Biomedical subjects

Daniel Benharroch

Publications and source records attributed to Daniel Benharroch.

18 recordsLinked to original sources

PubMed2006

Decidual NK cells regulate key developmental processes at the human fetal-maternal interface.

Human CD56(bright) NK cells accumulate in the maternal decidua during pregnancy and are found in direct contact with fetal trophoblasts. Several mechanisms have been proposed to explain the inability of NK cells to kill the semiallogeneic fetal cells. However, the actual functions of decidual NK (dNK) cells during pregnancy are mostly unknown. Here we show that dNK cells, but not peripheral blood-derived NK subsets, regulate trophoblast invasion both in vitro and in vivo by production of the interleukin-8 and interferon-inducible protein-10 chemokines. Furthermore, dNK cells are potent secretors of an array of angiogenic factors and induce vascular growth in the decidua. Notably, such functions are regulated by specific interactions between dNK-activating and dNK-inhibitory receptors and their ligands, uniquely expressed at the fetal-maternal interface. The overall results support a 'peaceful' model for reproductive immunology, in which elements of innate immunity have been incorporated in a constructive manner to support reproductive tissue development.

Angiogenesis Inducing Agents↗

PubMed2006

Collision sebaceous and basal cell carcinomas of the eyelid.

OBJECTIVE: To report a rare case of collision sebaceous and basal cell carcinomas of the eyelid. DESIGN: Interventional case report. METHODS: An 80-year-old woman presented with a nodular lesion at the center of the left lower eyelid. Small ulceration and madarosis were also present. RESULTS: The patient underwent excisional biopsy with frozen section control. Histopathology showed mixed sebaceous as well as basal cell carcinoma with uninvolved surgical margins. Oncologic survey did not disclose any other lesion. At 6-month follow-up, there was no evidence of recurrence, new lesions, or metastasis. CONCLUSION: Sebaceous and basal cell carcinomas can coexist in the eyelid within the same clinical lesion. Because of the potential risk of metastasis of sebaceous carcinoma, close follow-up of the patients is advisable.

Adenocarcinoma, Sebaceous↗

PubMed2006

Colitis cystica profunda and solitary rectal ulcer syndrome-polypoid variant: Two confusing clinical conditions.

Colitis cystica profunda and solitary rectal ulcer syndrome-polyoid variant are related chronic benign disorders with characteristic histological features. However, the clinical and endoscopic settings are confusing and misleading, suggesting other rectal conditions. We report a case of colitis cystica profunda and solitary rectal ulcer syndrome-polypoid variant that was misdiagnosed initially as an ulcerative proctitis. Since an occult malignancy could not be ruled out by superficial biopsies, the mass was removed by full-thickness transanal excision.

Journal Article↗

PubMed2006

Blastoschizomyces capitatus keratitis and melting in a corneal graft.

CASE REPORT: We present the first case, to our knowledge, of Blastoschizomyces capitatus keratitis and melting in a corneal graft. An 80-year-old man was treated for a large, severe corneal abscess and melting in the corneal graft of his right eye. Medical history was negative for hematologic disorders. Urgent penetrating keratoplasty was performed. COMMENTS: Corneal cultures grew B. capitatus. Systemic fluconazole and systemic and topical amphotericin B treatment were started. Three months after the last operation, no recurrence was observed and the graft remained clear. B. capitatus can rarely cause severe keratitis in patients even in the absence of hematologic disorders.

Aged, 80 and over↗

PubMed2005

Adherence of Hodgkin's disease-derived cell lines to the various lymph node compartments.

This adherence study was performed to clarify the trafficking of Hodgkin-Reed-Sternberg (HRS) cells in Hodgkin's disease (HD) and thus try to unravel the peculiar pathways of dissemination in the early stages of this malignant neoplasm. Using non-neoplastic human necropsy or biopsy lymph node as well as tonsillar tissue sections, we have studied the adherence of the KMH-2 and L-428 HD-derived cell lines and have compared it to that of peripheral blood lymphocytes (PBLs). In necropsy lymph nodes, cell lines predominantly adhered to sinuses and paracortex, whilst adhered PBLs were distributed more widely. In biopsy lymph nodes, adhesion to high endothelial venules (HEVs) was rarely observed, whilst cell lines were found to adhere to sinuses. Inhibition by EDTA pretreatment affected adherence to HEVs as well as to sinuses and paracortex to a similar degree. Our findings point to the possible importance of the lymph node sinuses and paracortex in relation to homing of the HRS cells and their dissemination during the early stages of HD. The results suggest a significant primary role of the extracellular matrix of the paracortex and sinuses in the homing of HRS cells, with the HEVs of only secondary importance.

Biopsy↗

PubMed2004

Diffuse large B-cell lymphoma with anaplastic features and focal low-grade mucosa-associated lymphoid tissue lymphoma component of the stomach.

We describe an 83-year-old man diagnosed as having diffuse, large B-cell lymphoma with anaplastic features and CD30 expression of the stomach. Focally, the tumor showed typical low-grade mucosa-associated lymphoid tissue lymphoma. We are not aware of a previous report on the transformation of low-grade gastric lymphoma of mucosa-associated lymphoid tissue type into an "anaplastic," large B-cell tumor.

Aged↗

PubMed2004

Hyperplastic mesothelial cells in subpleural lymph nodes mimicking metastatic carcinoma.

We describe a patient with a history of poorly differentiated adenocarcinoma of the stomach in whom hyperplastic mesothelial cell inclusions were present in subpleural lymph nodes. The involved lymph nodes were embedded in a lipoma in the parietal pleura. The role of histochemistry and immunohistochemistry in the differentiation of these inclusions from metastatic carcinoma is discussed.

Adenocarcinoma↗

PubMed2003

Differential effects of IL-1 alpha and IL-1 beta on tumorigenicity patterns and invasiveness.

In this study, we show that distinct compartmentalization patterns of the IL-1 molecules (IL-1alpha and IL-1beta), in the milieu of tumor cells that produce them, differentially affect the malignant process. Active forms of IL-1, namely precursor IL-1alpha (pIL-1alpha), mature IL-1beta (mIL-1beta), and mIL-1beta fused to a signal sequence (ssIL-1beta), were transfected into an established fibrosarcoma cell line, and tumorigenicity and antitumor immunity were assessed. Cell lines transfected with pIL-1alpha, which expresses IL-1alpha on the membrane, fail to develop local tumors and activate antitumor effector mechanisms, such as CTLs, NK cells, and high levels of IFN-gamma production. Cells transfected with secretable IL-1beta (mIL-1beta and ssIL-1beta) were more aggressive than wild-type and mock-transfected tumor cells; ssIL-1beta transfectants even exhibited metastatic tumors in the lungs of mice after i.v. inoculation (experimental metastasis). In IL-1beta tumors, increased vascularity patterns were observed. No detectable antitumor effector mechanisms were observed in spleens of mice injected with IL-1beta transfectants, mock-transfected or wild-type fibrosarcoma cells. Moreover, in spleens of mice injected with IL-1beta transfectants, suppression of polyclonal mitogenic responses (proliferation, IFN-gamma and IL-2 production) to Con A was observed, suggesting the development of general anergy. Histologically, infiltrating mononuclear cells penetrating the tumor were seen at pIL-1alpha tumor sites, whereas in mIL-1beta and ssIL-1beta tumor sites such infiltrating cells do not penetrate inside the tumor. This is, to our knowledge, the first report on differential, nonredundant, in vivo effects of IL-1alpha and IL-1beta in malignant processes; IL-1alpha reduces tumorigenicity by inducing antitumor immunity, whereas IL-1beta promotes invasiveness, including tumor angiogenesis, and also induces immune suppression in the host.

Adjuvants, Immunologic↗

PubMed2003

IL-1 is required for tumor invasiveness and angiogenesis.

Here, we describe that microenvironmental IL-1 beta and, to a lesser extent, IL-1 alpha are required for in vivo angiogenesis and invasiveness of different tumor cells. In IL-1 beta knockout (KO) mice, local tumor or lung metastases of B16 melanoma cells were not observed compared with WT mice. Angiogenesis was assessed by the recruitment of blood vessel networks into Matrigel plugs containing B16 melanoma cells; vascularization of the plugs was present in WT mice, but was absent in IL-1 beta KO mice. The addition of exogenous IL-1 into B16-containing Matrigel plugs in IL-1 beta KO mice partially restored the angiogenic response. Moreover, the incorporation of IL-1 receptor antagonist to B16-containing plugs in WT mice inhibited the ingrowth of blood vessel networks into Matrigel plugs. In IL-1 alpha KO mice, local tumor development and induction of an angiogenic response in Matrigel plugs was less pronounced than in WT mice, but significantly higher than in IL-1 beta KO mice. These effects of host-derived IL-1 alpha and IL-1 beta were not restricted to the melanoma model, but were also observed in DA/3 mammary and prostate cancer cell models. In addition to the in vivo findings, IL-1 contributed to the production of vascular endothelial cell growth factor and tumor necrosis factor in cocultures of peritoneal macrophages and tumor cells. Host-derived IL-1 seems to control tumor angiogenesis and invasiveness. Furthermore, the anti-angiogenic effects of IL-1 receptor antagonist, shown here, suggest a possible therapeutic role in cancer, in addition to its current use in rheumatoid arthritis.

Adenocarcinoma↗

PubMed2003

Selectins and anti-CD15 (Lewis x/a) antibodies transmit activation signals in Hodgkin's lymphoma-derived cell lines.

OBJECTIVE: The CD15 (Lewis x) cell surface oligosaccharide moiety is expressed in a variety of normal and tumor cells and recognized by selectins. The detection of CD15 on malignant Hodgkin-Reed-Sternberg (HRS) cells serves as a diagnostic marker of Hodgkin's lymphoma (HL). Retrospective studies suggest that the expression of nonsialylated CD15 molecules on HRS cells has a positive prognostic value while presence of sialylated CD15 may correlate with a poor outcome. However, the relevance of the CD15 antigen expression to the pathobiology of the disease is not clear. In this work, we studied the contribution of CD15 to cell adhesion and the activation of signaling cascades in two HL-derived cell lines, KMH-2 and L428. METHODS: Immobilized anti-CD15 monoclonal antibodies and recombinant E- and P-selectins were used to activate KMH-2 and L428 cells. Immunoblotting, immunoprecipitation, and the electrophoretic mobility shift assay were performed to detect tyrosine phosphorylation of c-Cbl, c-Jun nuclear translocation, and AP-1 DNA binding. RESULTS: Treatment of cells with antibodies against the sialylated and nonsialylated forms of CD15, or with immobilized selectins, induced changes in cell morphology. Tyrosine phosphorylation of c-Cbl, together with tyrosine phosphorylation of multiple protein substrates, was also induced. In addition, binding of the CD15 molecules induced nuclear translocation of c-Jun and an increase in AP-1 DNA binding activity. CONCLUSIONS: We suggest that CD15 has a dual physiological role, both as an adhesion molecule recognized by selectins and as a regulatory molecule upstream to specific intracellular signaling cascades with implications to the pathogenesis of HL.

Cell Adhesion↗

PubMed2003

Local delivery of IL-1 alpha polymeric microspheres for the immunotherapy of an experimental fibrosarcoma.

The immunotherapeutic effects of interleukin-1 alpha (IL-1 alpha) encapsulated within 1-5 microns-diameter poly (D, L-lactide) microspheres and delivered intratumorally into fibrosarcoma-bearing mice were investigated. Such microspheres are avidly taken up by macrophages, and directing IL-1 alpha into these cells may activate them to participate in antitumor responses in vivo. Treating of tumor-bearing mice with IL-1 alpha microspheres has increased their survival rate, as compared with control mice, untreated or treated with microspheres containing bovine serum albumin (BSA). In 20% of the IL-1 alpha-treated mice, a complete tumor regression was observed. The timing of treatment with IL-1 alpha microspheres was crucial; optimal survival and regression rates were observed in mice treated 24 hr postinjection of the tumor cells. Administration of three doses of IL-1 alpha microspheres on days 1, 8, and 15 postinjection of tumor cells resulted in longer survival rates. Histopathology studies on regressed tumors revealed extensive areas of tumor cell degeneration and necrotic tissue surrounded by a large number of inflammatory cells. A similar picture was observed when IL-1 alpha microspheres were administered into the footpad of control mice, whereas the tissue reaction to BSA microspheres was much milder. Thus, it appears that tumor regression is mainly due to the antitumor effects of IL-1 alpha. Further studies are being aimed at increasing the immunotherapeutic efficiency of microspheric IL-1 alpha, used as a single treatment or in combination with other treatment modalities.

Animals↗

PubMed2003

Extraction of the radial artery during transradial coronary angiography: an unusual complication.

The transradial approach is currently an accepted alternative for vascular access during percutaneous coronary interventions. Access-site complications, such as mild hematoma, hematic effusions, and reduced or absent radial pulse, have been reported. We report the occurrence of total extraction of the radial artery during sheath removal. The occurrence of this complication emphasizes the need for meticulous attention and prudence when a patient complains of local pain during sheath extraction.

Angina, Unstable↗

PubMed2002

Isolated splenic cat scratch disease in an immunocompetent adult woman.

We report a case of isolated splenic cat scratch disease in an immunocompetent woman. The clinical presentation of prolonged fever, night sweats, weakness, and intrasplenic lesions was highly suggestive of lymphoma. This is the second reported case of isolated splenic cat scratch disease in an adult and the first in a healthy adult.

Adult↗

PubMed2002

Is classical Hodgkin's disease indeed a single entity?

We present a retrospective clinicopathological study on the significance of the histologic type of classical Hodgkin's disease (HD) in a cohort of patients from southern Israel. This was performed to critically evaluate the generally accepted view that classical HD is a single clinicopathological entity and the resultant impression that its segregation into four different histologic types remains essential only for the pathologist in his diagnostic endeavor. We confirmed the existence of a uniform response of nodular sclerosis (NS), and mixed cellularity-lymphocyte depletion (MC-LD)-HD to treatment, consideration being given to other classical prognostic factors. We also accept the fact that histological type is not a significant independent factor in terms of survival. Our findings, however, do suggest that NS-HD, on the one hand, and MC-LD-HD, on the other, are distinct biologic entities. Cases of NS differ significantly from those of MC-LD-HD with regard to sex and age distribution, and in the expression of several antigens and gene products, including sialylated-CD15, CD30, LMP1 and the p53 and mdm-2 gene products.

Adolescent↗

PubMed2002

Inflammatory pseudotumor (plasma cell granuloma) of the pelvic cavity. A case report.

BACKGROUND: Inflammatory pseudotumor (IPT), also called plasma cell granuloma, is a rare, benign, tumorlike lesion composed of proliferating spindle cells admixed with an inflammatory infiltrate and usually affecting the lungs. Other locations can also be affected. CASE: An 18-year-old woman complained of abdominal pain and discomfort. Sonographic evaluation revealed a hyperechogenic mass measuring 32 x 36 mm and located between the right ovary and uterus. CBC showed mild leukocytosis. Laparoscopic resection of the mass revealed histologically an inflammatory pseudotumor. CONCLUSION: IPT may occur at any age and affects both sexes equally. The clinical presentation usually includes fever, leukocytosis and weight loss, although many cases are asymptomatic, especially in the pelvis. The lesion usually presents with distinct borders and a firm consistency and is tan to white. The course of IPT is usually benign and self-limited. Surgical resection is the most common therapy, whereas corticosteroids and, in rare cases, chemotherapy are used. Recurrences have been described. Because of the rarity of this condition, it is unusual for the diagnosis to be made preoperatively.

Adolescent↗

PubMedDate not supplied

Atraumatic rupture of the spleen associated with hemophagocytic syndrome and isolated splenic peliosis. Case report.

Atraumatic rupture of the spleen is an uncommon condition that may be associated with various etiologies. The hemophagocytic syndrome (HS) and isolated splenic peliosis are two rare conditions, each of which has previously been described in association with splenic rupture. We describe a unique case of atraumatic splenic rupture in which concurrent HS and splenic peliosis were diagnosed following splenectomy. Given that both these rare conditions have probably caused the splenic rupture, a possible association between these entities is discussed.

Cysts↗

PubMedDate not supplied

Genomic instability in drug-resistant human melanoma cell lines detected by Alu-I-arbitrary-primed PCR.

Destabilization of the genome seems to be an important step in the generation of drug resistance. Since malignant melanoma is extremely resistant to chemotherapy, we used human melanoma cell lines as a model to investigate the putative role of genomic instability in the appearance of drug resistance. Drug-resistant variants were obtained with MNNG, BiCNU, doxorubicin and 6-thioguanine selection of melanoma cell lines. Genomic alterations in variant cells were detected by arbitrarily primed PCR of Alu-I digested DNA (Alu-I-AP-PCR). Two differential DNA bands from 6-TG-resistant cell variants were sequenced. One is homologous to intron 25 of the neural cell adhesion molecule L1 and the second to endogenous retroviral LTR sequences. We have shown that drug-resistant melanoma cell lines accumulate genomic alterations that are efficiently detected by Alu I-AP-PCR and that drug-resistant variants show genomic instability, including variations in LTR sequences, which may be associated with the appearance of the drug resistance phenotype.

Alu Elements↗

PubMedDate not supplied

Identification of differentially expressed mRNA transcripts in drug-resistant versus parental human melanoma cell lines.

BACKGROUND: Malignant melanoma resistance to chemotherapy remains a major limitation to treatment. Our aim was to identify genes associated with drug resistance, in order to better understand the molecular events underlying the drug-resistant phenotype. MATERIALS AND METHODS: A human melanoma cell line and its drug-resistant variants obtained by selection with MNNG or 6-thioguanine were used. Alterations in gene expression were characterized by differential display reverse transcription-polymerase chain reaction (DDRT-PCR). Prominent mRNA fragments present in selected variants and not in the parental cells were identified and characterized by cloning and sequencing. Differential expression was confirmed by real-time RT-PCR. RESULTS: Three functionally distinct transcriptional products were demonstrated: the chaperonin subunit TCP 1-zeta-6A (CCT6A), the hyaluronan receptor CD44 and LPPR-2, the lipid phosphate phosphatase-related protein type-2. CONCLUSION: Genes with altered expression were identified in drug-resistant variants. The identified molecules may provide new insights into the molecular basis for melanoma resistance to chemotherapy.

Base Sequence↗