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Biomedical subjects

S M Cohen

Publications and source records attributed to S M Cohen.

At least 19 recordsLinked to original sources

Intraocular fluid cultures after primary pars plana vitrectomy.

To determine what organisms enter the eye and remain in the eye after pars plana vitrectomy, vitreous cavity aspirates were cultured postoperatively. Two of 33 (6%) consecutive eyes undergoing primary pars plana vitrectomy had positive cultures. One sample grew a single colony of Staphylococcus epidermidis, the second grew two colonies of Acinetobacter lwoffi. Neither of these eyes developed endophthalmitis. This study demonstrates that bacteria enter the eye at a low rate during pars plana vitrectomy and that the eye on which a vitrectomy has been performed is capable of clearing a low inoculum of bacteria.

Acinetobacter

Homeotic genes of the Bithorax complex repress limb development in the abdomen of the Drosophila embryo through the target gene Distal-less.

Homeotic genes encode transcription factors that are thought to specify segmental identity by regulating expression of subordinate genes. Limb development is repressed in the abdominal segments of the Drosophila embryo by the hometic genes of the Bithorax complex (BX-C). Localized expression of the homeobox gene Distal-less (DII) is required for leg development in thoracic segments. We have identified a minimal cis-regulatory enhancer element that directs DII expression in the larval leg primordia. We present evidence that the BX-C proteins repress DII expression in abdominal segments by binding to a small number of specific sites in this element. Mutating these sites eliminates BX-C protein binding and renders the element insensitive to BX-C-mediated repression in vivo. Repression of limb development in the abdomen appears to be controlled at the DII enhancer. Thus DII may serve as a downstream target gene through which the homeotic genes control abdominal segment identity in the Drosophila embryo.

Amino Acid Sequence

Acrolein initiates rat urinary bladder carcinogenesis.

Acrolein, a reactive, alpha,beta-unsaturated aldehyde which is ubiquitous in the environment, forms DNA adducts, is mutagenic, and is teratogenic. However, studies have not indicated a carcinogenic effect in rodent bioassays. Since it is present in cigarette smoke and is the toxic metabolite of cyclophosphamide with respect to the urinary tract, we investigated the possibility that acrolein might have carcinogenic activity toward the rat urinary bladder. We also evaluated whether it possessed initiating and/or promoting activity. To evaluate initiating activity, acrolein was administered at a dose of 2 mg/kg i.p. twice a week for 6 weeks followed by uracil as 3% of the diet for 20 weeks and then control diet for 6 weeks. N-[4-(5-Nitro-2-furyl)-2-thiazolyl]formamide (FANFT) as 0.2% of the diet followed by uracil was used as a positive control, and a negative control group was administered solvent control (water) i.p. during the 6-week initiation period followed by uracil. Acrolein followed by uracil produced an incidence of 18 of 30 rats (60%) with papilloma compared to 8 of 30 rats (27%) treated with solvent control followed by uracil. FANFT followed by uracil produced an incidence of 70% carcinomas and 30% papillomas, clearly indicating that it is a much more potent initiating agent than acrolein. Acrolein for 6 weeks followed by control diet produced no tumors. To evaluate promoting activity, groups of rats were fed FANFT for 6 weeks followed by acrolein. Acrolein administered during the initial 6 weeks and continued for the second phase of the experiment (to evaluate complete carcinogenic activity) resulted in severe toxicity. Administration of acrolein had to be terminated after 21 weeks of the experiment. The animals were maintained for 53 weeks of the experiment without further chemical treatment, and there was no evidence of papilloma or carcinoma development. This study clearly indicates that acrolein has initiating activity for the urinary bladder when administered by i.p. injection to the male F344 rat, but toxicity precluded evaluation of its promoting or complete carcinogenic activity.

Acrolein

Simulation modeling of carcinogenesis.

A discrete-time simulation model of carcinogenesis is described mathematically using recursive relationships between time-varying model variables. The dynamics of cellular behavior is represented within a biological framework that encompasses two irreversible and heritable genetic changes. Empirical data and biological supposition dealing with both control and experimental animal groups are used together to establish values for model input variables. The estimation of these variables is integral to the simulation process as described in step-by-step detail. Hepatocarcinogenesis in male F344 rats provides the basis for seven modeling scenarios which illustrate the complexity of relationships among cell proliferation, genotoxicity, and tumor risk.

Age Factors

Acute urinary tract toxicity of tetraethylorthosilicate in rats.

Acute stomach, kidney, and bladder toxicity was evaluated in F344 rats after gastric gavage of tetraethylorthosilicate (TES) at daily doses of 0, 0.111, 0.223, and 0.333 g. Five rats of each sex at each dose were sacrificed after 1, 2, and 4 days. In TES-treated groups, silicate accumulated in the stomach glands and the muscle layer of the forestomach and glandular stomach. Serum chemistries demonstrated acute onset of renal failure. In the kidneys, acute tubular necrosis, accumulation of silicates, and superficial necrotizing papillitis were observed. In the renal pelvis and bladder, there was urothelial simple hyperplasia, focal erosion of the mucosa, edema, and inflammation. These acute toxic changes were dose and time dependent, but significant sex differences were not observed. The microscopic changes in the urothelium were similar to those observed following administration of high doses of sodium saccharin to male rats in which urinary silicate precipitate and crystals form.

Animals

The effect of cyclophosphamide administration on the kidney of the rat.

In studies primarily designed to evaluate the effectiveness of chitosan as a treatment for cyclophosphamide-induced hemorrhagic cystitis in the rat, renal papillary necrosis and pyelonephritis were observed. Cyclophosphamide alone produced relatively mild renal changes. The combination of cyclophosphamide and intravesical instillation of acetic acid induced renal papillary necrosis (38 to 83% incidence) along with pyelonephritis, hydroureter and hydronephrosis. Chitosan, instilled in place of acetic acid, partially inhibited the induction of renal papillary necrosis. It appears that the presence of vesico-ureteral reflux with or without associated hydroureter and hydronephrosis is a prerequisite for cyclophosphamide-induced renal damage.

Acetates

Absence of ras oncogene activation in rat urinary bladder carcinomas induced by N-methyl-N-nitrosourea or N-butyl-N-(4-hydroxybutyl)nitrosamine.

Previously, we demonstrated point mutations of the H-ras gene in N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT)-induced rat urinary bladder carcinomas. In this study, ras oncogene activation was examined in urinary bladder carcinomas induced by N-(4-hydroxybutyl)nitrosamine (BBN) or N-methyl-N-nitrosourea (MNU) administration followed by uracil treatment. In the first experiment, MNU (20 mg/kg body wt) was i.p. injected into 11 male F344 rats twice a week for 4 weeks, followed by feeding 3% uracil for 20 weeks (MNU/uracil group). Ten rats were given only 3% uracil without MNU pretreatment. In the second experiment, 20 male F344 rats were given 0.05% BBN in the drinking water for 4 weeks, then fed 3% uracil for 20 weeks (BBN/uracil group). Another 20 rats were fed 3% uracil without the BBN pretreatment. Transitional cell carcinomas were induced in the urinary bladder of all rats in the MNU/uracil and BBN/uracil groups. Papillomas and hyperplasias were present in the rats given uracil without prior BBN or MNU. DNA and protein were extracted from the tumors (MNU/uracil or BBN/uracil groups) or from the scraped bladder epithelium (uracil alone groups). Sequences around codons 12, 13 and 61 of H-, K- and N-ras genes were examined by direct sequencing after polymerase chain reaction, and p21 was examined by Western blotting. No mutation was found within the examined sequences and p21 showed no changes in mobility. There was no difference in the level of p21 expression between rats treated with MNU/uracil or BBN/uracil compared to corresponding uracil alone groups. These results indicate that the ras oncogene was not activated in urinary bladder carcinomas induced by BBN or MNU in combination with uracil treatment, in contrast to previous findings with FANFT.

Animals

Ras involvement in cells transformed with 2-amino-4-(5-nitro-2-furyl)thiazole (ANFT) in vitro and with N-[4-(5-nitro-2-furyl)-2-thiazoyl]formamide in vivo.

N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) administration to rats followed by sodium saccharin results in transitional cell carcinomas of the bladder, of which 24% harbor an activated H-ras gene. Since 2-amino-4-(5-nitro-2-furyl)thiazole (ANFT) is the mutagenic and carcinogenic metabolite of FANFT in vivo, we wished to examine ras activation in in vitro ANFT-transformed rat bladder epithelial cells as well as four cell lines established in culture from in vivo FANFT-induced rat bladder tumors. Screening by Western blotting revealed no enhanced levels of p21ras in ANFT-transformed cells nor in cells established in culture from FANFT-induced rat bladder carcinomas. Further investigations using immunohistochemical staining with a different pan-reactive p21 monoclonal antibody (Cetus Corporation) specific for this method, however, showed two groups of cells from FANFT-induced rat bladder tumors had enhanced immunoreactivity. Apart from this, p21ras expression of most of the cells groups varied little from the controls. We examined the reported hot spots (exons 1 and 2) of each of the ras genes (H-, K- and N-ras) by direct sequencing of amplified DNA. No mutations were present. We conclude, therefore, that ANFT transformation of primary rat bladder epithelial cells in vitro may not in this case be mediated by ras activation, although this is difficult to determine since others have observed that optimal culture conditions can select for certain populations of cells without ras activation.

Animals

Development of a postoperative self-assessment form.

This paper describes a patient self-assessment form developed for use in a research study examining early discharge and transitional nursing follow-up care for women with abdominal hysterectomy. Transitional care nursing involves preparation for an early discharge from the hospital and nursing follow-up for convalescence at home through an 8-week recovery period. The goal of transitional care is to assist the client in regaining her preoperative level of self-care. This article will include a brief overview of the ongoing research study, a description of the role of the clinical nurse specialist (CNS) in transitional care, and the use of the self-assessment form. The form is applicable to numerous clinical settings.

Clinical Nursing Research

apterous, a gene required for imaginal disc development in Drosophila encodes a member of the LIM family of developmental regulatory proteins.

The apterous (ap) gene is required for the normal development of the wing and haltere imaginal discs in Drosophila melanogaster. ap encodes a new member of the LIM family of developmental regulatory genes. The deduced amino acid sequence of ap predicts a homeo domain and a cysteine/histidine-rich domain known as the LIM domain. In these domains ap is highly similar to the mec-3 and lin-11 proteins of Caenorhabditis elegans and to the vertebrate insulin enhancer-binding protein isl-1. ap is presumably required for transcriptional regulation of genes involved in wing and haltere development. The nature of the defects in homozygous null mutant flies is consistent with the pattern of ap expression in the larval imaginal discs. ap is also expressed in a complex pattern in the embryo, including portions of the peripheral nervous system (PNS) and central nervous system (CNS). A requirement for ap expression in the larval and adult CNS may be the underlying cause of the defects in hormone production and vitellogenesis described for ap mutations.

Amino Acid Sequence

Digital imaging techniques for dental alloy castability quantification.

In this study, mesh monitors cast from experimental compositions of a Ni-Cr-Be alloy are evaluated by the application of image analysis techniques. Castability values obtained by this method are then contrasted with those from three commonly employed manual counting procedures. While castability values obtained by all methods reflect the effect of compositional variations, a comparison of results with respect to evaluation method indicates that the image analysis technique consistently yields higher castability values, especially evident in the poorly casting groups. The apparent explanation for these observed differences is that with imaging, segments that are partially cast to varying degrees are not arbitrarily eliminated from the data, as is the usual practice in manual counting methods; therefore, castability values obtained by using the imaging technique will very closely reflect an actual alloy volume of each cast monitor.

Beryllium

Alternative measures of photosystem II electron transfer inhibition in anthraquinone-treated chloroplasts.

We have previously used chlorophyll fluorescence measurements at Fmax conditions (i.e. with Photosystem II electron acceptor QA reduced) to monitor the action of 9,10-anthraquinones on photosynthetic electron transport in plant chloroplasts. The present investigation employs two additional techniques to characterize the extent of electron transport inhibition induced by the addition of substituted anthraquinones to the suspending medium of spinach chloroplasts. Results are presented for spectrophotometric assays of the rate of electron transfer to an exogenous electron acceptor, 2,6-dichloroindophenol (DCIP) and for electrochemical determinations of the rate of oxygen evolution in anthraquinone-treated chloroplasts. In general, amino-substituted anthraquinones are ineffective inhibitors, maintaining electron transfer rates to DCIP at levels ranging from 50 to 90% of normal rates and yielding rates of O2 evolution averaging at 70% of the rate in untreated chloroplasts. In contrast, hydroxy-substituted anthraquinones efficiently block Photosystem II electron transport, resulting in low rates of DCIP photoreduction ranging from 0 to 20% of normal values and reducing O2 evolution rates to an average of 30% of the rate observed for untreated chloroplasts. Relative rates of DCIP photoreduction for anthraquinone-treated chloroplasts show a strong linear correlation with the reported relative Fmax chlorophyll fluorescence intensities. Relative O2 evolution rates are observed to correlate with the Stern-Volmer fluorescence quenching parameter Ksv. We suggest that slight differences in the extent of inhibitory activity of an anthraquinone as measured by the three techniques are consistent with certain known Photosystem II heterogeneities. The similarities in relative rankings of inhibitory effects for the 9, 10-anthraquinones, however, demonstrate that the three techniques employed (measurements of Fmax chlorophyll fluorescence, DCIP photoreduction rates, and O2 evolution rates) are alternative assays of anthraquinone-induced Photosystem II electron transport inhibition.

2,6-Dichloroindophenol

Epidemiology and etiology of bladder cancer.

Urinary bladder cancer has long been associated with specific etiologic factors, and our knowledge of these factors has increased during this century. The most important factor, even in industrialized societies, is cigarette smoking. Specific chemicals have also been identified as causing bladder cancer, as have a variety of occupational exposures to less well-defined specific agents. In other parts of the world, the association of bladder cancer with Balkan nephropathy, endemic blackfoot disease, and schistosomiasis provides additional leads for investigating, and potentially preventing, the process of carcinogenesis in humans. Many of the critical observations in our understanding of bladder cancer have been made by practicing physicians, and this is likely to continue. It is essential that physicians dealing with bladder cancer patients be attuned to potential etiologic factors, including cigarette smoking, various industrial exposures, or drug exposures to further our understanding of this issue. Bladder cancer is a potentially preventable disease and an important one, as indicated by the total number of cases and the extent of morbidity and death attributable to it around the world.

Caffeine