Biomedical subjects

C Cohen

Publications and source records attributed to C Cohen.

At least 199 records · Page 11Linked to original sources

PubMed1994

Immunohistochemical p53 in hepatocellular carcinoma and liver cell dysplasia.

Mutant tumor-suppressor gene p53 is reported in over 50% of hepatocellular carcinomas (HCC). We studied 60 HCC, 30 with large cell liver cell dysplasia (LCD), suggested to be a preneoplastic change progressing to HCC, in the adjacent non-neoplastic liver. Immunohistochemistry was performed for the presence of mutant p53 and hepatitis B surface (HBs) and core (HBc) antigens, using a labeled streptavidin-biotin technique with monoclonal (1/20) and polyclonal (1/40) anti-p53 and with anti-HBs (prediluted) and anti-HBc (1/400). Twenty-nine (48%) HCC were p53 immunopositive, with both antibodies in 9, 17 with monoclonal p53 only, and 3 with polyclonal p53 only. p53 immunoreactivity was present in 3 of 19 (16%) non-neoplastic livers, 4 of 20 (20%) cirrhotic livers, and one of 30 (3%) LCD. HBs and HBc, respectively, were present in 0% and 5% non-neoplastic livers, 20% and 10% cirrhotic livers, 7% and 10% LCD, and 3% and 5% HCC. None of the p53-positive HCC had HBV markers in adjacent liver. This frequency (48%) of p53 in HCC is similar to that in other countries. The data suggest a role for p53 mutations in hepatocarcinogenesis, even in the absence of HBV infection, apparently not progressing through LCD but occurring as a late event.

Carcinoma, Hepatocellular↗

PubMed1994

c-erbB-2 oncoprotein expression and amplification in pleomorphic adenoma and carcinoma ex pleomorphic adenoma: relationship to prognosis.

The c-erbB-2 protooncogene has been shown to be overexpressed and/or amplified in carcinomas of the breast, ovary, pancreas, and other organs. Several studies of human breast carcinoma noted an association of c-erbB-2 overexpression and amplification with poor prognosis. Recent studies have demonstrated c-erbB-2 protein expression in a variety of salivary gland neoplasms, most notably pleomorphic adenoma (PA), carcinoma ex pleomorphic adenoma (CAexPA), and adenocarcinoma. In this study, we analyzed c-erbB-2 expression in 15 PAs and 13 CAexPAs, using immunohistochemistry. In addition, differential polymerase chain reaction was used to evaluate c-erbB-2 gene amplification in these tumors. Low-level c-erbB-2 immunoreactivity was detected in three of 15 PAs. Among the CAexPAs, low-, intermediate-, and high-level immunoreactivity was seen in two, three, and two cases, respectively. The only cases showing c-erbB-2 amplification were the two CAexPA cases with high-level immunoreactivity. Based on statistical analysis of the 10 CAexPA patients with known outcome, no significant association of prognosis with c-erbB-2 expression or amplification was apparent.

Adenoma, Pleomorphic↗

PubMed1994

Comparative image cytometric DNA ploidy of liver cell dysplasia and hepatocellular carcinoma.

Large-cell liver cell dysplasia (LCD), suggested to be a preneoplastic change that progresses to hepatocellular carcinoma (HCC), has a reported frequency of DNA aneuploidy by flow cytometry intermediate between that of nonneoplastic liver (0%) and HCC (80%). We assessed DNA ploidy by image cytometry of Feulgen-stained 5-microns sections of 30 livers with LCD and of 60 HCCs (29 with LCD in adjacent nonmalignant liver). All 30 LCDs were aneuploid, 27 (90%) of which were multiploid--11 (41%) with hyperdiploid and hypertetraploid peaks. Forty-eight (80%) HCCs were aneuploid; in nine of 20 (42%) with a hyperdiploid peak, a hyperdiploid peak was also present in the LCDs, but in none was there less than 0.24 between DNA indices. Besides the 12 (20%) diploid HCCs, a diploid peak was present in four heterogenous, three multiploid, and six HCCs with two phenotypes and two genotypes, one of which was diploid. One aneuploid/hyperdiploid peak in each of 22 nonneoplastic and 24 cirrhotic livers did not have a corresponding LCD or HCC aneuploid peak. These data do not suggest that dysplastic hepatocytes form a single mutant clone that progresses to HCC.

Aneuploidy↗

PubMed1994

Liver cell dysplasia in alpha-1-antitrypsin deficiency.

Large cell liver cell dysplasia (LCD), a suggested preneoplastic change progressing to hepatocellular carcinoma, has been reported associated with alpha-1-antitrypsin deficiency which in some countries has an increased frequency of hepatocellular carcinoma. We examined the nonneoplastic liver from 13 alpha-1-antitrypsin deficiency patients for LCD and, using a labeled streptavidin-biotin technique, for immunohistochemical markers: AAT (1/200), hepatitis B surface (HBsAg, prediluted) and core (HBcAg, 1/400) antigens, and monoclonal (1/20) and polyclonal (1/40) mutant p53, a tumor suppressor gene. There were eight males and five females ranging from 2 mo to 76 yr (mean 40 yr). Nine livers showed cirrhosis, one chronic persistent hepatitis, one portal fibrosis, and two cholestatic hepatitis (in the two infants). The nine cases with LCD included five males and four females of mean age 46 yr (range, 17-71), eight with cirrhosis and one with portal fibrosis. Only one liver with LCD and cirrhosis had HBcAg in cirrhotic and dysplastic cells. No patient had developed hepatocellular carcinoma. All 13 livers were immunonegative for HBsAg and mutant p53, and immunopositive for AAT present in normal, cirrhotic, and dysplastic liver cells. Thus, LCD was identified in 82% of adult alpha-1-antitrypsin deficiency livers (69% including infantile patients), 89% with cirrhosis, and none with malignancy. HB expression was rarely present; serology for HB and/or hepatitis C was positive in 46% adults. Immunoreactive AAT was present in dysplastic cells. p53 gene mutations do not appear to have a role in the pathogenesis of LCD in alpha-1-antitrypsin deficiency.

Adolescent↗

PubMed1993

Arsenic poisoning in central Kentucky: a case report.

A recent case of chronic arsenic intoxication due to prolonged accidental ingestion of a commercially available crabgrass killer illustrates one of the more common etiologies of present day arsenic poisoning. A review of 20 years of arsenic poisoning at the University of Kentucky (21 cases) revealed no cases attributable to an industrial source. A tabulation of the 21 most recent cases is included.

Adolescent↗

PubMed1993

Pitch diversity in alpha-helical coiled coils.

Two complementary methods for measuring local pitch based on heptad position in alpha-helical coiled coils are described and applied to six crystal structures. The results reveal a diversity of pitch values: two-stranded coiled coils appear to have pitch values near 150 A; the values for three- and four-stranded coiled coils range closer to 200 A. The methods also provide a rapid and sensitive gauge of local coiled-coil conformation. Polar or charged residues in the apolar interface between coiled-coil helices markedly affect local pitch values, suggesting a connection between pitch uniformity and coiled-coil stability. Moreover, the identification of a skip residue (heptad frame shift) in the hemagglutinin glycoprotein of influenza virus (HA) allows interpretation of local pitch changes. These results on relatively short coiled-coil structures have relevance for the much longer fibrous proteins (many of which have skip residues) whose detailed structures are not yet established. We also show that local pitch values from molecular dynamics predictions of the GCN4 leucine zipper are in striking agreement with the high-resolution crystal structure--a result not readily discerned by direct comparison of atomic coordinates. Taken together, these methods reveal specific aspects of coiled-coil structure which may escape detection by global analyses of pitch.

Amino Acid Sequence↗

PubMed1993

Immunohistochemical localization of rat angiotensin II AT1 receptor.

To study receptors for angiotensin II, polyclonal rabbit anti-peptide antisera were prepared against the peptide QDDCPKAGRHC corresponding to amino acids 15-24 of the rat AT1A and AT1B receptors. Western analysis of rat tissues showed a major band of approximately 43 kDa. The antisera immunoprecipitated AT1-receptor protein produced in vitro. Immunohistochemical analysis of rat tissues showed intense staining of arterial and arteriolar smooth muscle. Other tissues that contained AT1-receptor protein included hepatocytes, the zona glomerulosa of the adrenal gland, and the smooth muscle of the bronchus, gut, ureter, and epididymis. In the kidney, intense staining was observed in all small arteries and arterioles. Both afferent and efferent arterioles contain approximately equal intensities of immunoreactive AT1 protein. The inner stripe of the outer medulla has a moderate level of receptors within thick ascending limb epithelium. Proximal tubular epithelium also expresses receptor protein. Glomerular immunoreactive AT1 protein is found within mesangial cells and varies in intensity among different rat strains. Lewis and Wistar rats demonstrated moderate glomerular staining, whereas the CD and Sprague-Dawley strains showed lesser levels of reactivity. The fact that glomerular mesangial cells are the primary locus of angiotensin II action within the glomerulus.

Amino Acid Sequence↗

PubMed1993

Outcomes for the mentally ill in a program for older homeless persons.

OBJECTIVE: The study evaluated the success of a generic service program for older homeless persons in improving the well-being of mentally ill clients. It attempted to identify factors that predicted the number of service encounters and outcome in seven areas, including housing, entitlements, physical and mental health, and sobriety. METHODS: All persons newly admitted to the program during a two-and-a-half-year period were asked to participate in structured interviews assessing their physical and mental health and their support networks. Two-thirds of those eligible, or 130, participated in the intake interviews. At three-year follow-up or last contact, outcome was compared for 41 psychiatric clients with psychotic symptoms or self-reported history of psychiatric hospitalizations and 89 clients with no psychiatric symptoms or previous hospitalizations. RESULTS: Persons with mental illness averaged 2.5 favorable outcomes, and a majority obtained temporary or permanent housing, improved their physical health, and secured entitlements. However, mentally ill clients had significantly fewer service encounters and favorable outcomes than clients who were not mentally ill. Types of presenting problems at intake were the only significant predictors of outcome for mentally ill clients. CONCLUSIONS: A generic service program for older homeless persons can successfully improve the well-being of mentally ill clients, although outcomes are less favorable for such clients than for clients who are not mentally ill.

Activities of Daily Living↗

PubMed1993

Pilot trial of cisplatin, radiation, and WR2721 in carcinoma of the uterine cervix: a New York Gynecologic Oncology Group study.

PURPOSE: A phase I trial of WR2721 was initiated to determine the maximal safe dose for incorporation into a consecutive 5-day schedule of cisplatin administered concurrently with radiation therapy in patients with cervical cancer. PATIENTS AND METHODS: WR2721 was administered at 340 to 910 mg/m2/d immediately before cisplatin. Cisplatin was administered at 20 mg/m2/d for 5 days every 3 weeks in combination with external-beam radiation therapy and at 100 mg/m2 after each brachytherapy treatment. Pelvic radiation consisted of external-beam therapy to a dose of 39.6 Gy, followed by brachytherapy with cesium 137 tandem and ovoid insertions to deliver 80 Gy to point A and 55 Gy to point B. RESULTS: Twenty patients were enrolled; 19 were assessable. The dose-limiting toxicity of WR2721 was hypotension. No patients developed serious sequelae, but hypotension required a reduction in the dose of WR2721 at the highest dose level tested. The major grade 3 or 4 toxicities included transient azotemia (five of 19), leukopenia (nine of 19), vomiting (four of 19), and neurotoxicity (two of 19). One patient experienced an anaphylactic reaction to cisplatin. CONCLUSION: The recommended dose of WR2721 administered in conjunction with cisplatin on a daily x 5 schedule plus radiation therapy is 825 mg/m2/d for 5 days.

Adenocarcinoma↗

PubMed1993

Incidence and natural history of phrenic neuropathy occurring during open heart surgery.

OBJECTIVE: To study the incidence of phrenic neuropathy following coronary artery bypass grafting and determine long-term outcome. DESIGN: Prospective observational. SETTING: Surgical ICU in a university hospital, out-patient follow-up. PATIENTS: Ninety-two consecutive patients undergoing open heart surgery. INTERVENTIONS: None. MEASUREMENTS: Chest radiographs (CXR) 48 to 72 h post-operatively, ultrasonography of diaphragm, phrenic nerve conduction studies, diaphragmatic electromyogram, each repeated every 1 to 3 months until normal. MAIN RESULTS: Seventy-eight of 92 (78 percent) patients had abnormal radiographs, 42 of 78 (54 percent) with abnormal CXRs had abnormal diaphragm motion, 24 of 42 (57 percent) with abnormal motion had phrenic neuropathy. Patients with normal diaphragm motion improved faster than those without; patients with normal nerve conduction (and abnormal motion) improved faster than those with abnormal nerve conduction. CONCLUSIONS: Phrenic neuropathy is relatively common if sensitive tests are utilized for diagnosis. Nerve conduction studies can predict duration of morbidity. Most patients have low morbidity and recover fully. Abnormal diaphragm motion alone is not diagnostic of phrenic nerve injury.

Aged↗

PubMed1993

Mammary Paget's disease and associated carcinoma. An immunohistochemical study.

Mammary Paget's disease has been said to result from epidermal spread by contiguity of primary intraductal carcinoma. To assess similar identity, we immunostained Paget's cells and underlying intraductal and/or invasive mammary carcinoma in 20 cases for cytokeratins, epithelial membrane antigen, gross cystic disease fluid protein-15, lysozyme, carcinoembryonic antigen, S100 protein, kappa-casein, and alpha-lactalbumin. Steroid receptor immunostain was positive in only one (5%) of the cases of Paget's disease and in two and four (approximately 15%) (for estrogen and progesterone receptor, respectively) of the cases of ductal carcinoma. In 18 patients (90%), the immunohistochemical profile was identical in Paget's cells and associated carcinoma for seven or more antigens. In one patient, there was a definite disparity in the antigenic profile; in another patient, this was dissimilar because of very focal staining in one site. The antigenic similarity between Paget's cells and underlying carcinoma in 18 (90%) of the cases of mammary Paget's disease suggested in favor of their common origin, ie, probably intraepidermal spread of ductal carcinoma. Origin from apocrine/eccrine structures, or multipotent cells in the epidermis, was suggested in a minority.

Biomarkers, Tumor↗

PubMed1993

Histologic and immunohistochemical evidence for considering ovarian myxoma as a variant of the thecoma-fibroma group of ovarian stromal tumors.

Ovarian myxomas recently have been reported as new, distinct pathologic entities that show a myxoid, moderately cellular proliferation of spindle and stellate cells interspersed with areas of fibrosis, hemorrhage, and delicate vascular spaces. These histologic features are frequently seen in the thecoma-fibroma group of ovarian stromal tumors. For this reason, we propose that ovarian myxomas are part of the spectrum of differentiation in thecomas-fibromas of the ovary. To provide histologic and immunohistochemical evidence for this proposal, four ovarian myxomas were compared with 48 primary ovarian stromal tumors in the thecoma-fibroma group from 46 patients. The thecoma-fibroma group of stromal tumors included 23 thecomas, 23 fibromas, and two sclerosing stromal tumors. We found significant (> 25% of histologic appearance) myxoid change in six thecomas and one sclerosing stromal tumor. This myxoid change resembled the histologic appearance of an ovarian myxoma. Immunohistochemical studies on paraffin-embedded material showed vimentin immunostaining in all tumors. Smooth-muscle actin was present in all of the myxomas, in two of the two sclerosing stromal tumors, and in 20 (90%) of the 23 thecomas, but it was present in only 11 (48%) of the 23 fibromas. Desmin staining was not present in any of the four ovarian myxomas or in the two sclerosing stromal tumors, and only three (13%) of the 23 thecomas showed focal staining for desmin. Nine (39%) of the 23 fibromas expressed desmin. S100 protein was expressed in one fibroma and one thecoma, weakly. None of the ovarian myxomas or the thecoma-fibroma group of stromal tumors expressed cytokeratins as detected by three different monoclonal antibody cocktails, ie, cytokeratin AE1/AE3, cytokeratin CAM 5.2, or cytokeratin MAK-6. The ovarian thecoma-fibroma group of stromal tumors form a histologic spectrum of lesions in which clear-cut distinguishing points between various entities are difficult to define. The myxoid change, present in the thecoma-fibroma group of tumors, was indistinguishable histologically and immunohistochemically from ovarian myxoma. For this reason, we propose that ovarian myxomas may be at one end of the spectrum of differentiation in the thecoma-fibroma group of tumors, in which no remaining stromal tumor is detectable.

Actins↗

PubMed1993

Pigmented pulmonary carcinoid tumor. An immunohistochemical and ultrastructural study.

We evaluated three cases of pigmented pulmonary carcinoid tumors that were retrieved from the files of the Armed Forces Institute of Pathology, Washington, DC. Clinical follow-up showed no indication of tumor recurrence or metastases, nor was there evidence of malignant melanoma. All three cases exhibited histologic features of typical carcinoid tumor; there were focal oncocytic changes in two cases. Finely dispersed, brown pigment, believed to be melanin, was distributed in two different patterns: in sustentacular cells (case 1) or within the tumor cells (cases 2 and 3). Fontana-Masson stain was positive in areas of this pigment in all cases. The tumor cells showed immunoreactivity for chromogranin, synaptophysin, keratin (AE1/AE3 and CAM-5.2), and S100 protein in all cases. Focal staining for vimentin and corticotropin was seen within neoplastic cells in two cases. The pigmented sustentacular cells in case 1 showed focal immunoreactivity for S100 protein and HMB-45. Ultrastructural studies of paraffin-embedded tissues were performed in two cases. They showed well-developed melanosomes in the pigmented sustentacular cells in case 1. In both cases, cytoplasmic neurosecretory-type granules were identified in neoplastic cells. These findings demonstrate that pigmented pulmonary carcinoid tumor has an immunohistochemical profile similar to that of typical pulmonary carcinoid tumor. In some instances, pigmented pulmonary carcinoid tumors may show ultrastructural evidence of melanocytic and neuroendocrine differentiation. These immunohistologic and ultrastructural findings distinguish pigmented pulmonary carcinoid tumor from malignant melanoma and support the concept of "multidirectional cellular differentiation."

Adult↗

PubMed1993

DNA ploidy of ameloblastoma and ameloblastic carcinoma of the jaws. Analysis by image and flow cytometry.

Ameloblastomas, the second most common odontogenic tumor, behave as benign locally aggressive tumors. Ameloblastic carcinomas, on the other hand, show histologic features of malignancy and may metastasize. By image cytometric analysis of Feulgen-stained sections from decalcified, formalin-fixed, paraffin-embedded tumors, we compared nuclear DNA content of 17 primary and five recurrent ameloblastomas and five ameloblastic carcinomas. Of the primary ameloblastomas, 14 (82%) were diploid; three (60%) of the five recurrent ameloblastomas were diploid. No significant difference in ploidy between primary and recurrent ameloblastomas or among plexiform, follicular, and acanthomatous types of ameloblastoma was demonstrated. Of the five ameloblastic carcinomas, four (80%) were aneuploid; ploidy was not significantly correlated with the incidence of metastasis. Flow cytometry was performed on three carcinomas; 100% concordance between image and flow cytometric data was seen. Aneuploidy is significantly more common in ameloblastic carcinomas than in ameloblastoma and is a strong predictor for malignant potential.

Adult↗

PubMed1993

Tolerance to the behavioral effects of chlordiazepoxide: pharmacological and biochemical selectivity.

There is a dynamic interaction between a drug's pharmacological effects and the behavioral context in which it is administered. The present study evaluated the influence of behavioral processes on the development of tolerance and cross-tolerance to the rate-decreasing effects of chlordiazepoxide in rats. Sprague-Dawley rats responded under a fixed-ratio 30 schedule of food delivery. Different groups of rats received 18 mg/kg/day of chlordiazepoxide either before (PRE, n = 8) or after (POST, n = 10) daily experimental sessions for 8 weeks. Cumulative dose-response curves for chlordiazepoxide were obtained before and during chronic chlordiazepoxide administration and during chronic saline administration. Cumulative dose-response curves for midazolam, FG 7142 (N-methyl-beta-carboline-3-carboxamide) flumazenil, pentobarbital, caffeine, morphine and d-amphetamine were determined before, during and 4.5 to 5 months after chronic chlordiazepoxide administration. Group PRE developed tolerance to chlordiazepoxide, whereas group POST did not develop tolerance. Although cross-tolerance developed to midazolam in both groups, it was greater in group PRE. Both groups showed comparable sensitization to FG7142 and neither group showed a significant change in sensitivity to any of the other drugs. Biochemical studies of gamma-aminobutyric acid (GABA)-related functioning in groups of rats that received chronic chlordiazepoxide administration either before (BIO-PRE, n = 6) or after (BIO-POST, n = 6) daily sessions found that GABA-stimulated 36Cl-uptake increased in both cortical and cerebellar preparations. However, GABA sensitivity in cerebellar tissue was significantly lower in group BIO-PRE compared with group BIO-POST. Thus, behavioral tolerance to chlordiazepoxide was associated with both pharmacological and biochemical effects, which suggests a relationship between behavioral tolerance to benzodiazepines and changes in the functional state of the GABA-benzodiazepine receptor complex.

Amphetamine↗

PubMed1992

Structure of tropomyosin at 9 angstroms resolution.

We have used molecular replacement followed by a highly parameterized refinement to determine the structure of tropomyosin crystals to a resolution to 9 A. The shape, coiled-coil structure and interactions of the molecules in the crystals have been determined. These crystals have C2 symmetry with a = 259.7 A, b = 55.3 A, c = 135.6 A and beta = 97.2 degrees. Because of the unusual distribution of intensity in X-ray diffraction patterns from these crystals, it was possible to solve the rotation problem by inspection of qualitative aspects of the diffraction data and to define unequivocally the general alignment of the molecules along the (332) and (3-32) directions of the unit cell. The translation function was then solved by a direct search procedure, while electron microscopy of a related crystal form indicated the probable location of molecular ends in the asymmetric unit, as well as the anti-parallel arrangement. The structural model we have obtained is much clearer than that obtained previously with crystals of extraordinarily high solvent content and shows the two alpha-helices of the coiled coil over most of the length of the molecules and establishes the coiled-coil pitch at 140(+/- 10) A. Moreover, the precise value of the coiled-coil pitch varies along the molecule, probably in response to local variations in the amino acid sequence, which we have determined by sequencing the appropriate cDNA. The crystals are constructed from layers of tropomyosin filaments. There are two molecules in the crystallographic asymmetric unit and the molecules within a layer are bent into an approximately sinusoidal profile. Molecules in consecutive layers in the crystal lie at an angle relative to one another as found in crystalline arrays of actin and myosin rod. There are three classes of interactions between tropomyosin molecules in the spermine-induced crystals and these give some insights into the molecular interactions between coiled-coil molecules that may have implications for assemblies such as muscle thick filaments and intermediate filaments. In interactions within a layer, the geometry of coiled-coil contacts is retained, whereas in contacts between molecules in adjacent layers the coiled-coil geometry varies and these interactions instead appear to be dominated by the repeating pattern of charged zones along the molecule.

Amino Acid Sequence↗

PubMed1992

A calcineurin-like phosphatase is required for catch contraction.

The ability of certain molluscan smooth muscles to maintain a prolonged state of contraction, termed 'catch', has been correlated with the activity of a calcineurin-like Ca(2+)-regulated phosphatase. The release of this phosphatase through extensive treatment of fibers with detergent, as shown by Western blots and a calmodulin-binding overlay assay, results in the loss of catch tension maintenance. This effect is reversed by perfusion of the fiber with brain calcineurin. These findings suggest that the activity of the calcineurin-like phosphatase, switched on during the onset of active contraction, plays a critical role in the maintenance of catch.

Animals↗

PubMed1992

Paramyosin inhibits complement C1.

We report here the results of studies showing that inhibition of C is a property of several invertebrate paramyosins. Paramyosins from Taenia solium, Schistosoma mansoni, and the mussel Mytilus edulis bind polymeric collagen and can be isolated from crude extracts of tissues by collagen affinity. These paramyosins inhibit C1 function whether the C1 is isolated or present in C2-deficient serum. Because T. solium paramyosin was the best inhibitor, we concentrated further studies on this molecule. T. solium paramyosin binds purified C1q in solution with a dose/response similar to C1r2S2. Further studies of the C1-paramyosin interaction indicate that: 1) C4 is not activated, 2) C4b2a decay is not affected, and 3) there is no effect on the efficiency of C3-9, as provided in EDTA-chelated guinea pig serum, in lysing SRBC. Thus, paramyosin inhibition is directed at the initiation of the classical pathway. The results suggest that paramyosins of helminthic parasites may have a role as modulators of the host immune response through C inhibition at C1.

Animals↗