PubMed Health⌕ Search

Biomedical subjects

R Kelly

Publications and source records attributed to R Kelly.

At least 37 records · Page 2Linked to original sources
PubMed2000

Contribution of increasing CO2 and climate to carbon storage by ecosystems in the United States.

The effects of increasing carbon dioxide (CO2) and climate on net carbon storage in terrestrial ecosystems of the conterminous United States for the period 1895-1993 were modeled with new, detailed historical climate information. For the period 1980-1993, results from an ensemble of three models agree within 25%, simulating a land carbon sink from CO2 and climate effects of 0.08 gigaton of carbon per year. The best estimates of the total sink from inventory data are about three times larger, suggesting that processes such as regrowth on abandoned agricultural land or in forests harvested before 1980 have effects as large as or larger than the direct effects of CO2 and climate. The modeled sink varies by about 100% from year to year as a result of climate variability.

Agriculture↗
PubMed2000

A T-cell-selective interleukin 2 mutein exhibits potent antitumor activity and is well tolerated in vivo.

Human interleukin 2 (IL-2; Proleukin) is an approved therapeutic for advanced-stage metastatic cancer; however, its use is restricted because of severe systemic toxicity. Its function as a central mediator of T-cell activation may contribute to its efficacy for cancer therapy. However, activation of natural killer (NK) cells by therapeutically administered IL-2 may mediate toxicity. Here we have used targeted mutagenesis of human IL-2 to generate a mutein with approximately 3,000-fold in vitro selectivity for T cells over NK cells relative to wild-type IL-2. We compared the variant, termed BAY 50-4798, with human IL-2 (Proleukin) in a therapeutic dosing regimen in chimpanzees, and found that although the T-cell mobilization and activation properties of BAY 50-4798 were comparable to human IL-2, BAY 50-4798 was better tolerated in the chimpanzee. BAY 50-4798 was also shown to inhibit metastasis in a mouse tumor model. These results indicate that BAY 50-4798 may exhibit a greater therapeutic index than IL-2 in humans in the treatment of cancer and AIDS.

Animals↗
PubMed2000

Salmonella prosthetic valve endocarditis.

We report the case of a 69-year-old man with an aortic valve bioprosthesis in whom a diagnosis of Salmonella typhimurium prosthetic valve endocarditis was made. During the prolonged hospital admission early aggressive antibiotic therapy and early valve replacement surgery were the deciding factors enabling him to survive this otherwise lethal condition.

Journal Article↗
PubMed2000

Choice biases in delayed matching-to-sample duration with pigeons: Manipulations of ITI and delay illumination.

Two experiments investigated the effects of similarity between intertrial interval (ITI) and delay illumation on the choose-short effect. Different groups of pigeons learned to match "short" (2 s) and "long" (6 or 8 s) food samples to green and red test stimuli in a matching-to-sample procedure with a 5-s training delay. Subsequent 10- and 20-s delay tests revealed choose-short effects if the ITI and delay were both illuminated (i.e., group ON-ON), if the ITI and delay were both dark (i.e., group OFF-OFF), and if the ITI was illuminated and the delay was dark (i.e., group ON-OFF). In addition, either a choose-short effect or a choose-long effect was observed if the ITI was dark and the delay was illuminated (i.e., group OFF-ON). Results are incompatible with the confusion/instructional failure view of the choose-short effect.

Animals↗
PubMed2000

Geranylgeranyltransferase I of Candida albicans: null mutants or enzyme inhibitors produce unexpected phenotypes.

Geranylgeranyltransferase I (GGTase I) catalyzes the transfer of a prenyl group from geranylgeranyl diphosphate to the carboxy-terminal cysteine of proteins with a motif referred to as a CaaX box (C, cysteine; a, usually aliphatic amino acid; X, usually L). The alpha and beta subunits of GGTase I from Saccharomyces cerevisiae are encoded by RAM2 and CDC43, respectively, and each is essential for viability. We are evaluating GGTase I as a potential target for antimycotic therapy of the related yeast, Candida albicans, which is the major human pathogen for disseminated fungal infections. Recently we cloned CaCDC43, the C. albicans homolog of S. cerevisiae CDC43. To study its role in C. albicans, both alleles were sequentially disrupted in strain CAI4. Null Cacdc43 mutants were viable despite the lack of detectable GGTase I activity but were morphologically abnormal. The subcellular distribution of two GGTase I substrates, Rho1p and Cdc42p, was shifted from the membranous fraction to the cytosolic fraction in the cdc43 mutants, and levels of these two proteins were elevated compared to those in the parent strain. Two compounds that are potent GGTase I inhibitors in vitro but that have poor antifungal activity, J-109,390 and L-269,289, caused similar changes in the distribution and quantity of the substrate. The lethality of an S. cerevisiae cdc43 mutant can be suppressed by simultaneous overexpression of RHO1 and CDC42 on high-copy-number plasmids (Y. Ohya et al., Mol. Biol. Cell 4:1017, 1991; C. A. Trueblood, Y. Ohya, and J. Rine, Mol. Cell. Biol. 13:4260, 1993). Prenylation presumably occurs by farnesyltransferase (FTase). We hypothesize that Cdc42p and Rho1p of C. albicans can be prenylated by FTase when GGTase I is absent or limiting and that elevation of these two substrates enables them to compete with FTase substrates for prenylation and thus allows sustained growth.

Alkyl and Aryl Transferases↗
PubMed2000

Blood cell lead, calcium, and magnesium levels associated with pregnancy-induced hypertension and preeclampsia.

This study compares the red blood cell (Rbc) levels of lead (Pb), calcium (Ca), and magnesium (Mg) in relation to blood pressure in 39 pregnant women in the third trimester of pregnancy. The study population included 20 women with normal pregnancies, 15 with mild hypertension, and 4 with severe hypertension and preeclampsia. The mean +/- SD for each group was calculated and the difference between the means of the normotensive and the other groups were compared by analysis of variance. Significant differences from normal to the preeclamptic pregnancies were in (1) elevated Rbc Pb (p < or = 0.001), (2) lower Rbc Ca (p < or = 0.001), and (3) lower Rbc Mg/Pb ratio (p < or = 0.0001). Pearson's rank correlation between blood pressure showed a direct relation to the Rbc Pb level (p < or = 0.01) and an inverse relation to the Rbc Ca and Mg/Pb ratio (p < or = 0.004, < or = 0.007). Apparently, prenatal blood pressure is directly proportional to Rbc Pb content and related or modified by Rbc Ca and Mg.

Adolescent↗
PubMed1999

Age of male circumcision and risk of prevalent HIV infection in rural Uganda.

OBJECTIVE: To assess whether circumcision performed on postpubertal men affords the same level of protection from HIV-1 acquisition as circumcisions earlier in childhood. DESIGN: Cross-sectional study of a population-based cohort. SETTING: Rakai district, rural Uganda. METHODS: A total of 6821 men aged 15-59 years were surveyed and venous blood samples were tested for HIV-1 and syphilis. Age at circumcision was dichotomized into men who were circumcised before or at age 12 years (prepubertal) and men circumcised after age 12 years (postpubertal). Postpubertal circumcised men were also subdivided into those reporting circumcision at ages 13-20 years and > or = 21 years. RESULTS: HIV-1 prevalence was 14.1% in uncircumcised men, compared with 16.2% for men circumcised at age > or = 21 years, 10.0% for men circumcised at age 13-20 years, and 6.9% in men circumcised at age < or = 12 years. On bivariate analysis, lower prevalence of HIV-1 associated with prepubertal circumcision was observed in all age, education, ethnic and religious groups. Multivariate adjusted odds ratio of prevalent HIV-1 infection associated with prepubertal circumcision was 0.39 [95% confidence interval (CI), 0.29-0.53]. In the postpubertal group, the adjusted odds ratio for men circumcised at ages 13-20 years was 0.46 (95% CI, 0.28-0.77), and 0.78 (95% CI, 0.43-1.43) for men circumcised after age 20 years. CONCLUSIONS: Prepubertal circumcision is associated with reduced HIV risk, whereas circumcision after age 20 years is not significantly protective against HIV-1 infection. Age at circumcision and reasons for circumcision need to be considered in future studies of circumcision and HIV risk.

Adolescent↗
PubMed1999

A unique cause of unconscious urinary incontinence.

The authors present a case of a healthy 55-year-old woman with a 1-year history of vaginal malodor and perineal dampness. A pyridium (phenazopyridine) pad test revealed a well-defined stain area no greater than 3 cm. Cystoscopic examination revealed multiple multilobulated polypoid neoplasms, which we feel probably represent pedunculated hemangiomas. Removal of the neoplasms cured the dampness, malodor and recurrent vaginal infections. We submit this case as a unique cause of extraurethral incontinence.

Female↗
PubMed1999

Presentation and outcome of sacral agenesis: 20 years' experience.

The underlying risk factors, presenting features, and outcome of 22 children with sacral agenesis and associated neuropathic bladder were studied retrospectively. The age of children at presentation was bimodally distributed, with peaks below 1 year and between 4 and 5 years of age. Ten patients presented after 1 year. The oldest was diagnosed at 12 years of age. In 12 children there was maternal diabetes, orthopaedic anomalies in 14, skin defects in 11, and anorectal/tracheooesophageal anomalies in three. Most children had persistent dribbling of urine on presentation associated with frequency, urgency, recurrent urinary tract infections, failure to respond to medication, and/or constipation. Twenty-one children had abnormal neurology in the lower limbs. Videourodynamics showed neuropathic vesicourethral dysfunction in all children and vesicoureteric reflux in 10. Nineteen had a history of urinary tract infections. Seven had renal scarring, with renal impairment in three at presentation. Clean intermittent catheterization was recommended for 20 of the children. Bladder or bowel surgery has been carried out in seven and neurosurgery performed in two. Twenty of the 22 children underwent operative procedures. Ten operations were performed before sacral agenesis was diagnosed. Over a third of the children have required psychological support. The combination of urinary symptomatology and any of the above risk factors should give rise to a high level of suspicion and low threshold to perform investigations to exclude sacral agenesis. All these children have abnormal bladder and urethral function which not only causes incontinence but puts the kidneys at risk. Early detection allows effective multidisciplinary input specifically aimed at continence, preservation of renal function, and adequate psychological support.

Abnormalities, Multiple↗
PubMed1999

Contribution of vaporization and boiling to thermal-spike sputtering by ions or laser pulses.

Here we consider what, in our terminology, we designate as normal vaporization, normal boiling, and phase explosion. In the case of vaporization, one is dealing with the emission of particles (atoms or molecules) from the extreme outer surface of either a solid or liquid for any temperature exceeding 0 K. In the case of boiling, one is (at least ideally) dealing with heterogeneously nucleated bubbles which diffuse to the outer surface of a liquid or solid and then escape, the latter being possible for temperatures equal to or exceeding the boiling temperature (T(b)). In the case of phase explosion one is dealing with the consequences of what happens when a liquid approaches the thermodynamic critical temperature (T(tc) or T(c)), and massive homogeneous nucleation takes place. Although these three mechanisms have been reviewed in reasonable detail in recent work, we will here present evidence, apparently not previously considered, that boiling, whether the distance scale is atomically small (5-15 nm, as for laser-pulse impact on a metal in the absence of thermal diffusion) or much larger, has a prohibitive kinetic obstacle because it requires bubble diffusion if the bubbles are formed other than at the outer surface. That is to say, boiling will never be a significant process whether with ion or laser-pulse impact. This leaves vaporization and phase explosion as the only possible thermal-spike processes capable of expelling material from an ion- or laser-pulse bombarded surface in a significant quantity. But even with vaporization it can be shown that a kinetic obstacle, although not as severe as for boiling, will enter. The final result is that only phase explosion will normally be relevant for sufficiently short time scales.

Journal Article↗
PubMed1999

Medical restrictions to driving: the awareness of patients and doctors.

The study was set up to investigate the awareness of elderly patients and medical doctors of medical restrictions to driving. Separate questionnaires were completed by patients and doctors. All were interviewed face-to-face, without prior warning and their immediate answers were recorded. In total, 150 elderly patients from the acute elderly care wards, rehabilitation wards and day hospital, and 50 doctors (including all grades from consultant to junior house officer) were interviewed. The main outcome measures were numbers of patients currently driving and previously driving; patients' awareness of how their medical condition affected their ability to drive; doctors' spontaneous knowledge of medical conditions which restrict driving, current licensing policy, and restrictions for five specific medical conditions (epilepsy, myocardial infarction, stroke, 5-cm abdominal aortic aneurysm, and diabetes). Only 21 patients were current drivers, and six of these should not have been driving. While 103 perceived themselves eligible to drive, 46 had medical restrictions to driving. Seventeen of the 47 patients who perceived themselves not eligible to drive possibly did not have restrictions to driving. Doctors' knowledge of the current licensing policy and action to be taken if a patient was not eligible to drive was very poor. Knowledge of medical restrictions to driving was scanty, with few doctors giving the correct driving restrictions for the five specific conditions. We recommend that education of doctors regarding medical restrictions to driving should begin at an undergraduate level and be continued throughout their postgraduate career.

Age Factors↗
PubMed1999

Outflow uropathy: occupational disorder?

This paper alerts physicians, health care workers, and employers to a probable connection between voluntary, infrequent voiding and urinary dysfunction. The dysfunction includes abnormal uroflow patterns, increased urethral resistance, abnormal post-void residuals, chronic trigonitis, and urethrovesical inflammatory polyps. A review of intermittent uroflow and obstructive uroflow patterns reveals that all females in this study worked long hours without voiding.

Adult↗
PubMed1998

Seroepidemiology of invasive pneumococcal disease in Queensland, 1990 to 1997.

Serotypes responsible for 842 cases of invasive pneumococcal disease in Queensland between February 1990 and October 1997 were identified. Type 14 caused 37.5% of episodes in children aged 0-4 years and 19.2% of adult cases. Types 6A, 6B, 14, 18C, and 19F were significantly more frequent in young children while types 3, 4, 7F, 9V and 23F predominated in adults. The regional incidence of type 14 and 7F disease differed significantly in Southeast and Far North Queensland. Coverage for 87% of children aged less than 5 years in this study would be provided by a recently advocated polysaccharide-protein conjugate vaccine containing capsular antigens of types 4, 6B, 9V, 14, 18C, 19F and 23F. Similarly, more than 90% of adults would be covered by the currently available 23- valent polysaccaride vaccine.

Adolescent↗
PubMed1998

A randomized, community trial of intensive sexually transmitted disease control for AIDS prevention, Rakai, Uganda.

OBJECTIVE: To describe the design and first-round survey results of a trial of intensive sexually transmitted disease (STD) control to reduce HIV-1 incidence. STUDY DESIGN: Randomized, controlled, community-based trial in Rakai District, Uganda. METHODS: In this ongoing study, 56 communities were grouped into 10 clusters designed to encompass social/sexual networks; clusters within blocks were randomly assigned to the intervention or control arm. Every 10 months, all consenting resident adults aged 15-59 years are visited in the home for interview and sample collection (serological sample, urine, and, in the case of women, self-administered vaginal swabs). Sera are tested for HIV-1, syphilis, gonorrhea, chlamydia, trichomonas and bacterial vaginosis. Following interview, all consenting adults are offered directly observed, single oral dose treatment (STD treatment in the intervention arm, anthelminthic and iron-folate in the control arm). Treatment is administered irrespective of symptoms or laboratory testing (mass treatment strategy). Both arms receive identical health education, condom and serological counseling services. RESULTS: In the first home visit round, the study enrolled 5834 intervention and 5784 control arm subjects. Compliance with interview, sample collection and treatment was high in both arms (over 90%). Study arm populations were comparable with respect to sociodemographic and behavioral characteristics, and baseline HIV and STD rates. The latter were high: 16.9% of all subjects were HIV-positive, 10.0% had syphilis, and 23.8% of women had trichomonas and 50.9% had bacterial vaginosis. CONCLUSIONS: Testing the effects of STD control on AIDS prevention is feasible in this Ugandan setting.

Acquired Immunodeficiency Syndrome↗
PubMed1998

High efficiency myogenic conversion of human fibroblasts by adenoviral vector-mediated MyoD gene transfer. An alternative strategy for ex vivo gene therapy of primary myopathies.

Ex vivo gene therapy of primary myopathies, based on autologous transplantation of genetically modified myogenic cells, is seriously limited by the number of primary myogenic cells that can be isolated, expanded, transduced, and reimplanted into the patient's muscles. We explored the possibility of using the MyoD gene to induce myogenic conversion of nonmuscle, primary cells in a quantitatively relevant fashion. Primary human and murine fibroblasts from skin, muscle, or bone marrow were infected by an E1-deleted adenoviral vector carrying a retroviral long terminal repeat-promoted MyoD cDNA. Expression of MyoD caused irreversible withdrawal from the cell cycle and myogenic differentiation in the majority (from 60 to 90%) of cultured fibroblasts, as defined by activation of muscle-specific genes, fusion into contractile myotubes, and appearance of ultrastructurally normal sarcomagenesis in culture. 24 h after adenoviral exposure, MyoD-converted cultures were injected into regenerating muscle of immunodeficient (severe combined immunodeficiency/beige) mice, where they gave rise to beta-galactosidase positive, centrally nucleated fibers expressing human myosin heavy chains. Fibers originating from converted fibroblasts were indistinguishable from those obtained by injection of control cultures of lacZ-transduced satellite cells. MyoD-converted murine fibroblasts participated to muscle regeneration also in immunocompetent, syngeneic mice. Although antibodies from these mice bound to adenoviral infected cells in vitro, no inflammatory infiltrate was present in the graft site throughout the 3-wk study period. These data support the feasibility of an alternative approach to gene therapy of primary myopathies, based on implantation of large numbers of genetically modified primary fibroblasts massively converted to myogenesis by adenoviral delivery of MyoD ex vivo.

Adenoviridae↗
PubMed1998

An improved protocol for the preparation of yeast cells for transformation by electroporation.

Pretreatment of yeast cells with lithium acetate (LiAc) and dithiothreitol (DTT) enhances the frequency of transformation by electroporation. The method shows improvements of 6-67-fold in wild-type strains derived from commonly used Saccharomyces cerevisiae genetic backgrounds. In addition, 15-300-fold improvement in transformation frequency was achieved with several mutant strains of S. cerevisiae that transformed poorly by conventional procedures. Both DTT and lithium acetate were necessary for maximal transformation frequencies. Pretreatment with lithium and DTT also resulted in an approximately 3-5-fold increase in the electroporation transformation frequency of the pathogenic fungus Candida albicans.

Blotting, Southern↗
PubMed1998

Alteration in myosatellite cell commitment with muscle maturation.

Myosatellite cells are myoblasts found between the basal lamina and sarcolemma of myofibers of postnatal mice. The extent to which these cells are programmed, upon differentiation, to express isoforms of contractile protein genes specific to the type of fiber with which they are associated has been evaluated in vitro using myosatellite cells derived from the soleus and the extensor digitorum longus muscles (EDL) of 4-day-old and adult transgenic mice, which express nuclear localizing beta-galactosidase (nlsbeta-gal) under the control of the promoter and 3' enhancer of the gene encoding fast myosin light chain 3F (MLC3F) (Kelly et al. [1995] J. Cell Biol. 129:383-396). Cultures were allowed to differentiate either as myocytes (mononucleated cells), to prevent possible modification of the myosatellite phenotype by other myonuclei in mosaic myotubes, or as myotubes. Transgene expression was age related, with 90% and 70% of the myocytes derived from the neonatal EDL and soleus muscles (muscles that had not yet achieved their mature phenotype), respectively, having nuclei encoding beta-gal; 61% and 32% of the myocyte nuclei derived from myosatellite cells of the adult EDL (a fast muscle) and the adult soleus muscle (a mixed muscle containing many slow myofibers), respectively, expressed this transgene. Because myosatellite cells found in adult muscles are the progeny of those found in the neonate, an alteration of myosatellite cell commitment to express this transgene occurs with muscle maturation. Because expression of the transgene in neonatal and adult muscle in vivo reflects the expression of the endogenous MLC3F gene (Kelly et al. [1995] J. Cell Biol. 129:383-396), it is likely that expression of the transgene by differentiated myosatellite cells reflects the extent of commitment of these cells to produce MLC3F. A hypothesis is presented that MLC3F is widely expressed in developing muscles but eliminated in myofibers that undergo maturation toward a slower phenotype.

Animals↗