Biomedical subjects
Publications and source records attributed to B Dunn.
Genetic and physical maps for the 16 chromosomes of Saccharomyces cerevisiae are presented. The genetic map is the result of 40 years of genetic analysis. The physical map was produced from the results of an international systematic sequencing effort. The data for the maps are accessible electronically from the Saccharomyces Genome Database (SGD: http://genome-www.stanford. edu/Saccharomyces/).
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Despite the recent cloning of BRCA1, BRCA2 and the mismatch repair genes, it will still be a long time before it is possible to specify any individual's risk for ovarian cancer based on her genotype. Most women concerned about their risk on the basis of one or two affected relatives do not belong to extensive ovarian cancer families. Risk calculations depend on a reliable genetic model for ovarian cancer derived, ideally, from the population from which an individual is drawn. We have carried out a segregation analysis using data collected from consecutive ovarian cancer patients in two different centres in the UK. Complex segregation analysis was carried out with the addition of diathesis as a separate parameter allowing other cancers, associated with ovarian cancer, to be taken into account. The use of diathesis in the derivation of this alternative model is described. Analysed under joint likelihood without diathesis, the gene frequency is 0.0028 and penetrance to age 70 years is 50%. This is in agreement with other published models. Incorporating diathesis into the model under joint likelihood gives similar parameters for a single locus model but gives the best fit with a two locus model where both genes are rare.
A histologic, immunohistochemical, and DNA ploidy analyses were performed on two cases of angiomatoid malignant fibrous histiocytoma to ascertain the histogenesis and relationship of endothelial, histiocytic, and fibroblastic elements. Both cases were slowly growing, grossly encapsulated. Subcutaneous masses resected from pediatric patients. Microscopically, the tumors were composed of solid masses of epithelioid and spindle cells with abnormal endothelial-lined and blood-filled cystic spaces surrounded by normal vascular structures and aggregates of lymphocytes occasionally forming germinal follicles. The tumor cells stained exclusively with CD34 and vimentin antibodies. Tumor-associated vessels stained for CD31, CD34, vimentin, and Ulex europaeus. Occasional cells within germinal follicles stained for lysozyme, CD68, and HAM56. Ploidy analysis of tumor cells showed intermediate aneuploidy with a DNA index of 1.14. Blood vessels within and surrounding the tumor as well as inflammatory cells were DNA euploid. These studies suggest that the tumor--though comprised of histologically and immunohistochemically benign-appearing euploid endothelial, fibroblastic, and inflammatory elements--contains an aneuploid population of undifferentiated mesenchymal cells.
BACKGROUND: If patients who are more severely ill have greater hospital costs for surgery, then health-care reimbursements need to be adjusted appropriately so that providers caring for more seriously ill patients are not penalized for incurring higher costs. The authors' goal for this study was to determine if severity of illness, as measured by either the American Society of Anesthesiologists Physical Status (ASA PS) or the comorbidity index developed by Charlson, can predict anesthesia costs, operating room costs, total hospital costs, or length of stay for elective surgery. METHODS: The authors randomly selected 224 inpatients (60% sampling fraction) having either colectomy (n = 30), total knee replacement (n = 100), or laparoscopic cholecystectomy (n = 94) from September 1993 to September 1994. For each surgical procedure, backward-elimination multiple regression was used to build models to predict (1) total hospital costs, (2) operating room costs, (3) anesthesia costs, and (4) length of stay. Explanatory candidate variables included patient age (years), sex, ASA PS, Charlson comorbidity index (which weighs the number and seriousness of coexisting diseases), and type of insurance (Medicare/Medicaid, managed care, or indemnity). These analyses were repeated for the pooled data of all 224 patients. Costs (not patient charges) were obtained from the hospital cost accounting software. RESULTS: Mean total hospital costs were $3,778 (95% confidence interval +/- 299) for laparoscopic cholecystectomy, $13,614 (95% CI +/- 3,019) for colectomy, and $18,788 (95% CI +/- 573) for knee replacement. The correlation (r) between ASA PS and Charlson comorbidity scores equaled 0.34 (P < .001). No consistent relation was found between hospital costs and either of the two severity-of-illness indices. The Charlson comorbidity index (but not the ASA PS) predicted hospital costs only for knee replacement (P = .003). The ASA PS, but not the Charlson index, predicted operating room and anesthesia costs only for colectomy (P < .03). CONCLUSIONS: Severity of illness, as categorized by ASA PS categories 1-3 or by the Charlson comorbidity index, was not a consistent predictor of hospital costs and lengths of stay for three types of elective surgery. Hospital resources for these lower-risk elective procedures may be expended primarily to manage the consequences of the surgical disease, rather than to manage the patient's coexisting diseases.
OBJECTIVE: The aim of this study was to compare the Pyloritek test (a 1-h rapid urease test) to the widely used CLO test. METHODS: Seventy-one patients undergoing upper endoscopy were studied. All patients gave informed consent. A single antral biopsy specimen was obtained for the CLO test, and another was obtained for the Pyloritek test. Additional specimens were obtained for culture and processed in the event of a discordant result. The Pyloritek assay was read at 1 h by one observer. The CLO test was read at 24 h by an observer blinded to the results of the Pyloritek assay. RESULTS: There were 18 males and 53 females, and the mean age (+/- SEM) was 53 +/- 17 yr. Thirty-two patients had a positive result on the CLO test, and 39 had a negative test result. Of the 32 patients with a positive CLO test result at 24 h, 31 were positive by the Pyloritek test at 1 h. All 39 patients with negative CLO test results had negative Pyloritek test results as well. There was one discordant result, a negative Pyloritek test result and a positive CLO test result. Culture demonstrated growth of Helicobacter pylori. The kappa value, a measure of the reliability of the Pyloritek test compared with the CLO test, was 0.972 (SE, 0.0284; 95% confidence interval, 0.925-1). Marginal cost-effectiveness analysis favored the Pyloritek test. CONCLUSIONS: Results of the Pyloritek test at 1 h and the CLO test at 24 h are comparable in terms of detection of urease activity.
BACKGROUND: In the present series of experiments, we examined the onset of cell proliferation and growth factor expression after balloon overstretch injury to porcine coronary arteries. METHODS AND RESULTS: Domestic juvenile swine underwent balloon overstretch injury to the left anterior descending and circumflex coronary arteries with standard percutaneous transluminal coronary angioplasty balloon catheters. To identify proliferating cells, 5-bromo-2-deoxyuridine (BrDU) was administered over a period of 24 hours before the animals were killed at either 1, 3, 7, or 14 days after injury. Immunohistochemistry was performed with monoclonal antibodies to BrDU and smooth muscle cell markers. Three days after injury, a large number of proliferating cells were located in the adventitia, with significantly fewer positive cells found in the media and lumen. Seven days after injury, proliferating cells were found primarily in the neointima, extending along the luminal surface. In situ hybridization for PDGF A-chain and beta-receptor mRNAs revealed that the expression of these two genes was closely correlated with the sites of proliferation at each time point. Studies in which BrDU was injected between days 2 and 3 and the animals were killed on day 14 suggested that the proliferating adventitial cells may migrate into the neointima. CONCLUSIONS: These data suggest that adventitial myofibroblasts contribute to the process of vascular lesion formation by proliferating, synthesizing growth factors, and possibly migrating into the neointima. Increased synthesis of alpha-smooth muscle actin observed in the adventitial cells after arterial injury may constrict the injured vessel and contribute to the process of arterial remodeling and late lumen loss after angioplasty.
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Percutaneous mitral balloon valvotomy (PMV) using the Inoue balloon catheter was attempted in 220 consecutive patients with severe symptomatic mitral stenosis. Their age range was 10-63 mean 30 +/- 10 years; 161 patients were females and 59 were males; 29 patients were in atrial fibrillation. Eleven patients were pregnant; 14 patients underwent previous surgical commissurotomy. The procedure was technically successfully performed in 215 (97.7%) patients. The mean fluoroscopy time was 15.5 +/- 6.4 min and mean procedure time was 109 +/- 79 min. Optimal results (group I) was achieved in 207 patients who have mitral score of 7 +/- 1. PMV resulted in decrease in left atrial pressure from 23 +/- 5 to 14 +/- 4 mm Hg (P < 0.001), the mean mitral valve gradient (MVG) decreased from 15 +/- 4 to 6 +/- 3 mm Hg (P < 0.001). The mitral valve area (MVA) by catheter increased from 0.7 +/- 0.2 to 1.7 +/- 0.5 cm2 (P < 0.001) and MVA as determined by echocardiography (2DE) increased from 0.8 +/- 0.1 to 1.9 +/- 0.3 cm2 (P < 0.001). The results were suboptimal in eight patients who have a mitral score of 10 +/- 1 (group II) MVA by catheter increased from 0.7 +/- 0.2 to 1 +/- 0.1 cm2 and Doppler MVA increased from 0.8 +/- 0.1 to 1.3 +/- 0.1 cm2. There were no deaths or thromboembolism. Two patients developed cardiac tamponade; mild mitral regurgitation (MR) developed in 24 patients (11%) and increased by one grade in another 22 patients (10%). Severe MR was encountered in three patients (1.4%). A small ASD (QP/QS < or = 1.3) was detected by oximetry in 5% of patients and by color-flow mapping in 26% of patients. One hundred fifty-eight patients from group I were followed up, for a mean of 32 +/- 12 months; MVA remained at 1.7 +/- 0.4 cm2. Seven patients developed mitral restenosis in group I, and 5 out of 8 patients developed restenosis in group II. We conclude that the hemodynamic results are good and comparable with those reported with double balloon technique. However, the Inoue balloon has several advantages over the double balloon technique: (1) low incidence of mitral regurgitation and ASDs; (2) shorter procedure and fluoroscopy time; and (3) low complication rates and the valve anatomy affects the immediate and late outcome of mitral balloon valvotomy.
The presence of H2A-H2B dimers in nucleosomes can inhibit the binding of transcription factors to chromatin templates. To study the roles of histones H2A and H2B in transcriptional repression in vivo, mutant forms of these histones were analyzed in two different assay systems. Two repression domains were identified in H2A. One domain includes residues that fall in the beginning of the H2A-H2B dimerization region, and the second is in the H2A N terminus, a region of potential interactions with nonhistone proteins. The function of H2A and H2B in one repression assay was found to be dependent on three SPT (suppressor of Ty) genes whose products are important for chromatin-mediated repression. These results suggest that repressive chromatin structure may be established through the interactions of the Spt proteins with these histones. In contrast, other proteins, the products of the HIR (histone regulation) genes, may function to direct H2A and H2B to specific promoters.
BACKGROUND: Many health-care institutions are emphasizing cost reduction programs as a primary tool for managing profitability. The goal of this study was to elucidate the proportion of anesthesia costs relative to perioperative costs as determined by charges and actual costs. METHODS: Costs and charges for 715 inpatients undergoing either discectomy (n = 234), prostatectomy (n = 152), appendectomy (n = 122) or laparoscopic cholecystectomy (n = 207) were retrospectively analyzed at Stanford University Medical Center from September 1993 to September 1994. Total hospital costs were separated into 11 hospital departments. Cost-to-charge ratios were calculated for each surgical procedure and hospital department. Hospitalization costs were also divided into variable and fixed costs (costs that do and do not change with patient volume). Costs were further partitioned into direct and indirect costs (costs that can and cannot be linked directly to a patient). RESULTS: Forty-nine (49%) percent of total hospital costs were variable costs. Fifty-seven (57%) percent were direct costs. The largest hospital cost category was the operating room (33%) followed by the patient ward (31%). Intraoperative anesthesia costs were 5.6% of the total hospital cost. The overall cost-to-charge ratio (0.42) was constant between operations. Cost-to-charge ratios varied threefold among hospital departments. Patient charges overestimated resource consumption in some hospital departments (anesthesia) and underestimated resource consumption in others (ward). CONCLUSIONS: Anesthesia comprises 5.6% of perioperative costs. The influence of anesthesia practice patterns on "downstream" events that influence costs of hospitalization requires further study.
The essential Ras-related GTPases Ypt1 and Sec4 act at distinct stages of the secretion pathway in the yeast Saccharomyces cerevisiae: Ypt1 is required for vesicular transport from the endoplasmic reticulum to the Golgi apparatus, whereas Sec4 is required for fusion of secretory vesicles to the plasma membrane. Here we use chimaeras of the two proteins to identify a 9-residue segment of Ypt1 that, when substituted for the analogous segment of Sec4, allows the chimaera to perform the minimal functions of both proteins in vivo. This segment corresponds to loop L7 of the p21ras crystal structure. Substitution of a 24-residue Ypt1 segment, including the residues just mentioned, together with 12 residues of Ypt1 corresponding to the 'effector region' of p21ras (loop L2; refs 7,8), transforms Sec4 into a fully functional Ypt1 protein without residual Sec4 function.
Between July 1986 and December 1990, 24 consecutive adult patients with native coarctation of the aorta underwent balloon dilatation. Their ages ranged from 15 to 55 (mean 25) years. Dissection of the aorta developed in one patient. The remaining 23 patients were restudied by catheterization and magnetic resonance imaging (MRI) 8 to 60 (mean 21) months after dilatation. Both studies were performed between 1 and 180 (mean 40) days of each other. The diameter of the aorta at the site of previous coarctation was measured on angiogram and MRI by two independent observers. The data were compared by means of linear regression analysis. The gradient across the previous coarctation site ranged from 0 to 20 (mean 7 +/- 7.3) mm Hg. The diameter of the aorta at the site of previous coarctation measured on angiogram was 13.7 +/- 3.7 mm and on MRI it measured 13.5 +/- 3.7 mm, with excellent correlation (r = 0.96, SEE = 0.92, p < 0.001). Two patients had small aneurysms 2 cm in diameter demonstrated by angiography and MRI, and two patients developed restenosis, diagnosed correctly by both cardiac catheterization and MRI. This study demonstrates that MRI provides excellent visualization of the anatomy of the aorta and is a good noninvasive method for follow-up of patients undergoing balloon coarctation angioplasty.
Nine adults who had been reared by mothers diagnosed with psychosis reported on their childhood experiences. Analysis of the retrospective data revealed the five common themes of abuse and neglect, isolation, guilt and loyalty, grievances about mental health services, and social supports. The resilience and coping strategies of the participants are examined, and implications for therapeutic interventions with such families are discussed.
This review provides an update on nutritional aspects of carotenoids (as distinct from retinoids), with specific relevance to anticarcinogenesis. Critical gaps remain in our knowledge of the nutritional functions of carotenoids despite an overwhelming accumulation of research data in areas tangential to human nutrition. In addition to their roles as precursors of retinol and retinoids, carotenoids have distinct functions of their own in animals and humans. In vitro they are antioxidants with a broad range of potencies. In vivo, they protect porphyrics against sunlight. The evidence for anticarcinogenic actions of beta-carotene in certain specified test situations is persuasive. Nevertheless, despite a large number of studies demonstrating protection by carotenoids, the characteristics that render a given carotenoid effective and the relative efficacy of the individual carotenoids are not known. Moreover, dose-response and pharmacokinetic relationships remain virtually unexplored. Research to uncover mechanisms of protection by carotenoids is, for technical reasons, painfully slow. Epidemiological studies reveal associations but not cause and effect. To explore cause and effect, intervention trials are underway, hampered by the paucity of data regarding optimal choice of carotenoid, dosage, and regimen. The in vitro test systems that would provide this information are not available because the molecular sites relevant to the chemopreventive action of carotenoids are obscure. Each of these problems has a solution, but not a simple one. Until these are resolved, blanket recommendations regarding supplementation will remain problematic. To this point, health authorities have not recommended dietary supplementation with carotenoids. Instead, they recommend increased consumption of yellow and dark green carotenoid-rich vegetables. In the future, an individual at risk for a particular carcinogenic process may be recommended a supplement of the most appropriate anticarcinogen, specific to their individual endowment of genetic and environmental risk factors. This review emphasizes not only what is known but also what is not known. Consequently we identify priorities for research that, if undertaken, will allow such recommendations to be made or discounted with more confidence.
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Novel sol-gel synthetic techniques were used to immobilize copper-zinc superoxide dismutase (CuZnSOD), cytochrome c, and myoglobin (Mb) by encapsulation in stable, optically transparent, porous silica glass matrices under mild conditions such that the biomolecules retained their characteristic reactivities and spectroscopic properties. The resulting glasses allowed transport of small molecules into and out of the glasses at reasonable rates but nevertheless retained the protein molecules within their pores. Chemical reactions of the immobilized proteins could be monitored by means of changes in their visible absorption spectra. Silica glasses containing the immobilized proteins were observed to have similar reactivities and spectroscopic properties to those found for the proteins in solution. For example, encapsulated CuZnSOD was demetallated and remetallated, encapsulated ferricytochrome c was reduced and then reoxidized, and encapsulated met Mb was reduced to deoxy Mb and then reacted either with dioxygen to make oxy Mb or with carbon monoxide to make carbonyl Mb.