in membrane expression of mu- or gamma-heavy chain isotype by malignant B NHL cells.

We investigated the possibility that T cells observed in lymph nodes involved by B-non-Hodgkin's lymphomas (B-NHL) may have a direct role in the expression of Mu- or Gamma- heavy chain isotype by autologous malignant B cells. T cells were separated from lymph nodes involved by B-NHL cells expressing either surface IgM (19 cases) or surface IgG (4 cases) and compared to peripheral blood T lymphocytes of healthy subjects (19 cases) for their ability to promote both IgG and IgM secretion in Cowan-activated normal B lymphocytes. The mean values of IgG/IgM ratios obtained under the influence of T cells associated with malignant B cells expressing either surface IgM or surface IgG were not statistically different to that obtained with the help of control T cells (0.60 and 0.62 versus 0.47, respectively). These results do not account for the hypothesis that autologous lymph node T cells may directly affect the expression of the heavy chain isotype by malignant B-NHL cells.

B-Lymphocytes↗

[Lymphocyte subpopulations during a longitudinal survey in an endemic malaria zone].

In a longitudinal survey conducted in savanna area (Burkina Faso, West Africa) where malarial transmission is seasonal, we studied modifications of T, B lymphocytes, NK cells, and CD4+, CD8+ and activated T subpopulations of 61 patients (31 adults and 30 children, among them 20 showed at least one malarial attack during the survey). Analysis was made by direct immunofluorescence on a cytofluorimeter. Our study did not show any significant differences in lymphocytes subpopulations according to age or presence of malarial attack. None of the lymphocyte markers in the peripheral blood are related to premunition, may be because host/parasite conflict mainly occurs in deep organs.

Adolescent↗

Divergent molecular phenotypes of KG1 and KG1a myeloid cell lines.

The cell line KG1 derived from a patient with erythroleukemia in myeloblastic relapse has the composite phenotype and functional repertoire of myeloblasts. In marked contrast, its subline KG1a has lost myeloid features, acquired new karyotypic markers, and has three characteristics associated with immature T cells: low-level expression of the T cell receptor beta mRNA (but not alpha) transcribed from a germline gene; high-level expression of T3 delta mRNA and intracellular, but not cell surface, T3 protein; and expression of the CD7/gp40 T cell-associated membrane antigen. Both KG1 and KG1a transcribe unrearranged IgH genes. These data suggest that either the KG1 cell line was derived from a common myeloid-lymphoid progenitor or that the KG1a subline phenotype is aberrant.

Antibodies, Monoclonal↗

Successful management of Histoplasma capsulatum infection of an abdominal aortic aneurysm.

A 65-year-old woman with disseminated histoplasmosis underwent resection of an atherosclerotic abdominal aortic aneurysm. Yeast forms of Histoplasma capsulatum were present in the aneurysm. Surgical resection and revascularization with a Dacron graft followed by systemic amphotericin B therapy and chronic ketoconazole suppressive therapy have resulted in a patient without symptoms 15 months postoperatively. It is important to be aware of the potential for artherosclerotic aortic aneurysm involvement by H. capsulatum.

Aged↗

Patient exposition and physician explanation in initial medical interviews and outcomes of clinic visits.

To replicate an earlier study and explore associations between verbal behaviors in patient-physician interactions and outcomes of care, 102 visits to a medicine walk-in clinic were tape-recorded, transcribed, and coded according to the Verbal Response Mode (VRM) system. Questionnaires given before and after the clinic visit and telephone interviews 1 week and 4 weeks after the visit were used to measure patient satisfaction, compliance, and change in symptoms. Data were collected on patients' sociodemographic characteristics, illness characteristics, and health beliefs. Two verbal exchanges were examined: in the medical history, the Patient Exposition exchange, which was measured as the frequency with which patients make statements about their illnesses in their own words; and in the conclusion, the Physician Explanation exchange, which was measured as the percentage of physician statements that are factual. These verbal indexes showed correlations with patient satisfaction, thus replicating the earlier study, but no significant correlations with compliance. Analysis of variance showed that the association between verbal exchanges and patient satisfaction remained after controlling for physician differences and for patient age, education, and belief in the controllability of the illness.

Adult↗

Induced type-B reticulum cell neoplasia of CBA mice. I. Phenotypic similarities between tumorigenic reticulum cells and normal accessory cells.

The phenotype and tumorigenicity of various cell types which occur in induced, transplantable type-B reticulum cell neoplasms of CBA strain mice have been examined. Evidence is presented that the neoplasms contain tumorigenic cells, morphologically defined as reticulum cells, having several phenotypic characteristics of the lymphoid dendritic and veiled accessory cells of normality, and macrophages and small lymphoid cells which are probably reactive cells of host origin.

Animals↗

Induced type-B reticulum cell neoplasia of CBA mice. II. Functional similarities between tumorigenic reticulum cells and normal accessory cells.

In a previous report, it was proposed on the basis of phenotypic evidence that the population of transplantable cells which constituted the major component of experimentally induced type-B reticulum cell neoplasms of CBA strain mice could be a neoplastic counterpart of lymphoid dendritic or veiled accessory cells. This has been further tested by an in vitro examination of their accessory function. Both similarities and differences in behaviour between the neoplastic cells and accessory cells prepared from spleens of normal mice were found. The possible significance of these properties is discussed in relation to the process of neoplastic change.

Animals↗

Neoplasms arising in CBA mice after transfer of spleen cells from syngeneic old donors.

Young (15-week-old) CBA/Ca mice were injected intravenously with spleen cells from individual young (15-week-old) or old (18-24-month-old) CBA/T6T6 mice. Samples of peripheral blood were taken at monthly intervals and cultured with phytohaemagglutinin (PHA) to stimulate T lymphocytes into mitosis. In the recipients of young lymphocytes, the percentage of donor cells dividing in these cultures remained low throughout the experiment, but in the recipients of old spleen cells, after an initial period when the percentage of donor cells declined, there was a marked increase in the percentage of donor cells. The interval between the injection and the increase in the proportion of donor cells was very variable. Ten of the 12 recipients of old lymphocytes developed tumours involving the spleen and mesenteric lymph node. They resembled type B reticulum cell neoplasms as described by Dunn & Deringer (1968), and all but two were transplantable. In addition, one mouse that had no evidence of tumour on histological examination nevertheless gave rise to a transplantable tumour. The five tumours on which chromosomal analysis was carried out proved to be of old donor cell origin. Two out of the five recipients of young cells also eventually developed tumours, but these arose later than the others, had a more granulocytic character, and did not transplant.

Age Factors↗

Staphylococcal protein-A is a potent T-cell mitogen of tonsillar lymphocytes.

Optimal conditions for the stimulation of human tonsillar lymphocytes by staphylococcal protein-A (SpA) are described. By stimulating fractions enriched or depleted of E-rosette forming cells, the response was shown to be predominantly a T-cell response. A comparison of stimulation by SpA with that of phytohaemagglutinin (PHA) proved SpA to be a potent T-cell mitogen. We suggest that SpA may be another useful mitogen for studying human T-cell growth and differentiation.

Humans↗

Suppression of liver cell proliferation by glucocorticoid hormone: a comparison of normally growing and regenerating tissue in the immature rat.

The influence of glucocorticoid hormone on the time-course of liver regeneration in the immature rat has been studied by direct measurement of the rate of DNA accretion after the stimulus of partial hepatectomy. In contrast to hepatocyte proliferation associated with normal growth, which almost completely abolished by small doses of glucocorticoid, it is shown that even enormous amounts of hormone produce, at most, about a halving of the intrinsic cell proliferation rate in regenerating liver. Although deceptively magnified by the exponential growth pattern of the hepatic remnant, the inhibition of cell proliferation is thus considerably less complete than that induced in normally growing liver by much lower doses of hormone, a finding at distinct variance with the conclusions of earlier studies based entirely upon observations of radioactive precursor incorporation rather than direct measurement of DNA accretion. The mechanism by which a regenerative stimulus causes hepatocyte proliferation to lose its normal sensitivity to suppression by glucocorticoid, and thereby to exhibit a steroid insensitivity characteristic of other tissues in which cell proliferation reflects cell replenishment rather than normal growth, remains unknown.

Animals↗

Teaching the medical interview: an intervention study.

To study the effects of teaching specific interviewing techniques on verbal behaviors and on health outcomes, internal medicine residents working in a screening clinic were assigned to either an experimental or a control group. The entire clinic visit was audiotaped, transcribed, and coded according to the Verbal Response Mode (VRM) system. Residents in the experimental group were taught interviewing behaviors (patient exposition and physician explanation) that had been found in previous studies to be associated with patient outcomes. Through telephone interviews, patient satisfaction, compliance, and symptom status were determined for all patients. Two hundred and sixty-eight interviews (156 in the experimental group and 112 in the control group) were included in the study. Training did increase patient exposition and physician explanation, but did not affect health outcomes. Residents' attitudes and behaviors during the training are described.

Communication↗