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Biomedical subjects

E Klein

Publications and source records attributed to E Klein.

At least 217 records · Page 12Linked to original sources

Discontinuation of lithium treatment in remitted bipolar patients: relationship between clinical outcome and changes in sleep-wake cycles.

In this preliminary report, we describe four patients in whom long-term lithium therapy was discontinued, combined with actigraphic monitoring to assess changes in motor activity and the sleep-wake cycle. Two patients experienced rapid relapse of manic symptomatology, while two remained stable throughout a 1-year follow-up. Actigraphic monitoring revealed disintegration of the sleep-wake cycle and increased motor activity in the relapsed patients only. It is suggested that actigraphic recordings can be used to monitor lithium discontinuation.

Ambulatory Care↗

Activation and fixation of C3 by human B cell lines is enhanced by interferon-gamma and tumor necrosis factor alpha.

Human B cell lines were tested for the capacity to convert C3 to C3b/iC3b through the alternative C pathway (ACP) and to fix the generated C3 fragments. The panel of lines included four Epstein-Barr virus (EBV)-negative Burkitt's lymphomas and their sublines converted with two EBV strains: the prototype B958 (B virus) and the nontransforming P3HR-1 (P virus). Comparison of these groups of parallel lines (derived from a single patient) showed that the EBV-carrying cells were more efficient in activation and fixation of C3. All cell lines activated C3 with higher efficiency when treated with interferon gamma or tumor necrosis factor alpha. After treatment, the comparative relationships between the sublines changed. The treated EBV-negative and the P virus converted sublines showed similar levels of ACP activation, while the B virus carrying sublines were more efficient. The amounts of bound C3 fragments on the activating cells correlated with the ACP efficiencies. In accordance with the elevated ACP activation capacity of the cells after cytokine treatment, the amounts of C3 fragments detected on their surfaces were higher. Among the lines tested, only two (BL28 and Ramos) were sensitive to C-mediated lysis. The lytic sensitivity of these two lines increased after treatment with the cytokines. The results indicate, therefore, that the cytokine-induced increase in ACP activation by Burkitt's lymphoma line is not sufficient to overcome resistance to C lysis.

B-Lymphocytes↗

Effect of transforming growth factor-beta 1 and -beta 2 on the proliferation of Burkitt lymphoma and lymphoblastoid cell lines.

We tested the effect of transforming growth factor (TGF)-beta 1 and TGF-beta 2 on the proliferation of human B cell lines. The panel was selected to give information whether (1) their origin, (2) their phenotype, (3) their Epstein-Barr virus (EBV) carrier state, influence their responsiveness. The growth of lymphoblastoid cell lines (LCL) was not inhibited by TGF-beta 1. The EBV-carrying Burkitt lymphoma (BL) lines, Daudi, Jijoye, Rael but not Raji were inhibited. Three EBV-negative BL lines and the majority of their converted sublines were sensitive. The cell lines tested expressed TGF-beta receptors and TGF-beta 1 transcripts. The proliferation of EBV-infected B cells was inhibited by TGF-beta, their sensitivity decreased, however, after 3 days. The results suggest that the activation state of the B cells is decisive for TGF-beta sensitivity and EBV influences it indirectly by changing the cell phenotype.

B-Lymphocytes↗

Alteration of macrophage activity in experimental septic shock in the rabbit.

We studied alteration in macrophage activity during experimental septic shock and the effect of the protease inhibitor Trasylol on these alterations. Studies were carried out on three groups of 6 rabbits of each. One group (A) served as a control and in the other two groups (B,C) septic shock was induced using the cecal ligation technique. Group B received i.v. Trasylol prior to and following cecal ligation. The clearance and reticuloendothelial system (R.E.S.) distribution of 125I labelled polyvinyl pyrrolidone (PVP) was used to study macrophage function. PVP was injected into all animals 18 h prior to cecal ligation. For 48 h following the operation, PVP blood levels were repeatedly measured and clearance calculated. The animals were then sacrificed, and total radioactivity of the various organs was measured. In the early stages after cecal ligation a significantly higher PVP clearance rate was noted in groups B and C (P less than 0.01); In the later stages of the experiment, however, group C demonstrated the slowest clearance rate with intermediate values in group B. The highest PVP concentrations were found in the liver and spleen. A significantly higher PVP concentration was noted in the spleen of the animals in group A and B as compared to group C (P less than 0.01) while the difference between group A and B was not significant. Our results indicate that septic shock reduces macrophage function as measured by the changes in PVP clearance and distribution. Injections of Trasylol seem to ameliorate these changes. The model of 125I PVP clearance seems to offer a convenient, valid and informative model for measurement of macrophage activity in pathological conditions.

Animals↗

Cell phenotype dependent expression of MHC class I antigens in Burkitt's lymphoma cell lines.

Burkitt's lymphoma (BL) is a highly malignant B cell tumor characterized by three types of chromosomal translocation which constitutively activate the c-myc oncogene by juxtaposing it to Ig coding sequences. Epstein-Barr virus (EBV) infection, hyperendemic malaria and HIV-caused immunosuppression are thought to contribute to the pathogenesis of the tumor. Cell lines derived from EBV carrying and EBV negative BLs often show altered MHC class I antigen expression. The defects include a lower expression of all HLA class I antigens compared to EBV transformed normal B-blasts, and selective down-regulation of certain HLA-A and HLA-C alleles. As a consequence BL cells are often resistant to cytotoxic T lymphocyte (CTL) mediated destruction. Alleles selective down-regulations are found only in cell lines that maintain the tumor cell phenotype while shift towards a more activated 'B-blast like' phenotype is accompanied by HLA class I up-regulation. A similar pattern of HLA class I expression can be found in a subpopulation of germinal center B cells which express a 'BL like' phenotype. Our findings suggest that the HLA class I expression of BL cells reflects the characteristics of the normal B cell precursor and is probably not the result of immune selection.

Antigens, CD↗

Requirement of MHC class I antigen expression on human tumors for in vitro recognition by autologous blood lymphocytes.

Expression of class I antigens on ex-vivo tumor cells was found to be required for their recognition by autologous blood lymphocytes in vitro. Lymphocyte stimulation (auto-tumor stimulation ATS) in mixed lymphocyte tumor cell cultures (MLTC) and cytolysis in short term assays (autologous lymphocyte-mediated cytotoxicity ALC) were positive with cells of a proportion of sarcoma and carcinoma patients. In addition to the class I antigens, these tumors also carried the adhesion molecule ICAM-1. Monoclonal antibodies (MAb) to the MHC class I, but not to class II antigens inhibited lymphocyte proliferation in the MLTC and lysis of tumor cells in the ALC tests. In a proportion of originally negative or low expressor tumors, in vitro treatment with Interferon gamma and tumor necrosis factor alpha induced the expression of class I antigens and/or ICAM-1. In the MLTC the cytokine treated tumor cells stimulated the blood lymphocytes and generated cytotoxic effectors which reacted also with the untreated tumor cells.

Cell Adhesion Molecules↗

Referral and screening patterns at a clinic for anxiety disorders; implications for the planning of clinical studies.

During a two year period (1988-1990), 302 patients who were referred to our anxiety disorder clinic were evaluated and diagnosed according to a screening procedure which will be described. Of these initial referrals, 171 met a DSM-3-R diagnosis of panic disorder (with or without agorophobia) or generalized anxiety disorder; 81 patients (27% of the initial referrals) participated in a double blind placebo controlled clinical trial with a dropout rate of 12%. The implications for the planning and design of referral and screening strategies at research oriented specialized clinics are discussed.

Adult↗

Role of endoscopic retrograde cholangiopancreatography in differentiating pancreatic cancer coexisting with chronic pancreatitis.

The pancreatographic appearance and the clinical presentation of ten patients presenting with adenocarcinoma of the head of the pancreas coexisting with chronic pancreatitis were compared with those of 45 patients with chronic pancreatitis (CP), without malignancy, investigated at the same time period. All ten patients, had typical pancreatographic findings of CP, combined with an elongated narrowing of the duct of Wirsung. Marked localized irregularity of the adjacent main duct and of side branches were found in all ten patients. Such findings were not detected in the other 45 patients with CP only. Ultrasonography or computed tomography have detected a definite pancreatic mass in only five of these patients, and in six patients with CP without malignancy. It is concluded that endoscopic retrograde cholangiopancreatography is highly accurate in detecting pancreatic cancer coexisting with CP. It is primarily helpful in elderly patients having severe degrees of CP to rule out cancer.

Aged↗

Potentiation of NK cytotoxicity by antibody-C3b/iC3b heteroconjugates.

The interaction of two Burkitt lymphoma lines, Raji and Rael, with human C and NK cells was analyzed. Raji cells activate the alternative C pathway (ACP) and then bind C3 fragments. Consequently, the cells become more sensitive to lysis by CR3-bearing NK cells but not to C lysis. In contrast, Rael cells are poor ACP activators, do not bind C3 fragments, and are therefore resistant to C-dependent NK lysis. As suggested earlier, the difference between Raji and Rael could be attributed to the presence or absence of CR2, respectively, on their surface. To potentiate C- and NK-dependent lysis of target cells, we generated heteroconjugates composed of a murine antitransferrin receptor mAb and of human C C3b or iC3b. Antibody-C3b conjugates induced C3 deposition on Rael cells and elevated C3 deposition on Raji cells in human serum. Both Raji and Rael cells coated with antibody-C3b conjugates were efficiently lyzed by the cytolytic ACP in human serum. This conjugate had a small enhancing effect on target cell lysis by NK cells which could be markedly increased by combined treatment of the target cell with antibody-C3b conjugate and C5-depleted human serum. On the other hand, antibody-iC3b conjugates efficiently potentiated lysis of target cells by NK cells in the absence of serum. The iC3b-directed cytotoxicity was mediated by CR3-bearing NK effector cells. Anti-C3 but not anti-mouse Ig antibodies abrogated the activity of the antibody-iC3b conjugate. These results further demonstrate that NK cytotoxicity may be potentiated by opsonizing the target cells with C3 fragments and suggest that antibody-C3b/iC3b conjugates could be potent tools for targeting and potentiation of the lytic action of both C and NK cells against tumor cells.

Antigen-Antibody Complex↗

Effect of the EBNA-2 gene on the surface antigen phenotype of transfected EBV-negative B-lymphoma lines.

Two EBV-negative B-lymphoma cell lines with different phenotypes were transfected with the Epstein-Barr virus EBNA-2 gene. The effects on the expression of 8 B-cell surface markers were analyzed by immunofluorescence methods. In one of the EBNA-2 transfected cell lines, the expression of the CR2 receptor CD21 was induced and the expression of CD23 was enhanced. The results suggest that the EBNA-2 gene is involved in the regulation of CD21 and CD23 in EBV-carrying cells.

Antibodies, Monoclonal↗

Medullomyoblastoma in an adult.

Medullomyoblastoma is a rare histologic variant of medulloblastoma. Of the 20 cases reported in the literature, 19 were in children ages 2.5 to 10.5 years and one was in a 26-year-old woman. In the reported adult case the myogenic component of the tumor was leiomyosarcomatous. The authors report a case of medullomyoblastoma with a rhabdomyosarcomatous component in a 40-year-old man with light microscopic, immunohistochemical, and ultrastructural findings. The histogenetic theories regarding this tumor include that it is a teratoma, or that the myogenic component arises from the perivascular or leptomeningeal ectomesenchyme, or pluripotential neuroectodermal cells, or endothelial cells. The authors' findings do not elucidate the histogenesis but argue against an endothelial origin of the rhabdomyoblastic component.

Adult↗

[Hemosuccus pancreaticus].

We describe a case of hemorrhage into the pancreatic duct, secondary to a bleeding aneurysm of the splenic artery. The problem of the diagnosis of this rare cause of upper gastrointestinal hemorrhage and therapeutic possibilities with their recurrency and mortality rates under short review of literature are discussed.

Aneurysm↗

Expression of interleukin-2 receptor on blood lymphocytes stimulated with allogeneic lymphocytes or autologous tumor cells. The mixed lymphocyte culture of allo-sensitized individuals and the auto-tumor stimulation show similar kinetics of activation.

The kinetics of interleukin-2 receptor (IL-2R) expression and the [3H]dT incorporation of blood lymphocytes after the first and the second stimulation with allogeneic leukocytes (primary and secondary MLC) or with the autologous tumor cells (primary and secondary MLTC) were compared. The expression of IL-2R paralleled the induction of DNA synthesis. The proportion of IL-2R+ cells of the unprimed donors peaked earlier in the secondary MLC as compared to the primary MLC (on days 3 and 5 respectively). In MLC of alloimmunized healthy individuals and in the MLTC of cancer patients the highest proportions of IL-2R+ cells were detected between days 2 and 3 after both the first and second stimulations. Thus the first in vitro stimulation in the MLTC showed similar kinetics to those of the secondary MLC of unprimed individuals and to the primary MLC response of the allo-immunized individuals. The findings in the MLTC substantiate the hypothesis that cancer patients can be sensitized to their own tumors. The kinetics of the appearance of the IL-2R together with the characteristics of the IL-2-propagated cultures provide useful information for the strategy of expansion of auto-tumor reactive lymphocyte populations.

Humans↗

Expression of the adhesion molecule ICAM-1 and major histocompatibility complex class I antigens on human tumor cells is required for their interaction with autologous lymphocytes in vitro.

In a group of 30 human tumors, comprising 12 lung, 14 ovarian, 2 breast carcinomas, 1 hypernephroma and 1 mid-gut carcinoid, the expression of major histocompatibility complex (MHC) class I molecules and the intercellular adhesion molecule 1 (CAM-1, CD54) was found to vary independently. Some tumors expressed both or neither of these molecules. Among 9/13 ICAM-1+ tumors, in which greater than 50% cells reacted with the anti-ICAM-1 monoclonal antibody (mAb) (LB-2), the class I antigen was also detected on greater than 50% of the cells. Only 2 ICAM-1+ tumors were class-I-. In 5/17 cases the tumors were MHC-class-I+ and ICAM-1-. Lymphocytes collected from the blood or from the tumor site were assayed for recognition on the tumor cells in the auto-tumor cytotoxicity test and in mixed lymphocyte tumor cell culture (MLTC). Positive results were obtained only with the MHC-class-I+/ICAM-1+ tumors. In vitro treatment of the tumor cell suspensions with interferon gamma and tumor necrosis factor alpha (TNF alpha) induced or enhanced the ICAM-1 and/or class I antigen expression in 8/12 cases. Of the tumor samples treatged, 8/9 acquired stimulatory capacity and 3/10 became susceptible to lysis by the lymphocytes. In 6/6 MLTC performed with the cytokine-treated tumor cells, cytotoxicity against the autologous tumor was generated. Three of these MLTC lymphocytes also lysed the untreated targets. mAb directed to class I antigens or to ICAM-1 inhibited both the stimulation by and the lysis of tumor cells when confronted with fresh lymphocytes. The cytotoxicity generated in the MLTC was also inhibited. If, however, the cytotoxic function was induced in MTLC containing interleukin-2 (5 U/ml), inhibition was obtained only by pretreatment of the targets with mAb against ICAM-1. The results show thus (a) that the lymphocytes react in vitro with tumor cells only if these express both MHC class I molecules and ICAM-1; (b) that expression of these molecules can be induced by interferon alpha and TNF alpha; (c) that cytotoxic effectors generated in the MLTC with cytokine-treated tumors can also act on the untreated tumor cells. The requirement of the two surface moieties for the interaction with lymphocytes was also substantiated by blockade with relevant mAb.

Antibodies, Monoclonal↗