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Biomedical subjects

K O'Brien

Publications and source records attributed to K O'Brien.

At least 127 records · Page 7Linked to original sources

Plasmid cloning vectors for the conjugal transfer of DNA from Escherichia coli to Streptomyces spp.

We have constructed cloning vectors for the conjugal transfer of DNA from Escherichia coli to Streptomyces spp. All vectors contain the 760-bp oriT fragment from the IncP plasmid, RK2. Transfer functions need to be supplied in trans by the E. coli donor strain. We have incorporated into these vectors selectable antibiotic-resistance markers (AmR, ThR, SpR) that function in Streptomyces spp. and other features that should allow for: (i) integration via homologous recombination between cloned DNA and the Streptomyces spp. chromosome, (ii) autonomous replication, or (iii) site-specific integration at the bacteriophage phi C31 attachment site. Shuttle cosmids for constructing genomic libraries and bacteriophage P1 cloning vector capable of accepting approx. 100-kb fragments are also described. A simple mating procedure has been developed for the conjugal transfer of these vectors from E. coli to Streptomyces spp. that involves plating of the donor strain and either germinated spores or mycelial fragments of the recipient strain. We have shown that several of these vectors can be introduced into Streptomyces fradiae, a strain that is notoriously difficult to transform by PEG-mediated protoplast transformation.

Bacteriophages↗

Primary relationships affect the psychological health of homosexual men at risk for AIDS.

Less is known about the effects of primary relationships on psychological health for homosexual men and women than for heterosexual men and women. Given the HIV/AIDS epidemic, the primary relationships of homosexual men are especially important to examine at the present time. Using questionnaire data collected from 259 homosexual men, this study examined the effects of status and quality of relationship on psychological health. Analysis indicated that homosexual men who are in primary relationships experience fewer depressive symptoms and greater well-being than other homosexual men but that being in a relationship does not predict changes in these outcomes over time. Men who report high quality of relationship show improvements over time in psychological health. These findings are discussed in light of the HIV/AIDS epidemic.

Acquired Immunodeficiency Syndrome↗

Evaluation of latex allergy in patients with meningomyelocele.

Seventy-six patients with meningomyelocele were evaluated for latex sensitivity by medical history and epicutaneous skin testing. Four different latex glove extracts, two nonlatex glove extracts, cornstarch, selected inhalant antigens, and negative and positive controls were used for skin testing. Forty-nine patients (64.5%) were skin test positive to latex extracts (latex-positive group). Twenty-four patients (49%) of the latex-positive group and none of the latex-negative group had histories of immediate reactions to latex products (P less than .001). The latex-positive group had a higher mean number of surgical procedures, 12.67 +/- 11.27, compared with 6.89 +/- 6.55 (P less than .001) in the latex-negative group. Twenty-three of the latex-positive patients (47%) used latex products daily compared to seven patients (26%) in the latex-negative group (P = .073). Twenty latex-positive patients (41%) had atopy compared with five patients (19%) of the latex negative group (P = .041). There was no significant difference between the two groups in age, sex, daily catheterization, or positive skin tests to cornstarch. All 76 patients tested negative to the nonlatex glove extracts. Ten control subjects tested negative for all latex and nonlatex glove extracts.

Adolescent↗

Impact of pharmaceutical company representatives on internal medicine residency programs. A survey of residency program directors.

To survey internal medicine residency program directors regarding interactions between their residents and pharmaceutical company (PC) representatives (PCRs) a questionnaire was sent to the directors of all Accreditation Council for Graduate Medical Education-approved internal medicine residency programs. The survey included 444 program directors, of whom 272 (61.16%) responded. The majority of program directors, 228 (83.8%), allowed PCRs to meet with residents during working hours and 241 (88.6%) permitted PC sponsorship of conferences. About half of the program directors were "moderately" or "very" concerned about the potential adverse effects of PC marketing on resident attitudes and prescribing practices. Seventy percent "agreed" or "strongly agreed" that the benefits of PC sponsorship outweigh the adverse effects and 41.5% believed that refusal to allow PCRs to meet with residents would jeopardize PC funding of other departmental activities. Most program directors reported that alternate funds for conferences were available if PC support was withdrawn. "Unethical" marketing activities were observed by 14.3% of program directors and 37.5% reported that residents had participated in PC-sponsored trips during the 3 years prior to the survey. At the time of this survey, only 35.3% of programs had developed formal policies regulating PCR activities and 25.7% provided residents with formal instruction on marketing issues. Knowledge of the current extent of PCR interactions with residents may be helpful to program directors in developing policies regulating PC-marketing activities.

Attitude of Health Personnel↗

Mineral homeostasis in obesity: effects of euglycemic hyperinsulinemia.

We explored the effects of insulin on mineral homeostasis in five lean and six moderately obese nondiabetic premenopausal women. Serum and urine minerals were measured before and during the steady-state phase of a euglycemic insulin clamp. Each subject participated in two insulin clamp studies on separate days at insulin infusion rates of 10 and 40 mU/m2/min. Euglycemic hyperinsulinemia was associated with (1) a significant increase in urinary calcium excretion when expressed per minute with no change in total serum calcium; (2) a decrease in urine and serum phosphate; (3) a decrease in serum potassium with no change in urine potassium; and (4) no measurable effects on urine or serum sodium. At any given insulin level, the obese individuals excreted significantly more calcium, phosphate, and potassium per minute than lean controls. While insulin administration had no effect on serum parathyroid hormone (PTH) or vitamin D levels, baseline serum 1,25(OH)2D concentration was significantly higher and serum ultrafilterable calcium was significantly lower in obese subjects than in lean controls.

Adult↗

Lipogenic potential of liver from morbidly obese patients with and without non-insulin-dependent diabetes.

Intra-abdominal liver biopsies were obtained during surgery from fasted obese patients with non-insulin-dependent diabetes mellitus (NIDDM), obese normoglycemic controls, and lean controls. Lipid synthesis was studied in freshly isolated hepatocytes and liver homogenates from the three groups of subjects. Incorporation of 3H2O into the lipids of hepatocytes was determined in the absence and presence of insulin (0.1 mumol/L). The activities of five enzymes involved in fatty acid synthesis, and the incorporation of 14C-glycerol-3-phosphate into lipids were determined in liver homogenates. Basal lipid synthesis by hepatocytes was not different in the three groups of patients. Insulin stimulated lipogenesis by 8% +/- 30% in the lean controls, 33% +/- 8% in the obese controls and 17% +/- 6% in the NIDDM patients. No significant differences in the activities of the five enzymes that are involved in de novo fatty acid synthesis among the three groups of patients were observed. Similarly, incorporation of 14C-glycerol-3-phosphate by liver homogenates, in the presence of saturating or submaximal concentrations of fatty acids, did not differ among the three groups. These results show that under the experimental conditions of this study, including the fasted state of the patients, the basal capacity of liver of NIDDM patients to synthesize fatty acids or glycerides is the same as that of liver from obese and lean controls. Thus, it is likely that an increase in fatty acid flux into a liver with normal lipogenic potential may contribute to the increased synthesis of triglycerides by the liver of these patients in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Regulation of proline utilization in Salmonella typhimurium: a membrane-associated dehydrogenase binds DNA in vitro.

The PutA protein is a membrane-associated enzyme that catalyzes the degradation of proline to glutamate. Genetic evidence suggests that in the absence of proline, the PutA protein also represses transcription of the putA and putP genes. To directly determine whether PutA protein binds to the put control region, we analyzed gel retardation of put control region DNA by purified PutA protein in vitro. The put control region is 420 bp. Purified PutA protein bound specifically to several nonoverlapping fragments of control region DNA, indicating the presence of multiple binding sites in the control region. Electrophoretic abnormalities and behavior of circularly permuted fragments of control region DNA indicate that it contains a region of intrinsically curved DNA. To determine whether the multiple binding sites or the DNA curvature are important in vivo, two types of deletions were constructed: (i) deletions that removed sequences predicted to contribute to DNA curvature as well as potential operator sites and (ii) deletions that removed only potential operator sites. Both types of deletions increased expression of the put genes but were still induced by proline, indicating that multiple cis elements are involved in repression. These data suggest a model for put repression that invokes the formation of a complex between PutA protein molecules bound at different sites in the control region, brought into proximity by a loop of curved DNA.

1-Pyrroline-5-Carboxylate Dehydrogenase↗

Orthodontic interactions: the relationships between the orthodontic services in England and Wales.

The manpower distribution and the amount of treatment undertaken by the three orthodontic treatment providing groups was calculated on a national and regional basis. There was marked regional variation in the distribution of orthodontic manpower. It was found that the total orthodontic treatment rate correlated with the distributions of specialist practitioners and general dental practitioners, but not with that of the salaried services. The manpower distribution of specialist practitioners and Community Orthodontists was also related. These results are discussed in terms of the effect of manpower distribution upon demand for treatment and the amount of treatment provided by the orthodontic services.

Adolescent↗

Interleukin-2 and high-dose cisplatin in patients with metastatic melanoma: a pilot study.

In this pilot study of metastatic melanoma, interleukin-2 (IL-2) and cisplatin (CDDP) chemotherapy were combined using an alternating schedule designed to explore potential synergism between these modalities. Bolus IL-2 was given at a dose of 600,000 IU/kg intravenously (IV) every 8 hours, days 1 to 5 and 15 to 19, followed by high-dose CDDP administered by two different regimens: (A) 135 to 150 mg/m2 IV bolus over 30 minutes with the chemoprotectant WR-2721 910 mg/m2 or (B) 50 mg/m2 IV over 2 hours every day for 3 days. The trial design allowed an assessment of response to each phase of therapy. Among 27 assessable patients, there were 10 (37%) overall responses, including three (11%) complete responses (CRs) with durations of 9, 16, and 30+ months. Tumor regression was noted in seven patients (partial response [PR], four; minor response [MR], three; response rate [RR], four of 27 [15%]) after IL-2 administration and in 14 patients (PR, 12; MR, two; RR, 12 of 27 [44%]) after CDDP treatment, demonstrating noncrossresistance between the components of the regimen. Major PRs (greater than 90% reduction of tumor burden) or CRs were only seen in patients responding to IL-2. Toxicity during IL-2 therapy was typical for high-dose IL-2 protocols and was reversible. Among the first 20 patients treated with CDDP regimen A, there were eight episodes of grade IV nephrotoxicity (creatinine level greater than 5.0 mg/dL), including three of six patients treated with an initial CDDP dose of 135 mg/m2. This side effect was more frequent among patients with liver metastasis (P less than .05, Fisher's exact test). No significant nephrotoxicity was noted in seven patients treated on regimen B. Although ototoxicity was frequent, minimal bone marrow and neurologic toxicity was noted. There were no treatment-related deaths. This combination showed at least additive activity against melanoma, and the more protracted CDDP schedule was well tolerated. This regimen may serve as a model for future combined immunotherapy and chemotherapy trials in metastatic melanoma.

Adult↗

Gallium-SPECT in the detection of prosthetic valve endocarditis and aortic ring abscess.

A 52-yr-old man who had a bioprosthetic aortic valve developed Staphylococcus aureus bacteremia. Despite antibiotic therapy he had persistent pyrexia and developed new conduction system disturbances. Echocardiography did not demonstrate vegetations on the valve or an abscess, but gallium scintigraphy using SPECT clearly identified a focus of intense activity in the region of the aortic valve. The presence of valvular vegetations and a septal abscess was confirmed at autopsy. Gallium scintigraphy, using SPECT, provided a useful noninvasive method for the demonstration of endocarditis and the associated valve ring abscess.

Abscess↗

Patient care plans for intershift report.

Inconsistent communication during intershift report had resulted in loss of vital information. This project was developed to implement the use of nursing care plans for intershift report on a 25-bed school-age unit. A review of literature showed an absence of any systematic method for intershift report. Classes that included a 20-minute video, written guidelines, and discussion were used to promote the use of nursing care plans for intershift report. A questionnaire was administered to the nursing staff 3 weeks after class to evaluate the project. The evaluation of use of the care plans indicated: (a) a more focused intershift report; (b) an improved structure for report, including important information about the child and family; (c) increased communication; (d) more practical up-to-date care plans; and (e) increased professionalism and collaboration.

Child↗

Regional distribution of cholecystokinin messenger RNA in rat brain during development: quantitation and correlation with cholecystokinin immunoreactivity.

The regional distribution of CCK-octapeptide (CCK) and CCKmRNA were studied in parallel in rat brain during development in order to characterize changes in gene expression in different structures at different periods of development and to determine whether differential regulation of translation and peptide turnover occurs, by correlating peptide and mRNA levels. CCK was characterized by Northern blot analysis. Methods were developed for quantitation of CCKmRNA by in situ hybridization (ISH) and compared with results obtained by slot blot analysis. Analysis of CCKmRNA by ISH showed that CCKmRNA was abundant in cerebral cortex, hippocampus, dentate gyrus, thalamus, inferior colliculus and periaqueductal grey in keeping with the high concentrations of CCK-like immunoreactivity in cell bodies located in these regions. Quantitation of CCKmRNA by computerized densitometric image analysis by reference to [35S]brain paste standards gave a similar pattern to that obtained by slot blot analysis of regional RNA extracts. Distinctive patterns of CCK development were seen. In cerebral cortex and hippocampus, a marked increase in peptide and mRNA levels was found from day 1 which showed a steady increase up to adult levels. However, in the thalamus, the highest levels of mRNA and peptide were reached at a much earlier stage, generally by 14d. In contrast, inferior and superior colliculus showed a delayed onset of peptide expression.

Animals↗

A clinical trial of aligning archwires.

The physical properties of a super-elastic archwire alloy (Titanol) and Nitinol were investigated by the means of a bending test. It was found that the alloy possessed super-elastic properties. A clinical trial was then carried out to compare the properties of two types of aligning archwire. Two groups of 20 patients with crowded dentitions were randomly allocated either Titanol or Nitinol, a conventional nickel-titanium alloy aligning archwire. High quality alginate impressions were taken after archwire placement in Edgewise fixed appliances and were repeated after a mean period of 35 days. The impressions were cast in dental stone and digitized using the Reflex Metrograph. The contact points of the teeth of the labial segments, together with four stable points in the rugae were recorded. This enabled the co-ordinates for the sequential study models to be superimposed upon one another, allowing tooth movement in three dimensions to be calculated. The measurement error expressed as error variance was 0.028 mm. The coefficient of reliability was 97 per cent. When tooth movement was analysed the mean movement per contact point for Titanol was 1.7 mm and for Nitinol 1.42 mm. This difference was not statistically significant (P less than 0.05, t-test). However, a clinical impression was that the super-elastic archwire proved superior to the Nitinol, because it was more readily engaged into grossly displaced teeth.

Adolescent↗

An analysis of retrospective data concerning the provision of orthodontic treatment by the community dental services.

The distribution of both community orthodontic and dental officer manpower has been reviewed, and both exhibit an unequal regional variation. The amount of orthodontic treatment provided was calculated, and expressed as a treatment rate and percentage of fixed: removable appliances fitted. There was a marked regional variation in the form of appliance utilized, and there was a significant relationship between community orthodontic manpower and the relative use of fixed appliances. However, the treatment rate was not related to the manpower distribution. The data collected, by the Department of Health, on the provision of orthodontic treatment was found to have some limitations in its usefulness for epidemiological purposes.

Adolescent↗