What transplantation can teach us about health care reform. The Ethics and Social Impact Committee.
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Female↗
Biomedical subjects
C Cohen
Publications and source records attributed to C Cohen.
Coiled-coil packing in spermine-induced tropomyosin crystals. A comparative study of three forms.
Electron microscope images of highly ordered spermine-induced microcrystals of tropomyosin have been analyzed to determine the packing of the molecular filaments. Negatively stained microcrystals terminate in a distinctive "double fringe", which reveals the location of the molecular ends. This information, together with the symmetry of the structure in projection, shows that the microcrystals can be accounted for by a packing scheme of four layers of molecules in the unit cell. Knowing the position of the symmetry elements relating the layers then allows the three-dimensional space group of the microcrystals to be established as C222(1). Using cryo-electron microscopy and simulation studies, the run of the filaments and their packing in the C222(1) form have been shown to be related to those in the spermine-induced C2 crystal of tropomyosin whose structure has been solved to 9 A by X-ray crystallography. This result allows us to infer the location of the molecular ends in the C2 crystal as well, and this inference has been confirmed by analysis of thin sections of the C2 crystal. The C222(1) microcrystal has also been shown to be closely related to the classical divalent cation tropomyosin paracrystal. Based on knowledge of the molecular packing in the divalent cation paracrystal, the polarity of the molecules has been deduced in the other two crystal forms. The tropomyosin filament packing in all these forms may be accounted for by coiled-coil close packing and specific cationic bridging of negatively charged zones on the molecule. Taken together the results reveal a hierarchy of interactions in these close-packed crystalline forms, whose principles may apply to the packing in other fibrous proteins. This study also shows the usefulness of co-ordinating results from cryo-electron microscopy with negative staining in the structure analysis of such ordered arrays, and how these findings can complement the results of low resolution X-ray crystallographic studies.
Animals↗
Alpha-helical coiled coils: more facts and better predictions.
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Crystallography, X-Ray↗
Liver disease following occupational exposure to 1,1,1-trichloroethane: a case report.
A patient with a progressive liver disease whose job involved substantial exposure to 1,1,1-trichloroethane (TCE) was seen. A comprehensive work-up ruled out nonoccupational etiologies for his liver condition. Neither the patient's history nor his liver histology suggested alcoholic cirrhosis. Removal of the patient from exposure to TCE led to significant improvement of his impaired liver function over a 3-month period. We conclude that this was a case of occupational liver disease induced by chronic exposure to TCE. This report joins other reports concerning hepatotoxicity of TCE which is considered the least toxic among the halogenated hydrocarbon solvents.
Adult↗
Epitope mapping of the alpha-chain of the insulin-like growth factor I receptor using antipeptide antibodies.
Insulin-like growth factor I (IGF I) is an important mitogen for vascular smooth muscle cells (VSMC). The IGF I receptor (IGF IR) is a heterotetramer composed of two cross-linked extracellular alpha-chains and two membrane-spanning beta-chains that contain a tyrosine-kinase domain. It has a high degree of sequence similarity to the insulin receptor (IR), and the putative ligand-specific binding site has been localized to a cysteine-rich region (CRR) of the alpha-chain. To obtain insights into antigenic determinants of the IGF IR, we raised a panel of site-specific polyclonal antibodies against short peptide sequences N-terminal to and within the CRR. Several antibodies raised against linear epitopes within the CRR bound to solubilized and native rat and human IGF IR by ELISA, did not cross-react with IR, but unexpectedly failed to inhibit 125I-IGF I binding. A polyclonal antibody directed against a 48-amino acid synthetic peptide, corresponding to a region of the CRR postulated to be essential for ligand binding, failed to react with either solubilized, reduced or intact IGF IR. Three antibodies specific for the N-terminus of the alpha-chain reacted with solubilized and native IGF IR. One of these, RAB 6, directed against amino acids 38-44 of the IGF IR, inhibited 125I-IGF I binding to rat aortic smooth muscle cells (RASM) and to IGF IR/3T3 cells (overexpressing human IGF IR) by up to 45%. Immunohistochemical analysis revealed strong IGF IR staining in the medial smooth muscle cell layer of rat aorta. These findings are consistent with a model wherein conformational epitopes within the CRR and linear epitopes within the N-terminus of the alpha-chain contribute to the IGF I binding pocket. These antibodies should provide a valuable tool to study structure-function relationships and in vivo regulation of the IGF IR.
Amino Acid Sequence↗
Characterization of cytochrome P4501A induction in medaka (Oryzias latipes) by samples generated from the extraction and processing of coal.
The objective of this study was to characterize cytochrome P4501A induction in medaka liver as a biomarker for detecting polyaromatic hydrocarbon (PAH)-type compounds in samples of processed coal or petroleum. Ethoxyresorufin-O-deethylase (EROD) activity in individual medaka livers was used to asses induction of P4501A following the addition of various samples to aquaria water. Samples included a known P4501A inducer, beta-naphthoflavone, and various processed coal samples, as well as a petroleum-pitch. The sensitivity of detecting significant EROD induction by adding samples to aquaria water was approximately 0.1 mg/L for most samples; however, a coal-tar pitch significantly increased EROD activity at 0.01 mg/L. Different samples induced EROD activity to different extents. All samples elicited a concentration-dependent increase in EROD activity, with maximum EROD induction 2 days after a single administration of xenobiotics to aquaria water. Western blot studies established that induction of EROD activity by all xenobiotics tested was associated with corresponding increased amounts of immunoreactive P4501A. EROD induction was not influenced by gender, by single or multiple xenobiotic exposures, nor by feeding or fasting animals during the course of xenobiotic exposure. The ability of xenobiotics to induce EROD activity in medaka liver did not always correlate with their genotoxic potential determined by bacterial mutagenesis assays. Induction of P4501A in medaka liver appears to provide a convenient, economical, reliable and sensitive indicator for the presence of PAH-type compounds in coal- or petroleum-derived samples.
Animals↗
Tolerance, cross-tolerance and dependence measured by operant responding in rats treated with triazolam via osmotic pumps.
Previous research has found that drugs with affinity for omega (benzodiazepine) sites differ in their abilities to produce tolerance and dependence. The present study therefore investigated the effects of ligands of omega (BZ) sites in rats that had been rendered tolerant to a benzodiazepine. Two experiments were carried out in separate groups of rats. Behavioral changes induced by chronic infusion of triazolam (3 mg/kg/day, SC, for 14 days) via osmotic pumps were studied in animals trained on a fixed ratio 10 schedule of food presentation. Control animals were implanted with pumps containing the vehicle. Test drugs were administered IP using cumulative dosing. In one experiment triazolam decreased response rates on days 1, 2 and 3 after implantation of the pumps and tolerance developed to this depressant effect. In the other experiment, vehicle and triazolam treated rats differed in their responding during chronic infusion but differences were not statistically significant on any particular day. Flumazenil (3.0-30 mg/kg) greatly decreased rates of responding on day 11 in triazolam treated rats. This effect may represent a precipitated withdrawal syndrome. However, no withdrawal effects on operant performance were observed upon pump removal. Chronic infusion of triazolam did not affect the sensitivity of rats to alpidem on day 11 (10-100 mg/kg) whereas it abolished the stimulant effect of bretazenil (0.1-1.0 mg/kg). Chronic triazolam treatment produced tolerance to the depressant effects of triazolam (1.0-3.0 mg/kg), lorazepam (0.3-3.0 mg/kg) and zopiclone (10 mg/kg) but no tolerance to those of CL 218,872 (3.0-30 mg/kg) and zolpidem (0.3-3.0 mg/kg) when tested 3-14 days after pump removal.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Immunohistochemical phenotype of ovarian granulosa cell tumors: absence of epithelial membrane antigen has diagnostic value.
Granulosa cell tumors (GCTs) represent 1.5% to 3% of primary and 6% to 10% of malignant ovarian neoplasms, and present little diagnostic difficulty in the typical case; however, other primary or metastatic tumors may mimic their various histologic patterns. For this reason, immunohistochemistry can be used to supplement routine histology to help determine a final tissue diagnosis. Previous reports on the utility of antibodies to intermediate filaments vary, as some investigators found keratin to be uniformly negative in GCTs while others reported immunoreactivity for keratin in 20% to 68% of cases. To determine the immunophenotype of granulosa cell tumors and to discover which antibodies are useful in differentiating GCTs from histologic look-alikes, we studied 52 GCTs, including 24 typical cases, 23 cases in which the diffuse pattern predominated, and five juvenile cases, with a panel of commercially available antibodies using an automated immunohistochemistry system. Immunoreactivity for granulosa cells in GCTs was as follows: 17 cases (32.7%) reacted with cytokeratin AE1/AE3, six cases (11.5%) reacted with cytokeratin MAK-6, three cases (5.8%) reacted with cytokeratin CAM 5.2, no case (0%) reacted with epithelial membrane antigen, 52 cases (100%) reacted with vimentin, no case (0%) reacted with desmin, 48 cases (92.3%) reacted with smooth muscle actin, and 26 cases (50%) reacted with S-100 protein. No attempt was made to quantify staining of background thecoma-like or fibroma-like elements in GCTs. Immunoreactivity was independent of the histologic subtype of GCT. Cytokeratin immunoreactivity showed a globoid pattern of staining and was consistent with the expression of 52.5-kD and 45-kD cytokeratins (8 and 18 of Moll's classification). For this reason, the presence of cytokeratin immunoreactivity by itself cannot be used to differentiate a primary or metastatic carcinoma from a GCT. The presence of smooth muscle actin and the absence of epithelial membrane antigen immunoreactivity are additional features that are characteristic of a GCT. S-100 protein immunoreactivity is a finding limited exclusively to GCTs among sex cord stromal tumors, and its presence may have some role in differentiating between Sertoli-stromal cell tumors and GCTs. Since epithelial membrane antigen immunoreactivity is present in many of the histologic look-alikes of GCTs, such as metastatic or primary carcinoma, the absence of staining in GCT has diagnostic value.
Adolescent↗
Effects of chronic treatment with triazolam on operant responding in rats.
The aims of the present study were to investigate the effect of the benzodiazepine antagonist, flumazenil, on operant responding in rats treated chronically with the short-acting hypnotic triazolam and to study the consequence of chronic triazolam treatment on the time course of effects of triazolam and zolpidem. Zolpidem is an imidazopyridine with a pharmacological and behavioral profile that differs from that of the benzodiazepine hypnotics. Rats were treated with saline or triazolam (1 or 3 mg/kg) twice daily for 5 days and were tested daily 1, 3, 5.5 or 7.5 h after injection. In addition, on the 5th day of chronic treatment all rats were injected with flumazenil (10 mg/kg) 10 min before session. The time course of effects of triazolam and zolpidem was determined after cessation of repeated saline or triazolam treatment. Tolerance to the depressant effect of 1 mg/kg of triazolam developed during long-term administration. Flumazenil decreased operant responding in rats pretreated with triazolam. The effect was statistically significant when rats had received 1 mg/kg of triazolam 3 h before the session or 3 mg/kg of triazolam 3, 5.5 or 7.5 h before the session. After cessation of chronic treatment, rats pretreated chronically with 3 mg/kg of triazolam displayed decreased sensitivity to triazolam and to 10 mg/kg but not 3 mg/kg of zolpidem. The present results indicate that chronic treatment with triazolam induces tolerance to the rate-decreasing effect of the drug and dependence as measured by flumazenil-induced disruption of operant responding. The limited degree of cross-tolerance between zolpidem and triazolam may suggest that their pharmacological mechanisms of action are distinct.
Animals↗
Caffeine antagonizes EEG effects of tobacco withdrawal.
Six current cigarette smokers and coffee drinkers were given combinations of 0, 150, or 300 mg caffeine and 0, 2, or 4 mg nicotine polacrilex following 12-h nicotine and caffeine abstinence. On one study day, subjects were allowed to smoke cigarettes and to drink caffeinated beverages and no drugs were given. Tobacco and caffeine abstinence impaired performance on the serial addition/subtraction and digit recall tasks; decreased scores on the MBG scale and ratings of "clear-headed" and "quick-witted"; and increased ratings of "irritability," "muscular tension," "headache," "drowsy," "clumsy," "feeble," and "dreamy." The deprivation caused characteristic EEG signs of nicotine withdrawal including increased theta power and decreased alpha frequency. These EEG effects were reversed by cigarette smoking and caffeine administration, but nicotine polacrilex was less effective. Deprivation-induced performance and subjective measures were not changed by administration of nicotine and caffeine combinations.
Adult↗
Recent developments in the behavioral pharmacology of benzodiazepine (omega) receptors: evidence for the functional significance of receptor subtypes.
Recent research in molecular biology has demonstrated the complexity of GABAA receptors and shown that benzodiazepine (BZ-omega) receptor subtypes have a structural reality. It is therefore appropriate to ask whether the different pharmacological effects produced by benzodiazepines (anticonvulsant activity, anxiety reduction, motor incoordination, learning deficits, characteristic discriminative stimulus effects, tolerance and dependence) are associated with activity at different receptor subtypes. The present paper reviews the literature dealing with the behavioral effects of novel BZ (omega) receptor ligands relevant to the question of the functional significance of the BZ1 (omega 1) and BZ2 (omega 2) receptor subtypes. The only drugs currently available with a considerable degree of selectivity are alpidem and zolpidem. These compounds have relatively high affinity for GABAA receptors containing the alpha 1 subunit (corresponding to the BZ1 (omega 1) subtype) and very low affinity for receptors with the alpha 5 subunit (corresponding to one type of BZ2 (omega 2) receptor). Pharmacological effects observed with these, and other, less selective compounds allow several tentative conclusions to be drawn: (a) Little is known of the role of subtype selectivity in anxiolytic or amnestic effects but compounds with low intrinsic activity may reduce anxiety without giving rise to sedation or motor incoordination and BZ1 (omega 1) selective drugs appear to disrupt memory only at sedative doses; (b) Selectivity for BZ1 (omega 1) receptors may be associated with sleep-inducing activity but not with motor incoordination, suggesting that BZ2 (omega 2) receptors may be of particular importance in mechanisms of muscle relaxation; (c) The discriminative stimulus effects of different BZ (omega) receptor ligands are not identical and differences may be related to receptor selectivity; (d) Compounds with BZ1 (omega 1) selectivity and compounds with low intrinsic activity produce little or no tolerance and dependence. A wider range of selective compounds will be necessary to investigate these factors in detail and many different pharmacological profiles can be expected from drugs with selectivity and different levels of intrinsic activity.
Animals↗
The role of caregiver social networks in Alzheimer's disease.
Although the theoretical importance of social networks in alleviating caregivers' mental distress when a family member has Alzheimer's disease is well-established, empirical support has been less definitive. For 58 patient-spouse caregiver dyads, we used an array of network variables within a causal model of stress. We found that: caregiver networks are associated with severity of illness but not duration; increased illness severity was associated with network members assuming new roles; social networks had indirect effects but no direct or buffering effects on caregiver psychological distress; religious attendance had direct and indirect effects on caregiver psychological distress. These findings point to the important, but complex, role that social networks play in affecting caregivers. However, because of its cross-sectional nature and the relatively small sample size, this study will require replication on larger samples using longitudinal analyses.
Adaptation, Psychological↗
Tumor angiogenesis as a prognostic factor in oral cavity tumors.
BACKGROUND: Lymph-node metastasis is the single greatest predictor of survival in patients with oral cavity cancers. Tumor angiogenesis has been correlated with metastasis in breast cancer and may have prognostic value in other tumors. PATIENTS AND METHODS: Sixty-six patients with clinically node-negative oral cavity squamous cell cancers were reviewed. Samples were cut and stained for factor VIII. The percentage of area of tissue stained for factor VIII was quantitated by a computerized image analyzer. Tumor depth was measured with an ocular micrometer to the nearest 0.1 mm. Variables were statistically examined against regional recurrence. RESULTS: The probability of metastasis (%) was 2 for tumor staining of < or = 10% and 93 for tumor staining > 10% (P < 0.0001). The tumor depth was < or = 4 mm in 10 and > 4 mm in 83 (P < 0.0001). Patients with < or = 4 mm and < or = 10% staining had a 2% rate of recurrence, and patients with > 4 mm and > 10% staining had a 100% rate of recurrence (P < 0.0001). CONCLUSION: Although tumor thickness was suggestive of predictability, only angiogenesis was a statistically significant predictor of recurrence in a multivariate analysis (P < 0.0001). Angiogenesis showed a strong correlation with regional recurrence and may be used as an independent prognostic indicator.
Adult↗
Tinea capitis caused by Trichophyton rubrum in a 67-year-old woman with systemic lupus erythematosus.
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Aged↗
Cathepsin-D and tumor associated antigen DF3 in salivary gland neoplasia. Differential diagnostic and prognostic applications.
Salivary gland tumors pose considerable difficulty in diagnostic and prognostic assessment based on the histopathologic features alone. Cathepsin-D is overexpressed in cancer cells where its concentration in the primary tumor is correlated with increased risk of metastasis. DF3 antigen is a tumor associated glycoprotein that is specific for malignant cells of glandular origin. We examined the distribution patterns of cathepsin-D and DF3 antigens in benign (n = 11) and malignant (n = 44) salivary gland tumors of various histologic types. The frequency of cathepsin-D expression is significantly increased (p < 0.001) in salivary gland carcinomas compared to benign mixed tumors (BMT). High levels of cathepsin-D expression was frequent in carcinomas ex BMT, mucoepidermoid carcinomas, poorly differentiated adenocarcinomas-NOS and adenoid cystic carcinomas (ACC). Acinic cell carcinomas and polymorphous low-grade adenocarcinomas were mostly negative. Intense cytoplasmic staining for DF3 antigen was noted in the tumor cells of mucoepidermoid carcinomas, carcinomas ex BMT and poorly differentiated adenocarcinomas-NOS whereas other types of salivary gland carcinomas exhibited either negative or only focal membrane staining. The noted differences in the reactive patterns of cathepsin-D and DF3 antigen among various histologic types of salivary gland carcinomas may have differential diagnostic and prognostic applications.
Adult↗
Evaluation of c-erbB-2 amplification in breast carcinoma by differential polymerase chain reaction.
Previous studies have found that amplification and overexpression of the c-erbB-2 oncogene in mammary ductal adenocarcinomas predicts decreased disease-free or overall survival. Information regarding the prognostic and pathogenetic significance of oncogene amplification has been limited by difficulty obtaining sufficient quantities of high molecular weight DNA for Southern blot analysis. Differential polymerase chain reaction (PCR) has been suggested as an alternative method for evaluating gene amplification and can be performed using formalin-fixed paraffin-embedded specimens. The authors of this study used differential PCR to detect c-erbB-2 gene amplification and immunohistochemistry to evaluate c-erbB-2 expression. A highly significant degree of concordance (P < .002) between c-erbB-2 amplification and expression was observed. Abnormalities of c-erbB-2 copy number or expression were more common in tumors with higher histologic grade, and trends were noted toward association with other prognostically unfavorable biologic markers, such as reduced progesterone receptor content and DNA aneuploidy.
Base Sequence↗
The high prevalence of unsafe sexual behaviors among acute psychiatric inpatients. Implications for AIDS prevention.
We conducted a study to determine the prevalence and sociodemographic distribution of unsafe sexual behaviors among psychiatric inpatients and to investigate an association between crack cocaine use and these behaviors. Two hundred thirty-nine patients admitted to two Philadelphia hospitals during a 12-month period were interviewed to obtain a detailed sexual history and substance abuse history. A history of multiple sex partners was reported by 42.6% of male patients and 13.0% of female patients (p < .01). A history of receptive anal intercourse in the past 6 months was reported by 11.6% of females and 2.1% of males (p < .05). Only about half the study subjects who were sexually active reported ever using a condom during the past 6 months. Crack cocaine use among males and cocaine use among females was statistically significantly associated with a history of having sex with a high risk partner. This study draws attention to the role of crack cocaine and other types of cocaine in the spread of human immunodeficiency virus infection in this population and the need for intensive acquired immunodeficiency syndrome prevention programs on inpatient psychiatric units.
Acquired Immunodeficiency Syndrome↗
Ketoprofen and prednisolone do not modulate neutrophil CR1, CR3 and Fc gamma RIII expression in healthy volunteers.
We assessed the effect of ketoprofen and prednisolone on the complement receptors (CR1 and CR3) and Fc gamma RIII expression on polymorphonuclears in an ex vivo study, using a randomized, single-blind, placebo-controlled, parallel design. Twenty-four healthy, male, Caucasian volunteers received either oral ketoprofen 100 mg twice daily, or prednisolone 5 mg twice daily, or placebo twice daily for 7.5 days. CR1, CR3 and Fc gamma RIII on unstimulated and FMLP-, C5a-, LTB4-, and GM-CSF-stimulated neutrophils were assessed using specific monoclonal antibodies and flow cytometry. No statistically significant drug effect was found for CR1, CR3, and Fc gamma RIII expression on polymorphonuclears. An in vitro study also yielded negative results. These findings do not support the hypothesis that the effect of non-steroidal antiinflammatory drugs on neutrophils is due to CR1, CR3, or Fc gamma RIII modulation.
Administration, Oral↗