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D Benharroch

Publications and source records attributed to D Benharroch.

At least 37 records · Page 2Linked to original sources
PubMed1998

ALK-positive lymphoma: a single disease with a broad spectrum of morphology.

The t(2;5)(p23;q35) translocation, associated with anaplastic large-cell lymphoma (ALCL), results in the expression of a chimeric NPM-ALK protein that can be detected by the ALK1 monoclonal antibody. This report describes the morphologic and phenotypic spectrum of 123 cases of lymphoma that all express ALK protein. The results provide strong evidence that the morphologic patterns of ALCL described in previous reports as representing possible subtypes of ALCL, eg, common type, lymphohistiocytic, or small cell patterns, are morphologic variants of the same disease entity. All of these morphologic patterns could be found within this series, and in some patients different subtypes coexisted in a single biopsy or were found in successive biopsies from a single patient. The link between these morphologic subtypes is further reinforced by the presence in all cases of a highly characteristic large cell, with an eccentric nucleus and an eosinophilic paranuclear region. We suggest that this cell can be considered as a major distinguishing feature of ALK-positive lymphomas. Another characteristic of these tumors was the perivascular pattern of neoplastic cell infiltration seen in a significant number of cases. In addition to ALK protein, all tumors expressed epithelial membrane antigen and lacked CD15, features that may be of value in differentiating ALCL from Hodgkin's disease. In the majority of cases (84%), malignant cells showed both a cytoplasmic and nuclear staining for ALK1 and thus presumably carried the 2;5 translocation, but staining was restricted to the cytoplasm in a few cases, suggesting that translocations other than t(2;5) may induce expression of ALK protein. We conclude from this study that ALK-positive neoplasms represent a distinct entity. Because their morphology is often neither anaplastic nor large cell, we suggest that they should henceforward be referred to as ALK lymphomas.

Adolescent↗
PubMed1998

Extensive apoptotic death of rat colonic cells deprived of crypt habitat.

Apoptosis in cells of different lineages is restrained by survival signals which depend upon cell-to-cell communication. The aim of this study was to determine whether colonic cells deprived of crypt ambient are doomed to die prior to their normal chronological demise. Apoptosis was studied in rat whole colonic tissue, in isolated intact crypts, and in colonic cell populations collected from the crypt axis at different stages of proliferation and differentiation. In a number of experiments, cell harvest was performed in the presence of either a tetrapeptide (YVAD-CMK) inhibitor of interleukin-1beta-converting enzyme (ICE), or tyrphostin A25, a protein tyrosine kinase inhibitor, or sodium-orthovanadate, a phosphatase inhibitor. DNA fragmentation was assessed by electrophoretic and nonisotopic-labeling procedures. The ultrastructure of colonic tissue specimens and isolated cells was examined by transmission electron microscopy. Apoptosis in whole colonic tissue and in isolated crypts was confined predominantly to cells resident in the upper crypt regions. In contrast, extensive apoptotic death was observed in isolated colonic cells, irrespective of their developmental stage and positional hierarchy within the crypt continuum at harvest time. An apoptotic gradient, however, was evident. Exposure to YVAD-CMK resulted in a marked decrease in the number of apoptotic cells. Treatment with tyrphostin A25 caused a sharp rise in the apoptotic index; conversely, vanadate significantly impeded apoptosis. Cumulatively, these results indicate that disordered intercellular communication provokes unscheduled ICE-mediated apoptosis of colonocytes, and that local signals along the crypt continuum control both the reprieve from death and the timely demise of distinct colonic cell populations. Attenuation of tyrosine phosphorylation may be a contributory event in the acquisition of the apoptotic phenotype.

Amino Acid Chloromethyl Ketones↗
PubMed1998

Tumor necrosis factor-alpha and interleukin-6 are differently expressed by fresh human cancerous ovarian tissue and primary cell lines.

The expression levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were evaluated in normal and cancerous ovarian tissue and primary cell lines (PCL). Seven normal and 10 cancerous, formalin-fixed ovarian samples were examined for TNF-alpha and IL-6 expression by immunohistochemical staining using polyclonal rabbit anti-human TNF-alpha and IL-6 antibodies. Fresh normal and cancerous specimens were also examined for TNF-alpha and IL-6 secretion by bioassay and immunoassay prior to and following in vitro stimulation with lipopolysaccharide (LPS). The levels of IL-6 and TNF-alpha were higher in cancerous tissues than in normal specimens. In vitro stimulation of normal and cancerous ovarian tissues and PCL revealed their capacity to secrete IL-6. Cancerous tissue and PCL secreted higher levels than normal tissue and PCL. Stimulation of both groups with LPS increased their capacity to secrete IL-6. Optimal secretion of IL-6 by the cancerous tissue was observed after 72 hours with or without LPS (10 microg/ml). Normal tissue secreted maximal levels of IL-6 after 96 hours with or without LPS. PCL from normal ovarian tissue secreted IL-6 constitutively and optimal expression was detected after 96 hours. Carcinoma PCL from cancerous ovarian tissue demonstrated optimal secretion of IL-6 after 24 hours. Stimulation of both types of cells with LPS, IL-1 or TNF-alpha increased their capacity to secrete IL-6. TNF-alpha activity was detected in vitro only in supernatants of ovarian cancerous tissue and only after LPS stimulation; optimal levels were detected after 48 hours and 1 microg/ml LPS. Our results indicate that IL-6 and TNF-alpha are expressed in cancerous ovarian tissue at a higher level than in normal ovarian tissues. Carcinoma cells of ovarian tissues are the main cellular source of these cytokines. The conditions controlling the secretion of these cytokines, under in vitro conditions, are different in cancerous and normal ovarian tissues.

Cell Line↗
PubMed1997

Association of the Epstein-Barr virus with Hodgkin's disease in Southern Israel.

Epstein-Barr virus (EBV) has been frequently documented in the putative neoplastic Hodgkin-Reed-Sternberg (HRS) cells, in lymph nodes from patients with Hodgkin's disease (HD). This association varies in different geographic areas and between industrialized and developing countries, as does the epidemiological pattern of the disease. In the present study of 106 cases of HD from the Soroka Medical Center in Beer-Sheva, which serves as the only hospital for most of the southern part of Israel, we found an association with EBV expression in only 30% of the patients; 45% of mixed cellularity (MC) cases compared with 21% of nodular sclerosis (NS) cases were positive for EBV. The number of patients in the 0-14-year-old age group was limited; however, 8 of these II children were EBV positive. This low association rate of HD with the presence of EBV sequences is probably related to the small number of children in our series. A low proportion of EBV-associated disease in older adults may be contributory. Other factors may be involved.

Adolescent↗
PubMed1997

Gluteal manifestation of advanced Hodgkin's disease.

Hodgkin's disease (HD) is a nodal malignancy with a characteristically axial pattern of spread and with contiguous progression via lymphatic channels. Even when dissemination occurs beyond the lymphoreticular system, certain patterns of associated spread are frequently evident. We describe a case of nodular sclerosis HD with a 12-year indolent course and late involvement of the gluteal muscle. Initially, stage was IVb with spleen and bone marrow involvement, complicated by a Coomb's positive hemolytic anemia. Following chemotherapy, the patient had a partial response with the subsequent long course of slowly progressive disease invading first the urinary bladder and, later, the gluteus. Involvement of the gluteal muscle is a rare event in HD. Spread to the gluteus occurred most likely by contiguity, via retroperitoneal lymph nodes.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Distinct patterns of expression of interleukin-1 alpha and beta by normal and cancerous human ovarian tissues.

Immunohistochemical staining of normal and cancerous ovarian tissues has demonstrated that both IL-1 alpha and IL-1 beta are more strongly expressed in cancerous than in normal tissues and are secreted mainly by epithelial cells. We have shown by bioassay and immunoassay that cancerous, but not normal ovarian tissues constitutively secrete IL-1 in vitro. Activation of cancerous ovarian tissues by lipopolysaccharide (LPS) increased its capacity to secrete IL-1. Normal ovarian tissues secreted low amounts of IL-1 only after prolonged stimulation (72-96 h) by high doses of LPS (10-100 micrograms/ml). On the other hand, constitutive IL-1 was detected in homogenates of normal ovarian tissues and stimulation by LPS increased its capacity to produce IL-1. IL-1 beta was the main type of IL-1 secreted by cancerous ovarian tissues. IL-1 alpha was detected at lower levels. In contrast, in normal tissues similar amounts of both IL-1 alpha and IL-1 beta were detected in the supernatants. The levels of both types of IL-1, and also the bioactivity of IL-1 were significantly higher in cancerous than in normal ovarian tissues. Established primary cell lines from normal ovarian tissues did not secrete IL-1 into supernatants but did express it at very low levels. Stimulation with LPS did not affect the capacity of these cell lines to secrete IL-1 but it increased their capacity to express it. In contrast, primary established epithelial cell lines from cancerous ovarian tissues did secrete and express high levels of IL-1 and these levels were increased under stimulation with LPS. Cancerous ovarian tissues did not only secrete higher levels of both IL-1 alpha and beta than normal ovarian tissues, but also the mechanism controlling the secretion of these factors in cancerous ovarian tissues seemed to be different from that found in normal ovarian tissues. Our results suggest that paracrine/autocrine factors may be involved in the regulation of both types of IL-1 secreted by ovarian tissues. These cytokines may play a role in regulating the physiological, pathophysiological and oncogenic processes of the ovary.

Cell Line↗
PubMed1996

Frequent expression of the cell death-inducing gene Bax in Reed-Sternberg cells of Hodgkin's disease.

The expression of a cell death-inducing gene, Bax, was investigated in 52 cases of Hodgkin's disease in parallel with Epstein-Barr virus and was compared with the immunodetection of other apoptosis-regulating proteins, Mcl-1, Bcl-2, and Bcl-x. Bax immunostaining was found in 92% of the cases, among them 28% with a strong signal in more than 75% of the Reed-Sternberg cells. Mcl-1 was positive in 80% of the cases, whereas Bcl-2 and Bcl-x were found in 53% and 88% of the cases, respectively. Of 48 (89%) Bax-positive tumors, 43 were found to express apoptosis-inhibiting proteins such as Mcl-1 or Bcl-2. With the exception of 1 case, all Bax-positive tumors also expressed either Bcl-2, Bcl-x, Mcl-1, or combinations of these anti-apoptotic proteins. No correlation was found between Bax expression and the presence of apoptotic cells as detected by morphology and the in situ 3' OH-DNA end-labeling technique. Our findings show that the apoptosis-inducing gene Bax expression is frequently expressed in Hodgkin's disease, providing a potential explanation for the good chemoresponses generally obtained for patients with this neoplastic disorder.

Apoptosis↗
PubMed1996

Pelvic granulocytic sarcoma.

Granulocytic sarcoma is an uncommon extraskeletal tumor most frequently associated with leukemia. We present a case of bone location with unusual pattern in a patient with no evidence of myeloproliferative disorder at presentation or follow-up.

Adult↗
PubMed1995

The neuropathology of cerebrotendinous xanthomatosis revisited: a case report and review of the literature.

Cerebrotendinous xanthomatosis (CTX), a rare autosomal-recessive lipid storage disease, has been well characterized clinically and biochemically, and recently also from the molecular biological aspect. However, only a very few publications deal with its neuropathology, and views on its pathogenesis vary. Based on a recently examined case, we propose that central-peripheral distal axonopathy is the major pathogenetic mechanism of nervous system injury in CTX. The latter is characterized by white matter pathology, typically in form of long tract involvement with the more distal parts of the tract more severely affected. Most severely affected are the cerebellar white matter, the optic pathways and the long tracts of the brain stem and spinal cord, particularly the pyramidal tracts, although there is hardly a CNS region which does not display some form of pathology. Lesions are characterized by loss of myelinated fibers and accumulation of lipid products in form of foamy macrophages, clear oil-red-O-positive spaces and crystalline clefts, accompanied by gliosis, occasional axonal spheroids, and in the cerebellum--the most severely affected structure--also by multi-nucleated foreign body giant cells. Demyelination is not seen, and ultrastructurally myelin sheaths are normally structured. Signs of axonal degeneration are also present in the spinal roots. We hypothesize that the basic enzymatic defect in CTX leads to accumulation of metabolites in the brain which may be neurotoxic and may impair the metabolic apparatus of neurons with resultant axonopathy and subsequent nonspecific lipid deposition in the injured tracts.

Adult↗
PubMed1995

Expression of c-myc and c-ras oncogenes in the neoplastic and non-neoplastic cells of Hodgkin's disease.

The oncogenes c-myc and c-ras are known to elicit a cooperative tumorigenicity. In this study we investigated their role in the pathogenesis of Hodgkin's disease. The expression of these oncogenes was determined in Hodgkin's disease patients by avidin-biotin peroxidase complex immunohistochemical staining and was compared to their expression in patients with non-Hodgkin's lymphomas and inflammatory reactive lymph nodes. Of 29 examined patients with different histological types of Hodgkin's disease, 21 (72.4%) showed an elevated expression of c-myc and 28 (96.5%) of c-ras. Although this expression was marked especially in the neoplastic Reed-Sternberg cells, it was also noted in the numerous reactive cells present in the involved lymph nodes. By contrast, a much lower frequency of increased expression of these oncogenes was recorded in 19 patients with different grades of non-Hodgkin's lymphoma and in 29 patients with inflammatory reactive lymph nodes. The elevated expression of c-myc and c-ras in the neoplastic Reed-Sternberg cells may reflect an oncogenic event that directly activates these genes. However, their increased expression in the surrounding non-neoplastic cells probably results from signal transduction induced by certain growth-promoting factors possibly released by the Reed-Sternberg cells and that act paracrinally to stimulate the proliferation of the neighboring cells. Furthermore, the continuous c-ras elevation may impair the normal cell cycle control and thereby promote mutagenesis and overt malignancy.

Gene Expression↗
PubMed1995

Novel therapeutic strategies against cytomegalovirus infection.

Murine CMV (MCMV) presents a model for the study of the role of the immune system in the pathogenesis of human CMV (HCMV) infection. MCMV causes T cell immune impairment in the infected mice, manifested by suppressed responses to T cell mitogens and a profound reduction of Con A induced IL-2 production. Thymic humoral factor (THF-gamma 2) is an octapeptide which was first isolated from calf thymus, characterized and chemically synthesized. This peptide has been shown to have immunoregulatory effects in various systems. Systemic treatment of MCMV-infected mice with THF-gamma 2 resulted in the enhancement of protective efficacy of MCMV immune spleen cells and the reconstitution of mitogenic responses and IL-2 secretion.

Adoptive Transfer↗
PubMed1994

[Malignant lymphomas of the head and neck].

Review of 122 head and neck lymphomas diagnosed between 1976 and 1992 revealed 40 extranodal lymphomas. In 30 of them follow-up was available. We review the demographic, clinical, histological and immunohistochemical features of the 30 extranodal lymphomas according to site of origin. Comparison is made between these extranodal lymphomas and nodal non-Hodgkin's lymphomas and cases of Hodgkin's disease first diagnosed in the head and neck area.

Adolescent↗
PubMed1994

Floral variant of follicular lymphoma. Immunological and molecular studies support a neoplastic process.

In recent reports of the so-called "floral variant" of follicular lymphoma, an unusual variant of follicular lymphoma mimicking progressive transformation of germinal centers, questions have been raised regarding whether this process represents a malignant lymphoma. We studied 19 examples of the floral variant of follicular lymphoma and report our light microscopic, immunohistochemical, and molecular diagnostic findings. Morphologic changes consisted of effacement of normal lymph node architecture by follicles composed of atypical lymphocytes. The follicles were surrounded by prominent mantle zones that invaginated irregularly into the follicle centers, often imparting a "floral" appearance. Sufficient material was available for immunophenotypic or genotypic studies in 15 biopsies. Twelve of 15 cases studied by immunohistochemistry demonstrated phenotypes supporting a diagnosis of lymphoma. Five demonstrated light-chain restriction; one was an immunoglobulin-negative B-cell neoplasm; and six, in which only formalin-fixed, paraffin-embedded tissue was available, demonstrated overexpression of the bcl-2 protein. Southern blot analysis revealed evidence of clonal immunoglobulin heavy-chain gene rearrangement in all five cases tested. Overall, 12 of the 15 biopsies studied with these techniques showed immunologic or genotypic support for malignant lymphoma. The results of this study demonstrate that the floral variant of follicular lymphoma does indeed represent a malignant lymphoma.

Adult↗
PubMed1993

Cytokine-induced tumor immunogenicity: endogenous interleukin-1 alpha expressed by fibrosarcoma cells confers reduced tumorigenicity.

A direct correlation between the constitutive expression of IL-1 alpha and reduced tumorigenicity of fibrosarcomas was observed. This was established in fibrosarcoma cell lines which produce IL-1 alpha 'spontaneously', possibly as an aberration of oncogene-mediated transformation or upon IL-1 alpha gene transfer. In fibroblasts intracellular or membrane-associated IL-1 alpha is expressed, whereas the secreted form of the cytokine (IL-1 beta) is absent. Studies on the mechanisms of tumor regression of the IL-1 alpha-positive fibroblastoid cell lines indicated that IL-1 alpha potentiates the development of tumor cell-specific CTLs, which are of importance for tumor eradication. Thus, IL-1 alpha induces enhanced helper T cell activity which provides auxiliary signals for the growth/development of CTLs. Non-adaptive effector cells, activated locally by IL-1 alpha-expressing fibrosarcoma cells, also contribute to the eradication of IL-1 alpha-expressing fibrosarcomas. Local IL-1 alpha expression potentiated antigen presentation, by the malignant fibroblasts as well as by tissue-resident antigen-presenting cells, thus further potentiating anti-tumor immune responses. Mice, in which IL-1 alpha-producing tumors were regressed, developed an immune memory and rejected a challenge with an IL-1 non-producing violent tumor cell line. Endogenous IL-1 alpha activates a cytokine cascade (i.e., IL-6, CSF), produced by the malignant cells and possibly also by stromal cells. However, IL-1 alpha expression is essential for fibrosarcoma eradication, while other cytokines possibly amplify and sustain its action.(ABSTRACT TRUNCATED AT 250 WORDS)

3T3 Cells↗
PubMed1993

Pathogenetic aspects of persimmon bezoars. A case-control retrospective study.

To prove that ingestion of unpeeled persimmon is necessary for the development of a persimmon phytobezoar, we interviewed 15 patients, in most of whom this condition developed after peptic ulcer surgery. We compared the study group with a control group of 15 patients who had undergone peptic ulcer surgery but did not have a bezoar. In contrast with the control group, most patients with bezoars had ingested unpeeled fruits (p < 0.01). While ingestion of persimmon carried a 9.8-fold risk of bezoar development, ingestion of the unpeeled fruit increased the risk of this complication 56 times over that of age- and sex-matched controls. We recommend that patients who have undergone ulcer surgery be warned particularly against eating unpeeled persimmons.

Bezoars↗