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Biomedical subjects

M B Cohen

Publications and source records attributed to M B Cohen.

At least 19 recordsLinked to original sources
PubMed1996

Expression of CD44 isoforms in human prostate tumor cell lines.

We have examined the expression of the transmembrane glycoproteins CD44 in four human prostate tumor cell lines. Expression was examined at the protein level by flow cytometric analysis and Western blot, and at the mRNA level by reverse transcription-polymerase chain reaction (RT-PCR). All four cell lines (DU145, LNCaP, PC3, and ND1) expressed the standard CD44 isoform (CD44s) at the mRNA level and all cell lines except LNCaP expressed CD44s at the protein level. All four cell lines contained one or more isoforms containing the v6 region (exon 10) at the mRNA level, which has been associated with metastatic potential. However, a subpopulation of LNCaP and ND1 cells showed protein expression of v6. In addition, soluble CD44 isoforms were identified in cultured supernatants from all cell lines except LNCaP. These results show that CD44 isoforms are expressed on human prostate tumor cell lines, including the expression of variant isoforms containing the v6 region, and provide a rationale for the further study of this cellular adhesion molecule in prostate cancer. In addition, preliminary results indicate altered expression of CD44 in human prostatic adenocarcinomas examined immunohistochemically.

Animals↗
PubMed1996

Infectious gastroenterocolitides in children: an update on emerging pathogens.

The recognition that bacterial infections induce signal transduction responses in infected epithelial cells also provides new avenues to consider as novel forms of therapy. For example, the chemokine interleukin-8, which attracts neutrophils to sites of mucosal infection, is produced by epithelial cells of gastric and intestinal origin in response to bacterial infection. Inhibitors of chemokine production or inhibition of the biologic effects of neutrophil chemoattractants have the potential to reduce both mucosal inflammatory responses and the attendant clinical sequelae. Eukaryotic cells also respond to infection with elevations in cytosolic second messengers, including inositol triphosphate (IP3) and calcium ([Ca2+]i). In intestinal epithelium, these second messengers can mediate the diarrheal response to infection. Calcium/calmodulin inhibitors may have a beneficial effect in treating those gastrointestinal infections mediated through changes in the level of cytosolic free calcium. DuPont and colleagues showed, for example, that oral therapy with zaldaride maleate relieves symptoms of disease and shortens the duration of diarrhea in travelers with ETEC-induced diarrhea. Evaluation of additional signal transduction responses to microbial infections should provide both new insights into the pathogenesis of gastrointestinal infectious diseases and novel approaches to consider for the prevention and therapy for these human illnesses.

Antidiarrheals↗
PubMed1996

The role of neovascularization in the survival of an arterialized venous flap.

This study compares survival of arterialized venous flaps placed on normal and impaired recipient beds in New Zealand White rabbit ear. Fasciocutanous flaps (4 x 5 cm) were perfused by an arteriovenous anastomosis; outflow was provided by one vein. In group 1, the arterialized venous flap was sutured into its bed on the ear; in group 2, a sheet of silicone was placed between the flap and the ear, providing an experimentally impaired recipient bed. Flap survival was expressed as a percentage of the total flap surface by means of a computerized image analysis system. Excellent survival (> or =95 percent) was noted in 16 of 21 arterialized venous flaps in group 1 versus 2 of 21 in group 2 (p < 0.01). Partial survival (50 to 94 percent) was observed in 2 of 21 arterialized venous flaps in group 1 and 15 of 21 in group 2. Poor survival (<50 percent) was noted in 3 of 21 in group 1 and in 4 of 21 in group 2. Microangiography was used to illustrate arteriovenous fistulas, the vascular network within the flaps, and neovessels in the periphery of the flaps. These data indicate that neovascularization is necessary for optimal survival of arterialized venous flaps in this experimental rabbit ear model.

Animals↗
PubMed1996

Splenectomy complicating left nephrectomy.

PURPOSE: We attempted to clarify the details of incidental splenectomy complicating left nephrectomy. MATERIALS AND METHODS: We reviewed the literature and operations involving splenectomy performed during left nephrectomy between 1984 and 1994 at our university. Factors reviewed included patient characteristics, renal pathology, mechanisms of injury, blood transfusions and postoperative complications. RESULTS: Of the 418 left nephrectomies 18 (4.3%) resulted in splenectomy via a transperitoneal approach. Patients with a large or upper pole renal lesion, malignancy or advanced age are increasingly likely to undergo unanticipated splenectomy. CONCLUSIONS: Our results, combined with recommendations from the Centers for Disease Control and Prevention, suggest that all patients older than 65 years undergoing left transperitoneal nephrectomy or those at increased risk for splenic injury should receive preoperative pneumococcal vaccination.

Age Factors↗
PubMed1996

Cytopathology and the pathology resident. A survey of residency program directors.

OBJECTIVE: To collect information on the status of cytopathology training in the United States. DESIGN: Questionnaire survey mailed in June 1994. SETTING: Pathology residency training programs in the United States. PARTICIPANTS: Pathology residency directors. MAIN OUTCOME MEASURES: Training length, numbers of cytology specimens, teaching methods and topics, and graduated responsibility. RESULTS: Of the 196 surveys mailed, 101 (52%) programs responded. The average length of required training was 3 months. The perceived optimal training time averaged 4.5 months, however, with 80% of programs requiring less than their stated optimum. The median numbers of gynecologic, nongynecologic, and fine-needle aspiration biopsy specimens examined per resident were 1100, 500, and 200, respectively. Cytopreparatory techniques, laboratory management, computer systems, and immunocytochemistry were included in over 75% of cytopathology training programs. Teaching at the microscope was rated as the most important teaching method by 90% of respondents. The majority of senior residents performed fine-needle aspiration biopsy procedures and screened and signed out cases with direct faculty supervision, but fewer than 20% of programs allowed senior residents to independently sign out specimens. CONCLUSIONS: Recommendations based on this review include a minimum training time of 3 months, improved training in both fine-needle aspiration biopsy techniques and gynecologic cytology, continuous exposure to cytopathologic techniques, and increased graded responsibility for senior residents.

Education, Medical, Graduate↗
PubMed1996

Low-grade transitional cell carcinoma of the urinary bladder: application of select cytologic criteria to improve diagnostic accuracy [corrected].

The cytologic diagnosis of low-grade transitional cell carcinoma of the bladder is difficult, and the reported sensitivity of a positive diagnosis ranges from 0 to 73%. Using regression analysis, our laboratory previously reported the criteria of increased nuclear/cytoplasmic ratios, irregular nuclear membranes, and cytoplasmic homogeneity as indicative of low-grade transitional cell carcinoma. To examine the validity of these criteria, six observers examined 88 bladder-wash specimens (39 transitional cell carcinomas and 49 benign) and, using the selected criteria, graded each wash for the probability of malignancy. Diagnostic accuracy was measured using the receiver operating characteristic curve and the likelihood ratio. Overall observer accuracy was 76%, the sensitivity of a definitive negative diagnosis was 82%, and the specificity of a definitive positive diagnosis was 96%. We conclude that key cytologic criteria can be learned and effectively applied with high accuracy. Observer variation in diagnostic categories might reflect different confidence levels and probabilities of transitional cell carcinoma.

Carcinoma, Transitional Cell↗
PubMed1995

Differential sensitivity of human prostatic cancer cell lines to the effects of protein kinase and phosphatase inhibitors.

We investigated the effect of protein kinase and phosphatase inhibitors on the growth of six human prostatic cancer cell lines: DU145, PC3, ND1, LNCaP, ALVA31 and JCA1. We studied okadaic acid and sodium orthovanadate as serine/threonine and tyrosine protein phosphatase inhibitors, respectively, and staurosporin and genistein as a serine/threonine and tyrosine protein kinase inhibitors, respectively. All inhibitors examined exhibited a dose-dependent growth inhibitory effect on prostatic cancer cell lines. Our data indicate that prostatic cancer cell lines express unique biochemical properties since the degree of growth inhibition varied greatly and was dependent on the specific cell line and inhibitor studied. In addition, we found that surface expression of endoglin (CD105) changed by treatment with all inhibitors in most of the cell lines. These data also indicate that endoglin appears to be involved both in protein phosphatase and kinase mediated phosphoprotein turnover.

Alkaloids↗
PubMed1995

Differential expression of endoglin on fetal and adult hematopoietic cells in human bone marrow.

Endoglin, a glycoprotein that is expressed by human endothelial cells, binds TGF-beta 1 and -beta 3 with high affinity. It was originally identified with the 44G4 mAb that was produced against a human pre-B cell line. We now report that another anti-pre-B cell mAb, 29-G8, reacts with pro-B and pre-B leukemic cells, but not with mature B and T cells, and recognizes a different epitope of endoglin. The 29-G8 mAb bound specifically to recombinant endoglin and immunoprecipitated a phosphorylated homodimeric glycoprotein with subunits of M(r) 95,000 from the 697 pre-B cell line. This new Ab removed all of the molecules identified by the prototypic 44G4 anti-endoglin Ab, but the reverse was not true. A subpopulation of 29-G8+ endoglin molecules on this pre-B cell line was unreactive with the 44G4 mAb, thus suggesting that these anti-endoglin Abs see different epitopes that may discriminate different species of endoglin molecules. Flow cytometric analysis with the 29-G8 mAb revealed two endoglin-positive subpopulations in fetal bone marrow: early B-lineage precursor cells (CD19+ and CD34+), and proerythroblasts (CD71+ and glycophorin A+). In adult bone marrow, only the proerythroblast subpopulation was observed. Stromal cells derived from fetal bone marrow also reacted strongly with the 29-G8 and 44G4 Abs, and these cells responded with enhanced proliferation after stimulation with either TGF-beta 1 or the anti-endoglin Abs. Thus, endoglin, a specialized component of the TGF-beta receptor system, may play a physiologic role in the stromal-hemopoietic cell interactions occurring during development.

Adult↗
PubMed1995

Immunohistochemical localization of guanylin in the rat small intestine and colon.

Guanylin is an endogenous mammalian ligand which binds to guanylate cyclase C (GC-C), the Escherichia coli heat-stable enterotoxin receptor. This interaction results in intestinal Cl- and fluid secretion, which is largely, if not exclusively, mediated through the cystic fibrosis transmembrane regulator (CFTR). Using in situ hybridization, we have previously localized guanylin mRNA to villus epithelial cells of the rat small intestine and to superficial epithelial cells of the rat colon. In the present study, we demonstrate immunoreactive guanylin in a subpopulation of goblet cells in the rat jejunum and ileum. In the colon, there was immunostaining of superficial epithelial cells and goblet cells. The immunohistochemical localization of guanylin parallels the observed distribution of guanylin mRNA. Localization of guanylin in goblet cells leads us to speculate that an in vivo function of guanylin regulated, CFTR-mediated Cl- secretion is to hydrate intestinal mucin.

Animals↗
PubMed1995

Urinary system.

BACKGROUND: Although site-specific cancer frequencies and incidence rates for the United States are regularly reported by the National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results (SEER) program, they have not been reported by histologic type within a specific site. This report presents data for 76,303 cancers of the urinary tract by histologic type. METHODS: Cancer data were obtained from the SEER program. Urinary tract cancers were eligible if they were histologically confirmed, in situ or invasive, and diagnosed between 1973 and 1987. The urinary tract was divided into the following sites: kidney and renal pelvis, ureter, urinary bladder, urethra, and other urinary. Histologic types were evaluated by site, age, sex, race, incidence, and survival. RESULTS: Of the 76,303 cancers, 72.0% were transitional cell carcinomas and 22.0% were adenocarcinomas. Adenocarcinoma was the most common histologic type in the kidney and renal pelvis (also referred to as renal cell carcinoma), whereas transitional cell carcinoma was the most common histologic type in the remainder of the urinary tract. For the more common histologic types, age-adjusted incidence rates were always higher among males than females. CONCLUSIONS: Because adenocarcinomas represent most kidney and renal pelvis cancers and transitional cell carcinomas represent most urinary bladder cancers, these histologic types largely explain incidence and survival trends reported for these two common cancer sites. Future population-based cancer epidemiologic studies should try to focus more on specific histologic types within a cancer site to better clarify risk factors and incidence and survival trends for cancer.

Adult↗
PubMed1995

Adenomyoepithelioma of the breast: fine-needle aspiration biopsy and histologic findings.

Adenomyoepithelioma is an uncommon tumor of the breast which clinically presents as a discrete nodule and histologically is composed of lumenal spaces lined by a mixture of epithelial and myoepithelial cells. It has a spectrum of histologic appearances which are gradually gaining wider recognition. There are, however, only a few descriptions of the fine-needle aspiration biopsy (FNAB) findings in adenomyoepithelioma. We report the FNAB and histologic features of a mammary adenomyoepithelioma which contained a prominent epithelial component including a focus of marked epithelial atypia. This expands the spectrum of FNAB findings which have been reported in adenomyoepithelioma.

Aged↗
PubMed1995

Efficacy of automated cervical cytology screening.

The Papanicolaou stained cervicovaginal smear (Pap smear) is a gynecologic cytologic screening tool that has dramatically reduced the incidence and mortality of cervical cancer. Recently, a number of problems with the Pap smear test, including severe cytotechnologist shortages, lack of internal quality controls, and high false negative rates have been emphasized by the scientific community and the general public. To address some of these problems, there has been increased development of a number of automated and semiautomated cytologic screening systems. A semiautomated screening system (PAPNET) was used to retrospectively evaluate 527 conventionally prepared Pap smears from 500 consecutive unselected patients. This system scanned the slides and displayed 128 of the most "abnormal" areas of each slide on a monitor. A screener reviewed these "abnormal" images in a blinded fashion and decided whether they represented variants of normal cytology, were inadequate for evaluation, or were abnormal and warranted manual review of the material. The screener's evaluations were then compared to the previously made diagnosis and discrepancies were reviewed. After review of the images from 500 patients, 343 (69%) were deemed to be normal cytology, 140 (28%) were abnormal and needed manual review, and 17 (3%) were inadequate. Of the 343 called normal using this system, 338 were previously called normal and five patients were previously diagnosed with either atypical squamous cells of undetermined significance (ASQUS) or low grade squamous intraepithelial lesions (LGSIL). Of the 140 thought to need review, 43 were previously diagnosed with squamous or glandular disease and 97 were previously diagnosed as normal. Slides from the apparent false negatives and false positives were again reviewed in a blinded fashion.(ABSTRACT TRUNCATED AT 250 WORDS)

False Negative Reactions↗
PubMed1995

Expression of cellular adhesion molecules on human prostate tumor cell lines.

By flow cytometric analysis we have examined the expression of cellular adhesion molecules (CAMs) on the surface of four different human prostate tumor cell lines: DU 145, from a brain metastasis; PC 3, from a bone metastasis; LNCaP.FGC, from a lymph node metastasis; and a primary tumor cell line, ND 1. The corresponding ligands for the expressed CAMs were, by and large, extracellular matrix proteins. We detected high-level expression of ICAM-1 on three of the four prostate cell lines, whereas LNCaP cells were negative. We observed unstable, heterogeneous expression of E-cadherin in the cell lines DU 145, PC 3, and ND 1. Flow cytometric cell sorting enabled us to divide PC 3 cells into negative and bright positive subpopulations but, after several cell divisions in culture, sorted cells returned to the original heterogeneous phenotype. The laminin-specific alpha 6 beta 4 integrin was not expressed by LNCaP, and was expressed at a low level and heterogeneously on DU 145 and PC 3 cell lines. In contrast, ND 1 cells, derived from a primary tumor, showed homogeneous and high-level expression of the alpha 6 beta 4 integrin. All of the prostate cell lines expressed the RGD-dependent binding of alpha 3 beta 1 and alpha 5 beta 1 integrins and did not reveal non-RGD-dependent alpha 4 beta 1 integrin expression. This finding provides a stimulus to investigate the inhibition capacity of RGD-containing peptides on the metastatic behavior of prostate tumor cells.

Cadherins↗
PubMed1995

Survival of human prostate carcinoma, benign hyperplastic prostate tissues, and IL-2-activated lymphocytes in scid mice.

Mice, homozygous for the mutation severe combined immunodeficiency (scid) and also segregating for the mutation hypogonadal (hpg), were tested for their potential use as an in vivo model system for studying the growth of human prostate cancer and benign hyperplastic prostate tissue grafts. Fresh human prostate cancer or benign hyperplastic prostate tissue was implanted subcutaneously into androgen-replete C.B. 17 scid/scid males, and into androgen-deficient hpg/hpg scid/scid or androgen-replete +/? scid scid males. The tissue grafts grew in both androgen-replete and androgen-deficient host mice. When dihydrotestosterone (DHT) was administered at tissue grafting, both the incidence and size of the tissue grafts increased. Histology of tissue from tumors in the androgen-deficient hpg/hpg scid/scid host showed either undifferentiated tumors or adenocarcinomas with few glandular structures. These data suggest the androgen deficient environment selected for growth of androgen-independent tumor tissue. Finally, when interleukin-2 (IL-2)-activated tumor-infiltrating lymphocytes were injected into scid/scid hosts, the cells were found to survive and could be identified in the spleen of the recipient mice. These results indicate that growth of human prostate tissues and IL-2-activated lymphocytes in scid/scid mice is a viable model system for in vivo studies of prostatic disease.

Adenocarcinoma↗