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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

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Noninvasive determination of aortic input impedance and external left ventricular power output: a validation and repeatability study of a new technique.

OBJECTIVE: The study was designed to test whether aortic input impedance and left ventricular power output can be accurately assessed noninvasively. BACKGROUND: Aortic input impedance describes both the pulsatile and nonpulsatile artery load encountered by the left ventricle. Until now, this measure of afterload has only been determined by invasive techniques. METHODS: The aortic pressure wave was estimated by recording the calibrated carotid artery pressure wave noninvasively with use of a micromanometer-tipped probe by the technique of applanation tonometry. Flow was determined with pulsed wave Doppler measurement of ascending aortic velocity profile and aortic diameter. In 18 subjects undergoing cardiac catheterization, invasive measurements were taken to assess the accuracy of noninvasive data. In 17 other subjects noninvasive measurements were taken on different days to assess the reproducibility of results. RESULTS: Noninvasive pressure measurements correlated well with invasive data: systolic pressure (mm Hg), noninvasive 126 +/- 28 versus invasive 127 +/- 28, r = 0.96, p less than 0.001; diastolic pressure (mm Hg), noninvasive 71 +/- 10 versus invasive 66 +/- 7, r = 0.60, p less than 0.02; augmentation index (%), noninvasive 23.9 +/- 9.3 versus invasive 30.7 +/- 11.9, r = 0.87, p less than 0.001. Doppler-measured cardiac output was closely correlated with invasively measured flow (liters/min): Doppler, 5.3 +/- 1.2 versus invasive, 5.5 +/- 1.3, r = 0.98, p less than 0.001. Impedance and left ventricular power variables calculated from noninvasive and invasive techniques were also closely related: systemic vascular resistance (dynes.s.cm-5), noninvasive 1,479 +/- 488 versus invasive 1,502 +/- 498, r = 0.91, p less than 0.001; characteristic impedance (dynes.s.cm-5), noninvasive 137 +/- 52 versus invasive 136 +/- 79, r = 0.92, p less than 0.001; pulsatile power (mW), noninvasive 249 +/- 94 versus invasive 291 +/- 103, r = 0.91, p less than 0.001; mean power (mW), noninvasive 1,107 +/- 319 versus invasive 1,144 +/- 266, r = 0.93, p less than 0.001. Repeated measures of impedance variables and power output showed coefficients of variation of less than 9%. CONCLUSIONS: Measurement of noninvasive impedance by this technique provides an accurate and repeatable assessment of mean and pulsatile cardiac load.

Aorta↗

Clinical results of decompressive dermotomy-fasciotomy.

Seventy-three dermotomy-fasciotomies (DFs) were performed in 68 patients from 1986 to 1991. A database record was compiled on each patient. Variables included age, mode of injury, method of initial wound closure, and associated injuries. A multivariate stepwise logistic regression analysis was performed to determine which variables were associated with wound complications. Thirty-eight percent of patients who underwent DF developed wound complications. One hundred percent of those patients with postoperative arterial or graft thrombosis developed wound complications (p less than 0.01) as did 78% of those with thromboembolic disease (p less than 0.05). Conversely, only 5% of those who underwent closure of their DF wounds utilizing skin grafts developed wound complications (p less than 0.01) as compared with 51% of those who underwent secondary or primary closure only. Subsequent analysis of the remaining patients, excluding those with severe soft tissue injury, showed an association between location of DF (upper versus lower extremity) and the development of wound complications that approached statistical significance (p less than 0.06). DF is frequently necessary in the treatment of patients with compartment syndrome but is associated with significant morbidity. This study suggests that closure of DF wounds utilizing skin graft allows for continued osteofascial decompression while concomitantly minimizing invasive sepsis.

Adolescent↗

Selections from current literature: treatment of hypertension.

The three papers reviewed for this issue deal with unrelated aspects of hypertension, illustrating the broad range of questions that still exist about optimal diagnosis and management. Physicians have for years been unsure about the efficacy, safety, and impact on morbidity of treating ISH. The result of these concerns has been that many, if not most patients with ISH never received treatment. The SHEP data are a powerful argument for routine treatment of ISH, which would represent a new standard of care for this condition. Only clinical experience and future trials will indicate whether treatment of ISH in the general population will be accompanied by the low incidence of side effects and morbidity observed in the more highly selected population of the SHEP trial. The study of Zeller et al. adds to the evidence that less is more, or at least the same, when it comes to treatment of hypertensive urgencies. The practice of oral 'loading' doses was not shown to improve therapeutic results. It is still not completely clear what criteria physicians should use in making a decision about inpatient parenteral therapy versus outpatient oral therapy. In patients with evidence of acute onset and end-organ injury, it is probably prudent to admit. In the absence of these risk factors, institution of an outpatient oral antihypertensive regimen can probably be accomplished with safety and at dramatically lower cost. The study of Koren et al. demonstrated a marked additional risk when LVH was present in hypertensive patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Laboratory and field evaluation of five repellents against the black flies Prosimulium mixtum and P. fuscum (Diptera: Simuliidae).

Deet (N,N-diethyl-3-methyl-benzamide), the lactone CIC-4 ([2-hydroxy-methyl-cyclohexyl] acetic acid lactone), the USDA Proprietary Chemicals AI3-37220 (1- [3-cyclohexen-1-ylcarbonyl]-2-methylpiperidine) and ++[3-35765 (1-[3-cyclohexen-1-ylcarbonyl] piperidine), and the U.S. military extended duration repellent formulation (EDRF) of deet were evaluated for repellency in the laboratory and field against the black flies Prosimulium mixtum and P. fuscum. CIC-4, AI3-37220, and AI3-35765 were as effective as deet at repelling P. mixtum and P. fuscum in laboratory and field experiments. Only the EDRF provided significantly longer protection than the deet standard against these black flies in the field.

Animals↗

Multiple transmission of Plasmodium gallinaceum (Eucoccida: Plasmodiidae) during serial probing by Aedes aegypti (Diptera: Culicidae) on several hosts.

Mosquitoes salivate before ingesting blood, and sporozoites are transmitted during this phase of feeding. In the laboratory, malaria-infected Aedes aegypti were allowed to probe on a series of three chicks during a 5-min period. Probing on each host was interrupted after 10 s. Our results demonstrate that up to three hosts can be serially infected with avian malaria during a 5-min period.

Aedes↗

A zinc finger protein from Candida albicans is involved in sucrose utilization.

A sucrose-inducible alpha-glucosidase activity that hydrolyzes sucrose in Candida albicans has been demonstrated previously. The enzyme is assayable in whole cells and was inhibited by both sucrose and maltose. A C. albicans gene (CASUC1) that affects sucrose utilization and alpha-glucosidase activity was cloned by expression in a Saccharomyces cerevisiae suc2 mutant (2102) devoid of invertase genes. CASUC1 enabled the S. cerevisiae mutant to utilize both sucrose and maltose. DNA sequence analysis revealed that CASUC1 encodes a putative zinc finger-containing protein with 28% identity to a maltose-regulatory gene (MAL63) of S. cerevisiae. The gene products of CASUC1 and MAL63 are approximately the same size (501 and 470 amino acids, respectively), and each contains a single zinc finger located at the N terminus. The zinc fingers of CASUC1 and MAL63 comprise six conserved cysteines (C6 zinc finger) and are of the general form Cys-Xaa2-Cys-Xaa6-Cys-Xaavariable-Cys-Xaa2-Cys-+ ++Xaa6-Cys (where Xaan indicates a stretch of the indicated number of any amino acids). Both contain five amino acids in the variable region. CASUC1 also complemented the maltose utilization defect of an S. cerevisiae mutant (TCY-137) containing a defined mutation in a maltose-regulatory gene. The sucrose utilization defect of type II Candida stellatoidea, a sucrase-negative mutant of C. albicans, was corrected by CASUC1. Determinations of alpha-glucosidase activity in whole cells revealed that activity was restored in transformants cultivated on either sucrose or maltose. To our knowledge, this is the first zinc finger-encoding gene, as well as the first putative regulatory gene, to be identified in C. albicans.

Amino Acid Sequence↗