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S Alkan

Publications and source records attributed to S Alkan.

At least 55 records · Page 3Linked to original sources
PubMed1997

Visualization of human herpesvirus type 8 in Kaposi's sarcoma by light and transmission electron microscopy.

BACKGROUND: Human herpesvirus type 8 (HHV-8) has been associated with Kaposi's sarcoma, body cavity-based lymphoma (BCBL), and multicentric Castleman's disease through DNA, in situ hybridization, and serologic studies. HHV-8 has been visualized only in HHV-8-positive/Epstein-Barr virus (EBV)-negative/ cytomegalovirus (CMV)-negative BCBL cell lines, but not in HHV-8-positive/EBV-negative/ CMV-negative Kaposi's sarcoma lesions. DESIGN: Kaposi's sarcoma of the skin, lymph node, and spleen from three patients with AIDS were analysed for HHV-8, EBV and CMV DNA by polymerase chain reaction (PCR), for HHV-8 RNA (Tl.1 riboprobe) by in situ hybridization (ISH), for viral inclusions by light microscopy, and for herpesviruses by transmission electron microscopy (TEM). Sections were also labeled with Tl.1 counterstained with CD34, an endothelial cell marker. RESULTS: The skin lesion was DNA PCR-positive for HHV-8 and CMV (nested, but not single PCR), the lymph node was positive for HHV-8 and EBV, and the spleen was positive for only HHV-8. TEM revealed infection by a virus displaying the typical morphology and cytopathicity of herpesviruses. Hexagonal nucleocapsids and mature enveloped virions were present in vasoformative spindle cells and mononuclear cells, often resembling lymphocytes. Extrapolating from TEM to standard light microscopy on hematoxylin and eosin-stained paraffin sections, eosinophilic, targetoid intranuclear inclusions were identified within spindle cells which often lined vascular lumina. The Tl.1-riboprobe labeled CD34+ spindle cells containing intranuclear inclusions, as well as mononuclear cells within Kaposi's sarcoma and residual lymphoid tissue. CONCLUSION: The herpesvirus visualized in Kaposi's sarcoma lesions has morphologic and cytopathic features typical of human herpesviruses, productively infects vasoformative spindle cells and mononuclear cells, and is consistent with HHV-8. It can also form intranuclear inclusions that are identifiable by light microscopy in hematoxylin and eosin sections and by ISH.

Herpesvirus 8, Human↗
PubMed1996

Follicular lymphoma with involvement of the splenic marginal zone: a pitfall in the differential diagnosis of splenic marginal zone cell lymphoma.

Follicular lymphomas (FL) involving the spleen arise in and expand the germinal centers of the white pulp, whereas mantle cell lymphomas arise in the mantle zone and surround the benign germinal center. The recently described marginal zone cell lymphoma (MZCL) is a B-cell neoplasm characterized by concentric expansion of cells around the follicle, with or without infiltration of the mantle zone or germinal center. In addition, the immunoglobulin heavy chain gene is rearranged although none of the MZCL reported have been shown to be positive for the bcl-2 gene translocation by molecular studies. We report a patient with FL showing preferential involvement of the marginal zone of spleen morphologically mimicking a primary splenic MZCL. The patient reported here had a well-documented previous lymph node diagnosis of FL. The immunoglobulin heavy chain gene and bcl-2 gene rearrangement analysis confirmed the clonal origin of both the original FL, as well as the lymphoma, with a marginal zone pattern in the spleen.

Base Sequence↗
PubMed1996

Analysis of immunoglobulin heavy chain gene rearrangement in myoepithelial sialadenitis by polymerase chain reaction.

Myoepithelial sialadenitis (MESA) can often be difficult to distinguish from low grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). The authors have previously studied a series of 25 patients with MESA and identified histologic and immunologic features predictive of extrasalivary lymphoma (ESL). The authors have now analyzed formalin-fixed, paraffin-embedded salivary gland tissue from 21 of these patients (and 1 new patient) for immunoglobulin heavy chain (IgH) gene rearrangement by a semi-nested polymerase chain reaction (PCR) technique to compare monoclonality by IgH PCR with clinical outcome (median follow-up 6.7 years, range 3 months-19.4 years) and the paraffin section immunophenotype. The PCR technique employed consensus primers from variable (FR3A) and joining regions (LJH, VLJH) of the IgH gene. A monoclonal PCR product was detected in 16 of 28 specimens from 13 of 22 patients. By Fisher's exact test, a monoclonal PCR pattern did not correlate (P > .05) with development of ESL, broad strands of monocytoid B-cells, plasma cell light chain restriction by immunoperoxidase, or CD43 coexpression on monocytoid B cells by immunoperoxidase. This study suggests that the majority of MESA lesions harbor monoclonal B-cell populations and that clonality does not predict progression to clinically overt lymphoma. Acquired salivary gland MALT, in the form of MESA, may progress to a process that is clonal but not necessarily malignant. Extranodal lymphoma develops in a minority of patients with this lesion.

Adult↗
PubMed1995

Cyclin D1 protein expression in mantle cell lymphoma.

BACKGROUND: The t(11;14)(q13;q32) is a chromosomal abnormality usually associated with mantle cell (centrocytic) lymphomas, although it has occasionally been reported in other chronic lymphoproliferative disorders such as chronic lymphocytic leukemia, prolymphocytic leukemia, splenic lymphoma with villous lymphocytes, and multiple myeloma. This abnormality results in the translocation of the bcl-1 oncogene from chromosome 11 to the immunoglobulin heavy chain locus on chromosome 14. The bcl-1 oncogene is a member of the cyclin gene family, and high levels of cyclin D1 mRNA are consistently found in malignant B cell proliferations with t(11;14). PATIENTS AND METHODS: We examined cyclin D1 protein expression in 33 patients with low grade lymphoproliferative disorders and 2 patients with reactive hyperplasias by Western blot analysis using a polyclonal antibody. RESULTS: 8/11 mantle cell lymphomas, 0/11 chronic lymphocytic leukemias, 0/4 hairy cell leukemias, 0/2 Sezary syndrome, 0/2 monocytoid B-cell lymphomas, 0/3 follicular lymphomas, and 0/2 reactive hyperplasias had overexpression of cyclin D1. Cytogenetic analysis was performed in four cases of mantle cell lymphoma; three of these cases had the t(11;14), one of which was hypotetraploid with two copies of t(11;14). Immunophenotypically, all cases of mantle cell lymphoma and chronic lymphocytic leukemia had coexpression of CD5 and CD20. CONCLUSION: Mantle cell lymphoma may be difficult to discriminate from chronic lymphocytic leukemia, a more indolent disease, on morphologic and immunophenotypic grounds. Our findings suggest that analysis of cyclin D1 protein expression may be helpful in differentiating mantle cell lymphomas from other low grade lymphoproliferative disorders.

Antigens, Neoplasm↗
PubMed1995

Polymerase chain reaction detection of immunoglobulin gene rearrangement and bcl-2 translocation in archival glass slides of cytologic material.

Cytologic evaluation of lymph node fine-needle aspirates and serous effusions is a rapid and useful means for establishing the diagnosis of a variety of lymphoproliferative disorders. However, in some instances, cytologic findings are not sufficient to establish a diagnosis of lymphoma, thus necessitating the use of ancillary procedures, the most frequent of which is immunophenotyping. In this respect, the usefulness of molecular markers, such as clonal immunoglobulin gene rearrangements or chromosomal translocations, have been less well evaluated. Follicular lymphoma constitutes an interesting disease for such a study because these tumors possess characteristic histopathologic features and contain two potential molecular markers, that is, a clonal immunoglobulin gene rearrangement and a bcl-2 gene translocation [t(14;18)]. In the present study, we evaluated, retrospectively, the cytologic material from four lymph node fine-needle aspirates and one pleural effusion of five patients with biopsy-proven follicular lymphoma. In four of the cases, definitive diagnosis of lymphoma had not been possible solely from cytologic evaluation. DNA was isolated from archival air-dried samples present on glass slides and amplified by the polymerase chain reaction (PCR) for detection of either a clonal immunoglobulin heavy chain gene rearrangement or bcl-2 translocation (major breakpoint region). An immunoglobulin heavy chain gene rearrangement was detected in four of five patients, and two patients had the bcl-2 translocation by PCR. The effusion case was identical by gel electrophoresis with product amplified from a lymph node biopsy of the same patient and DNA extracted directly from fresh pleural effusion cells.(ABSTRACT TRUNCATED AT 250 WORDS)

B-Lymphocytes↗
PubMed1995

Hematological Effects of Human Immunodeficiency Virus Infection.

Anemia, thrombocytopenia, and neutropenia are common manifestations in patients with human immunodeficiency virus infection that become more frequent and severe with progression from the asymptomatic state to acquired immunodeficiency syndrome (AIDS). Causes of anemia in AIDS include nutritional deficiencies, infection, and marrow suppression by antiretroviral drugs and by the disease itself. Autoimmune hemolysis and blood loss from gastrointestinal lymphoma or Kaposi sarcoma may also contribute. Granulocytopenia may be due to infection, autoimmunity, or bone marrow suppression by drugs or the immunodeficiency virus. Lymphopenia, the classic hallmark of the disease, typically affects T-helper cells first and worsens as the disease advances. Lymphopenia is a result of the direct cytopathic effects of the virus. Thrombocytopenia can occur from antibodies causing an idiopathic thrombocytopenic purpura-like state from bone marrow suppression or from thrombotic thrombocytopenic purpura. A prolonged partial thromboplastin time due to a coagulopathy caused by lupus anticoagulant causing has been described. A variety of malignancies occurs.

Journal Article↗
PubMed1995

Epstein-Barr virus and bcl-2 protein overexpression are not detected in the neoplastic cells of nodular lymphocyte predominance Hodgkin's disease.

Recent studies have indicated that nodular lymphocyte predominance Hodgkin's disease (nLP-HD) is a B-cell lymphoma. Although molecular events in the neoplastic transformation of B-cells are not well understood, Epstein-Barr virus infection and bcl-2 protein overexpression have been postulated to have etiologic roles in some lymphomas. Epstein-Barr virus has been demonstrated in the Reed-Sternberg cells of Hodgkin's disease cases (other than nLP-HD) as well as in some B-cell lymphomas; bcl-2 overexpression is found in the majority of follicular lymphomas. The biologic role for bcl-2 in HD is controversial. Some reports have indicated the presence of bcl-2 gene rearrangements, associated with the t(14;18) (q32;q21), detected by the polymerase chain reaction in HD; recent studies have failed to confirm this finding. Reports in the literature describe only a few such analyses in the nLP-HD subtype. To address these conflicting issues, we examined 12 cases of nLP-HD to determine whether bcl-2 protein expression (by immunohistochemistry) and Epstein-Barr virus (by in situ hybridization) could be detected in the Reed-Sternberg variants. None of the cases showed expression of bcl-2 protein or Epstein-Barr virus RNA in the neoplastic cells. Epstein-Barr virus does not appear to play an important role in the pathogenesis of nLP-HD. Similarly, we cannot substantiate a role for bcl-2 in the development of this type of Hodgkin's disease.

Base Sequence↗
PubMed1994

Chemiluminescent and enzyme-linked immuno assays for sensitive detection of human IFN-gamma.

We have produced and characterized 4 mAbs to human IFN-gamma and established sensitive, non-radioactive immuno-assays. The first two assays use microtiter plates as the solid phase and enzymes or chemiluminescence (acridinium ester) for development. The use of chemiluminescence instead of peroxidase increased the sensitivity of the assay by a factor of about 75. The third and the fourth assays utilize polystyrene beads as the solid phase and enzymes or acridinium ester for development. The use of beads also increased the sensitivity of detection. The most sensitive IFN-gamma detection was achieved by the combination of bead with acridinium ester. In this configuration we were able to detect about 0.2 pg/ml IFN-gamma (1/250th of a unit). These chemiluminescent immunoassays (CLIA) appear to be more sensitive than existing ELISAs or radioimmunoassays and may find new application areas.

Animals↗
PubMed1993

Interferon alpha increases the frequency of interferon gamma-producing human CD4+ T cells.

An increased ratio of T helper type 2 (Th2)- vs Th1-like cells contributes to the immune dysregulation in allergic disease situations and in many chronic infections, including AIDS. Th2-type immune responses are characterized by Th cells that produce increased levels of interleukin-4 (IL-4) and decreased levels of interferon gamma (IFN-gamma). The induction of either a Th1- or a Th2-like phenotype may be critically controlled by the antigen-presenting cells and their cytokines, e.g., IFN-alpha. In this study we have determined the frequencies of potential IL-4- and/or IFN-gamma-producing T cells in the peripheral blood of randomly selected healthy individuals, and analyzed whether IFN-alpha controls IL-4 and/or IFN-gamma production. Purified CD4+ or CD8+ T cells were stimulated for 24 h via the T cell receptor/CD3 complex in the presence or absence of IFN-alpha, and single IL-4- and IFN-gamma-secreting cells were detected in enzyme-linked immunospot assays. In the absence of IFN-alpha, CD4 cells produced IFN-gamma at frequencies of 1:50-300, and produced IL-4 at frequencies of 1:110-<1:100,000. Addition of IFN-alpha during the activation of CD4 cells increased the levels of IFN-gamma mRNA. As a consequence, the numbers of IFN-gamma-producing CD4 cells and the amounts of secreted IFN-gamma increased 10-fold. In contrast, IFN-alpha did not increase the frequency of IL-4-secreting CD4 cells. In the absence of IFN-alpha, addition of exogenous IL-4 to cultures of CD4 cells suppressed IFN-gamma secretion by 70%. However, in the presence of IFN-alpha, IL-4 did not display any suppressive effect. Compared with CD4 cells, CD8 cells produced IFN-gamma more frequently (1:5-10) but IL-4 less frequently (1:5,300 to < 1:100,000). IFN-alpha did not display any effect on the frequency of either IFN-gamma or IL-4 production by CD8 cells. Taken together the results indicate that IFN-alpha increases the frequency of IFN-gamma-secreting CD4 Th cells and antagonizes the suppressive effect of IL-4 on IFN-gamma production. As a consequence, IFN-alpha may favor the induction and maintenance of Th1-like cells and thereby counteract Th2-driven allergic immune responses.

Acquired Immunodeficiency Syndrome↗
PubMed1993

The influence of major trauma on the regulatory levels of interleukin-1 (IL-1) and IL-2 in human mononuclear leukocytes.

The monokine Interleukin-1 (IL-1) and the lymphokine IL-2 are playing a crucial role within the course of an intact cell mediated immune response (CMI). It was the objective of this study to further elucidate the cytokine associate mechanisms of dysfunctional T-cell activation following major burn and mechanical trauma. Via comparative analysis of mRNA expression and protein release the major regulatory levels of IL-1 and IL-2 release under stressful conditions were to be determined in mitogen respectively LPS stimulated PBMC (peripheral blood mononuclear cells) cultures on consecutive days (D) 1, 3, 5, 7 and 10 post injury. Further, we wanted to scrutinize if inadequate IL-2 production post-trauma is possible due to a defective transduction of extracellular signals to the T-cell nucleus. In order to answer this question IL-2 mRNA expression and IL-2 protein releases were determined in PBMC cultures using the phosphokinase C (PKC) activator phorbol ester (PMA) as a costimulus together with PHA. When analyzing the cumulative data for IL-1 beta we saw until D 5 post-trauma a considerable impairment of the protein release in LPS stimulated PBMC cultures and recovery thereafter. In only a few individual PBMC cultures we saw a concurrence between the IL-1 beta mRNA signal intensity and the protein production. In the majority of the autoradiographies analyzed, the mRNA expression for IL-1 beta was considerably more distinct compared to controls while the corresponding protein release values were on control level or below. These results implicate that the suppression of IL-1 beta post-trauma is regulated mainly on a posttranscriptional level. Since Prostaglandin E2 (PGE2) has been found to have a vigorous impact on the IL-1 beta synthesis on the translational level, we assume that the high PGE2 levels post-trauma inhibit--via cAMP--sufficient IL-1 beta synthesis on the posttranscriptional level. IL-2 protein synthesis as well as mRNA expression in mitogen (PHA) stimulated PBMC cultures following trauma, was persistently and significantly depressed compared to controls during the time of observation. The addition of PMA as a costimulus to PHA, could induce very distinct mRNA signals for IL-2 with a signal intensity which was comparable to that found in the cells of healthy controls. Also the quantity of IL-2 protein release in the vast majority of all patients PBMC cultures following PHA/PMA induction was within the control range.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1990

Transforming growth factor beta 2 differentially modulates interleukin-1 beta- and tumour-necrosis-factor-alpha-stimulated phospholipase A2 and prostaglandin E2 synthesis in rat renal mesangial cells.

Treatment of rat glomerular mesangial cells with transforming growth factor beta 2 (TGF beta 2) stimulates prostaglandin E2 (PGE2) synthesis. Actinomycin D, cycloheximide and diclofenac attenuate the TGF beta 2-induced PGE2 formation. As shown previously, two proinflammatory cytokines, interleukin 1 beta (IL-1 beta) and tumour necrosis factor alpha (TNF alpha), are potent stimuli for PGE2 and phospholipase A2 secretion from mesangial cells. We report here that, whereas TGF beta 2 potentiates the IL-1 beta- and TNF alpha-evoked PGE2 production, it strongly inhibits the phospholipase A2 secretion induced by both cytokines. In addition, the inhibitory effect of TGF beta 2 on phospholipase A2 secretion is not due to the augmented PGE2 formation.

Animals↗
PubMed1990

Chicken growth-associated protein (GAP)-43: primary structure and regulated expression of mRNA during embryogenesis.

Growth-associated protein (GAP)-43 is a neuron-specific phosphoprotein whose expression is associated with axonal outgrowth during neuronal development and regeneration. In order to investigate the expression of this gene product in the early developing nervous system we have isolated and sequenced a cDNA for chicken GAP-43. The predicted amino acid sequence for chicken GAP-43 displays extensive similarity to that of the mammalian protein, particularly in the amino-terminal region, to which functional domains of the protein have been assigned. The cDNA hybridizes with two RNAs of differing molecular weights on Northern blots; both appear to be regulated similarly. These RNAs first appear in the brain on embryonic day 3 (E3), suggesting that GAP-43 begins to be expressed when neuroblasts become post-mitotic. In situ hybridization analysis reveals that GAP-43 RNA is expressed by several neural structures in the chick embryo, including derivatives of the neural tube, neural crest, and neuroectodermal placodes.

Amino Acid Sequence↗