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Biomedical subjects

S Finkelstein

Publications and source records attributed to S Finkelstein.

At least 19 recordsLinked to original sources
PubMed2001

JC virus infection in allograft kidneys: analysis by polymerase chain reaction and immunohistochemistry.

BACKGROUND: Polyoma virus nephropathy after transplantation is believed to be primarily due to the BK virus. We hypothesized that some cases may be associated with the JC polyoma virus (JCV), which is also known to be latent in the kidney. METHODS: We sought polymerase chain reaction evidence of JCV infection in needle biopsy specimens with and without viral nephropathy. Cases positive by polymerase chain reaction were studied by immunohistochemistry for VP-1 antigen expression. RESULTS: JCV DNA was found in 7 (36.8%) of 19 allograft kidney biopsy specimens with viral nephropathy and 0 (0%) of 19 native or allograft biopsy specimens without viral nephropathy. Immunohistochemistry localized JCV to the nuclei of tubular epithelial cells in one case. CONCLUSIONS: JCV is detectable in a subset of renal allograft kidneys with polyoma virus nephropathy. The tubular epithelium is identified as a site capable of supporting JCV viral capsid protein VP-1 expression, and hence viral replication.

Biopsy↗
PubMed2001

Rapamycin blocks sexual development in fission yeast through inhibition of the cellular function of an FKBP12 homolog.

FKBP12 is a ubiquitous and a highly conserved prolyl isomerase that binds the immunosuppressive drugs FK506 and rapamycin. Members of the FKBP12 family have been implicated in many processes that include intracellular protein folding, transport, and assembly. In the budding yeast Saccharomyces cerevisiae and in human T cells, rapamycin forms a complex with FKBP12 that inhibits cell cycle progression by inhibition of the TOR kinases. We reported previously that rapamycin does not inhibit the vegetative growth of the fission yeast Schizosaccharomyces pombe; however, it specifically inhibits its sexual development. Here we show that disruption of the S. pombe FKBP12 homolog, fkh1(+), at its chromosomal locus results in a mating-deficient phenotype that is highly similar to that obtained by treatment of wild type cells with rapamycin. A screen for fkh1 mutants that can confer rapamycin resistance identified five amino acids in Fkh1 that are critical for the effect of rapamycin in S. pombe. All five amino acids are located in the putative rapamycin binding pocket. Together, our findings indicate that Fkh1 has an important role in sexual development and serves as the target for rapamycin action in S. pombe.

Amino Acid Sequence↗
PubMed2001

Myopodin, a synaptopodin homologue, is frequently deleted in invasive prostate cancers.

Prostate cancer is one of the leading causes of cancer-related deaths for men in the United States. Like other malignancies, prostate cancer is underscored by a variety of aberrant genetic alterations during its development. Although loss of heterozygosity or allelic loss is frequently identified among prostate cancers, few genes have been identified thus far as critical to the development of invasive prostate cancers. In this report, we used the recently developed technology, the "differential subtraction chain," to perform a genome-wide search for sequences that are deleted in an aggressive prostate cancer. Among the deleted sequences, we found that one sequence was deleted in >50% of prostate cancers we tested. We mapped this sequence to chromosome 4q25 by screening the Genebridge 4 hamster radiation panel with primers specific to this probe, and subsequently identify a 54-kb minimal common deletion region that contains the sequence encoding myopodin. Sequence analysis indicates that myopodin shares significant homology with synaptopodin, a protein closely associated with podocyte and neuron differentiation. Further study shows that frequent complete or partial deletions of the myopodin gene occurred among invasive prostate cancer cases (25 of 31 cases, or 80%). Statistical analysis indicates that deletion of myopodin is highly correlated with the invasiveness of prostate cancers, and thus may hold promise as an important prognostic marker for prostate cancers.

Amino Acid Sequence↗
PubMed2001

Hepatocellular carcinomas in native livers from patients treated with orthotopic liver transplantation: biologic and therapeutic implications.

The gross and histopathologic characteristics of 212 nonfibrolamellar hepatocellular carcinomas (HCCs) discovered in native livers removed at the time of liver transplantation were correlated with features of invasive growth and tumor-free survival. The results show that most HCCs begin as small well-differentiated tumors that have an increased proliferation rate and induce neovascularization, compared with the surrounding liver. But at this stage, they maintain a near-normal apoptosis/mitosis ratio and uncommonly show vascular invasion. As tumors enlarge, foci of dedifferentiation appear within the neoplastic nodules, which have a higher proliferation rate and show more pleomorphism than surrounding better-differentiated areas. Vascular invasion, which is the strongest predictor of disease recurrence, correlates significantly with tumor number and size, tumor giant cells and necrosis, the predominant and worst degree of differentiation, and the apoptosis/mitosis ratio. In the absence of macroscopic or large vessel invasion, largest tumor size (P <.006), apoptosis/mitosis ratio (P <.03), and number of tumors (P <.04) were independent predictors of tumor-free survival and none of 24 patients with tumors having an apoptosis/mitosis ratio greater than 7.2 had recurrence. A minority of HCCs (<15%) quickly develop aggressive features (moderate or poor differentiation, low apoptosis/mitosis ratio, and vascular invasion) while still small, similar to flat carcinomas of the bladder and colon. In conclusion, hepatic carcinogenesis in humans is a multistep and multifocal process. As in experimental animal studies, aggressive biologic behavior (vascular invasion and recurrence) correlates significantly with profound alterations in the apoptosis/mitosis ratio and with architectural and cytologic alterations that suggest a progressive accumulation of multiple genetic abnormalities.

Apoptosis↗
PubMed2001

p53 protein expression and gene mutation in phyllodes tumors of the breast.

The malignant potential of mammary phyllodes tumors is difficult to assess on initial pathologic examination. Studies on the p53 tumor suppressor gene have shown that it has an important role in the development of a variety of malignancies, yet the specific contribution to the pathogenesis and development of the malignant potential of phyllodes tumor is largely unknown. We studied p53 protein expression in 25 cases of phyllodes tumors histologically classified as either malignant (12 cases) or benign (13 cases). Using microdissection approach, we also analyzed the p53 gene sequence in a case that demonstrated progression from benign to malignant phenotype. Nuclear p53 staining was detected in various proportions (1-90%) of neoplastic stromal cells of malignant tumors. No staining was found in benign tumors. Progression from benign to malignant phenotype was associated with a significant increase in the accumulation of p53 (more than 20 times). This was caused by an underlying missense mutation in exon 7, resulting in a change from Arg248 to Trp248 in the malignant component of the tumor. Stromal p53 over-expression was observed only in neoplasms histologically classified as malignant and was associated with an increased proliferation index (MIB-1 staining). These two markers may be used as useful adjuncts in the diagnosis of malignancy in difficult cases or when only a limited sample size is available. Somatic mutation in exon 7 of p53 gene in malignant phyllodes tumor points toward the importance of p53 in the malignant transformation of phyllodes tumors.

Breast Neoplasms↗
PubMed2001

Change of patients' perceptions of TeleHomeCare.

The study's objectives were to measure patients' perceptions of a telehomecare system before and after they have participated in it and identify the features of the system that patients perceived differently after experiencing it. The study setting was the TeleHomeCare Project, which uses videoconferencing and Internet equipment to enable interactions between patients and nurses. An instrument that measures perceptions of telehomecare was used. Patients viewed a videotape that demonstrates a "virtual home care visit" and filled out the questionnaire (pre-test). They were then randomly assigned to a control group receiving standard care or to an experimental group receiving videoconferencing and Internet access in addition to standard care. Both groups filled out the questionnaire when exiting the system (post-test). Paired t-tests were performed to compare total scores and responses to each of the items within the groups and an unpaired t-test was used to compare change of perceptions between groups. The control group consisted of 11 patients, and the experimental group included 17 patients. There was no statistically significant change of perception in the control group. The experimental group showed an overall more positive perception of the system after their experience (total score increase by 6.059, p < 0.0001), and the mean score difference was higher compared to the control group (mean 6.241, p < 0.0001). Elderly patients evaluated their telehomecare experience as being positive, and they felt more comfortable with the technology, believing that the nurse can understand their medical problem over the television. This suggests that telehomecare has the potential for wide acceptance among patients.

Aged↗
PubMed2001

Facilitators and barriers to adherence with home monitoring using electronic spirometry.

Adherence with prescribed therapies is a key factor in maintaining health in persons with chronic illnesses. The purpose of this descriptive study (which is one segment of a larger study being conducted to develop decision rules for early detection of infection or rejection in posttransplant patients) is to explore facilitators and barriers to adherence with home monitoring. Use of latent analysis revealed that the facilitators to adherence were health promotion, commitment to research, and following advice. Barriers to adherence were poor health status, laziness, and time conflict. Health professionals can use this information to plan strategies to promote adherence to home monitoring.

Female↗
PubMed2000

Cytogenetics, immunostaining for fibroblast growth factors, p53 sequencing, and clinical features of two cases of cystosarcoma phyllodes.

BACKGROUND: We present cytogenetics and fibroblast growth factor immunohistochemistry in one case of cystosarcoma phyllodes with localized disease and one with metastatic spread. The p53 gene was sequenced in the malignant case. METHODS AND RESULTS: Karyotype analysis used trypsin-Giemsa banding. Immunohistochemistry of FGF1, FGF2, FGFR1 and p53 used avidin-biotin detection of the primary antibody. One case had a mosaic female karyotype and three clones: one normal, one with trisomy 7, and one with both trisomy 5 and a rearranged chromosome 1. In the second case, a resected pulmonary metastasis had the karyotype 43-47,XX,+mar1,+mar2[6]/43-46,XX, +del(7)(p10)[3],+mar2[1][cp3]/46,XX[10]. These tumors expressed FGF1, FGF2, and FGFR1. The malignant case showed immunostaining for p53 protein, but a wild-type gene sequence. CONCLUSION: The karyotype of cystosarcoma phyllodes is complex, with wide case-to-case variation. These tumors express members of the FGF family. Metastatic behavior can occur in the presence of a wild-type p53 gene.

Adult↗
PubMed2000

A questionnaire for the assessment of patients' impressions of the risks and benefits of home telecare.

Home telecare is a promising method of improving access to care for rural and urban populations. It requires, however, that patients accept the installation and use of equipment in their home. How patients perceive home telecare may influence its acceptability and diffusion. We developed a questionnaire to assess patients' impressions of the risks and benefits of home telecare. A preliminary 20-item questionnaire was developed and tested on 32 subjects. It proved to be of acceptable reliability (Cronbach's alpha of 0.8) and validity, but three items appeared to be redundant. The final 17-item version was tested twice on 10 more subjects and was found to have high test-retest reliability. Most subjects showed an overall positive attitude towards home telecare and agreed it could improve their health. Many were concerned about being able to trust the equipment. The questionnaire can be used to investigate the acceptance of telemedicine and to improve the design of applications.

Attitude to Health↗
PubMed1999

Human polyoma virus-associated interstitial nephritis in the allograft kidney.

BACKGROUND: Asymptomatic polyoma virus infection documented by urine cytology or serology is well known, but the clinical course of biopsy-proven interstitial nephritis is not well defined. METHODS: Twenty-two cases were identified by histology, immunostaining, in situ hybridization, electron microscopy, or polymerase chain reaction. RESULTS: The clinical features mimicked acute rejection (n=19), chronic rejection with incidental diagnosis at nephrectomy (n=2), or drug toxicity (n=1). Histology showed homogenous intranuclear inclusions. In situ hybridization showed BK virus (BKV) to be the predominant species, but polymerase chain reaction documented JC virus co-infection in one of five cases so tested. Electron microscopy in seven cases showed 20-51-nm virions. The two cases diagnosed at nephrectomy received no therapy. Initial antirejection therapy in 12 cases led to clearance of the virus in 1/12 (8%), partial therapeutic response in 3/12 (25%), and graft loss in 8/12 (67%) cases. The last recorded creatinine in patients with functional grafts ranged from 1.9 to 7.0 (median: 4.5) mg/dl, 0.4-45 (median: 4.0) months after initial diagnosis. The remaining eight cases treated by reduction of immunosuppression at the outset have been free of graft loss for 0.2-10.0 (median: 4.8) months since diagnosis, and clearance of virus has been documented in three of six (50%) cases. The serum creatinine in these patients is 1.7-6.0 (median: 2.4) mg/dl, 0.2-10 (median: 4.8) months after diagnosis. Follow-up biopsies performed 1-23.5 months after diagnosis show chronic allograft nephropathy. CONCLUSIONS: Polyoma virus tubulo-interstitial nephritis-associated graft dysfunction usually calls for judicious decrease in immunosuppression and monitoring for acute rejection. Development of methods to serially quantify the viral load in individual patients could potentially improve clinical outcome.

Adolescent↗
PubMed1998

Increased rate of nondisjunction in sex cells derived from low-quality semen.

The relationship between chromosomal nondisjunction and semen quality was studied in two groups of males who differ highly in their semen quality: 12 individuals with low-quality semen caused by varicocele, and 8 subjects with high-quality semen, selected from sperm donors for in vitro fertilization. Chromosomal nondisjunction was inferred from the rate of disomy found in mature sperm cells. To determine the rate of disomy, we applied fluorescence in situ hybridization using satellite-specific probes for chromosomes 1, 15, 18, X and Y. In sperm cells of males with low-quality semen, the mean rate of disomy for each of the autosomes and of hetero-disomy for the sex chromosomes (XY) was significantly higher than that observed in the high-quality semen samples: more than 15-fold higher for chromosomes 1 and 15, and 7-fold higher for chromosomes 18 and XY. Yet, the homo-disomy rate for each of the sex chromosomes (XX and YY) was almost the same in both types of semen. The large discrepancy between the low- and high-quality semen in the rate of sex chromosome hetero-disomy versus the similar rate of homo-disomy strongly suggests that the abnormal chromosomal segregation in meiocytes of males with low-quality semen resulted from chromosomal nondisjunction at the first meiotic division. The results indicate that men showing poor semen quality are at an increased risk for meiotic nondisjunction, similar to women at the end of their reproductive years.

Adult↗
PubMed1998

Promoting adherence to an electronic home spirometry research program after lung transplantation.

Adherence with any long-term treatment or research protocol is a challenge; this has been found to be the case with lung transplant recipients participating in an electronic home spirometry research program. Because the purpose of the current study is to develop a system for detecting early infection and rejection in lung transplant recipients, regular transmission of data by subjects to the research data center is imperative to the success of the study. Various adherence-promoting strategies have been developed by the research team to increase subject adherence with the program. An increased adherence rate has been reported after implementation of these various strategies, yet work remains to promote continually regular participation in the program by all subjects. It remains a challenge for the research team to devise creative and effective strategies for increasing adherence to regular spirometer use to provide data to develop a computerized system for detecting early infection and rejection of transplanted lung tissue.

Algorithms↗
PubMed1998

Bronchioloalveolar adenocarcinoma of lung: monoclonal origin for multifocal disease.

In an attempt to understand the histogenesis and molecular pathogenesis of multifocal bronchioloalveolar lung carcinoma (BAC) we studied 28 cases of BAC using a topographic genotyping approach for the presence of K-ras exon 1 mutations and p53 loss of heterozygosity (LOH). This analytical approach demonstrated K-ras exon 1 mutations in 12.5% of solitary BACs, 40% of BACs with microscopic or macroscopic satellite lesions, and 60% of BACs with intrathoracic metastases. In all cases with K-ras mutations, the identical point mutation was present in the primary, satellite, and intrathoracic metastatic lesions. When p53 LOH was demonstrated in the primary lesion, it was also detected in the satellites and intrathoracic metastases. No significant association was noted between the presence of K-ras mutations and p53 LOH. The results strongly support a monoclonal origin of multifocal BACs. Furthermore, the findings support the theories explaining the origin of multifocal BAC by intraalveolar route of spread, intrapulmonary lymphatic spread, or aerosolization leading to implantation at different sites. A trend toward an increased frequency of K-ras mutations and p53 LOH in BACs with satellites or metastases compared to solitary BACs was noted.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1998

Complete spontaneous regression of pulmonary metastatic melanoma.

BACKGROUND: Complete spontaneous regression of melanoma metastatic to the lungs is a rare event. OBJECTIVE: To report a case of biopsy-proven melanoma metastatic to the lung with complete spontaneous regression. METHODS: Multidisciplinary case report. RESULTS: A 35-year-old white female was diagnosed with metastatic melanoma to the lung. A pleural biopsy confirmed the diagnosis. Partial spontaneous regression was noted by a staging computed tomography scan prior to enrollment in an investigational protocol. Complete spontaneous regression occurred over 5 months without any form of conventional or alternative therapy, and the patient remains disease-free 3 years after diagnosis. CONCLUSIONS: Our case represents the seventh case of complete spontaneous regression of melanoma metastatic to the lung, and the only case with histologic confirmation of both the primary and pulmonary metastatic lesions. The patient was pregnant twice between the time of her initial diagnosis of primary melanoma and pulmonary metastatic disease.

Adult↗
PubMed1997

Loss of the gene encoding mannose 6-phosphate/insulin-like growth factor II receptor is an early event in liver carcinogenesis.

This report shows that loss of heterozygosity at the mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R) locus occurred in 5/8 (63%) dysplastic liver lesions and 11/18 (61%) hepatocellular carcinomas (HCCs) associated with the high risk factors of hepatitis virus infection and liver cirrhosis. Mutations in the remaining allele were detected in 6/11 (55%) HCCs, including deletions in a polydeoxyguanosine region known to be a target of microsatellite instability. M6P/IGF2R allele loss was also found in cirrhotic tissue of clonal origin adjacent to these dysplastic lesions and HCCs, demonstrating that M6P/IGF2R inactivation occurs early in liver carcinogenesis. In conclusion, HCCs frequently develop from clonal expansions of phenotypically normal, M6P/IGF2R-mutated hepatocytes, providing further support for the idea that M6P/IGF2R functions as a liver tumor-suppressor gene.

Aged↗
PubMed1997

K-ras and p53 mutations in aberrant crypt foci and colonic tumors from colon cancer patients.

Aberrant crypt foci (ACF) are microscopic lesions which can be detected, after methylene blue staining, in the overtly normal looking colonic mucosa of cancer patients. ACF have been postulated to be precursor lesions which develop into colorectal cancer. Mutations of K-ras and p53 are two important genetic events implicated in colon carcinogenesis. Mutations in K-ras are detectable at earlier stages, while mutations in p53 are detectable at later stages of colon carcinogenesis. Our objective was to compare the nature of genetic alterations in K-ras (codon 12 and 13) and in p53 (exon 4-9) between ACF and corresponding colonic tumors from cancer patients. ACF with > or =20 crypts/focus were harvested from overtly normal looking colonic mucosa of cancer patients at a distance of (approx.) 5 cm from the site of colonic tumors. The colonic tumors and ACF samples were compared for K-ras codon 12 and 13 base pair sequence, using DNA sequencing and for p53 (exon 5-9) allelic types, using PCR-SSCP and DNA sequencing. The results demonstrated a perfect correlation in terms of the type of K-ras allele (wild or mutated) between the ACF (> or =20 crypts/focus) and corresponding colonic tumors in 11/13 cancer patients. Analyses of p53 mutations demonstrated the presence of p53 mutations in colonic carcinomas from 10/13 patients. However, p53 mutations could be detected in an ACF from only 1/13 patient. The results provides further evidence to the role of ACF as precursor to colon cancer. The presence of an identical K-ras as well as p53 mutation in an ACF and the corresponding colonic carcinoma in a patient suggests the possibility of existence of ACF that may be at a more advanced stage in the sequence of colonic tumorigenesis than others. In conclusion, the results suggest that a subset of ACF with higher multiplicity might be considered more likely to progress to more advanced lesions and should be explored as markers of colon cancer risk.

Adenoma↗