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Biomedical subjects

R Kelly

Publications and source records attributed to R Kelly.

At least 91 records · Page 5Linked to original sources
PubMed1995

Postnatal lung function in preterm lambs: effects of a single exposure to betamethasone and thyroid hormones.

OBJECTIVE: We determined the effect of a single direct fetal injection of corticosteroid and thyroid hormones on postnatal pulmonary function in preterm lambs. STUDY DESIGN: Initially fetal sheep (126 days' gestation) randomly received saline solution, betamethasone (Celestone Soluspan, 0.5 mg/kg), betamethasone plus triiodothyronine (5 micrograms/kg), or betamethasone plus thyroxine (15 micrograms/kg) as a single injection. Forty-eight hours later (128 days' gestation) the fetuses were delivered and ventilated for 50 minutes. In a second protocol fetuses were delivered at 128 days' gestation, after only 24 hours of hormone exposure. RESULTS: Betamethasone treatment improved compliance nearly twofold after 24 or 48 hours of exposure. Efficiency of ventilation also improved after steroid therapy; this effect was augmented 48 hours after thyroxine exposure (but not triiodothyronine). No thyroxine effect was noted after 24 hours of exposure. Maximal lung volume increased by 80% after steroid treatment and doubled in response to combination betamethasone and thyroxine therapy. Alveolar pool sizes of saturated phosphatidylcholine and surfactant protein A were comparable for all groups exposed for 48 hours. CONCLUSIONS: A single fetal exposure to betamethasone improves postnatal pulmonary function after 24 or 48 hours. Addition of thyroxine (but not triiodothyronine) augments this effect at 48 hours.

Animals↗
PubMed1995

Myosin light chain 3F regulatory sequences confer regionalized cardiac and skeletal muscle expression in transgenic mice.

The myosin light chain IF/3F locus contains two independent promoters, MLC1F and MLC3F, which are differentially activated during skeletal muscle development. Transcription at this locus is regulated by a 3' skeletal muscle enhancer element, which directs correct temporal and tissue-specific expression from the MLC1F promoter in transgenic mice. To investigate the role of this enhancer in regulation of the MLC3F promoter in vivo, we have analyzed reporter gene expression in transgenic mice containing lacZ under transcriptional control of the mouse MLC3F promoter and 3' enhancer element. Our results show that these regulatory elements direct strong expression of lacZ in skeletal muscle; the transgene, however, is activated 4-5 d before the endogenous MLC3F promoter, at the time of initiation of MLC1F transcription. In adult mice, transgene activity is downregulated in muscles that have reduced contributions of type IIB fibers (soleus and diaphragm). The rostrocaudal positional gradient of transgene expression documented for MLC1F transgenic mice (Donoghue, M., J. P. Merlie, N. Rosenthal, and J. R. Sanes. 1991. Proc. Natl. Acad. Sci. USA. 88:5847-5851) is not seen in MLC3F transgenic mice. Although MLC3F was previously thought to be restricted to skeletal striated muscle, the MLC3F-lacZ transgene is expressed in cardiac muscle from 7.5 d of development in a spatially restricted manner in the atria and left ventricular compartments, suggesting that transcriptional differences exist between cardiomyocytes in left and right compartments of the heart. We show here that transgene-directed expression of the MLC3F promoter reflects low level expression of endogenous MLC3F transcripts in the mouse heart.

Animals↗
PubMed1995

The social dynamics of HIV transmission as reflected through discordant couples in rural Uganda.

OBJECTIVE: To describe the role of men and women as sources of HIV transmission and to estimate HIV incidence among discordant couples resident in diverse rural communities in Uganda. SETTING: Rakai, a rural district in Uganda, East Africa. METHODS: A population-based cohort study, which has been conducted as annual serological and behavioral surveys since 1989. Community clusters were stratified into trading centers on main roads, intermediate trading villages on secondary roads and agricultural villages off roads. In the 1990 survey round, serological data were available for 79 discordant and 411 concordant HIV-negative couples aged 13-49 years. The present analysis examines sex-specific seropositivity associated with place of residence and the incidence of seroconversion among discordant couples between 1990 and 1991. RESULTS: Seventy-nine discordant couples were followed; the HIV-positive partner was male in 44 couples (57%) and female in 35 couples (43%). There was marked variation in the sex of the seropositive partner by place of residence: women were the HIV-positive partner in 57% of couples from trading centers, 52% from intermediate villages, and 20% from agricultural communities (P < 0.008). Condom use was higher in discordant couples in which the man was the uninfected partner (17.1%) rather than the woman (9.5%). HIV-positive women, but not HIV-positive men, reported significantly more sexual partners and more genital ulcers than seronegative individuals of the same sex. Seroincidence rates among men and women in discordant relationship were 8.7 and 9.2 per 100 person-years (PY), respectively, which was much higher than in concordant seronegative couples (men, 0.82; women, 0.87 per 100 PY). CONCLUSIONS: In this Ugandan population, men are the predominant source of new infections in rural villages. Risk factors and preventive behaviors vary with the sex of the infected partner, and seroconversion rates are similar in both sexes.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Postnatal lung function in lambs after fetal hormone treatment. Effects of gestational age.

We previously found that a single dose of betamethasone in combination with thyroxine given by intramuscular injection to fetal sheep 48 h before preterm delivery at 128 d gestation improved postnatal lung function. We have now asked how the combination of 0.5 mg/kg betamethasone and 15 micrograms/kg T4 given by a single fetal intramuscular injection changes lung response 48 h after treatment at 121 and 135 d gestation. At 121 d gestation the fetal hormone treatment significantly improved postnatal lung function. Compliance increased by 55%, arterial PO2 increased from 39 to 215 mm Hg, PCO2 decreased from 109 to 79 mm Hg, and maximal lung volumes increased by 112%. The hormone treatment decreased the severity of the respiratory failure, although these very preterm lambs still had severe respiratory failure. At 135 d gestation, the fetal hormone treatment decreased the ventilatory pressure requirements that were needed to normalize PCO2 values from 30 to 21 cm H2O. Compliance increased by 40%, and maximal lung volumes increased by 33%. Alveolar or lung tissue, saturated phosphatidylcholine, or alveolar SP-A pool sizes did not change with hormone treatment at 135 d gestation. We conclude that fetal hormone treatment significantly improved postnatal lung function at both gestational ages, although the characteristics of the responses were different.

Animals↗
PubMed1995

Myogenic conversion of mammalian fibroblasts induced by differentiating muscle cells.

Somite-derived skeletal myoblasts are supposed to be the sole source of muscle fibre nuclei during pre- and postnatal development, but evidence is accumulating for unorthodox contributions to muscle fibre nuclei from other cell types. For example, in tissue culture, fibroblasts can fuse with dysgenic myoblasts and restore correct membrane function. We report here the results of a series of experiments investigating this phenomenon and its possible mechanism. 10T1/2 cells, infected with a replication defective retrovirus encoding the bacterial enzyme beta-galactosidase, fused to form beta-galactosidase positive, differentiated myotubes when cocultured with differentiating uninfected C2C12 or primary myogenic cells, but this did not occur when they were cocultured with other cells such as 3T3 fibroblasts or PC12 pheochromocytoma cells. Myogenic conversion ranged from 1 to 10% of the 10T1/2 cell population and required close cell interaction between the different cells types: it was not induced by conditioned medium or extracellular matrix deposited by C2C12 cells. Myogenic conversion was also observed in vivo, after injection of similarly infected 10T1/2 cells into regenerating muscle. Conversion was seen also after coculture of uninfected 10T1/2 cells with primary chick myoblasts, thus demonstrating that it was not dependent upon viral infection and that there is no species or class barrier in this phenomenon. Primary fibroblasts, isolated from different organs of transgenic mice carrying a Lac Z marker under the control of a muscle-specific promoter, restricting beta-galactosidase expression to striated muscle cells, also underwent myogenic conversion, when cocultured with C2C12 myoblasts.(ABSTRACT TRUNCATED AT 250 WORDS)

3T3 Cells↗
PubMed1995

En bloc aortic resection for bulky metastatic germ cell tumors.

Between 1989 and 1993, 97 patients with stages B3 and/or C nonseminomatous germ cell tumors of the testes underwent induction chemotherapy followed by retroperitoneal lymph node dissection. Of these patients 6 (ages 22 to 41 years) had gross extension of tumor into the aortic adventitia at operation, which necessitated en bloc aortic and, on 3 occasions, iliac artery resection for complete tumor removal. Aortic continuity was restored by a woven Dacron tube or bifurcated graft. All grafts were covered with omentum. There were no postoperative vascular complications. Pathological study of the residual retroperitoneal disease demonstrated that 2 patients had mature teratoma only, 2 had mature teratoma with occasional nests of immature teratoma and 2 had residual yolk sac, embryonal or choriocarcinoma elements. The latter 2 patients underwent postoperative salvage chemotherapy with varying combinations of bleomycin, etoposide, ifosfamide and cisplatin. At 4 to 55 months 4 patients were disease-free, while 2 died of metastatic disease. No problems related to the aortic reconstruction have occurred. This small experience demonstrates that, if necessary, complete surgical en bloc extirpation of bulky metastatic germ cell tumors and the aorta/iliac artery can be performed safely with a satisfactory long-term outcome.

Adult↗
PubMed1994

Isolation and sequence of the t-RNA ligase-encoding gene of Candida albicans.

The gene encoding tRNA ligase from Candida albicans was isolated from a genomic library by complementation of a Saccharomyces cerevisiae strain containing a disrupted structural gene, RLG1, encoding tRNA ligase. The cloned gene also complements a temperature-sensitive allele of RLG1. Sequence analysis revealed a single 2499-nt coding region. The gene encodes a protein of 833 amino acids that is 42% identical to S. cerevisiae tRNA ligase. Hybridization to chromosomes of C. albicans separated by pulsed-field gel electrophoresis located the gene to chromosome 1, the smallest C. albicans chromosome.

Amino Acid Sequence↗
PubMed1994

Heterologous transformation of Zalerion arboricola.

A heterologous DNA-mediated transformation system was developed for the pneumocandin-producing fungus Z. arboricola that was based on either conferral of hygromycin B resistance or complementation of a nitrate reductase mutant. Hygromycin-resistant transformants were selected with plasmid pCSN43 which contains the E. coli hygromycin B phosphotransferase gene under the control of Aspergillus nidulans trpC transcription signals. Transformation frequencies were about four transformants per microgram of circular DNA and could be improved four- to six-fold by linearizing the transforming DNA. The transformants differed from one another with respect to the copy number of the integrated plasmid and the site of integration. Adding an autonomously-replicating sequence (AMA1) from A. nidulans to pCSN43 enhanced transformation three-fold and produced, in addition, numerous abortive transformants. However, it is unlikely that the AMA1 sequence promoted plasmid replication in Z. arboricola. Nitrate reductase mutants of Z. arboricola were isolated by positive selection on chlorate-containing medium, and one mutant was subsequently transformed with pSTA700 which contains the nitrate reductase gene (niaD) from Cephalosporium acremonium. Introduction of the niaD gene restored sensitivity to chlorate in the mutant; therefore, using the niaD gene as a selectable marker provides a system for both positive and negative selection. To our knowledge, this is the first report describing transformation of a member of the genus Zalerion.

Acremonium↗
PubMed1994

Papulonecrotic tuberculide and erythema induratum as presenting manifestations of tuberculosis.

We describe a patient with two tuberculides, erythema induratum and papulonecrotic tuberculide. At presentation these were the only manifestations of tuberculosis and they responded dramatically to antituberculous therapy. With the rise in incidence of tuberculosis in Western countries these and other presentations of tuberculosis will be seen with increasing frequency and may provide the only clue to the underlying diagnosis.

Adult↗
PubMed1994

Anesthetic management in epidermolysis bullosa: review of 129 anesthetic episodes in 32 patients.

BACKGROUND: Anesthetic and monitoring instrumentations such as endotracheal intubation may cause skin and mucosal damage with potentially serious consequences in patients with epidermolysis bullosa (EB). OBJECTIVE: This study defines the risks of skin and mucosal damage from anesthetic and monitoring techniques in patients with EB and formulates management guidelines. METHODS: We retrospectively analyzed the outcome of 129 anesthetic episodes in 32 patients with various types of EB. RESULTS: Serious complications did not occur in any patient with EB from the use of endotracheal intubation, face mask, nerve blocks, local anesthetics, and intravenous or intramuscular anesthetic agents. CONCLUSION: With appropriate precautions, patients with EB can undergo standard anesthetic techniques with only minor and infrequent complications.

Adolescent↗
PubMed1994

Time course of changes in lung mechanics following fetal steroid treatment.

We studied the effect of a single-dose, corticosteroid treatment on preterm lambs (gestational age: 128 d). A low, medium, or high betamethasone dose (0.1, 0.5, and 2.0 mg/kg) or saline control was administered directly to the fetus by ultrasound-guided intramuscular injection 48 h before delivery. A second group received either the high dose of betamethasome or saline 24 h before delivery. The lambs were delivered at 128 d gestation, anesthetized with ketamine, and ventilated for 50 min. Respiratory system elastance and resistance were measured at 10-min intervals using multiple linear regression analysis of pressure, flow, and volume. Similarly, estimates of lung mechanics were calculated from transpulmonary pressure. The viscoelastic time constant (tau) was calculated by fitting an exponential to the pressure changes occurring after occluding the airway during expiration. Excised lung volume at 40 cm H2O and lung weight were used to calculate specific elastance and resistance correcting for lung size using volume or weight, respectively. Of the 13 lambs in the 48-h high-dose betamethasone group, five developed pulmonary interstitial emphysema (PIE) as did 3 of 11 animals in the high-dose group treated 24 h before delivery. These animals were analyzed separately. The lambs receiving medium- or high-dose (24 and 48 h predelivery) betamethasone had significantly lower elastance and a trend toward lower resistance when compared with the control groups. Ten minutes after delivery, the animals that developed PIE all had elastance values comparable to that of the control animals despite corticosteroid treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1994

Family physicians' disagreements with the US Preventive Services Task Force recommendations.

BACKGROUND: The 1989 recommendations of the US Preventive Services Task Force (USPSTF) represent an emerging consensus about which clinical preventive services should be delivered. However, practicing physicians disagree with a number of the recommendations in the Task Force prevention guidelines, and the reasons for disagreement have not been widely explored. METHODS: A survey questionnaire assessing physician agreement or disagreement with the USPSTF recommendations was sent to all 1784 active members of the Ohio Academy of Family Physicians in October 1990. A factor analysis was performed on the items with which at least 5% of physicians disagreed. Associations of physician demographics and attitudes with the factor scores were then examined. RESULTS: At least 5% of the 898 responding physicians disagreed with 67 of 150 USPSTF recommendations. Physicians disagreed with the USPSTF recommendations in three ways: (1) they believed that screening for some cancers is appropriate, even though not recommended by the USPSTF; (2) they believed that screening for other diseases in some populations is appropriate, even though not recommended by the USPSTF; and (3) they disagreed with some USPSTF recommendations for screening that is considered time-consuming or intrusive. Further analyses showed that practice setting and experience with the USPSTF guidelines were predictive of all three disagreement factors. Physician age, race, residency training, and reasons for disagreement were associated with two of the three factors. CONCLUSIONS: Physician disagreement with the USPSTF recommendations was not random but clustered into three distinct factors. An opportunity exists to design educational interventions for targeted subgroups of physicians. The views of practicing physicians should be incorporated into future guidelines.

Adult↗
PubMed1993

Selections from current literature: using aspirin for primary or secondary prevention.

It seems evident that low doses (75 mg/day) of aspirin are adequate for attempts to prevent thrombotic occlusion of blood vessels. There are no data to suggest that different doses should be used based on whether primary or secondary prophylaxis is planned. However, even low doses of aspirin are associated with relatively small numbers of serious haemorrhagic complications. These complications are outweighed by the benefits of therapy in many examples of secondary prevention in high-risk groups that have already experienced an event or symptoms because of underlying vascular disease. Primary prophylaxis is a more controversial area. There is generally less to gain, and more to lose, when measures are applied to large numbers of asymptomatic people. Based on the available data, the conservative approach for aspirin use will be to reserve primary prophylaxis for those people with the highest estimated risk.

Aspirin↗
PubMed1993

Lung responses to ultrasound-guided fetal treatments with corticosteroids in preterm lambs.

Maternal corticosteroid treatments augment lung function in the human preterm infant. However, not all fetuses respond, the response requires > or = 48 h of exposure, and multiple maternal doses expose the mother to potential risks. To evaluate the potential of direct fetal therapy, we used ultrasound to direct fetal intramuscular or intravascular injections of corticosteroids or saline in sheep and subsequently delivered the preterm lambs at 128 days gestational age to assess postnatal lung function. Relative to saline-injected controls, 0.5 or 2 mg/kg betamethasone given as a single intramuscular dose 48 h before delivery increased compliance and the efficiency of ventilation (as measured by an indicator that included ventilatory pressures and CO2 values) nearly twofold (P < 0.05). Lung volumes, measured from deflation pressure-volume curves, also increased (P < 0.05). However, the 2 mg/kg dose caused severe pulmonary interstitial emphysema in 5 of 13 lambs, suggesting adverse effects. An intravascular fetal dose of 12.5 mg/kg hydrocortisone or an intramuscular dose of 0.1 mg/kg betamethasone had no effect on postnatal lung function. In separate studies, the 2 mg/kg dose improved all indicators of lung function almost twofold after only 24 h of fetal exposure and delivery at 128 days gestational age (P < 0.01). There was a dose-dependent suppression of the postnatal cortisol surge in treated animals, although fetal treatment did not alter cord cortisol levels. Single-dose fetal hormone treatments can cause large and rapid improvements in postnatal lung function in preterm lambs.

Adrenal Cortex Hormones↗