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Biomedical subjects

C Bennett

Publications and source records attributed to C Bennett.

At least 73 records · Page 4Linked to original sources

Expression of lactoferrin in human stomach.

The expression of the haeme-binding protein, lactoferrin, was studied in human gastric tissues displaying normal, benign hyperplastic or malignant histology. A single 2.5-kb mRNA was detected in only 14% (2/14) of normal resections. This was similar to the finding that 85% of tumours were also negative, with 4/27 positive. In contrast, samples with superficial or atrophic gastritis had a high frequency of expression, with 5/7 and 9/14 positive respectively. The higher incidence of lactoferrin mRNA in antral samples was a reflection of the greater proportion of these compared with body resections of patients with gastritis. No expression was seen in any of 5 gastric carcinoma cell lines. High levels were observed in the cardia, in contrast to complete absence in the oesophagus. Immunocytochemistry showed localization of lactoferrin in cells of both antral and body glands. Chief cells, but not adjacent parietal cells, were strongly stained. In tissues exhibiting superficial or atrophic gastritis we observed a greater degree and intensity of staining as compared with samples with normal histology. We also observed some staining of tumour cells, though this was very patchy. Lactoferrin may have a role in mucosal iron transport in both normal and highly proliferating tissue, but does not appear to be significantly associated with malignant lesions.

Adenocarcinoma↗

Lower urinary tract reconstruction following cystectomy: experience and results in 126 patients using the Kock ileal reservoir with bilateral ureteroileal urethrostomy.

Between May 1986 and February 1990, 126 consecutive men underwent lower urinary tract reconstruction by means of bilateral ureteroileal urethrostomy using a Kock ileal reservoir. The early complication rate was 11.1%. Late complications requiring rehospitalization or reoperation have been surprisingly few: 1 for prolapse of the afferent antirefluxing nipple valve, 1 for calculi and 4 for artificial urinary sphincter placement due to unsatisfactory continence. Good continence has been achieved in 94% of the patients during the day and in 84% at night. Tumor recurred in the pelvis in 5 patients, with 4 requiring cutaneous urinary diversion. All patients had progression or died of metastatic disease. Our experience has yielded extraordinary results in terms of patient acceptance with few late complications or need for reoperation.

Adult↗

The legal clinic: helping social workers master the legal environment in health care.

The social environment for all is becoming increasingly legalized. This fact is evidenced in the extensive entitlement regulations and ethical decision-making processes surrounding health care consumers and professional providers. The authors of this paper describe a program designed to educate social workers in an acute care hospital to the legal issues and considerations that influence decision-making and interventions in social work practice. The purpose of the paper is two-fold: to highlight the program planning process in establishing and institutionalizing a Legal Clinic for social work, and secondly to stress the significance of legal content in the knowledge base of social workers in health care settings.

Education, Continuing↗

Ultrasound and HIDA: scanning in evaluating bile leaks after cholecystectomy.

Ultrasound and 99Tcm-HIDA scanning were compared in the evaluation of postoperative biliary leakage after cholecystectomy. In thirty-five patients the abdomen was scanned and imaged on the first postoperative day. Isotope activity in the right upper quadrant and whole abdomen was determined to obtain an activity ratio. Ultrasonography was also performed. Accumulation of 99Tcm-HIDA in the gall bladder bed or over the surface of the liver was regarded as evidence of a bile leak. Eleven patients had abnormal 99Tcm-HIDA images (activity ratios of 0.20-0.77, mean 0.51) but only five patients had loculated fluid on ultrasound scanning. Twenty-four patients had normal 99Tcm-HIDA images (activity ratios of 0-0.17, mean 0.21), but fifteen of these had loculated fluid on ultrasound scanning. We conclude that bile leaks occur in 30% of patients following cholecystectomy and are best detected by 99Tcm scanning rather than ultrasonography.

Adult↗

Cloning and expression of bovine brain inositol monophosphatase.

Inositol monophosphatase is a key enzyme of the inositol phosphate second messenger signaling pathway. It is responsible for the provision of inositol required for synthesis of phosphatidylinositol and polyphosphoinositides and has been implicated as the pharmacological target for lithium action in brain. Using oligonucleotide probes based on partial amino acid sequence data for the bovine brain enzyme, several overlapping cDNA clones of 2-3 kilobases in length have been isolated. All contain an open reading frame encoding a 277-amino acid protein. No significant sequence homology was found with any known protein. The open reading frame was inserted into a bacterial expression vector in order to confirm the presumed identity of the protein. The expressed protein reacted with an anti-inositol monophosphatase monoclonal antibody. In addition, the protein was enzymically active and indistinguishable from the bovine brain enzyme with respect to Km values for substrate and Li+ sensitivity of inositol 1-phosphate hydrolysis.

Amino Acid Sequence↗

Cloning and expression of the delayed-rectifier IsK channel from neonatal rat heart and diethylstilbestrol-primed rat uterus.

cDNAs encoding a delayed-rectifier-type K+ channel were cloned from both neonatal rat heart and ovariectomized, diethylstilbestrol-primed rat uterus by using the polymerase chain reaction. Both clones have nucleotide sequences identical to that encoding the rat kidney IsK channel [Takumi, T., Ohkubo, H. & Nakanishi, S. (1988) Science 242, 1042-1045] and encode a putative protein of 130 amino acids. Injection of RNA transcripts of the cDNAs into Xenopus oocytes resulted in the expression of a slowly activating, voltage-dependent K+ current. An antisense oligonucleotide, derived from the sequence of the clone, specifically inhibited the expression of the slow, outward current observed in cells injected with mRNAs isolated from the parent tissues (i.e., kidney, heart, and uterus), indicating that the cloned gene underlies the major K+ current expressed from RNA isolated from these tissues.

Amino Acid Sequence↗

Expression of the pS2 gene in normal, benign and neoplastic human stomach.

The expression of the estrogen-regulated breast-cancer-associated pS2 gene was examined in 75 stomach resections taken from 45 patients. The 600-base pS2 mRNA was found in all of the 47 non-neoplastic samples at varying levels: in the histologically normal group we observed a Poisson-type distribution, whereas 79% of the tissues exhibiting dysplastic features expressed high levels of transcript. Tumour samples expressed relatively lower pS2 mRNA, with only 18% having high levels and 43% with no detectable expression. These differences were not correlated to tumour grading, stage or site. No amplification or rearrangement of the pS2 gene was found. Immunohistochemical analysis of formalin-fixed paraffin sections, using a polyclonal antibody against pS2 protein, showed specific staining of both cytoplasm and membrane of epithelial cells in the neck region of antral and body glands as well as in luminal secretions. Immunoreactivity was observed in the sub-nuclear region of foveolar cells, with specialized gland and goblet cells in atrophic gastritis being negative. Heterogeneous but strong focal cytoplasmic staining was seen in tumour cells as well as in dysplastic epithelium. Two gastric cell lines, KATO III and MKN-45, derived from poorly differentiated adenocarcinomas also expressed pS2, whereas 3 other lines from well differentiated parental tumours did not. Genomic analysis revealed a BamHI polymorphism in Kato III cells and in the non-expressing MKN-28 cells. Immunostaining to pS2 protein was also demonstrated in the cytoplasm of KATO III cells, but neither these nor any of 30 tissues examined showed any positivity with a monoclonal antibody (MAb) to estrogen receptor. Our results suggest that pS2 is normally expressed in human stomach, possibly in association with secretory activity, and becomes down-regulated during malignancy.

Blotting, Northern↗

Expression of growth factor and epidermal growth factor receptor encoded transcripts in human gastric tissues.

Expression of mRNA-encoding transforming growth factors alpha and beta (TGF alpha and beta), epidermal growth factor receptor (EGFR), and platelet-derived growth factors (PDGF) A and B chains was examined in 63 human gastric biopsies. Despite considerable individual variation, transcript levels were generally higher in 16 paired gastric tumors compared with surrounding epithelium. Marked increases were observed for the TGFs and c-sis, whereas EGFR mRNA was poorly expressed; there was no correlation with pathological staging of the cancers. In the nonneoplastic tissues, 14 had normal histology and 27 displayed superficial (SG) or atrophic gastritis (AG). Transcript levels greater than or equal to + were similar between these categories for all the growth factors, but were about 50% higher for EGFR in the tissues with gastritis. Concurrent expression of TGF alpha and EGFR (greater than or equal to + level) was more frequent in the paired tumors (38%) than in adjacent nonmalignant tissue (6%) and was seen in only one of 14 (7%) normal samples, in three of 19 (16%) of those with AG, and none of eight of those displaying SG. High levels of TGF beta and PDGFA mRNA were expressed in gastric ulcers, with little or no TGF alpha and EGFR transcripts; in contrast both TGFs and EGFR message were found in normal oesophagus. Stomach tissues are thus capable of synthesizing a variety of growth factors. These may be associated with nonneoplastic hyperplasia and/or malignant proliferation. Coexpression of TGF alpha/EGFR supports the possibility of an autocrine loop sustaining tumor growth which is different from the mechanisms responsible for normal cellular proliferation.

Adult↗

Evaluating institutional performance in AIDS-associated Pneumocystis carinii pneumonia: a risk adjustment approach.

Mortality during hospital care of AIDS-associated Pneumocystis carinii pneumonia (PCP) varies as much as 3-fold among reporting institutions. Prognostic factors for death during an episode of PCP have been identified that may be useful risk adjustors for quality-of-care studies. We illustrate a risk adjustment approach to evaluating institutional performance for PCP using a pilot data set from two Southern California hospitals differing widely in crude PCP death rates (61 vs 27%). Using admission AaDO2, hemoglobin and age in a logistic prediction model for hospital death, we found that outcomes in 90% of cases could be accurately classified. Nearly all of the "excess" mortality of the poor outcome hospital could be explained by greater pulmonary severity on admission. We discuss four conceptual issues in design of AIDS quality-of-care studies: confounding by therapeutic intention, defining relevant treatment components, determining the range of co-morbidity, and truncation of the episode of care.

Acquired Immunodeficiency Syndrome↗

Isolation and characterization of two different insulins from an amphibian, Xenopus laevis.

The South African clawed toad, Xenopus laevis, is a versatile laboratory model of vertebrate development. To study the role of insulin during embryogenesis, we have recently cloned preproinsulin cDNAs from this species. Unexpectedly, we identified two preproinsulin cDNAs corresponding to two different nonallelic genes that code for similar but distinctly different insulins. We now report the isolation, amino acid sequence, and characterization of both of these insulins from pancreatic extracts of adult toads, confirming that both Xenopus preproinsulin genes are expressed. Xenopus insulins represent the first amphibian insulins to be characterized. Xenopus insulin I and Xenopus insulin II are more similar to each other than they are to insulins of other species. In addition, Xenopus insulins are more similar to mammalian and bird insulins, than they are to fish insulins, implying a closer evolutionary link to terrestrial vertebrates than to most aquatic vertebrates. A homogeneous preparation of Xenopus insulin I showed high reactivity in a pork insulin RIA. Xenopus insulin I was approximately 2-fold more potent than pork insulin in binding to insulin receptors on human IM-9 lymphocytes and 1.5-fold more potent than pork insulin in stimulating glucose oxidation in rat adipocytes. We were unable to purify Xenopus insulin II sufficiently for immunological and biological characterization.

Amino Acid Sequence↗

State policies and the financing of acquired immunodeficiency syndrome care.

State policies, with respect to the operation of Medicaid programs and the regulation of private health insurance, affect who gets what care, how much is spent, and who ultimately pays. A RAND Corporation study was used to assess States and the District of Columbia in terms of the effects of their Medicaid and health insurance regulations on people with acquired immunodeficiency syndrome and other human immunodeficiency virus-related illnesses. State characteristics are used to explain the individual State policy rankings.

Acquired Immunodeficiency Syndrome↗

The Worcester development project: general practitioner satisfaction with a new community psychiatric service.

General practitioners in the Worcester development project area were interviewed about their experience of using the new community based psychiatric services. Of those who remembered the previous asylum based services most thought the new services were an improvement in many respects and were satisfied with the care provided for their patients. However, there were difficulties in obtaining emergency admissions, and criticisms of the social work service being slow to respond to requests for help. General dissatisfaction was expressed about feedback, particularly from the community psychiatric nursing service. General practitioners are expected to have a key role in the coordination of community services. However, most general practitioners interviewed had no particular interest or training in psychiatry. This, coupled with the inadequate information they received and the possibility of their workload increasing as more patients move out of hospital, raises questions about how they may be helped to fulfil this coordinating role in community psychiatric services.

Attitude of Health Personnel↗

A pilot study of three potential vaccines for leprosy in Bombay.

Three vaccines, BCG Glaxo alone (vaccine A), BCG Glaxo plus 10(7) killed Mycobacterium vaccae (vaccine B), and BCG Glaxo plus 10(7) killed M. leprae (vaccine C), were given to groups of selected children. The effects of these vaccines on subsequent quadruple skin testing 1-3 years after vaccination were compared. All three vaccines equally and significantly (p less than 0.00001) increased positivity to tuberculin, but only vaccine B was found to significantly enhance development of skin-test positivity to leprosin A (p less than 0.002). The data support the evidence previously obtained in rural Iran that the combination of BCG with killed M. vaccae is likely to be a better vaccine for leprosy than is BCG alone.

Adolescent↗

Effect of hypoglycin A on insulin release.

Thirty experimental and fifteen control Wistar rats were studied to determine whether hypoglycin A influences insulin levels in the body to contribute to the state of hypoglycemia usually observed in Jamaican vomiting sickness, a condition arising after ingestion of unripe ackees. This fruit also grows in other Caribbean islands, as well as North and Central America. Hypoglycin A is one of the toxic compounds found in unripe ackees and is capable of inducing hypoglycemia. A fall in blood glucose occurred after administration of hypoglycin A. The lowest level of 42.60 +/- 4.84 mg/dl was attained 3 hr after administration of the drug. This alteration of blood glucose from the fasting level of 80.31 +/- 5.20 mg/dl was significant (P less than 0.01). The blood glucose level in the control rats showed no significant change from the fasting level. The insulin level in portal and peripheral blood showed no significant change. Results showed that, although hypoglycin A induced severe hypoglycemia after intravenous application, there was no significant change in insulin levels. This observation suggests that hypoglycin A has a mechanism of action other than an alteration in insulin levels to induce hypoglycemia.

Animals↗

Construction of a low pressure reservoir and achievement of continence after "diversion" and in end stage vesical dysfunction.

Creation of a continent low pressure urinary reservoir was attempted in 33 patients: 11 with a supravesical diversion, 6 with a vesicostomy, 9 treated by catheter drainage and 7 with end stage bladder disease. The common problems were poor urine storage associated with bladder fibrosis, defunctionalization and decentralization or spinal cord injury coupled with a poorly functional urethral continence mechanism. The over-all outcome at a mean of 21 months (range 4 months to 11 years) was excellent in terms of upper tract function, reservoir capability and continence.

Adult↗