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Biomedical subjects

M C Jacob

Publications and source records attributed to M C Jacob.

At least 37 records · Page 2Linked to original sources
PubMed1995

Neutrophil activation by anti-beta 2 glycoprotein I monoclonal antibodies via Fc gamma receptor II.

Murine monoclonal antibodies (mAbs) to human beta 2-glycoprotein I (beta 2GPI), a plasma protein required for the binding of some antiphospholipid antibodies, have been shown to possess lupus anticoagulant properties and to activate platelets via Fc gamma receptor (Fc gamma R) crosslinking. Here we investigated their ability to induce polymorphonuclear leukocyte (PMN) functional responses. The six mAbs (IgG1 isotype) tested in combination with beta 2GPI led to a concentration-dependent activation of human PMNs as appreciated by granule release, H2O2 production, and cytosolic Ca2+ increase. This activation process was accompanied by the enhancement of PMN-mediated heparan sulfate loss from the endothelial cell line EA.hy 926 without evidence for cell lysis or detachment. F(ab')2 fragments of one of the mAbs bound to PMNs in a beta 2GPI-dependent manner but were devoid of activating effects. Carbamylated beta 2GPI was unable to mediate PMN-antibody binding and subsequent activation. In addition, cationization of beta 2GPI or removal of its sialic acid groups led to higher efficiency in binding to the PMN surface and triggering activation in comparison with the untreated protein. Thus, the process of PMN activation depends on mAb binding to these cells through both Fab (via beta 2GPI) and Fc domains, as confirmed by the suppression of all responses upon treatment with an anti-Fc gamma RII, but not anti-Fc gamma RIII, antibody. Our data suggest a model of cellular activation by beta 2GPI-dependent antiphospholipid antibodies.

Antibodies, Monoclonal↗
PubMed1995

Autotumour reactive T-cell clones among tumour-infiltrating T lymphocytes in B-cell non-Hodgkin's lymphomas.

Seventy-three T-cell clones (TCC) were established from tumour-infiltrating lymphocytes-T (TIL-T) derived from lymph nodes involved by B-cell non-Hodgkin's lymphomas (B-NHL) in nine patients with different histological subtypes and clinical stages. 40 TCC (55%) expressed the CD25 Ag and were also able to proliferate in the presence of irradiated autologous B-NHL cells. Among them, 23 autotumour (AuTu) proliferative TCC were found not to proliferate to autologous EBV-transformed B-cell lines, indicating that the proliferative reactivity of these TCC was preferentially directed at autologous B-NHL cells. Tested against autologous B-NHL cells, only three AuTu proliferative TCC (CD8+) showed a significant level of cytotoxicity (specific lysis > 15%). In blocking experiments, the AuTu proliferative reactivity of three TCC from one patient was strongly inhibited by anti-DR and anti-DQ mAbs, whereas that of three TCC from another patient was not affected by either anti-MHC class I or class II (DR, DP, DQ) mAbs. These findings suggest that the recognition of autologous B-NHL cells by AuTu proliferative TCC may occur through MHC-restricted as well as MHC-unrestricted mechanisms.

Cell Division↗
PubMed1994

Anger expression and chronic pain.

Intensity of angry feelings and styles of expressing anger were examined for their relationship to measures of the chronic pain experience. Subjects were 142 chronic pain patients. Multiple regression analyses revealed that a style of inhibiting the expression of angry feelings was the strongest predictor of reports of pain intensity and pain behavior among a group of variables including demographics, pain history, depression, anger intensity, and other styles of anger expression. In a similar manner anger intensity contributed significantly to predictions of perceived pain interference and activity level. More conservative hierarchical regression analyses supported these findings. Results are consistent with explanatory models of pain and disability that hypothesize an etiologic role of a pervasive inability to express intense negative emotions, particularly anger.

Adult↗
PubMed1994

A prospective study of donor insemination recipients: secrecy, privacy, and disclosure.

OBJECTIVES: To study prospectively the attitudes and behaviors of heterosexual couples undergoing donor insemination. DESIGN: Couples undergoing donor insemination completed psychological questionnaires before treatment regarding psychiatric symptoms, self-esteem, marital adjustment, and their attitudes about privacy or disclosure. PARTICIPANTS: Forty-one of 82 heterosexual couples participated. MEASURES: A donor insemination questionnaire, a self-esteem scale, the Brief Symptom Inventory, and the Dyadic Adjustment scale were used. RESULTS: Psychiatric symptoms, self-esteem, and marital adjustment were all in the normal range. The amount of time taken by the couple to decide to do donor insemination was not related to reported psychiatric symptoms, self-esteem, marital adjustment, or marital satisfaction. Ninety-five percent of the couples believed a psychological consultation should be a mandatory part of the donor insemination treatment. The greatest concern the couples had about the donor child was its genetic and medical background. Thirty-eight percent of the couples did tell or planned to tell others about using donor insemination to conceive, and only 27% of the couples planned to tell the child of his or her donor origin. CONCLUSIONS: The results of this study support those of others, which have indicated that the majority of donor recipients are psychologically well adjusted and have average marital adjustment. In addition, this prospective study replicated the findings of other retrospective studies, indicating that most donor insemination recipients do not plan to tell the child of his or her donor origin. Additional prospective studies are needed to determine if attitudes and behavior regarding disclosure change over time.

Adaptation, Psychological↗
PubMed1993

t(11;18)(q21;q21) may delineate a spectrum of diffuse small B-cell lymphoma with extranodal involvement.

We describe a patient with stage IV non-Hodgkin's lymphoma (NHL) and a t(11;18)(q21;q21) translocation. He presented with a gastric small B-cell lymphocytic lymphoma, expressing IgAL immunoglobulins without expression of CD10, CD5, and CD23 antigens. The lymphoma was the final development of a 6-year history of a monoclonal IgAL increase complicated by severe renal failure due to membranoproliferative glomerulonephritis. The clinical, histological, immunologic, and cytogenetic features of this patient are very similar to those observed in the five other patients with t(11;18) reported to date. This translocation therefore seems to delineate a new subtype of diffuse small B-cell lymphoma with involvement of mucosal sites. Involvement of the BCL2 oncogene on 18q21 could not be detected using molecular techniques with 5' as well as 3' BCL2 probes, indicating that other, so far unknown, genes relevant to lymphoid differentiation could be located in 18q21 and 11q21.

Antigens, CD↗
PubMed1993

Neopterin levels in plasma during a longitudinal study in an area endemic for malaria.

Neopterin levels in plasma were measured during a longitudinal study of 75 patients living in an area endemic for malaria. The maximum levels were observed in August/September, the period of peak transmission of the disease. During the dry season, levels remain elevated. No relationship was found between the level of neopterin and the individual's immune status against malaria. Tumor necrosis factor (TNF), activated T lymphocytes subpopulations, soluble interleukin 2 receptors, and anti-circumsporozoite protein antibodies were not correlated with neopterin levels during the period of peak transmission. In contrast, neopterin levels were correlated with anti-Plasmodium falciparum antibodies detected by immunofluorescence. It was concluded that, in a population of chronic parasite carriers subjected to repeated infestations, neopterin was a good indicator of slowly acquired immunity in stable transmission area, but it poorly reflected acute immune responses.

Adolescent↗
PubMed1993

Chronic pain: intrusion and accommodation.

Cognitive-behavioral and self-management perspectives on chronic pain emphasize the central role that patient's appraisals of their pain problems may have in determining aspects of the pain experience. This paper reports the development of a self-report instrument measuring two aspects of patients' appraisals of their pain and its impact on their lives. Two reliable and meaningful scales were derived via factor analysis, and a second sample was submitted to confirmatory factor analysis. Further analyses offered support for the internal consistency and stability of the scales. Pain Intrusion is related to greater depressive symptom severity and pain behaviors reflecting affective distress. Pain Accommodation is related to self-reports of greater self-control, viewing oneself as a problem-solver, fewer depressive symptoms, and fewer pain behaviors reflecting affective distress. This report introduces these constructs and the Chronic Pain Intrusion and Accommodation Scales that measure them, and discusses their theoretical and clinical relevance.

Adaptation, Psychological↗
PubMed1992

CD45RA expression by CD4 T lymphocytes in tumors invaded by B-cell non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD).

Little is known about the role of tumor infiltrating T lymphocytes (TIL-T) in the pathogenesis of malignant diseases and collaboration between normal and malignant cells has not yet been proved. In the present work, we have investigated whether immune T lymphocytes exist in tumors invaded by B-cell non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD). Therefore, we have studied the reactivity of the CD45RA monoclonal antibody, which discriminates between naive and memory CD4 T lymphocytes. Our results showed far lower percentages of CD4+ CD45RA+ in malignant lymphoma (30.3 +/- 15.0% in B-cell NHL, and 37.4 +/- 18.6% in HD) than in reactive hyperplasia (54.7 +/- 13.2%), leading to the conclusion of an accumulation of immune cells in tumor microenvironment. A further heterogeneity in the relative proportion of naive and memory TIL-T was also observed within lymphoma (range: 11 to 68% in B-cell NHL, 5 to 69% in HD). In B-cell NHL, it was related to histological features, as documented by the Kiel classification (P = .028), and to a stronger extent to cytological characteristics analysed with the Grenoble classification (P less than .0001): class 1 NHL, which are essentially indolent NHL displayed lower naive cells (22.2 +/- 7.4%) than class 3 NHL, which are more aggressive (40.1 +/- 16.1%). Among the monoclonal antibodies (mAb) defining the B-cell clone phenotype or activation state (CD19, CD20, CD21, CD22, CD23, CD24, CD5, CD10, CD11a, and Ki67), only CD23 (P = .0003) and Ki67 (P = .0007) revealed statistical association with the percentage of naive CD4 lymphocytes. No correlation could be demonstrated with the proportion of whole TIL-T, activated CD3 DR TIL-T, or CD4 subset.

Adult↗
PubMed1992

Lupus-like anticoagulant properties of murine monoclonal antibodies to beta 2-glycoprotein I.

The lipid-binding inhibitor of coagulation, beta 2-glycoprotein I (beta 2GPI), has been shown to form the antigen to which some autoantibodies against anionic phospholipids (aPL) are directed. Six murine monoclonal antibodies (MAbs) of the IgG1 isotype were raised against human beta 2GPI and could be subdivided into three groups on the basis of mutual competition experiments. MAbs 9G1 and 8C3 (group A) markedly inhibited the binding of immunoglobulins from aPL-positive sera to beta 2GPI-coated wells. Using a lipid-based solid-phase radioimmunoassay, the MAbs interacted with both anionic phospholipids and phosphatidylethanolamine, but not phosphatidylcholine, in a beta 2GPI-dependent manner. A cross-reaction between beta 2GPI from several (including bovine) species was seen with one of the MAbs (9G1). All six MAbs induced dose-dependent prolongation of the DAPTT, DRVVT, KCT and TTI clotting times of human plasma, whereas 9G1 was the sole antibody to be inhibitory with plasma from bovine origin. Synergistic inhibitory effects were observed with MAbs used in pairs provided that they did not compete with each other for beta 2GPI binding. The anticoagulant activity of the MAbs was fully neutralized by the addition of freeze-thawed platelets. The MAbs described here resemble lupus anticoagulants in several respects which makes them valuable to study the involvement of beta 2GPI in the autoimmune thrombotic pathophysiology.

Animals↗
PubMed1991

Measurement of anti-phospholipid antibodies by ELISA using beta 2-glycoprotein I as an antigen.

The requirement of plasma cofactor beta 2-glycoprotein I for binding autoantibodies against anionic phospholipids has been reported. We describe the development of an enzyme-linked immunosorbent assay (ELISA) for anti-phospholipid antibodies using highly purified beta 2-glycoprotein I for coating microtitre plates. Intra- and interassay coefficients of variation, determined with serum pools of low, medium and high positivity, ranged between 3% and 18%. 54 sera from patients with systemic lupus erythematosus and related autoimmune disorders were analyzed by this assay; the results correlated well to those obtained in an ELISA using anionic phospholipids on the solid phase (r = 0.85, P less than 0.001). The two ELISA systems showed similar sensitivities although 8/31 positive sera scored negative in the beta 2-glycoprotein I ELISA. The latter group of eight sera showed significantly higher anti-phosphatidylcholine/anti-phosphatidylserine binding ratios than the group of 23 sera which scored positive in both assays. This new assay should permit accurate measurement of most of the clinically relevant anti-phospholipid antibodies and avoid inconsistencies likely to arise from secondary interactions that characterize lipid-based ELISA.

Amino Acid Sequence↗
PubMed1991

Membrane cell permeabilization with saponin and multiparametric analysis by flow cytometry.

Saponin, a detergent like molecule, can permeabilize cell membranes without destroying them, and thus can be used for the detection of intracellular antigens on intact cells with a flow cytometer. First experiments were reported that demonstrated the detection of intracytoplasmic antigens such as intermediate filaments and CD3 in T acute lymphoblastic leukemia (ALL). Further experiments were also performed to prove that intranuclear structures were equally accessible: dyes such as propidium iodide (PI) and monoclonal antibodies (mAb) such as Ki67 could penetrate the nucleus and lead to the analysis of DNA content and to the discrimination between the different cell cycle phases (G0, G1, S, G2-M). This rapid and sensitive method retained sufficient integrity of cells being treated to enable differentiation of cell types on the basis of morphology. Furthermore, it did not alter membrane expression of most antigens. Therefore, it was of particular interest for multiparametric analysis, especially for simultaneous study of membrane and intracellular structures.

Aneuploidy↗
PubMed1991

t(18;22)(q21;q11) with rearrangement of BCL2 as a possible secondary change in a lymphocytic lymphoma.

We report a lymphocytic lymphoma showing a combination of two characteristic neoplasia-associated chromosomal changes: trisomy 12, commonly observed in chronic lymphocytic leukemia and lymphocytic lymphoma, and t(18;22)(q21;q11), a variant form of the t(14;18)(q32;q21) found in most follicular lymphomas. Southern blot analysis was performed using probes for the 5' end of the BCL2 gene (18q21) and for the J lambda as well as C lambda immunoglobulin genes (22q11). With these two probes, a unique rearranged fragment was detected. Thus the t(18;22)(q21;q11) can be considered as a variant translocation of t(14;18)(q32;q21). The karyotypic analysis supports the assumption that in our case trisomy 12 occurred first, and t(18;22) appeared during tumor progression as part of the clonal evolution. This is at variance with the typical t(14;18), which has never been found to occur as a secondary change.

Blotting, Southern↗
PubMed1991

The Pain Behavior Check List (PBCL): factor structure and psychometric properties.

The construct of "pain behaviors" as observable and measurable manifestations of pain occupies a central role in Fordyce's operant model of pain. The present study was designed to evaluate the multidimensional nature of the construct and to explore the psychometric properties of a newly developed self-report instrument called the Pain Behavior Check List (PBCL). Subjects were 126 chronic pain patients who completed an initial version of the PBCL and other standardized questionnaires as part of their evaluation by the West Haven VAMC. Factor analysis identified four factors labeled Distorted Ambulation, Affective Distress, Facial/Audible Expressions, and Seeking Help. Substantial reliability and stability estimates for the total PBCL and the subscales support the potential clinical and theoretical utility of the instrument.

Affect↗
PubMed1991

Impaired clonogenic potential of CD25 positive T cells in lymph nodes involved by B cell non-Hodgkin's lymphomas.

In vivo activated T cells (CD25+) present in lymph nodes involved by B-non-Hodgkin's lymphomas (B-NHL) were investigated here for their ability to proliferate in vitro. CD25-/CD25+ T cells were isolated using a rosette method with magnetic beads, then the frequency of proliferating T lymphocyte-precursors (PTL-P) in both populations was assessed by limiting dilution experiments, in the presence of IL2, PHA and allogeneic spleen cells as feeders. In a total of 16 cases studied, growing microcultures were observed in all cases for CD25- T cells (mean value of PTL-P frequency: 1/32; range 1/10 - 1/2899) but in 6 cases only for CD25+ T cells (mean value of PTL-P frequency: 1/441; range 1/119 - 1/3736); the absence of any proliferative cultures in the 10 other cases indicated that the number of PTL-P was inferior to 1/12480. These results suggest that the proliferative potential of CD25+ T cells infiltrating lymph nodes involved by B-NHL is paradoxically decreased.

Clone Cells↗
PubMed1991

Non-Hodgkin's lymphomas with t(11;14)(q13;q32): a subset of mantle zone/intermediate lymphocytic lymphoma?

We here describe 13 patients with non-Hodgkin's lymphoma (NHL) and a translocation t(11:14)(q13:q32). They were part of a series of 163 patients with NHL and an abnormal karyotype, serially referred to our institution between January 1984 and 1990. Patients with t(11:14) seem to present several common and interesting features. Males are more frequently affected than females, and old people more than young. They present at diagnosis with advanced disease and usually show involvement of epithelium and bone marrow. With respect to histologic diagnoses, these patients are usually considered to be of low-grade malignancies. However, most of them do very poorly, have short complete remission and frequent relapses whatever the treatment. As a whole, the median survival rate is rather low. The cytologic, histologic as well as the immunologic patterns tend to be uniform: tumours are composed of small cells and display features of mantle zone/intermediate lymphocytic lymphoma. They express high IgM and low IgD levels and more commonly bear Ig lambda light chains. They also express all pan-B antigens (except CD23) as well as the CD5 antigen, but usually lack the CD10. According to these characteristics, these tumours could be placed in between lymphocytic lymphomas (which usually express CD23) and follicular lymphomas (which commonly lack IgD and CD5 and bear CD10 as well as a t(14:18).

Adult↗
PubMed1991

Detection, isolation and functional studies of CD25+ T cells in lymph nodes involved by B-cell non-Hodgkin's lymphomas.

We searched for the presence of IL2 receptor (CD25) on T cells as an activation marker in lymph nodes involved by B-cell non-Hodgkin's lymphomas (B-NHL). In 26 malignant lymph nodes studied, the number of CD25+ T cells among total T cells was usually low when assessed by immunofluorescence analysis (mean +/- SD: 6.7% +/- 11.2%), but greatly increased when an immunomagnetic rosette method was used (mean +/- SD: 17.5% +/- 16.6%). In six cases, CD25-/CD25/CD25+ cells were isolated by immunomagnetic separation, with a purity greater than 97% for both populations. Expansion of CD25-/CD25+ T cells was obtained with IL2 and PHA, then conditioned media (CM) were prepared. No IL2 activity was found in CM from both CD25-/CD25+ T cells when tested on CTLL2 cells. BCGF and BCDF mu/gamma activities were assayed on normal B cells stimulated with soluble or insolubilized anti-mu antibodies(BCGF) or with Cowan I (BCDF). Results of production of all these activities were comparable for both populations, and thus do not favour the possibility that CD25+ T cells closely associated with malignant B-NHL cells in lymph nodes may influence their proliferation (BCGF) or expression/secretion of heavy chain isotype (BCDF mu/gamma).

Cell Count↗