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Biomedical subjects

M B Cohen

Publications and source records attributed to M B Cohen.

At least 109 records · Page 6Linked to original sources
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↗
PubMed1995

Diversity and modulation of plasminogen activator activity in human prostate carcinoma cell lines.

Baseline cellular plasminogen activator (PA) activity, and the cellular proteins responsible for variations in PA activity were evaluated in three human prostate carcinoma cell lines. Net PA activity in the cell lines PC-3, DU-145, and LNCaP was measured using a plasminogen-dependent fibrin lysis assay. These three cell lines were then analyzed to determine the specific protein(s) responsible for differences in PA activity. mRNA and protein levels of cellular urinary PA (uPA), tissue PA (tPA), PA inhibitor 1 (PAI1), PA inhibitor 2 (PAI2), and uPA receptor (uPAr) were measured using Northern analysis and ELISA assays. Net cellular PA activity in the three cell lines varied over a 3-fold range (PC3 > DU145 >> LNCaP). Net PA activity in the fibrinolysis assay demonstrated a direct correlation with mRNA transcript levels of uPA, tPA, PAI1, and uPAr (PC-3 > DU-145 > LNCaP). uPA protein was identified in both the PC-3 and the DU-145 lines. tPA, PAI1, and PAI2 proteins were identified only in PC-3 cells. In general, cellular protein levels correlated with mRNA levels. These findings demonstrate that prostate carcinoma cell lines vary in their net PA activity. This variability results from both qualitative and quantitative differences in the cellular expression of PA regulatory proteins.

Blotting, Northern↗
PubMed1995

Efficacy of pindolol for treatment of vasovagal syncope.

The purpose of this study was to evaluate the efficacy, safety, and tolerance of pindolol as initial therapy for vasovagal syncope. Head-up tilt table testing (HUT) was performed on 192 patients for syncope or near-syncope of unknown cause. Forty-four (23%) patients had a positive HUT for vasovagal syncope, and 28 (64%) received oral pindolol as initial therapy. Three patients were lost to follow-up; of the remaining 25 patients (mean age 60 +/- 22 years), 15 were women, 14 had syncope, and 11 had near-syncope. At 14 +/- 6 months' follow-up, 16 (64%) patients were without recurrence or side effects from pindolol. Of the 9 patients who stopped taking pindolol, 3 were switched to another regimen for recurrent symptoms, 2 stopped because of side effects, and 4 did not comply with the regimen. In conclusion, pindolol appears to be safe and effective as initial treatment for vasovagal syncope.

Adolescent↗
PubMed1995

Nephrotoxicity of ionic and nonionic contrast media in 1196 patients: a randomized trial. The Iohexol Cooperative Study.

The incidence of nephrotoxicity occurring with the nonionic contrast agent, iohexol, and the ionic contrast agent, meglumine/sodium diatrizoate, was compared in 1196 patients undergoing cardiac angiography in a prospective, randomized, double-blind multicenter trial. Patients were stratified into four groups: renal insufficiency (RI), diabetes mellitus (DM) both absent (N = 364); RI absent, DM present (N = 318); RI present, DM absent (N = 298); and RI and DM both present (N = 216). Serum creatinine levels were measured at -18 to 24, 0, and 24, 48, and 72 hours following contrast administration. Prophylactic hydration was administered pre- and post-angiography. Acute nephrotoxicity (increase in serum creatinine of > or = 1 mg/dl 48 to 72 hours post-contrast) was observed in 42 (7%) patients receiving diatrizoate compared to 19 (3%) patients receiving iohexol, P < 0.002. Differences in nephrotoxicity between the two contrast groups were confined to patients with RI alone or combined with DM. In a multivariate analysis, baseline serum creatinine, male gender, DM, volume of contrast agent, and RI were independently related to the risk of nephrotoxicity. Patients with RI receiving diatrizoate were 3.3 times as likely to develop acute nephrotoxicity compared to those receiving iohexol. Clinically severe adverse renal events were uncommon (N = 15) and did not differ in incidence between contrast groups (iohexol N = 6; diatrizoate N = 9). In conclusion, in patients undergoing cardiac angiography, only those with pre-existing RI alone or combined with DM are at higher risk for acute contrast nephrotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1995

A cluster of cytochrome P450 genes of the CYP6 family in the house fly.

A cluster of genes of the CYP6 family was found in a series of overlapping lambda DASH clones from a genomic library of the house fly, Musca domestica. Four complete genes, CYP6A3, CYP6A4, CYP6A5, and CYP6C1, and fragments of two other genes, CYP6A6 and CYP6C2, were closely linked on a 24-kb segment of DNA. Restriction fragment length polymorphism (RFLP) analysis of PCR-amplified segments of two of the genes showed that the cluster is localized on chromosome V of the house fly. Each gene contained a short intron of 57 to 125 bp interrupting a conserved Glu codon, as in the previously described CYP6A1 gene. The gene fragment CYP6A6 consisted only of the coding region downstream from this intron, i.e., about one-third of the complete P450. The gene fragment CYP6C2 was missing a short amino-terminal part of the coding region, and may represent the two last exons of a larger gene. Gene duplication and chromosomal inversion events may explain the origin of this cluster. The P450 proteins deduced from the nucleotide sequences shared 39-71% amino acid identity with each other. This low identity and the lack of evidence of recent gene conversion events suggested that this cluster may be evolutionarily ancient and that homologous clusters may be found in other holometabolous insects. Evidence for transcription of the genes and for correct splicing of the introns was obtained by northern blotting and reverse transcription polymerase chain reaction (RT-PCR) experiments. No overexpression was observed in any of three insecticide-resistant house fly strains. RT-PCR and sequencing also revealed the existence of other genes or alleles closely related to the members of this cluster.

Amino Acid Sequence↗
PubMed1995

Pathology and probability. Likelihood ratios and receiver operating characteristic curves in the interpretation of bronchial brush specimens.

Diagnoses in pathology often are qualitative, such as atypical or suspicious, and consequently are thought to have limited clinical value. To investigate the utility of a qualitative diagnostic system, seven pathologists retrospectively evaluated 100 bronchial brush specimens using the following categories: definitely benign, probably benign, possibly malignant, probably malignant, and definitely malignant. The likelihood ratio (LR) and receiver operating characteristic (ROC) curve, two statistical probabilistic measurements, were used to calculate diagnostic accuracy among individuals and groups. The results show: (1) the LR for individual diagnostic categories varied among observers, resulting in different clinically malignant probabilities; (2) observer experience did not appear to play a role in overall diagnostic accuracy, except in the diagnosis of small cell carcinoma; (3) observers operate at higher levels of diagnostic accuracy with, rather than without, clinical history. The authors conclude that qualitative diagnoses contain important information and can be interpreted effectively with LR and ROC.

Bronchi↗