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Biomedical subjects

I Benjamin

Publications and source records attributed to I Benjamin.

At least 37 records · Page 2Linked to original sources
PubMed1997

Molecular structure and dynamics at liquid-liquid interfaces.

The structural, dynamical, and electrical properties of the interface between two immiscible liquids are described. The adsorption of solute molecules and the processes of ion transfer across the interface and of electron transfer at the interface are discussed. The microscopic perspective is emphasized by focusing on selected recent experimental results and on results obtained from molecular dynamics and Monte Carlo computer simulations. The validity of some of the existing models of the interface is examined. A proper account of the molecular structure of the interface is important for understanding solvation and charge transfer processes at the interface.

Adsorption↗
PubMed1997

Immuno and functional characterization of CFTR in submandibular and pancreatic acinar and duct cells.

Cystic fibrosis results from defective Cl- channel activity mediated by the cystic fibrosis transmembrane conductance regulator (CFTR) gene product. In the gastrointestinal tract this is manifested in abnormal salivary secretion and pancreatic insufficiency. This is generally attributed to defective Cl- transport by the ductal system of the glands. We provide the first immunocytochemical and functional evidence for expression of CFTR protein and Cl- current in rat and mouse submandibular gland (SMG) and pancreatic acinar cells, a site proximal to the ductal system of these secretory glands. Monoclonal and polyclonal antibodies recognizing COOH-terminal epitopes of CFTR show that duct and acinar cells from the two glands express CFTR in the luminal membrane. Specificity of the polyclonal antibody was verified by absence of staining in duct and acinar cells of the SMG of cf-/cf- and delta F/delta F mice. Identification of CFTR in acinar cells was aided by demonstrating coexpression of CFTR and type 3 inositol 1,4,5-trisphosphate receptors in the luminal pole of acini and absence of type 3 inositol 1,4,5-trisphosphate receptors in ducts. Electrophysiological characterization in single SMG duct and acinar cells shows the presence of a protein kinase A-activated, voltage- and time-independent, ohmic Cl- current and absence of repolarization-dependent tail currents, all of which are kinetic properties of the CFTR-dependent Cl- channel. In addition, the channel was activated by the nonhydrolyzable ATP analog 5'-adenylylimidodiphosphate and the benzimidazalone NS-004. Channels activated by all activators were inhibited by glibenclamide and a known inhibitory antiserum [anti-CFTR-(505-511)]. Combined immunologic, functional, and pharmacological evidence allows us to conclude that acinar cells of the SMG and pancreas express functional CFTR-dependent Cl- channels. Because this site is proximal to the duct, modification of activity of this channel in acinar cells is likely to contribute to abnormal salivary secretion and pancreatic insufficiency typical of cystic fibrosis.

Animals↗
PubMed1996

Clinical and pathological features of ovarian cancer in women with germ-line mutations of BRCA1.

BACKGROUND: We tested the hypothesis that ovarian cancers associated with germ-line mutations of BRCA1 have distinct clinical and pathological features as compared with sporadic ovarian cancers. METHODS: We reviewed clinical and pathological data on patients with primary epithelial ovarian cancer found to have germ-line mutations of BRCA1. Survival among patients with advanced-stage cancer and such mutations was compared with that in control patients matched stage, grade, and histologic subtype of the tumors. A combination of single-strand conformation and sequencing analyses was used to examine the 22 coding exons and intronic splice-donor and splice-acceptor regions of BRCA1 for mutations in pathological specimens. Alternatively, some patients were known to be obligate carriers of the mutant BRCA1 gene because of their parental relationships with documented mutant-gene carriers. RESULTS: We identified 53 patients with germ-line mutations of BRCA1. The average age at diagnosis was 48 years (range, 28 to 78). Histologic examination in 43 of the 53 patients showed serous adenocarcinoma. Thirty-seven tumors were of grade 3, 11 were of grade 2, 2 were of grade 1, and 3 were of low malignant potential. In 38 patients, the tumors were of stage III; 9 patients (including those with tumors of low malignant potential) had stage I disease, 5 had stage IV, and 1 had stage II. As of June 1996, with a median follow-up among survivors of 71 months from diagnosis, 20 patients had died of ovarian cancer, 27 had no evidence of the disease, 4 were alive with the disease, and 2 had died of other diseases. Actuarial median survival for the 43 patients with and advanced-stage disease was 77 months, as compared with 29 months for the matched controls (P<0.001). CONCLUSIONS: As compared with sporadic ovarian cancers, cancers associated with BRCA1 mutation appear to have a significantly more favorable clinical course.

Actuarial Analysis↗
PubMed1996

Mutations of the BRCA2 gene in ovarian carcinomas.

Inherited mutations in the recently discovered BRCA2 gene are believed to be responsible for a significant fraction of early-onset hereditary breast cancers. Unlike BRCA1, however, which confers a high risk to both breast and ovarian cancer, the incidence of ovarian cancer appears to be much lower In BRCA2-linked families, causing uncertainty as to the relevance of BRCA2 to hereditary ovarian cancer. Numerous allelotype studies indicate that allelic deletions Including the BRCA2 locus on chromosome 13q are common in ovarian cancers in general, suggesting that somatic mutations of this gene may be involved in sporadic ovarian tumorigenesis. The purpose of this study was to test the hypothesis that germline or somatic mutations of BRCA2 are associated with hereditary and/or sporadic ovarian cancers, respectively. The entire 10.2-kb coding region of BRCA2 was screened for mutations in 130 consecutive ovarian tumors, the only selection criterion being a pathological diagnosis of epithelial ovarian carcinoma. Loss of heterozygosity at markers flanking BRCA2 was observed in 56% of the tumors. Four germline mutations and two somatic mutations were identified; two of the germline mutations are recurrent, having been previously described. Remarkably, the patients with germline mutations were late-onset cases with no medical or family histories suggestive of hereditary cancer. These data suggest that mutations of BRCA2 are rare in sporadic ovarian cancers, and that the proportion of ovarian cancers resulting from hereditary predisposition may be higher than previously suspected based on estimates derived from studies of highly penetrant genetic loci.

Aged↗
PubMed1996

OncoLink: a cancer information resource for gynecologic oncologists and the public on the Internet.

The Internet is a computer network accessible to over 30 million computers users worldwide. By default, it has become the "information superhighway" that is growing at an explosive rate of between 1 and 2 million new users per month. Internet contains thousands of information of interest to cancer patients and healthcare professionals. Identifying the outstanding "golden" resources from the chaos is difficult. To address this problem and to provide information specific to gynecologic oncology, we developed a cancer information server called "OncoLink" at our institution that is available at no cost 24 hr per day, 7 days per week to all Internet users. OncoLink has two major goals: (1) To provide quality, original content for cancer patients and healthcare professionals and (2) to provide well-organized, consistent access to existing Internet cancer resources. This service may be used by anyone with a Microsoft Windows, Apple Macintosh, or UNIX computer. The service is rich in multimedia content containing text, pictures, illustrations, sound, and video. The information includes (1) original content written by authors at our institution, (2) original content submitted by authors from other institutions and, (3) publicly available information from other resources. Patient-oriented articles, physician-oriented review articles, and NIH, NCI, and FDA documents are available. All content is reviewed by an Editorial Board prior to posting. We have kept a detailed log file of each time the system has been accessed by an Internet user. OncoLink went online in March 1994. During the first 18 months (542 days) of operation, the service received 4,051,901 request for information from 105,589 unique Internet addresses worldwide. There is tremendous public and professional demand for online cancer information via the Internet. We feel that the Internet is an outstanding vehicle for providing quality cancer information for gynecologic oncologist other healthcare professionals, and the public.

Computer Communication Networks↗
PubMed1996

Adenovirus-mediated gene therapy of ovarian cancer in a mouse model.

OBJECTIVE: Our purpose was to test the feasibility of adenovirus-mediated gene therapy of ovarian cancer. STUDY DESIGN: Ovarian cancer cell lines were exposed to an adenovirus vector expressing a reporter gene (lacZ) and to the same vector bearing the herpes simplex virus thymidine kinase gene (Ad.RSVtk) followed by ganciclovir. lacZ expression and growth inhibition were quantitated. Immunodeficient mice were injected intraperitoneally and subcutaneously with human ovarian cancer cells and treated with Ad.RSVtk and ganciclovir. Statistical analyses included one-way analysis of variance and t tests. RESULTS: Staining for lacZ demonstrated viral transduction in vitro. After exposure to Ad.RSVtk all cell lines showed significant (p < 0.0001, analysis of variance) cytotoxicity to ganciclovir. Human ovarian tumor cells established subcutaneously or intraperitoneally in immunodeficient mice responded to therapy with Ad.RSVtk followed by ganciclovir. Treated mice had a 10- to 20-fold lower subcutaneous tumor burden than did control mice. Additionally, no intraperitoneal tumors were observed in treated mice. CONCLUSIONS: Ovarian cancer cells are readily transduced with recombinant adenovirus and become sensitive to ganciclovir after transduction with Ad.RSVtk. These data support the development of this method for human clinical trials.

Adenoviridae↗
PubMed1996

Expression and mutational analysis of P53 in stage IB and IIA cervical cancers.

OBJECTIVE: This study evaluates overexpression of the p53 protein and point mutation in the P53 gene in a group of patients with stage IB and IIA cervical cancer. STUDY DESIGN: We reviewed the medical records of all patients who underwent radical hysterectomy for the treatment of stage IB and IIA cervical cancer between 1980 and 1985 at Memorial Sloan-Kettering Cancer Center. Overexpression of p53 protein was determined with the use of immunohistochemistry on fixed and paraffin-embedded tissue. Two blocks were selected for each tumor, and tissue sections from each block were tested with both monoclonal (Ab-6) and polyclonal (CM-1) anti-p53 antibodies. Molecular analysis for determination of specific P53 gene mutations was performed with single-strand conformation polymorphism analysis. A group of 132 patients was identified for inclusion in the study. RESULTS: Fifty-eight of 132 tumors (44%) showed overexpression of the p53 protein and were subjected to molecular analysis. Discrepancy between pairs of blocks (7/132, 5.3%) and between antibodies for the same block (5/264, 1.9%) was uncommon. High-level overexpression was rare (5/132, 3.8%). No difference in survival was found on the basis of overexpression of p53 protein. Only one of the 58 cases (1/58, 1.7%) that showed overexpression of the p53 protein exhibited a point mutation (exon 8) in P53 by single-strand conformation polymorphism. This case had a low level of overexpression of p53 protein on immunohistochemistry. CONCLUSIONS: Low levels of overexpression of p53 were frequently seen in early cervical cancers (40/132, 30%). However, mutation of the P53 gene was rarely seen in these tumors. Overexpression of p53 protein as detected by immunohistochemistry is not predictive of a somatic mutation in the P53 gene in cervical cancer. Molecular analysis is required for confirmation of P53 mutations in these tumors.

Female↗
PubMed1996

Racial differences in survival from gynecologic cancer.

OBJECTIVE: To determine whether survival from gynecologic cancer is different between African-American and white patients at an inner-city hospital with both a large clinic and a private service. METHODS: We studied 538 patients (89 African American, 449 white) diagnosed with cervical, uterine, or ovarian cancer at a single institution from January 1, 1989 through December 31, 1993. Information was obtained on age, stage, site of disease, histology, and type of health insurance (public or commercial). Insurance coverage was used as a proxy for socioeconomic status. Overall survival was estimated by the method of Kaplan and Meier and compared by the log-rank test. Cox proportional hazard modeling was used to evaluate the effects of multiple factors on survival. RESULTS: African-American patients were significantly older and were more likely to have cervical cancer and public insurance than white patients. Overall survival was worse for African-American patients than for white patients (P < .05). However, stage for stage, there was no significant difference in survival between the groups. There was also no difference when patients were grouped by insurance status. African Americans had a significantly worse survival for cervical cancer than whites, and African-American patients older than 65 years had a worse survival than whites of similar age. On multivariate analysis, only stage and insurance coverage were significant predictors of survival. CONCLUSIONS: African-American patients with gynecologic cancer at our institution have worse overall survival than white patients. The survival difference seems to be due predominantly to differences in socioeconomic status and stage at diagnosis.

Black People↗
PubMed1996

Technical and editorial administration of a World-Wide-Web site during a period of rapid growth: the OncoLink experience.

OncoLink is a cancer information resource on the World-Wide-Web (WWW) that provides a wide variety of information for cancer patients and healthcare providers. Since its introduction in March, 1994 it has enjoyed success as demonstrated by an over 31-fold increase in usage as of February, 1996. Current utilization exceeds 1.1 million accesses per month. The content of OncoLink has also expanded greatly, with new items being added daily. In addition, OncoLink has been the recipient of numerous awards from a variety of agencies and organizations. During this period of rapid growth, the complexity of managing and maintaining OncoLink has likewise increased. This work may be divided into three categories: content editing, technical (or production) editing, and web site maintenance. Consequently, we have developed numerous administrative procedures to handle this workload. After implementing these new administrative strategies, we were able to greatly reduce the need for face-to-face meetings of our Editorial and Production Staffs. This paper describes our experience with developing efficient strategies for managing the daily operation of OncoLink during a period of rapid growth.

Computer Communication Networks↗
PubMed1995

Scattering of water from the glycerol liquid-vacuum interface.

Molecular dynamics calculations of the scattering of D2O from the glycerol surface at different collision energies are reported. The results for the trapping probabilities and energy transfer are in good agreement with experiments. The calculations demonstrate that the strong attractive forces between these two strongly hydrogen bonding molecules have only a minor effect on the initial collision dynamics. The trapping probability is influenced to a significant extent by the repulsive hard sphere-like initial encounter with the corrugated surface and, only at a later stage, by the efficiency of energy flow in the multiple interactions between the water and the surface molecules.

Chemical Phenomena↗
PubMed1995

Expression and mutation analysis of the p53 gene in uterine papillary serous carcinoma.

BACKGROUND: The status of p53 protein expression was determined by immunohistochemistry and correlated with genetic analysis and clinical outcome in patients with uterine papillary serous carcinoma (UPSC). METHODS: Twenty-two patients with UPSC were identified and immunohistochemical staining of p53 protein was performed. Staining was analyzed by quantitating nuclear reactivity in 500 randomly counted cells per specimen. DNA analysis was performed on the tumors using single-strand conformation polymorphism (SSCP) analysis of exons 4-10 of the p53 gene, followed by DNA sequencing of all variants. Clinical data and patient status were ascertained from chart reviews. RESULTS: Sixteen of the 22 (73%) tumors were scored as p53-overexpressing as determined by immunohistochemical analysis. Patients whose tumors overexpressed p53 had a statistically significant shorter survival than those whose tumors did not (P < 0.022). DNA analysis of the 22 tumors revealed five with mutations of the p53 gene. Only three of these mutations were observed in tumors that overexpressed p53. CONCLUSIONS: A relatively large percentage of UPSC tumors exhibited high p53 immunoreactivity. Overexpression is correlated with poor prognosis. Positive immunohistochemistry for p53 protein in UPSC is not necessarily indicative of a genetic mutation.

Aged↗
PubMed1995

Platinum-based chemotherapy for advanced-stage serous ovarian carcinoma of low malignant potential.

PURPOSE: To evaluate the effect of platinum-based chemotherapy on tumor response in patients with advanced-stage serous ovarian carcinoma of low malignant potential. PATIENTS AND METHODS: We conducted a retrospective review of hospital records, pathology slides, and office charts of patients identified as having Stage III or IV serous ovarian cancer of low malignant potential. RESULTS: Between November 1979 and April 1993, 21 patients with advanced-stage serous ovarian carcinoma of low malignant potential received platinum-based chemotherapy following initial cytoreductive surgery. The amount of residual disease was recorded in 20 patients; 8 (40%) had macroscopic residual tumor < 2 cm in largest diameter, and 12 (60%) had only microscopic disease. Sixteen patients underwent a second-look laparotomy following chemotherapy; 10 (62.5%) had no evidence of disease, 1 (6%) had a partial response, 2 (12.5%) had stable disease, and 3 (19%) had progressive disease. During a mean follow-up of 64 months, only 1 patient had died of disease. She had progressive disease noted at second-look laparotomy. Five of 6 patients who did not have a complete response to initial chemotherapy underwent further therapy with oral etoposide (1), intraperitoneal platinum (2), intraperitoneal mitoxantrone (1), or both (1). The sixth patient received no further therapy. Three of the patients subsequently receiving salvage intraperitoneal therapy underwent a third-look laparotomy. Two had partial responses noted, while the third patient had stable disease. CONCLUSIONS: Platinum-based chemotherapy is effective in achieving surgically documented responses in patients with advanced-stage serous ovarian tumors of low malignant potential. The benefit of this therapy in improving survival is unproven.

Adult↗
PubMed1995

Advances in surgery for gynecologic malignancies.

Surgery has a significant role in the management of most gynecologic cancers. Recent developments in the diagnosis and management of ovarian, cervical, endometrial, and vulvar cancer are worthy of addressing in this review. Significant advances have occurred in the understanding of molecular genetic lesions, leading to a predisposition for ovarian cancer that may have a profound influence on prophylactic oophorectomy. Interval debulking surgery may provide a survival advantage for patients with advanced ovarian cancer. The loop electrosurgical excision procedure has become an integral part of the management of preinvasive disease of the cervix. Advances in the application of surgical stapling devices may lead to reduced operative time and blood loss for radical hysterectomy. Recent studies have addressed the adequacy of endometrial biopsy for the evaluation of postmenopausal bleeding. Advances in lymphatic mapping techniques have led to a novel application to the intraoperative identification of the sentinel node in vulvar cancer.

Endometrial Neoplasms↗
PubMed1995

Hepatic venous outflow obstruction in patients with polycystic liver disease: pathogenesis and treatment.

Polycystic liver disease is commonly asymptomatic but may present with hepatomegaly, abdominal distension, and dull abdominal pain. Transudative ascites is a rare manifestation in these patients but may occur when portal hypertension is present resulting from associated hepatic fibrosis or after deroofing procedure of a cyst. Exudative ascites might suggest hepatic venous outflow obstruction. Four cases are described where hepatic venous outflow obstruction occurred in patients with polycystic liver disease. Three patients had orthotopic liver transplantation and one had a mesocaval shunt. Of the two patients that survived orthotopic liver transplantation both have shown considerable improvement in their symptoms. None of the patients had any confirmed procoagulant disorder. The mechanism of hepatic venous outflow obstruction in these patients seems to be mechanical compression of hepatic veins by the cysts and associated formation of thrombi in small hepatic vein tributaries. Patients with severe polycystic kidney/liver disease are at risk of hepatic venous outflow obstruction and the onset of this complication is heralded by tender hepatomegaly and presence of exudative ascites.

Adult↗