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Biomedical subjects

Iris Barshack

Publications and source records attributed to Iris Barshack.

26 records · Page 2Linked to original sources

Immunity to heat shock protein 65--an additional determinant in intimal thickening.

Inflammation occurring consequent to vessel injury is thought to play an important role in atherosclerosis and restenosis. Autoimmunity to HSP65 has been shown to accelerate early atherogenesis in rabbits and mice, whereas in humans epidemiological data support this contention. In the current study, we explored the possibility of HSP65 influencing the extent of neointimal growth in the rat carotid injury model. Rats were either immunized with recombinant mycobacterial HSP65, heat killed preparation of Mycobacterium tuberculosis (MT), or with PBS, all emulsified in incomplete Freund's adjuvant. Animals were boosted with a similar protocol 3 weeks following the primary immunization and 2 weeks later carotid injury was applied in all animals by balloon inflation. Upon sacrifice 2 weeks later, sera were obtained for measurement of anti-HSP65 antibodies by ELISA, splenocytes were assessed for proliferative response to in vitro priming with HSP65, and carotid arteries were removed for evaluation of neointimal growth. Rats immunized with HSP65 exhibited a brisk and sustained humoral immune response to HSP65, and cellular immunity was also evident by thymidine uptake to splenocytes primed with the respective protein. Neointimal/medial ratio was significantly increased in HSP65 immunized rats, in comparison with MT injected and control animals. In conclusion, immunity to HSP65 can play a role in accelerating restenosis following arterial injury. These results should be further investigated in humans as they may provide a possible link between infections and restenosis/accelerated arteriosclerosis.

Animals↗

Immunohistochemical analyses of colon cancer in I1307K APC mutation carriers compared with noncarriers.

The I1307K APC germline mutation is associated with an increased risk to colorectal cancer (CRC). Whether and to what extent the somatic features and the molecular pathways of cancer development in mutation carriers differ from colorectal cancer in noncarriers remains unknown. To gain insight into this issue, 52 Israeli patients with CRC, 24 of whom were I1307K APC mutation carriers, were analyzed. The expression pattern of genes known to be involved in the pathogenesis of sporadic CRC was assessed immunohistochemically: E-cadherin, beta-catenin, deleted in colon cancer (DCC), and p53. In addition, tumors were genotyped for somatic activating mutations in Ki-ras oncogene. Mutation carriers and noncarriers were comparable in age at diagnosis (64.3 +/- 10.1 years for carriers and 60.8 +/- 14.1 years for noncarriers), tumor location in the colon, and disease stages. Tumors of I1307K mutation carriers displayed positive p53 immunostaining and loss of beta-catenin, E-cadherin, and DCC expression more often compared with noncarriers, although none of these differences reached statistical significance. Mutation frequencies in the Ki-ras gene were similar in both groups. In conclusion, the molecular pathways in CRC in I1307K APC mutation carriers are seemingly similar to those of sporadic cases, but a larger study is clearly needed.

Case-Control Studies↗

Cholesterol crystal embolization to the digestive system: characterization of a common, yet overlooked presentation of atheroembolism.

In the 1359 published patients with multiorgan cholesterol crystal embolism (CCE), the digestive system seems to be the third most frequently affected system. Yet, this system received hitherto only little attention in the medical literature. Therefore, the aim of the present study was to clinically characterize the subset of patients with CCE involving the digestive system, based on our institutional experience and a review of the literature. Cases with CCE in a 7-yr period (1995-2001) were sought in the computerized records of our medical center. Of the CCE patients, those with digestive system involvement that could be related to CCE were included in this study. The clinical features of CCE were determined and compared with those found in published series. Fourteen cases with CCE were identified, giving an annual incidence of 0.8 per 10(5). Digestive system involvement was found in five (36%) of the 14 patients. All five patients had established atherosclerosis. Precipitating factors were vascular manipulations or anticoagulation treatment in four of these five patients. Two patterns of disease appeared: acute catastrophic multiorgan disorder with poor prognosis and chronic and more indolent GI disease. Abdominal pain, GI bleeding, fever, and diarrhea were the most common manifestations, resulting from bowel infarction, mucosal ulcerations, hepatocellular liver disorder, and/or pancreatitis. CCE is a systemic disorder with a frequent involvement of the digestive system and protean clinical manifestations. It should, therefore, be considered in any gastroenterological patient with atherosclerosis and recent vascular manipulations or systemic anticoagulation.

Aged↗

Rhino-orbital and rhino-orbito-cerebral mucormycosis.

BACKGROUND: Rhino-orbito-cerebral mucormycosis (ROCM) is a devastating infection of immunocompromised hosts. We present our experience with 19 ROCM cases and attempt to define preferred diagnostic and treatment protocols. METHODS: All had tissue biopsies obtained studied by direct smear, histologic studies, and cultures. Imaging was obtained in 14 cases. RESULTS: Sixteen patients presented between August and November. Six had mixed fungal infections. Seven patients had end-stage underlying disease or infection and did not undergo surgery and 4 had an indolent form of disease. Patients were treated by surgery and by amphotericin B. The overall survival was 47%. CONCLUSIONS: ROCM may have seasonal incidence peaking in the fall and early winter. The therapeutic approach should be unchanged in cases of mixed fungal infections. Amphotericin B with aggressive debridement remains the mainstay of treatment. Early recognition and treatment are essential. A presentation and survival-dependent classification of ROCM are offered.

Adult↗

Different beta-catenin immunoexpression in carcinoid tumors of the appendix in comparison to other gastrointestinal carcinoid tumors.

Carcinoid tumor of the appendix is an endocrine tumor that is histologically similar to, but biologically less aggressive than carcinoids arising from other parts of the gastrointestinal tract. In this study, we examined E-cadherin, beta-catenin, DCC, p53 and Ki67 immunoexpression in cases of carcinoid of the appendix and made a comparison with non-appendiceal carcinoid tumors. Nine cases of appendiceal carcinoid and 11 biopsies of carcinoid of other parts of the gastrointestinal tract, five cases of the small intestine and six of the stomach were immunohistochemically evaluated for Ki67, p53, DCC, E-cadherin and beta-catenin. Two main patterns of beta-catenin staining were observed. The first pattern was characterized as membranous and cytoplasmic, and was seen mainly in the peripheral cells of the nests. The second pattern was diffuse, predominantly membranous. Most (five of seven) appendiceal carcinoids and only three of 11 non-appendiceal cases showed the first staining pattern (p < 0.05). Immunoexpression of E-cadherin and DCC was similar in both groups. p53 and Ki-67 immunostaining revealed stronger nuclear positivity in the non-appendiceal carcinoid tumors (statistically not significant). We found a pattern of beta-catenin immunostaining in typical carcinoid tumors of the appendix that was different from the pattern seen in non-appendiceal carcinoid tumors. This alteration suggests that carcinoid of the appendix may represent a different subtype of carcinoid tumors with different immunohistochemical and biological behavior.

Adult↗

Suppression of myosin-induced and adoptively transferred myocarditis by prior treatment with complete Freund's adjuvant.

BACKGROUND: We evaluated the effect of pretreatment with complete Freund's adjuvant (CFA) on experimentally induced myocarditis concomitant with the assessment of antigen-specific properties of disease-triggering lymphocytes. METHODS AND RESULTS: Rats pretreated with CFA a week prior to myosin immunization developed a significantly attenuated myocardial inflammation as compared to control-treated animals. Furthermore, prior administration of CFA virtually abolished histological evidence of myocarditis induced by transfer of antimyosin lymphocytes. CFA administered subcutaneously prior to myosin immunization resulted in a significant reduction in lymph node cell reactivity to myosin. Assessment of cultured medium from lymphocytes obtained from CFA-pretreated myosin-immunized rats revealed reduced levels of interferon gamma but an increased production of IL-10, suggesting an induction of a Thl to Th2 switch. CONCLUSIONS: Thus, CFA treatment suppressed both myosin-induced as well as adoptively transferred myocarditis concomitant with induction of antigen-specific unresponsiveness to myosin and skewing of the immune response in favor of a Th2-dominated profile.

Adjuvants, Immunologic↗

Wet SEM: a novel method for rapid diagnosis of brain tumors.

The authors present the application of wet SEM for histopathological assessment, a technology for imaging fully hydrated samples at atmospheric pressure in a scanning electron microscope (SEM). Both transmission and scanning electron microscopy techniques usually require long and complex sample preparation of the tissues. In marked contrast, a rapid preparation of tissues is described for evaluation by SEM imaging. The wet SEM technology successfully demonstrated both histological and ultrastructural features of several CNS tumors: Rosette formation and intracytoplasmic lumens were observed in ependymoma; numerous fibrillary processes in fibrillary astrocytoma; and focal rosette formation with no intracytoplasmic lumens in medulloblastoma. Application of this method simultaneously with frozen section may improve rapid intraoperative diagnosis of these intracranial tumors.

Astrocytoma↗

A novel method for "Wet" SEM.

Progress in the processing of wet tissues, without the need of fixation and complex preparation procedures, may facilitate the microscopic examination of tissues and cells. Microscopic examination of tissues is a central tool in clinical diagnosis as well as in diverse areas of research. The authors present the application of Wet SEM, a technology for imaging fully hydrated samples at atmospheric pressure in a scanning electron microscope (SEM). The technique is based on 2 principles. First, samples are imaged in sealed specimen capsules and are separated from the evacuated interior of the electron microscope by a thin, electron-transparent partition membrane that is strong enough to sustain a 1-atm pressure difference. Second, imaging is done in a SEM, based on detection of backscattered electrons, which penetrate a few microns into the specimen and thus give information on the cellular level.

Colitis↗