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Biomedical subjects

R Kelly

Publications and source records attributed to R Kelly.

At least 73 records · Page 4Linked to original sources
PubMed1997

Pectin and methyl cellulose do not affect intestinal function in patients after ileal pouch-anal anastomosis.

OBJECTIVES: Although ileal pouch-anal anastomosis is the procedure of choice for most patients with ulcerative colitis or familial adenomatous polyposis, most patients have problems with stool frequency and/or consistency. Although most clinicians recommend fiber supplementation for these patients, we could find no studies that prove the efficacy of this practice. The first purpose of this study was to document the effect of fiber supplementation on intestinal function in patients after ileal pouch-anal anastomosis. Because pectin, a soluble fiber supplement, has been reported to slow gastric and intestinal transit, we also hypothesized that pectin would be a superior fiber supplement in these patients. The second purpose, therefore, was to determine whether the effects of pectin on intestinal transit would result in decreased stool frequency in patients with an ileal pouch. METHODS: Thirteen patients who had undergone ileal pouch-anal anastomosis for ulcerative colitis were entered into a 9-wk crossover study. The protocol consisted of three 2-wk study periods, each of which was preceded by a 1-wk washout period. During the three study periods patients supplemented their diets, in random order, with Citrucel, 1 tablespoon twice daily; pectin, 1 tablespoon twice daily; or no supplement. Patients maintained detailed dietary and bowel function diaries. RESULTS: The effects (mean +/- SE) of Citrucel and pectin supplementation are summarized in Table 1. There was no significant effect of either supplement on stool frequency, pouch function, bloating, or stool consistency. In addition, there were no differences in continence. CONCLUSIONS: We found no evidence to support the common practice of fiber supplementation in patients with an ileal pouch. Furthermore, this study did not find that stool frequency decreased during supplementation with pectin. We conclude that there is little role for fiber supplementation in patients with an ileal pouch.

Adult↗
PubMed1997

Infection and transmission of Plasmodium gallinaceum (Eucoccida: Plasmodiidae) in Aedes aegypti (Diptera: Culicidae): effect of preinfection sugar meals and postinfection blood meals.

Frequency of sugar feeding and blood feeding can have an impact on the infection by and transmission of malaria parasites. Data presented here indicate that frequent blood feeding has a deleterious effect on infection by malaria parasites in Aedes aegypti. In addition, mosquitoes that do not blood feed, but instead feed on sugar alone after an infected blood meal, have a higher rate of parasite transmission than mosquitoes fed additional blood meals.

Aedes↗
PubMed1996

Isolation and sequence analysis of the cDNA encoding delta 1-pyrroline-5-carboxylate reductase from Zalerion arboricola.

A cDNA encoding delta 1-pyrroline-5-carboxylate reductase (P5CR) was isolated from the pneumocandin (Pmo)-producing fungus, Zalerion arboricola (Za), by complementation of a P5CR-deficient mutant (pro3) of Saccharomyces cerevisiae (Sc). The cloned cDNA was placed under control of the Sc galactokinase (GAL1) promoter and restored P5CR activity to the pro3 mutant. Sequence analysis revealed that the Za P5CR-encoding cDNA encodes an approx. 35 kDa protein with substantial amino acid (aa) identity to P5CR from another filamentous fungus, Neurospora crassa (Nc). Za P5CR exhibits a moderate degree of aa identity to P5CR from plants, bacteria, human and Sc. This is the first gene to be isolated from Za.

Amino Acid Sequence↗
PubMed1996

Differential release of prostaglandins by organ cultures of human fetal trachea and lung.

Human fetal lung at 16-19 weeks gestation has a partially differentiated epithelium, and in organ culture, distal airsacs dilate and the epithelium autodifferentiates to type I and II pneumatocytes, processes regulated by endogenous prostaglandin PGE2. Human fetal trachea, at the same gestation, has a terminally differentiated mucociliary epithelium but after 4-6 d in organ culture, develops squamous metaplasia. Tracheal cultures restricted to 3 d have normal phase-contrast and light microscopy appearances and immunohistochemical reactivities (epithelium: cytokeratin 7,8,18; glutathione S-transferase pi-isozyme; epithelial membrane antigen and mesenchyme; desmin; vimentin). In human fetal trachea organ cultures, the predominant prostaglandins released are 6-keto-PGF1 alpha, PGF2 alpha, and PGE2, a pattern similar to that previously described for human adult trachea and lung. In fetal lung cultures, 13,14-dihydro-15-keto-PGF2 alpha is the major prostaglandin released with lesser amounts of 13,14-dihydro-15-keto-PFG2 alpha,PGF2 alpha,PGE2, and 6-keto-PGF1 alpha. Human fetal lung in vitro has the competence to self-differentiate, as early as 12 weeks gestation and presence of high levels in fetal lung of the inactive metabolite 13,14-dihydro-15-keto-PGE2 relative to PGE2 suggests that active prostaglandin catabolism may be one of the mechanisms to retard this stage of maturation in vivo by limiting PGE2 availability. Surprisingly, the profile of prostaglandins released from fetal lung organ culture does not change to that of a mature lung with terminal differentiation of the epithelium, and this may indicate differences in the expression of key prostaglandin-metabolizing enzymes in developing human fetal lung in culture and with in utero ontogeny.

Animals↗
PubMed1996

Differing patterns of mechanical response to direct fetal hormone treatment.

A single combined intramuscular dose of betamethasone and l-thyroxine (T4) or placebo was injected into the shoulder of fetal lambs 48 hours prior to delivery at days 121 (n = 14), 128 (n = 25) or 135 (n = 20) of gestation. Respiratory mechanics were calculated using multiple linear regression analysis. Both respiratory system resistance (RRS) and elastance (ERS) decreased approximately 4 fold between gestational days 121 (D121) and 135 (D135). Both variables were also reduced by hormone treatment. Reduction in ERS was due to a reduction in both lung (EL) and chest wall (EW) components. In absolute terms EW decreased with gestational age; however, EW as a proportion of total elastance (% EW) increased. Inclusion of a volume-dependent elastance term in the multiple linear regression model enabled us to separate total elastance into volume-independent (E1) and volume-dependent (E2V) components. E1 decreased almost 8-fold compared with only a 2.5-fold fall in E2V between D121 and D135. %E2, the proportion of ERS which is volume-dependent and which provides an index of overventilation, doubled over this time period. Hormone treatment affected E1 and E2V components equally hence %E2 was not altered. Both excised lung volume and end expiratory alveolar volume increased with gestational age and with treatment. The response to treatment was qualitatively similar at each of the gestational ages examined, however, for all mechanics variables, except resistance and E1, the magnitude of response to treatment was significantly smaller in D135 animals compared with other age groups.

Airway Resistance↗
PubMed1996

Comparison of angioscopy, intravascular ultrasound imaging and quantitative coronary angiography in predicting clinical outcome after coronary intervention in high risk patients.

OBJECTIVES: The purpose of this study was to identify qualitative or quantitative variables present on angioscopy, intravascular ultrasound imaging or quantitative coronary arteriography that were associated with adverse clinical outcome after coronary intervention in high risk patients. BACKGROUND: Patients with acute coronary syndromes and complex lesion morphology on angiography are at increased risk for acute complications after coronary angioplasty. Newer devices that primarily remove atheroma have not improved outcome over that of balloon angioplasty. Intravascular imaging can accurately identify intraluminal and intramural histopathologic features not adequately visualized during coronary arteriography and may provide mechanistic insight into the pathogenesis of abrupt closure and restenosis. METHODS: Sixty high risk patients with unstable coronary syndromes and complex lesions on angiography underwent angioscopy (n = 40) and intravascular ultrasound imaging (n = 46) during interventional procedures. In 26 patients, both angioscopy and intravascular ultrasound were performed in the same lesion. All patients underwent off-line quantitative coronary arteriography. Coronary interventions included balloon (n = 21) and excimer laser (n = 4) angioplasty, directional (n = 19) and rotational (n = 6) atherectomy and stent implantation (n = 11). Patients were followed up for 1 year for objective evidence for recurrent ischemia. RESULTS: Patients whose clinical presentation included rest angina or acute myocardial infarction or who received thrombolytic therapy within 24 h of procedure were significantly more likely to experience recurrent ischemia after intervention. Plaque rupture or thrombus on preprocedure angioscopy or angioscopic thrombus after intervention were also significantly associated with adverse outcome. Qualitative or quantitative variables on angiography, intravascular ultrasound or off-line quantitative arteriography were not associated with recurrent ischemia on univariate analysis. Multivariate predictors of recurrent ischemia were plaque rupture on preprocedure angioscopy (p < 0.05, odds ratio [OR] 10.15) and angioscopic thrombus after intervention (p < 0.05, OR 7.26). CONCLUSIONS: Angioscopic plaque rupture and thrombus were independently associated with adverse outcome in patients with complex lesions after interventional procedures. These features were not identified by either angiography or intravascular ultrasound.

Angioplasty, Balloon, Coronary↗
PubMed1996

Validity of indirect assessment of writing competency for deaf and hard-of-hearing college students.

Indirect tests of writing competency are often used at the college level for a variety of educational, programmatic, and research purposes. Although such tests may have been validated on hearing populations, it cannot be assumed that they validly assess the writing competency of deaf and hard-of-hearing students. This study used a direct criterion measure of writing competency to determine the criterion validity of two indirect measures of writing competency. Results suggest that the validity of indirect writing tests for deaf and hard-of-hearing baccalaureate-level students is weak. We recommend that direct writing tests be used with this population to ensure fair and accurage assessment of writing competency.

Journal Article↗
PubMed1996

Inhaled nitric oxide in cardiac failure: vascular versus ventricular effects.

Inhaled nitric oxide (INO) is a powerful and selective pulmonary vasodilator in pulmonary hypertension, including that related to cardiac disease. Recently, NO was shown to have a direct negative inotropic action on the myocardium, but whether INO can impair left ventricular (LV) function is not known. We administered INO during right heart catheterisation in 10 subjects with LV failure and secondary pulmonary hypertension. INO was delivered for 10 min at concentrations of 10, 20, and 40 ppm in spontaneous respiration. Average age was 49.9 years (range 19-59 years), and mean LV ejection fraction EF (LVEF) was 19.9% (range 15-27%). INO produced an average decrease in pulmonary vascular resistance (PVR) of 40% as compared with baseline (p < 0.0001) with no significant change in systemic vascular resistance (SVR). There was no significant difference in the haemodynamic response to the three doses of INO. The large decrease in PVR was due mainly to an increase in pulmonary capillary wedge pressure (PCWP). Cardiac index (CI) rose in 7 patients and was unchanged in 2. One patient had a marked increase in PAWP and a marked decrease in CI during administration of INO, which rapidly reversed after discontinuation of INO. This study demonstrates that the administration of INO to patients with impaired cardiac reserve may result in marked increase in ventricular preload with little benefit to pulmonary pressures. In view of the known in vitro effects of NO and the marked haemodynamic changes demonstrated in response to INO in this study, caution should be exercised when using INO in this population.

Administration, Inhalation↗
PubMed1996

An animal model for human melanoma.

Experimental animal models that are directly relevant to human melanoma are lacking. We propose the Angora goat as a potentially useful field model with experimental potential and to this end have examined the prevalence and site distribution of all skin cancers in 28 Angora goat herds in Queensland, Australia. The prevalence of benign melanocytic lesions (lentigines) and their experimental induction by sunlight were also investigated. Among 1731 goats over 2 years of age, 139 malignant skin tumors were excised from 95 affected animals. The prevalence of squamous cell carcinoma (SCC) was 3.8% and of melanoma, 2.2%. Main site of occurrence of melanoma (83%) was the dorsal surface of the ear; in contrast SCC occurred mostly (84%) on the perineum. Lentigines were darker and more prevalent on the exposed compared with the unexposed surface of the ear in Angoras, analogous to the higher prevalence of nevi on the exposed compared with the less exposed inner surface of the arm in humans. Lentigines, which were also found on the perineum though lighter in color than on the dorsal ear, were absent in young animals under 3 months but were numerous in 1-3 year olds. Furthermore in an experimental substudy eight goats, having one flank repeatedly shorn and the contralateral flank left unshorn, revealed consistently more solar lentigines on the shorn flank (P < 0.05) when both sides were examined after 9 months. Histopathological examination of paired skin biopsies from five of these goats also showed more abundant pigmentation in skin from the exposed, as compared with the unexposed flank. These findings indicate that sunlight induces tumors and lentigines in goats in a highly site-specific manner. The Angora goat model may suggest paradigms for explaining the site differences observed for human melanoma and may also be useful in the future clarification of molecular changes following carcinogenic levels of sun exposure.

Animals↗
PubMed1996

Isolation of a gene involved in 1,3-beta-glucan synthesis in Aspergillus nidulans and purification of the corresponding protein.

Saccharomyces cerevisiae has two highly homologous genes, FKS1 and FKS2, which encode interchangeable putative catalytic subunits of 1,3-beta-glucan synthase (GS), an enzyme that synthesizes an essential polymer of the fungal cell wall. To determine if GS in Aspergillus species is similar, an FKS homolog, fksA, was cloned from Aspergillus nidulans by cross-hybridization, and the corresponding protein was purified. Sequence analysis revealed a 5,716-nucleotide coding region interrupted by two 56-bp introns. The fksA gene encodes a predicted peptide of 229 kDa, FksAp, that shows a remarkable degree of conservation in size, charge, amino acid identity, and predicted membrane topology with the S. cerevisiae FKS proteins (Fksps). FksAp exhibits 64 and 65% identity to Fks1p and Fks2p, respectively, and 79% similarity. Hydropathy analysis of FksAp suggests an integral membrane protein with 16 transmembrane helices that coincide with the transmembrane helices of the Saccharomyces Fksps. The sizes of the nontransmembrane domains are strikingly similar to those of Fks1p. The region of FksAp most homologous to the Saccharomyces FKS polypeptides is a large hydrophilic domain of 578 amino acids that is predicted to be cytoplasmic. This domain is 86% identical to the corresponding region of Fks1p and is a good candidate for the location of the catalytic site. Antibodies raised against a peptide derived from the FksAp sequence recognize a protein of approximately 200 kDa in crude membranes and detergent-solubilized active extracts. This protein is enriched approximately 300-fold in GS purified by product entrapment. Purified anti-FksAp immunoglobulin G immunodepletes nearly all of the GS activity in crude or purified extracts when Staphylococcus aureus cells are used to precipitate the antibodies, although it does not inhibit enzymatic activity when added to extracts. The purified GS is inhibited by echinocandins with a sensitivity equal to that displayed by whole cells. Thus, the product of fksA is important for the activity of highly purified preparations of GS, either as the catalytic subunit itself or as an associated copurifying subunit that mediates susceptibility of enzymatic activity to echinocandin inhibition.

Amino Acid Sequence↗
PubMed1996

Effect of interval from fetal corticosteriod treatment to delivery on postnatal lung function of preterm lambs.

The effect of altering the interval from treatment to delivery on postnatal lung function of the preterm lamb is unknown. We treated groups of 8-10 singleton fetal sheep with 0.5 mg/kg betamethasone by fetal injection and evaluated postnatal lung function 40 min after preterm delivery at 123 days gestation 2 days after treatment or at 128 days gestation 2, 4, and 7 days after treatment relative to groups of 4-8 saline-injected control animals. At 123 days, betamethasone significantly improved arterial PCO2, dynamic thoracic compliance, and ventilatory efficiency index and doubled lung gas volume relative to a control group. Fetal treatment with betamethasone 2, 4, or 7 days before delivery at 128 days also improved these same indicators of lung function relative to controls, and the magnitude of the improvements was the same for all indicators and independent of treatment-to-delivery interval. Betamethasone suppressed the normal postnatal increase in plasma cortisol after 2 and 4 days of exposure but not after 7 days of exposure. Betamethasone also increased fetal and postnatal triiodothyronine concentrations after 2 days of exposure but not at 4 or 7 days of exposure. Although the hormone effects were transient, postnatal lung functional responses to betamethasone persisted over the 2- to 7-day interval from treatment to delivery.

Adrenal Cortex Hormones↗
PubMed1996

Activation of different myogenic pathways: myf-5 is induced by the neural tube and MyoD by the dorsal ectoderm in mouse paraxial mesoderm.

Newly formed somites or unsegmented paraxial mesoderm (UPM) have been cultured either in isolation or with adjacent structures to investigate the influence of these tissues on myogenic differentiation in mammals. The extent of differentiation was easily and accurately quantified by counting the number of beta-galactosidase-positive cells, since mesodermal tissues had been isolated from transgenic mice that carry the n-lacZ gene under the transcriptional control of a myosin light chain promoter, restricting expression to striated muscle. The results obtained showed that axial structures are necessary to promote differentiation of paraxial mesoderm, in agreement with previous observations. However, it also appeared that the influence of axial structures could be replaced by dorsolateral tissues, adjacent to the paraxial mesoderm. To elucidate which of these tissues exerts this positive effect, we cultured the paraxial mesoderm with a variety of adjacent structures, either adherent to the mesoderm or recombined in vitro. The results of these experiments indicated that the dorsal ectoderm exerts a positive influence on myogenesis but only if left in physical proximity to it. In contrast, lateral mesoderm delays the positive effect of the ectoderm (and has no effect on its own) suggesting that this tissue produces an inhibitory signal. To investigate whether axial structures and dorsal ectoderm induce myogenesis through common or separate pathways, we dissected the medial half of the unsegmented paraxial mesoderm and cultured it with the adjacent neural tube. We also cultured the lateral half of the unsegmented paraxial mesoderm with adjacent ectoderm. The induction of the myogenic regulatory factors myf-5 and MyoD was monitored by double staining of cultured cells with antibodies against MyoD and beta-galactosidase since the tissues were isolated from mouse embryos that carry n-lacZ targeted to the myf-5 gene, so that myf-5 expressing cells could be easily identified by either histochemical or immunocytochemical staining for beta-galactosidase. After 1 day in culture myogenic cells from the medial half expressed myf-5 but not MyoD, while myogenic cells from the lateral half expressed MyoD but not myf-5. By the next day in vitro, however, most myogenic cells expressed both gene products. These data suggest that the neural tube activates myogenesis in the medial half of paraxial mesoderm through a myf-5-dependent pathway, while the dorsal ectoderm activates myogenesis through a MyoD-dependent pathway. The possible developmental significance of these observations is discussed and a model of myogenic determination in mammals is proposed.

Animals↗
PubMed1996

Compartment syndromes of the hand.

We retrospectively reviewed the records of nineteen patients who had been managed with fasciotomy because of compartment syndrome of the hand. The patients were five months to sixty-seven years old and included ten adults and nine children. Seventeen patients were followed for an average of twenty-one months (range, one to fifty-eight months), one patient was lost to follow-up after discharge, and one patient died four days postoperatively. All of the patients had a tense, swollen hand and elevated pressure in at least one interosseous compartment. Eight patients also had a compartment syndrome of the forearm. The compartment syndromes developed after intravenous injections (eleven patients); after a gunshot wound, a crush injury, or a complication related to the use of an arterial line (two patients each); and after a complication related to an arthrodesis of the wrist or a crush injury due to prolonged pressure on the upper extremity secondary to a drug overdose (one patient each). Fifteen patients had an obtunded sensorium-either because of a serious illness or injury or secondary to prolonged anesthesia-when the compartment syndrome was recognized. In thirteen of these patients, including eight children and five adults, the compartment syndrome developed because of a complication related to the intravenous or intra-arterial administration of drugs. Carpal tunnel release and decompression of the involved compartments led to a satisfactory result for thirteen of the seventeen patients who were followed. The remaining four patients (including two children who had an amputation, one child who had impaired function of the hand secondary to brain damage, and one adult who had extensive involvement of the forearm and complete loss of function of the hand) had a poor result. All four of these patients had been obtunded when the compartment syndrome developed. The treating physician should maintain a high index of suspicion for a compartment syndrome of the hand when managing seriously ill, obtunded patients-particularly children-who are receiving multiple intravenous or intra-arterial injections.

Adolescent↗
PubMed1995

Lack of functional retinoblastoma protein mediates increased resistance to antimetabolites in human sarcoma cell lines.

Growth inhibition assays indicated that the IC50 values for methotrexate (MTX) and 5-fluorodeoxyuridine (FdUrd) in HS-18, a liposarcoma cell line lacking retinoblastoma protein (pRB), and SaOS-2, an osteosarcoma cell line with a truncated and nonfunctional pRB, were 10- to 12-fold and 4- to 11-fold higher, respectively, than for the HT-1080 (fibrosarcoma) cell line, which has wild-type pRB. These Rb-/- cell lines exhibited a 2- to 4-fold increase in both dihydrofolate reductase (DHFR) and thymidylate synthase (TS) enzyme activities as well as a 3- to 4-fold increase in mRNA levels for these enzymes compared to the HT-1080 (Rb+/+) cells. This increase in expression was not due to amplification of the DHFR and TS genes. Growth inhibition by MTX and FdUrd was increased and DHFR and TS activities and expression were correspondingly decreased in Rb transfectants of SaOS-2 cells. In contrast, there was no significant difference in growth inhibition among these cell lines for the nonantimetabolites VP-16, cisplatin, and doxorubicin. A gel mobility-shift assay showed that parental SaOS-2 cells had increased levels of free E2F compared to the Rb-reconstituted SaOS-2 cells. These results indicate that pRB defective cells may have decreased sensitivity to growth inhibition by target enzymes encoded by genes whose transcription is enhanced by E2F proteins and suggest mechanisms of interaction between cytotoxic agents and genes involved in cell cycle progression.

Antimetabolites, Antineoplastic↗
PubMed1995

Redistribution of synaptic vesicles and their proteins in temperature-sensitive shibire(ts1) mutant Drosophila.

From an extract of Drosophila melanogaster head homogenates, a membrane fraction can be isolated that has the same sedimentation properties as vertebrate synaptic vesicles and contains Drosophila synaptotagmin. The fraction disappears from homogenates of temperature-sensitive (ts) mutant shibire(ts1) (shi(ts1)) flies paralyzed by exposure to non-permissive temperatures, and reappears on return to permissive temperatures. Since reversible, temperature-dependent depletion of synaptic vesicles is known to occur in shibire(ts1) flies, we conclude that the fraction we have identified contains synaptic vesicles. We have examined the fate of synaptic vesicle membrane proteins in shibire flies at nonpermissive temperatures and found that all of these vesicle antigens are transferred to rapidly sedimenting membranes and codistribute with a plasma membrane marker by both glycerol velocity and metrizamide density sedimentation and by confocal microscopy. Three criteria were used to establish that other neuron-specific antigens--neuronal synaptobrevin and cysteine-string proteins--are legitimate components of synaptic vesicles: cosedimentation with Drosophila synaptotagmin, immunoadsorption, and disappearance of these antigens from the vesicle fractions in paralyzed shibire flies.

Amino Acid Sequence↗
PubMed1995

Myoblast differentiation during mammalian somitogenesis is dependent upon a community effect.

The differentiation potential of early mammalian myogenic cells was tested under clonal culture conditions. Cells were isolated from paraxial mesoderm and limb buds of transgenic mouse embryos at 9.5 days after conception and grown in culture at clonal density either on collagen-coated dishes or on various feeder cell layers. The transgene used contained a reporter gene encoding beta-galactosidase with a nuclear localization signal under the control of regulatory sequences from the gene for fast myosin light chain 3, so that beta-galactosidase staining indicated the presence of differentiated muscle cells. After 5 days in culture, the number and size of beta-galactosidase-positive (beta-gal+) clones were recorded. Cells isolated from somites I-V (the last five somites to have formed) or from unsegmented paraxial mesoderm did not give rise to any beta-gal+ clones. Cells isolated from somites VI-X or from the forelimb bud gave rise to beta-gal+ clones, but only on feeder cells. Cells from somites XI or older gave rise to beta-gal+ clones independently of the substrate. However, when cells isolated from unsegmented paraxial mesoderm or somites I-V were cultured with nontransgenic cells from the trunk (including neural tube and notochord), differentiation occurred on condition that the cells were in a three-dimensional aggregate, even though their specific position in the somite had been lost. By culturing explants ranging in size from 1 to < 100 cells in the presence of an inhibitor of cell division, we determined that a minimal number of 30-40 cells is required for mesodermal cells to differentiate.

Animals↗
PubMed1995

Regulatory, design, and analysis aspects of complex stability studies. US Food & Drug Administration.

Drug stability studies are expensive and time consuming. Multiple batches are studied to ensure that a product will consistently remain within specifications for its entire expiration dating period. Some of these studies involve the same drug products in similar packages or in multiple strengths. Application of sound statistical design principles can reduce the amount of testing required. We extend the principles stated in the Food & Drug Administration's 1987 publication Guideline for Submitting Documentation for the Stability of Human Drugs and Biologics to setting expiration dating periods for more complex situations.

Drug Packaging↗