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Biomedical subjects

S Daugherty

Publications and source records attributed to S Daugherty.

13 recordsLinked to original sources

Role of mobile DNA in the evolution of vancomycin-resistant Enterococcus faecalis.

The complete genome sequence of Enterococcus faecalis V583, a vancomycin-resistant clinical isolate, revealed that more than a quarter of the genome consists of probable mobile or foreign DNA. One of the predicted mobile elements is a previously unknown vanB vancomycin-resistance conjugative transposon. Three plasmids were identified, including two pheromone-sensing conjugative plasmids, one encoding a previously undescribed pheromone inhibitor. The apparent propensity for the incorporation of mobile elements probably contributed to the rapid acquisition and dissemination of drug resistance in the enterococci.

Adhesins, Bacterial↗

Complete genome sequence and comparative analysis of the metabolically versatile Pseudomonas putida KT2440.

Pseudomonas putida is a metabolically versatile saprophytic soil bacterium that has been certified as a biosafety host for the cloning of foreign genes. The bacterium also has considerable potential for biotechnological applications. Sequence analysis of the 6.18 Mb genome of strain KT2440 reveals diverse transport and metabolic systems. Although there is a high level of genome conservation with the pathogenic Pseudomonad Pseudomonas aeruginosa (85% of the predicted coding regions are shared), key virulence factors including exotoxin A and type III secretion systems are absent. Analysis of the genome gives insight into the non-pathogenic nature of P. putida and points to potential new applications in agriculture, biocatalysis, bioremediation and bioplastic production.

Bacterial Proteins↗

Student responses to the gross anatomy laboratory in a medical curriculum.

Working with cadavers, whether through active dissection or by examination of prosected specimens, constitutes a potential stressor in medical education although there is no consensus on its effect. Some reports have suggested that it creates such a strongly negative experience that it warrants special curricular attention. To assess the issue for ourselves, we administered surveys to the freshman medical students taking the Anatomical Sciences course in the problem-based Alternative Curriculum (A.C.) at Rush Medical College for four consecutive years. We found that although a vast majority of students expressed a positive attitude toward the experience, both before and after taking the course, there remains a small percentage of students for whom human dissection may initially be a traumatic experience. We offer explanations for our findings, comments on disparate results from other studies and suggestions for appropriate responses by anatomy faculty, who must address these student needs.

Anatomy↗

Food shopping practices are associated with dietary quality in low-income households.

ABSTRACT Nutrition education for low-income audiences often focuses on building skills in food shopping and food resource management to help families receive the best nutrition from the resources they have available. However, empirical evidence for the effect of food shopping practice on dietary quality has been limited. This article presents new analyses from two studies that found an association between food shopping practices and diet quality. Logistic regression of data from 957 respondents from the 1996 National Food Stamp Program Survey found that food shopping practices were significantly (p </= .05) associated with the availability of nutrients in the food the households used during a week. Similarly, analysis of baseline data from 5159 women from selected counties of states who participated in the Expanded Food and Nutrition Education Program found that food shopping practices were significantly (p </= .05) associated with increased consumption of nutrients as measured through a single 24-hour recall. These findings suggest that food shopping practices are an important area for nutrition education with low-income audiences.

Diet↗

Measuring beneficiary knowledge in two randomized experiments.

This article reports results of two studies that measured beneficiaries' knowledge of the Medicare program and related health insurance options using pre- and post-experimental designs. Knowledge was measured using multiple item indexes before and after receiving new informational materials developed by the Centers for Medicare & Medicaid Services (CMS) as part of the National Medicare Education Program (NMEP). Beneficiaries in both studies showed statistically significant gains in knowledge after receiving the new materials. Policy implications for the measurement of knowledge and creation of future versions of the materials are discussed.

Aged↗

A randomized controlled trial of filgrastim for the treatment of hospitalized patients with multilobar pneumonia.

This study assessed the safety and efficacy of filgrastim (r-metHuG-CSF [recombinant human methionine granulocyte colony-stimulating factor]), when combined with intravenous (IV) antibiotics, in the treatment of hospitalized adult patients with multilobar community-acquired pneumonia (CAP). Four hundred eighty patients were randomized to receive placebo (n=243) or filgrastim 300 microg/day (n=237), in addition to standard therapy. Treatment with study drug was continued for 10 days, until the peak white blood cell (WBC) count reached 75x109/L, until discharge from the hospital, until death, or until IV antibiotics were discontinued. Study-related observations continued through day 29. Filgrastim increased WBC counts (baseline median, 13.3x109/L; median peak, 43. 8x109/L). The 2 treatment groups were not statistically different with respect to the study end points; however, there was a trend toward reduction of mortality in patients with pneumococcal bacteremia. Although further studies will be required to validate this observation, filgrastim was safe and well tolerated when administered to patients with multilobar CAP.

Adult↗

Renal cell carcinoma of end-stage renal disease: a histopathologic and molecular genetic study.

Renal cell carcinomas (RCC) are responsible for the deaths of 3% to 4% of patients with ESRD. The clear cell carcinoma of the kidney, which comprises 80% of sporadic RCC within the general population, shows a deletion of gene sequences in the short arm of chromosome 3 (3p) in as many as 100% of cases. The von Hippel-Lindau tumor suppressor gene at 3p25-26 is found to be mutated in the nondeleted allele in 57% of these sporadic clear cell carcinomas. This study was undertaken to determine the histopathologic types of RCC occurring in ESRD patients in the United States and to investigate the frequency with which 3p genetic changes can be found in these ESRD tumors. Seventeen end-stage kidneys containing RCC were collected from 15 ESRD patients at ten US medical centers. The tumors were classified by Thoenes' histopathologic typing. DNA extracted from paraffin blocks of tumor and nontumorous tissue was analyzed by single-stranded conformational polymorphism analysis for von Hippel-Lindau mutations and by microsatellite amplification for deletion of 3p gene sequences. Twenty-one RCC were identified in the 18 kidneys. The 21 RCC were classified histopathologically as follows: clear cell, compact, three cases; chromophilic, tubulopapillary, 15 cases; chromophilic, compact, three cases. Among the three clear cell carcinomas, one showed 3p genetic loss. None of the chromophilic RCC showed a 3p deletion and none of 19 tumors studied by single-stranded conformational polymorphism analysis disclosed von Hippel-Lindau mutations. In contrast to the general population, clear cell RCC with 3p abnormalities represent only a small proportion of the renal carcinomas in this collection of ESRD tumors. The findings indicate that the genetic changes underlying the development of most ESRD tumors are different from those occurring in sporadic clear cell RCC and do not characteristically involve the inactivation of a 3p tumor suppressor gene.

Adult↗

Cloning, expression, and mutagenesis of phosphatidylinositol-specific phospholipase C from Staphylococcus aureus: a potential staphylococcal virulence factor.

Staphylococcus aureus secretes a phosphatidylinositol (PI)-specific phospholipase C (PI-PLC) which is able to hydrolyze the membrane lipid PI and membrane protein anchors containing glycosyl-PI. The gene for PI-PLC (plc) was cloned from S. aureus into Escherichia coli. Oligonucleotide probes based on partial protein sequence and polyclonal antibodies raised against the purified protein were used to identify positive clones. E. coli transformed with a plasmid containing the plc gene expressed PI-PLC enzyme activity which was abolished by mutagenesis with a tetracycline resistance gene. The plc gene was present in all 15 S. aureus strains examined but not in any of 6 coagulase-negative staphylococcal species. The plc gene contained 984 bp and coded for a mature protein with a calculated molecular mass of 34,107 Da. Amino acid sequence comparisons indicated that the staphylococcal plc gene was similar (51 to 56%) to the PI-PLCs from Bacillus cereus, Bacillus thuringiensis, and Listeria monocytogenes. The recombinant PI-PLC expressed in E. coli was purified and exhibited biochemical properties identical to those of the native PI-PLC from S. aureus. PI-PLC production was decreased in agr mutant strains of S. aureus. However, PI-PLC production by both agr+ and agr mutant strains exhibited a similar dependence on the type of medium used. These data suggested that PI-PLC production was regulated by both agr-dependent and agr-independent mechanisms.

Amino Acid Sequence↗

Reduction of sexual activities in females taking antiepileptic drugs.

Studies of male or sexually unspecified populations have revealed loss of libido and decreased sexual function in patients with epilepsy taking antiepileptic drugs. The relative contributions of antiepileptic drugs, seizures, brain injury, and social factors have not been clearly delineated. We studied sexual activity in a group of females taking antiepileptic drugs, and defined a subgroup with pronounced hyposexuality.

Adult↗

Hemodynamic effects of direct angiotensin II blockade compared to converting enzyme inhibition in rat model of heart failure.

The purpose of this investigation was to compare the chronic effects of converting enzyme inhibition with captopril to direct blockade of angiotensin II (AII) with DuP 753 in the rat model of heart failure. Rats with chronic heart failure postinfarction were treated for 2 weeks with either captopril (2 g/L, N = 9) in their drinking water or with DuP 753 (40 mg/kg/day for two weeks by gastric gavage, N = 10), or placebo (N = 9). At this dose, DuP 753 shifted the log dose-pressor response curve to AII parallel to the right by two orders of magnitude in both chronically treated normal and heart failure rats. In rats with heart failure, DuP 753 and captopril reduced left ventricular end-diastolic pressure from 26.7 +/- 1.5 to 14.2 +/- 3.0 (P less than .01) and 15.8 +/- 2.2 mm Hg (P less than .05), respectively, left ventricular end-diastolic volume index from 2.71 +/- 0.10 to 2.03 +/- 0.17 (P less than .05) and 2.18 +/- 0.15 (P less than .05), respectively; venous compliance increased from 2.27 +/- 0.06 to 2.80 +/- 0.18 (P less than .05) and 3.02 +/- 0.21 mL/mm Hg/kg (P less than .01), respectively. There were no significant changes in left ventricular weight/body weight ratio, mean aortic pressure, heart rate, or right atrial pressure. There was a trend, but not significant, for a reduction in total blood volume from 65.8 +/- 1.1 to 59.4 +/- 3.0 and 64.9 +/- 3.9 mL/kg, respectively. Thus, direct blockade of AII with DuP 753 or with converting enzyme inhibition with captopril produces similar hemodynamic changes in rats with heart failure after myocardial infarction.

Administration, Oral↗

Peripheral circulatory control of cardiac output in diabetic rats.

Diabetes is believed to be associated with impaired systolic and diastolic function of the heart; however, some investigators have found that diabetic rats have increased cardiac output. We investigated changes in the peripheral circulation that could account for an increased cardiac output in diabetic rats (n = 30), 4 wk after a single tail vein injection of streptozotocin (60 mg/kg), and age-matched control rats (n = 31). Compared with controls, diabetic rats exhibited decreased (P less than 0.05) mean arterial pressure, characteristic aortic impedence, and total peripheral resistance; however, cardiac index and stroke volume index were increased. Aortic compliance, mean circulatory filling pressure, central venous pressure, pressure gradient for venous return, and venous compliance were unchanged in the diabetic rats compared with control. Baseline left ventricular end-diastolic pressure and end-diastolic volume were increased in the diabetic rats. Following a volume load of 30 ml/kg, cardiac index and stroke volume index increased less in the diabetic than in the control rats (35 vs. 102% and 69 vs. 105%, respectively). Thus, even with impaired systolic function, cardiac output is increased or maintained in diabetic rats because of the combination of decreased afterload and maintenance of preload.

Animals↗

Abnormal cardiac function in the streptozotocin-diabetic rat. Changes in active and passive properties of the left ventricle.

To provide an integrated assessment of changes in systolic and diastolic function in diabetic rats, we measured conscious hemodynamics and performed ex vivo analysis of left ventricular passive-elastic properties. Rats given streptozotocin (STZ) 65 mg/kg i.v. (n = 14) were compared with untreated age-matched controls (n = 15) and rats treated with insulin after administration of STZ (n = 11). After 7 d, diabetic rats exhibited decreases in heart rate and peak developed left ventricular (LV) pressure during aortic occlusion. After 26 d of diabetes there were significant decreases in resting LV systolic pressure, developed pressure, and maximal +dP/dt, whereas LV end-diastolic pressure increased and the time constant of LV relaxation was prolonged. The passive LV pressure-volume relationship was progressively shifted away from the pressure axis, and the overall chamber stiffness constant was decreased. However, "operating chamber stiffness" calculated at end-diastolic pressure was increased at 7 d, and unchanged at 26 d. LV cavity/wall volume and end-diastolic volume were increased after 26 d of diabetes. Myocardial stiffness was unchanged at both time intervals. All of the above abnormalities were reversed by the administration of insulin. We conclude that the hemodynamic and passive-elastic changes that occur in diabetic rats represent an early dilated cardiomyopathy which is reversible with insulin.

Animals↗