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R Kelley

Publications and source records attributed to R Kelley.

At least 37 records · Page 2Linked to original sources
PubMed1997

The k43 gene, required for chorion gene amplification and diploid cell chromosome replication, encodes the Drosophila homolog of yeast origin recognition complex subunit 2.

Lethal alleles of the Drosophila k43 gene result in small or missing imaginal discs, greatly reduced mitotic index, and fragmented and abnormally condensed chromosomes. A female-sterile allele of k43 specifically reduces chorion gene amplification in ovarian follicle cells. k43 was cloned by chromosomal walking, and the identification of the k43 gene was confirmed by phenotypic rescue and sequence analysis of mutant alleles. The sequence analyses reveal that the k43 gene encodes the Drosophila homolog of the yeast origin recognition complex subunit 2 (Orc2p), a protein required for replication origin function and transcriptional silencing in yeast. These results suggest an evolutionarily conserved role for Orc2p in eukaryotic chromosomal DNA replication.

Animals↗
PubMed1997

Estimation of contact tympanic membrane temperature with a noncontact infrared thermometer.

STUDY OBJECTIVE: To investigate the agreement between contact tympanic membrane (TM) and noncontact infrared ear thermometers in children. METHODS: Twenty-three children (ages .5 to 10 years) undergoing elective tympanostomy tube placement were studied. An assistant used standard technique to record temperature with an infrared ear thermometer before and after TM temperature was obtained with a bead thermistor placed against the anterior-inferior quadrant of the TM. RESULTS: Mean temperatures were not significantly different: initial IR ear, 36.66 degrees +/-.33 degrees C; TM, 36.71 degrees +/- .42 degrees C; final infrared ear, 36.57 degrees +/- .33 degrees C. The mean bias (difference between initial individual IR ear and TM temperatures) of -.05 degrees +/-.29 degrees C and the 95% limits of agreement of +.53 degrees to -.63 degrees C indicate an acceptable confidence (error range within 3.2% of average TM temperature) for use of the initial infrared ear temperature as an estimate of TM temperature. CONCLUSION: The IR ear thermometer provides an accurate estimate of TM temperature in healthy children and may accurately reflect core body temperature.

Child↗
PubMed1997

Detecting pediatric nosocomial infections: how do infection control and quality assurance personnel compare?

OBJECTIVE: To compare how well infection control (IC) and quality assurance (QA) personnel in a specialty setting identify the presence, type (nosocomial or community-acquired), and (if nosocomial) site of infection. METHODS: In 1994, we mailed a survey that included 21 pediatric case histories to IC and QA personnel in pediatric settings in the United States (children's hospitals and medical school-affiliated hospitals with pediatric wards of > 30 beds). From the case histories presented, the respondents were asked to determine whether an infection was present and, if so, whether it was nosocomial or community-acquired. If the infection was nosocomial, the respondent was asked to determine the site of the infection (e.g., urinary tract, bloodstream). RESULTS: From the 289 hospitals to which surveys were mailed, 131 respondents (45.3%) completed 212 surveys. Of the 212 returned surveys, 120 (56.6%) were completed by IC personnel and 92 (43.4%) were completed by QA personnel. Among the 183 respondents from acute care pediatric settings, 92.3% of IC personnel (96/104) and 54.4% of QA personnel (43/79) correctly identified at least 75% of the nosocomial infections (n = 14; p < 0.0001). IC and QA personnel were similar in ability to identify community-acquired infection (88/104 vs 70/79, respectively; p = 0.436). IC personnel were significantly more likely than QA personnel to accurately identify the following sites of infection: respiratory tract infection without secondary bloodstream infection, necrotizing enterocolitis, urinary tract infection with and without secondary bloodstream infection, primary bloodstream infection, surgical site infection, gastroenteritis, esophagitis, and clinical sepsis. CONCLUSIONS: Overall, IC personnel were more accurate than QA personnel in determining whether a nosocomial infection was present and in correctly determining most sites of infection. Both IC and QA personnel had difficulty identifying venous infection and respiratory tract infection with secondary bloodstream infection. Both IC and QA personnel could thus benefit from more concise definitions or further training in detection of these sites of nosocomial infections. In addition, QA personnel did not perform overall as well as IC personnel in identifying nosocomial infections and their sites; this finding suggests the need for QA personnel to be provided specific training on detection of nosocomial infections and validation of their ability to do so. Nosocomial infection surveillance should be the responsibility of those trained and proved capable of detecting these infections.

Child↗
PubMed1997

Resolution of subependymal cysts in neonatal holocarboxylase synthetase deficiency.

Holocarboxylase synthetase deficiency is typically a biotin responsive disorder that presents with lactic acidosis, tachypnea, temperature instability, and shock in neonates (Briones et al.1989 and Fuchshuber et al. 1992). The primary defect in cases studied to date appears to be the decreased affinity of HCS for its substrate, biotin (Gompertz et al. 1971). Supplemental biotin can provide sufficient substrate to increase HCS enzymatic function and thereby permit biotinylation of the four carboxylase apoenzymes (Briones et al. 1989). We report an infant with HCS deficiency who presented with lactic acidosis, shock, and hypertonia. Subependymal cysts were identified on cranial ultrasound and subsequently confirmed by MRI. Six months following biotin supplementation, she is developmentally normal and MRI of the brain shows complete resolution of the cysts.

Biotin↗
PubMed1997

High incidence of T-cell tumors in E2A-null mice and E2A/Id1 double-knockout mice.

The basic-helix-loop-helix (bHLH) proteins encoded by the E2A gene are broadly expressed transcription regulators which function through binding to the E-box enhancer sequences. The DNA binding activities of E2A proteins are directly inhibited upon dimerization with the Id1 gene product. It has been shown that disruption of the E2A gene leads to a complete block in B-lymphocyte development and a high frequency of neonatal death. We report here that nearly half of the surviving E2A-null mice develop acute T-cell lymphoma between 3 to 10 months of age. We further show that disruption of the Id1 gene improves the chance of postnatal survival of E2A-null mice, indicating that Id1 is a canonical negative regulator of E2A and that the unbalanced ratio of E2A to Id1 may contribute to the postnatal death of the E2A-null mice. However, the E2A/Id1 double-knockout mice still develop T-cell tumors once they reach the age of 3 months. This result suggests that E2A may be essential for maintaining the homeostasis of T lymphocytes during their constant renewal in adult life.

Animals↗
PubMed1995

Prenatal detection of the cholesterol biosynthetic defect in the Smith-Lemli-Opitz syndrome by the analysis of amniotic fluid sterols.

The Smith-Lemli-Opitz (SLO or RSH) syndrome is an autosomal recessive disorder characterized by a recognizable pattern of minor facial anomalies, congenital anomalies of many organs, failure to thrive, and mental retardation. Its cause is a defect in cholesterol biosynthesis characterized by abnormally low plasma cholesterol levels and concentrations of the cholesterol precursor 7-dehydrocholesterol (7DHC) elevated up to several thousand-fold above normal. We used capillary column gas-chromatography to quantify sterols in amniotic fluid, amniotic cells, plasma, placenta, and breast milk from a heterozygous mother who had previously given birth to an affected son and in cord blood and plasma from her affected newborn daughter. The cholesterol concentration in amniotic fluid at 16 weeks gestation was normal, but 7DHC, normally undetectable, was greatly elevated. In cultured amniocytes, the level of 7DHC was 11% of total cholesterol, similar to cultured fibroblasts from patients with SLO syndrome. At 38 weeks, a girl with phenotype consistent with the syndrome was born. Cholesterol concentrations were abnormally low in cord blood and in the baby's plasma at 12 weeks, while levels of 7DHC were grossly elevated, confirming the prenatal diagnosis. The mother's plasma cholesterol increased steadily during gestation but remained below the lower 95% limit reported for normal control women. We conclude that it is now possible to detect the SLO syndrome at 16 weeks gestation by analyzing amniotic fluid sterols.

Amniotic Fluid↗
PubMed1994

Electrospray ionization mass spectrometry of recombinantly engineered antibody fragments.

Mass spectrometry has been used to confirm the correct protein expression of Fab and F(ab')2 fragments of the humanized anti-p185HER2 antibody huMAb4D5. These data demonstrate that electrospray ionization mass spectrometry can be used routinely to measure the masses of purified proteins as large as 100 kDa, with an accuracy of < or = 0.02%. This level of accuracy is helpful in demonstrating the faithful translation and proper posttranslational modification of these proteins. Accurate and reliable mass assignments by electrospray ionization mass spectrometry are achieved by calibrating with protein mass standards, optimizing resolution, and using methods to improve sample purity. On-line reversed-phase high-performance liquid chromatography/mass spectrometry has been employed to improve sample purity and thereby increase sensitivity. Disulfide reduction to yield the component subunits provides additional confirmation of the correct amino acid sequence with greater absolute mass accuracy. A volatile reducing agent such as tributylphosphine provides a convenient method to generate subunits for mass measurement while requiring little or no further sample purification.

Humans↗
PubMed1994

Essential role for a heterogeneous nuclear ribonucleoprotein (hnRNP) in oogenesis: hrp40 is absent from the germ line in the dorsoventral mutant squid.

The Drosophila melanogaster hrp40 proteins are abundant nuclear pre-mRNA-binding proteins that are similar to the heterogeneous nuclear ribonucleoprotein (hnRNP) A/B proteins of vertebrates. Recently, hrp40 has been shown to be encoded by the squid gene, which is required for dorsoventral axis formation during oogenesis. Eggs and embryos from homozygous squid mothers are severely dorsalized, and complete deletion of the squid gene results in lethality. Here we have examined the expression and localization of hrp40 in wild-type and squid mutant ovaries. Using a monoclonal antibody specific for hrp40, the same isoforms of hrp40 are detected in both wild-type and squid ovaries, but the amount of hrp40 is reduced in squid ovaries. Furthermore, immunolocalization of hrp40 in wild-type egg chambers shows that hrp40 is present in the nurse cells, oocyte, and follicle cells. In contrast, in squid mutant egg chambers, hrp40 is absent from the germ-line-derived nurse cells and oocyte, but it is detected in the somatic follicle cells. The absence of hrp40 from the germ-line-derived cells of developing egg chambers is likely to lead to the striking dorsalized phenotype of squid eggs. In addition, dramatic stage-specific changes in the cellular localization of hrp40 are seen; the protein found in the nurse cell nuclei during early stages of oogenesis migrates to the cytoplasm at later stages. These findings reveal dynamic patterns of expression and localization of hnRNP proteins during development and provide evidence for an essential role for hnRNP proteins.

Amino Acid Sequence↗
PubMed1994

Varicella in children with perinatally acquired human immunodeficiency virus infection.

Thirteen children with human immunodeficiency virus infection acquired perinatally and with varicella were identified. Clinical and epidemiologic information, including the use of varicella immune globulin and acyclovir, was obtained and testing for antibodies to varicella-zoster virus was done. The 13 children infected with human immunodeficiency virus had an uncomplicated clinical course, and many had a significant antibody response to varicella-zoster virus.

Acyclovir↗
PubMed1993

Effects of successful cardiac transplantation on plasma endothelin.

After cardiac transplantation, cyclosporine-treated patients exhibit a high incidence of systemic hypertension, the mechanism of which is not known. Endothelin, a potent vasoconstrictor peptide of endothelial origin, may be activated by cyclosporine-induced endothelial injury and therefore may mediate post-transplant hypertension. In the present study, we tested whether immunoreactive endothelin-1 could be detected by radioimmunoassay in the plasma of cardiac transplant recipients and if levels correlated with hemodynamic characteristics, cyclosporine level, or renal function as assessed by serum creatinine. Plasma endothelin was measured in 22 stable cyclosporine-treated patients 9 days to 3 years after successful orthotopic cardiac transplantation before routine hemodynamic assessment and surveillance endomyocardial biopsy. Fifteen patients were receiving chronic therapy for hypertension. Plasma endothelin-1 was 5.2 +/- 1.8 pg/ml (range 3.1 to 10.5), which was increased compared with that in 12 normal subjects (1.9 +/- 0.3 pg/ml; range 1.4 to 2.4); the difference was statistically significant (p < 0.0001). Repeated sampling in 8 patients at weekly intervals identified a persistent increase in endothelin with only modest variability. Endothelin-1 did not correlate with any hemodynamic variable, serum creatinine or cyclosporine level. Thus, endothelin-1 is increased after successful orthotopic cardiac transplantation. In the absence of discrete correlations with hemodynamic variables, serum creatinine or cyclosporine levels, both the characteristics and mechanisms for increased endothelin in recipients of cardiac transplants require further evaluation.

Cyclosporine↗
PubMed1993

Effect of standard-dose versus high-dose epinephrine on myocardial high-energy phosphates during ventricular fibrillation and closed-chest CPR.

STUDY OBJECTIVE: To evaluate the effects of standard-dose versus high-dose epinephrine on myocardial high-energy phosphate metabolism during resuscitation from cardiac arrest. DESIGN: Prospective, nonrandomized, controlled study using a swine model of cardiac arrest and resuscitation. INTERVENTIONS: After anesthesia, intravascular pressure instrumentation, and ten minutes of ventricular fibrillation arrest, closed-chest CPR was begun. After three minutes of CPR, animals were allocated to receive either 0.02 mg/kg i.v. standard-dose epinephrine (eight) or 0.2 mg/kg i.v. high-dose epinephrine (nine). The animals underwent thoracotomy and rapid-freezing transmural myocardial core biopsy for high-energy phosphate analysis 3.5 minutes after epinephrine administration. High-energy phosphate values were blindly determined using high-pressure liquid chromatography. RESULTS: Intravascular pressure (mm Hg) and high-energy phosphate (nmol/mg protein) results for standard-dose epinephrine versus high-dose epinephrine are, respectively, coronary perfusion pressure, 15.3 +/- 7.8 versus 23.7 +/- 5.5 (P = .0009); phosphocreatine, 0.4 +/- 0.8 versus 6.2 +/- 4.4 (P = .0003); adenosine triphosphate, 9.8 +/- 4.8 versus 12.7 +/- 5.7 (P = .30); adenosine diphosphate, 5.4 +/- 2.1 versus 6.1 +/- 1.3 (P = .41); and adenylate charge, 0.68 +/- 0.12 versus 0.72 +/- 0.12 (P = .87). CONCLUSION: High-dose epinephrine does not deplete myocardial high-energy phosphate when given in this model of prolonged ventricular fibrillation. High-dose epinephrine increases coronary perfusion pressure compared with standard-dose epinephrine. High-dose epinephrine administration repletes phosphocreatine during closed-chest CPR, thereby increasing myocardial energy stores.

Adenosine↗
PubMed1992

Plasma endothelin correlates with the extent of pulmonary hypertension in patients with chronic congestive heart failure.

BACKGROUND: Endothelin is a family of potent vasoconstrictor peptides of vascular endothelial origin. Although it has been proposed that the vasoconstrictor effects of endothelin are produced at the local vascular level, increased plasma concentration of endothelin has been identified in cardiovascular disorders. METHODS AND RESULTS: We tested whether immunoreactive endothelin-1 could be detected by radioimmunoassay in plasma of congestive heart failure patients and whether levels correlated with hemodynamic characteristics. Twenty congestive heart failure patients (New York Heart Association class II-IV) were sampled in the morning after an overnight fast, before medication. Cardiac index was decreased to 2.14 +/- 0.45 l/m/m2, and pulmonary wedge pressure was increased to 22 +/- 7 mm Hg. The ranges of pulmonary pressures were: systolic, 22-100 mm Hg, mean, 13-61 mm Hg, and diastolic, 8-42 mm Hg. The endothelin-1 level was 9.07 +/- 4.13 pg/ml (range, 4-19 pg/ml), which was increased compared with 12 normals (3.7 +/- 0.6 pg/ml; range, 2.8-4.7 pg/ml); the difference was statistically significant (p less than 0.0001). Endothelin-1 significantly correlated with pulmonary pressures (systolic, r = 0.78; mean, r = 0.80; diastolic, r = 0.77; all p less than 0.003) and pulmonary vascular resistance (r = 0.65, p less than 0.01). Endothelin-1 strongly correlated with the resistance ratio (pulmonary vascular resistance/systemic vascular resistance) (r = 0.88, p less than 0.0001). Stepwise multiple regression analysis confirmed the significance of these observations. CONCLUSIONS: Elevated immunoreactive endothelin-1 specifically correlated with the extent of pulmonary hypertension in congestive heart failure patients. Whether endothelin-1 is a regional mediator of pulmonary hypertension or a marker for its occurrence requires additional evaluation.

Adult↗
PubMed1990

Sexual issues and research in counseling the postmyocardial infarction patient.

This article reviews the literature relevant to the postmyocardial infarction (MI) patient and sexual activities. It begins with an analysis of the published accounts of the physiologic effects of sexual activity (including intercourse) and the anticipated concerns associated with coital deaths. The article includes an examination of the need for sexual counseling in any treatment and rehabilitation setting. In addition, general sexual adjustment guidelines for the uncomplicated post-MI patient are presented.

Fear↗