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Biomedical subjects

R S Weinstein

Publications and source records attributed to R S Weinstein.

At least 127 records · Page 7Linked to original sources

The prognostic value of DNA ploidy combined with histologic substaging for incidental carcinoma of the prostate gland.

Although current methods of histologic substaging for incidental prostatic carcinoma are useful, they offer only general indications of potential tumor behavior. To further define the biologic tendencies of stage A cancers, an examination was made of the role of DNA ploidy combined with histologic staging in archival material selected to achieve both a representative sample and long-term follow-up. With histology alone, 36% of stage A2 cancers and 9% of A1 neoplasms were progressive. Adding DNA flow cytometry to histology resulted in a significant improvement in the capacity of pathologic evaluation to predict outcome. Progression occurred in 67% of aneuploid stage A2 prostate cancers and in none of the nonaneuploid stage A1 tumors. Despite current limitations in the interpretation of DNA histograms from archival tissue, flow cytometry has significant potential in the pathologic evaluation of incidental prostatic carcinomas.

Aged↗

Correlates of amylase and lipase levels in chronic dialysis patients.

Serum lipase and amylase isoenzymes were measured in 44 chronic hemodialysis patients, 16 CAPD patients and 22 normal volunteers. The enzyme levels of the two patient groups were similar and were significantly higher than those of the volunteer group. The ratio of pancreatic to salivary amylase was similar in all three groups. Anuric patients in both dialysis groups had higher enzyme levels than those with residual urine output. Linear regression analysis was done to attempt to identify factors which were good predictors of enzyme levels. Although no such factors were found in the hemodialysis group, in the CAPD group there were significant correlations between the degree of azotemia and the magnitude of enzyme elevations. Further studies are needed to determine the relative importance of oversecretion and underexcretion in the genesis of the amylase and lipase elevations found in dialysis patients.

Amylases↗

Cell junctions and the biological behaviour of cancer.

Quantitative and qualitative abnormalities in intercellular junctions have been described in a broad spectrum of human and animal cancers. Current efforts are aimed at exploring the possibility that some of these defects may account for the hallmarks of malignancy, namely tumour invasion and metastasis. This approach is hampered by a paucity of information on the natural history of human cancer. There is evidence from quantitative electron microscopy studies of urinary bladder carcinomas induced by a chemical carcinogen in Fischer rats that decreased intercellular adhesion, mediated in part by intercellular junctions, does not contribute to the invasive potential of tumours. However, it may account for increased cell shedding at the tumour surface. The increased leakiness of malignant epithelium is attributed to defects in occludens junctions. The defects appear to represent a failure to assemble intramembrane fibrils into fully competent occludens junctions, rather than a blockage of fibril synthesis. Gap junctional deficiencies are not an invariant in cancers. Further, gap junctional deficiencies are present in human cervical carcinoma-in-situ. These deficiencies are present many hundreds of cell generations before the development of invasive tumours. This argues against the hypothesis that gap junctions per se contribute to the biological behaviour (i.e. invasion) of malignant tumours.

Animals↗

Ethanol-induced alterations in human erythrocyte shape and surface properties: modulatory role of prostaglandin E1.

Exposure of human erythrocytes to ethanol (1 to 20% by vol) in Ca2+ and Mg2+-free phosphate-buffered saline, pH 7.4, transformed biconcave discs into spiculated echinocytes within 3 min at 25 degrees C. The effects of ethanol were concentration-and time-dependent, but reversible by washing in the incubation buffer system within 60 min of initial exposure to ethanol. After prolonged ethanol exposure (180 min), washing of cells resulted in the formation of stomatocytes (cup-forms). Ethanol-induced echinocytosis was also accompanied by a 30% enhancement in the agglutinability of erythrocytes by ligands with high affinity for negative surface charge (poly-L-lysine and wheat germ agglutinin, 20 microliters/ml) without any alterations in surface charge topography. Concomitant exposure of erythrocytes to prostaglandin E1 (100 nM) selectively prevented the enhancement of ligand-mediated agglutinability, but did not modify cell shape. These data indicate that certain erythrocyte surface properties may not be directly influenced by cell shape and suggest a unique modulatory action of prostaglandin E1 on shape-transformed cells.

Alprostadil↗

Decreased trabecular width and increased trabecular spacing contribute to bone loss with aging.

Resistance to fracture depends not only on the total amount of trabecular bone but also on the size and distribution of the trabeculae. We used an image analysis computer to make direct measurements of trabecular width and separation in 33 normal subjects, aged 20 to 80 years. Multiple regression analysis showed that an increase in the distance between adjacent trabeculae accounted for 67.6% of the reduction in trabecular bone area in normal subjects with advancing age, with an additional 23.2% attributed to decreased trabecular width (P less than 0.001). The role of trabecular atrophy in the loss of bone with age was clearly established from the direct relationship between trabecular bone area and the independently measured trabecular width (r = 0.763, P less than 0.001). Effective treatment could increase trabecular bone by thickening the remaining trabeculae. It is, however, unlikely that treatment would replace trabeculae that have been removed or would restore biomechanical strength to the skeleton.

Adult↗

Modulation of the metastatic phenotype by 13-cis-retinoic acid.

KLN 205 murine squamous carcinoma cells were grown in medium supplemented with the retinoid 13-cis-retinoic acid (RA) to study the relationship between RA-induced cell surface changes and alterations of the metastatic phenotype. Modulation of the cell surface glycoconjugate expression was measured by flow cytometric analysis of the RA-treated tumor cells stained with fluoresceinated lectins. RA treatment (5 X 10(-6) and 5 X 10(-7) M) altered the glycoconjugate expression of KLN 205 cells in a selective, dose-dependent fashion. Tumor cells grown in RA-supplemented medium for more than 4 days demonstrated greatly increased binding of fluoresceinated Griffonia simplicifolia I lectin, peanut lectin, wheat-germ lectin, concanavalin A, and soybean lectin (P less than .001), but the increased binding of Ulex europaeus lectin was of a much smaller magnitude (P = .02). After 15 days of growth in these noncytotoxic or cytostatic concentrations of RA, malignant KLN 205 cells had a greatly decreased proclivity to metastasize, as measured by the lung colony assay (P = .0003). The RA-induced cell surface glycoconjugate changes preceded the decrease in experimental metastatic potential. Since enzymatic (neuraminidase) alteration of the tumor cell surface to produce glycoconjugate expression similar to that seen in RA-treated cells also reduced the ability of the KLN 205 cells to form lung colonies (P = .0022), it is suggested that RA-induced alteration of the cell surface carbohydrate antigens is related to the decreased experimental metastatic potential seen in tumor cells treated with RA.

Animals↗

Telepathology and the networking of pathology diagnostic services.

Telepathology is the practice of pathology over a long distance. Components of a telepathology system include the following: a remote-controlled light microscope attached to a high-resolution video camera; a pathologist workstation incorporating controls for manipulating the microscope and a high-resolution video monitor; and a telecommunications linkage. An immediate challenge is to establish the specifications for a telepathology system. Breast tissue has served as a model. Receiver operator characteristic curve studies show that the pathologist's ability to discriminate benign from malignant breast tumors is similar using either a conventional light microscope or a video monitor with approximately 1000 lines of resolution. The percentage of cases for which pathologists render an "equivocal" diagnosis is the same for the two modalities. Telepathology may be an effective way to provide on-line consultations in difficult cases and to provide hospitals in remote areas with immediate access to anatomic pathology services.

Computer Communication Networks↗

Pygmalion and the student: age and classroom differences in children's awareness of teacher expectations.

This study explores age and classroom differences in children's awareness of teacher expectations and in the relation between awareness and self-expectations. In a sample of 579 children and their teachers in 30 first- (6-7-year-olds), third- (8-9-year-olds), and fifth-grade (10-11-year-olds) classrooms, assessed in the fall, younger children were found to be less accurate than fifth graders in predicting teacher expectations and in reporting differential patterns in their own interactions with the teacher. Yet first graders identified classroom differences in the degree of differential teacher treatment toward high and low achievers that were associated with differences in the expectations that high and low teacher-expectancy students reported for themselves. Fifth graders appeared more likely than younger children to mirror teacher expectancies in their self-descriptions regardless of the degree of differential treatment reported in the classroom environment.

Achievement↗

Flow cytometric analysis of deparaffinized nuclei in urinary bladder carcinoma. Comparison with cytogenetic analysis.

Both cytogenetic analysis and flow cytometry (FCM) have prognostic efficacy in the analysis of transitional cell carcinoma (TCC) of urinary bladder. To correlate results of the two methods, we studied a unique group of patients whose tumors had undergone prospective conventional cytogenetic analysis. Paraffin blocks of these tumors were processed for FMC, then analyzed for nuclear DNA content. Of the 34 tumors processed, 30 (88%) yielded interpretable DNA histograms. In 26 (87%) of these, there was good correlation between the two methods with respect to the presence or absence of a hyperdiploid cell line. Discrepancies may have resulted from sampling error or from interpretation of a tetraploid peak as a prominent G2M region. Retrospective FCM analysis of paraffinized TCC tissue correlates well with conventional, prospective cytogenetic analysis and is applicable to the majority of urinary bladder transitional cell carcinomas.

Adult↗

Ultrastructure of tight junctions in prostaglandin-exposed rat stomach.

The effect of intragastric misoprostol, a synthetic prostaglandin E1 methyl ester analog, on the morphology of rat stomach was studied by transmission and scanning electron microscopy. Adult male Sprague-Dawley rats received misoprostol at dose levels ranging from 50 to 1000 micrograms/kg body weight and were sacrificed after 30 min. At all dose levels, normal organelle ultrastructure was maintained in epithelial cells on the surface, within gastric pits, and lining the gastric glands. Quantitative freeze-fracture electron microscopy was used to examine the influence of misoprostol on epithelial-cell tight junctions, major structural components of the mucosal barrier. The numbers of intramembrane fibrils and the depths of the tight-junction complexes did not differ significantly between controls and animals exposed to 1000 micrograms/kg misoprostol (P greater than 0.05). Therefore, alterations in gastric epithelial tight-junction ultrastructure do not appear to account for the cytoprotective effect of misoprostol.

Alprostadil↗

Blood group-related antigens as markers of malignant potential and heterogeneity in human carcinomas.

The expression of BGR-Ags is often aberrant in human carcinomas. The observation that BGR-Ag expression in human bladder carcinomas correlates with prognosis for patients with these tumors is especially interesting in light of the numerous reports of correlations between cell surface glycosylation and malignant phenotype in experimental animal tumors. Many observations suggest how this relation might be mediated. It seems reasonable to anticipate that the study of the BGR-Ags and their expression in carcinoma may emerge from its current predominantly descriptive phase and become an important part of the investigation of human tumor biology.

Antigens, Neoplasm↗

Multiple immunoreactive forms of osteocalcin in uremic serum.

Circulating osteocalcin, which normally reflects the rate of bone formation, is elevated in uremia. In 18 patients receiving maintenance hemodialysis, serum osteocalcin levels were directly related to the bone formation rate (r = 0.88, P less than 0.001), osteoblastic osteoid surface density (r = 0.65, P less than 0.01), and osteoclastic resorptive surface density (r = 0.75, P less than 0.001). Multiple regression analysis showed that osteocalcin levels remained positively correlated with osteoclastic resorption when the bone formation rate was held constant (P less than 0.01). The intimation that the coupling of bone formation and resorption could not explain the relationship between osteocalcin and resorption led us to determine whether fragments of this abundant matrix protein are released by bone resorption and retained in uremia. Sera from dialysis patients with renal osteodystrophy were fractionated by sequential gel filtration and HPLC, and assayed for immunoreactive osteocalcin. When normal serum was analyzed, a single sharp peak was found. In pooled sera from patients with high osteoclastic resorptive surfaces identified by histomorphometry, we found five additional immunoreactive peaks, while three additional peaks were detected in sera from patients with lower osteoclastic surfaces. Bio-Gel P-10 chromatography showed that these multiple peaks were of lower molecular weight than intact osteocalcin. We suggest that the liberation of bone matrix by osteoclasts contributes to the circulating osteocalcin immunoreactivity in uremia.

Adult↗

Stimulation of rat bladder epithelial DNA synthesis by intravesical instillation of distilled water.

Two commonly used cystoscopic infusion fluids were examined to determine whether their infusion stimulates DNA synthesis of the bladder epithelium. Following a single intravesical dose of 0.5 ml of distilled water or 1.5% L-glycine solution, rats were killed periodically up to 1 week. A transient but significant increase in epithelial cell [3H]thymidine labeling was observed at 48 hr after distilled water instillation. Glycine solution did not stimulate DNA synthesis.

Animals↗