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Biomedical subjects

P Bowers

Publications and source records attributed to P Bowers.

At least 19 recordsLinked to original sources
PubMed2001

Computational method to assign microbial genes to pathways.

We present techniques that mine fully sequenced microbial genomes for functional relationships between genes. We show that genes related by one of four techniques are more likely to belong to the same cellular pathways. Furthermore, we demonstrate that the pathway of an uncharacterized gene may be inferred from those of its functionally related partners. Therefore, we are now able to assign most of the genes within bacteria to cellular pathways.

Computational Biology↗
PubMed2000

Loss-of-function mutations in the EGF-CFC gene CFC1 are associated with human left-right laterality defects.

All vertebrates display a characteristic asymmetry of internal organs with the cardiac apex, stomach and spleen towards the left, and the liver and gall bladder on the right. Left-right (L-R) axis abnormalities or laterality defects are common in humans (1 in 8,500 live births). Several genes (such as Nodal, Ebaf and Pitx2) have been implicated in L-R organ positioning in model organisms. In humans, relatively few genes have been associated with a small percentage of human situs defects. These include ZIC3 (ref. 5), LEFTB (formerly LEFTY2; ref. 6) and ACVR2B (encoding activin receptor IIB; ref. 7). The EGF-CFC genes, mouse Cfc1 (encoding the Cryptic protein; ref. 9) and zebrafish one-eyed pinhead (oep; refs 10, 11) are essential for the establishment of the L-R axis. EGF-CFC proteins act as co-factors for Nodal-related signals, which have also been implicated in L-R axis development. Here we identify loss-of-function mutations in human CFC1 (encoding the CRYPTIC protein) in patients with heterotaxic phenotypes (randomized organ positioning). The mutant proteins have aberrant cellular localization in transfected cells and are functionally defective in a zebrafish oep-mutant rescue assay. Our findings indicate that the essential role of EGF-CFC genes and Nodal signalling in left-right axis formation is conserved from fish to humans. Moreover, our results support a role for environmental and/or genetic modifiers in determining the ultimate phenotype in humans.

Abnormalities, Multiple↗
PubMed1999

Left-right axis malformations associated with mutations in ACVR2B, the gene for human activin receptor type IIB.

Targeted disruption of the mouse activin receptor type IIB gene (Acvr2b) results in abnormal left-right (LR) axis development among Acvr2b-/- homozygotes [Oh and Li, 1997: Genes Dev 11:1812-1826]. The resulting malformations include atrial and ventricular septal defects, right-sided morphology of the left atrium and left lung, and spleen hypoplasia. Based on these results, we hypothesized that mutations in the type IIB activin receptor gene are associated with some cases of LR axis malformations in humans. We report here characterization of the ACVR2B genomic structure, analysis of ACVR2B splice variants, and screening for ACVR2B mutations among 112 sporadic and 14 familial cases of LR axis malformations. Two missense substitutions have been identified, one of which appears in two unrelated individuals. Neither of these nucleotide changes has been found in 200 control chromosomes. We conclude that ACVR2B mutations are present only rarely among human LR axis malformation cases.

Activin Receptors, Type II↗
PubMed1998

Courtship behaviour of ostriches (Struthio camelus) towards humans under farming conditions in Britain.

1. The courtship behaviour of adult male and female ostriches was observed in the presence and absence of human beings. 2. Courtship behaviours in both males and females were more prevalent in the presence of humans. 3. Exposure to a human for a short period did not stimulate courtship behaviour in the period immediately after the human had withdrawn. 4. Courtship behaviour towards humans may be important in the reproductive success of ostriches in a farming environment.

Agriculture↗
PubMed1993

Effect of patient characteristics and disease manifestations on the outcome of acute otitis media at 2 months.

BACKGROUND: Optimal therapy for acute otitis media (AOM) is controversial and there is no consensus regarding which antibiotic to use, how long to administer it, or whether antibiotics are effective at all. Knowledge of the effects of patient characteristics and disease manifestations is needed to individualize treatment and to evaluate large-scale trials. METHODS: Data originated from 2251 patients with AOM, aged newborn to 15 years, who participated in a prospective primary care study in eight countries. At the initial visit, medical history, symptoms, physical findings, and treatment data were recorded. Follow-up 2 months later identified changes in treatment and outcome. RESULTS: Patients younger than 13 months were less likely to have recovered than those aged 13 months to 15 years (P = .05). Using univariate analysis for infants aged 12 months or younger, male sex, prior episodes of AOM, and serous otitis media were associated with poor outcome. For older patients, poor outcome was associated with initial history of ear tubes, prophylactic antibiotic use, ear discharge, decreased hearing, serous otitis media; and past episodes of AOM; the symptom of decreased hearing; and the finding of pus exuding from the tympanic membrane. Using multivariate analysis for infants aged 12 months or younger, a history of serous otitis media (odds ratio [OR], 2.3; 95% confidence interval [CI], 0.95-5.7), past episodes of AOM (OR, 1.9; 95% CI, 0.82-4.5), and male sex (OR, 1.7; 95% CI, 1.0-3.0) made independent contributions to poor outcome. For children aged 13 months to 15 years, significant variables included pus drainage (OR, 2.2; 95% CI, 1.5-3.3), a history of ear tubes (OR, 2.3; 95% CI, 1.5-3.6), past episodes of AOM (OR, 1.8; 95% CI, 1.3-2.34), and a history of serous otitis media (OR, 1.4; 95% CI, 1.0-1.9). CONCLUSIONS: Patient characteristics and disease manifestations are significant determinants of AOM outcome.

Acute Disease↗
PubMed1993

Analysis of skull anthropometric measurements in patients with neurofibromatosis type-1.

RATIONALE AND OBJECTIVES: The authors studied selected anthropometric measurements of plain postero-anterior and lateral skull roentgenograms to ascertain whether these were useful in distinguishing patients with clinically probable neurofibromatosis type-1 from controls. METHODS: A retrospective review of medical records of patients for whom skull roentgenograms were available was conducted. Patients were assigned to one of three groups: definite neurofibromatosis type-1 (DNF), probable neurofibromatosis type-1 (PNF), and controls. A blinded analysis of 29 measurements, 9 qualitative assessments, and 3 area/volume calculations was performed. RESULTS: There were 58 patients (29 controls, 14 DNF, and 15 PNF). The majority (75%) of all predetermined landmarks could be ascertained in 43 of these subjects. After age and gender were held constant, analysis of covariance showed that both DNF and PNF subjects could be distinguished from controls, but not from each other when comparing the mean: sella turcica height (P < .001), sella turcica depth (P < .005), skull width (P < .001), skull length (P < .002), skull height (P < .003), and skull volume (P < .0001). CONCLUSIONS: Anthropometric analysis of skull roentgenograms coupled with results of clinical examination improves the ability to distinguish between patients with DNF and PNF from controls.

Adolescent↗
PubMed1990

Diagnosis and antibiotic treatment of acute otitis media: report from International Primary Care Network.

STUDY OBJECTIVE: The relation between a history of disorders suggestive of acute otitis media, symptoms, and findings of an examination of the tympanic membrane and doctors' certainty of diagnosis. Also, to examine differences in prescribing habits for acute otitis media among doctors from different countries. DESIGN: Questionnaires were completed by participating doctors for a maximum of 15 consecutive patients presenting with presumed acute otitis media. SETTING: General practices in Australia, Belgium, Great Britain, Israel, The Netherlands, New Zealand, Canada, Switzerland, and the United States. PATIENTS: 3660 Children divided into the three age groups 0-12 months, 13-30 months, and greater than or equal to 31 months. MAIN OUTCOME MEASURES: General practitioners' responses to questions on their diagnostic certainty and resolution of patients' symptoms after two months. RESULTS: The diagnostic certainty in patients aged 0-12 months was 58.0%. This increased to 66.0% in those aged 13-30 months and 73.3% in those aged greater than or equal to 31 months. In all age groups diagnostic certainty was positively associated with the finding of a tympanic membrane that was discharging pus or bulging. Redness of the membrane and pain were also associated with certainty in patients aged 13-30 months, and a history of decreased hearing or recent upper respiratory infection was positively associated in patients aged greater than or equal to 31 months. The proportion of patients prescribed antibiotics varied greatly among the countries, from 31.2% in The Netherlands to 98.2% in both Australia and New Zealand, as did the duration of treatment. Patients who did not take antibiotics had a higher rate of recovery than those who did; the rate of recovery did not differ between different types of antibiotic. CONCLUSIONS: Doctors' certainty of diagnosis of acute otitis media was linked to patient's age. Improved criteria or techniques for diagnosing acute otitis media, especially in very young children, need to be developed. Antibiotic treatment did not improve the rate of recovery of patients in this study.

Acute Disease↗
PubMed1988

The effects of 6-azacholest-4-en-3 beta-ol-7-one, an inhibitor of cholesterol 7 alpha-hydroxylase, on cholesterol metabolism and bile acid synthesis in primary cultures of rat hepatocytes.

6-Azacholest-4-en-3 beta-ol-7-one (azacholesterol) was shown to be a specific inhibitor of cholesterol 7 alpha-hydroxylase. It inhibited cholesterol hydroxylation by a rat liver microsomal preparation with non-competitive kinetics and a Ki of 4 microM. No evidence was found for a time-dependent inhibition of activity. Azacholesterol did not inhibit acyl-CoA: cholesterol acyltransferase or 3-hydroxy-3-methylglutaryl coenzyme A reductase in rat liver microsomal preparations, or cholesterol esterification and synthesis in primary cultures of rat hepatocytes. The synthesis of bile acids was inhibited by azacholesterol in these cells in a dose-dependent way. When bile acid synthesis was inhibited by azacholesterol, newly-synthesized cholesterol from exogenous mevalonate was secreted by the hepatocyte cultures into the cell culture medium in several-fold excess over control incubations. No changes in the secretion of cholesteryl ester occurred in the presence of azacholesterol. This observation suggests that newly synthesised cholesterol that has entered the substrate pool for hydroxylation is no longer accessible to the substrate pool for esterification. This is further evidence for the compartmentation of cholesterol metabolism in the hepatocyte.

Animals↗
PubMed1987

The role of acyl-CoA: cholesterol acyltransferase in the metabolism of free cholesterol to cholesteryl esters or bile acids in primary cultures of rat hepatocytes.

Sandoz compound 58-035 has been shown to inhibit acyl-CoA: cholesterol acyltransferase activity in a variety of cell types. We have shown that it does not inhibit rat liver microsomal cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme of bile-acid synthesis, but it does inhibit acyl-CoA: cholesterol acyltransferase in both the microsomal fraction and in rat hepatocyte monolayers. To test the role of acyl-CoA: cholesterol acyltransferase in these cells, monolayers were incubated over 5 h in the presence and absence of 58-035 and in the presence of increasing amounts of mevalonic acid to provide a source of cholesterol. The addition of mevalonic acid increased the secretion of bile acids by the cells, and this was further increased by the addition of 58-035. The secretion of cholesteryl esters was conversely inhibited by the addition of 58-035. The results help define the role of acyl-CoA: cholesterol acyltransferase in determining the fate of intracellular cholesterol.

Amides↗
PubMed1986

EEG "maturational lag" profiles: follow-up analyses.

Nineteen children who had EEG diffuse slow frequency profiles suggesting a maturational lag were retested 1 to 2 years later receiving both EEG and psychometric assessments. They were compared to 18 children who also had been tested previously but did not have the slow frequency profile. Children with the maturational lag profile displayed varying degrees of EEG developmental change upon retest; i.e., some showed the expected developmental change while others remained the same. Within this group, there were significant relationships between the degree of EEG change and psychometric scores. Those that demonstrated the most EEG change had higher psychometric indices, and these relationships were not obtained in the comparison group. These findings suggest developmental heterogeneity with respect to brain maturation as measured by the EEG and also suggest that test-retest EEG data can clarify a maturational lag diagnosis.

Adolescent↗
PubMed1982

A comparative study of 99mTc and 131I in thyroid scanning.

Thyroid scans performed with both 99mTc pertechnetate (99mTcO4) and (131I) were compared in 46 patients with palpable thyroid nodules to determine whether 131I scanning is any longer a necessary procedure. A discrepancy between the two types of scan existed in only three cases, in one of which the thyroid nodule showed uptake of 99mTcO4 but not of 131I. Subsequent surgery revealed a thyroid malignancy in this patient. In each of the other two discrepancies a nodule "cold" on 99mTcO4 scanning was apparently functioning on 131I scanning, and was found to be benign at surgery. As the convenience and lower radiation absorbed dose of 99mTcO4 patients compared with 131I make it a better scanning agent, it is recommended that 99mTcO4 scans of the thyroid be first nodules. If these nodules prove to be functioning equally with paranodular tissue, a 131I scan should also be performed to help exclude a possible thyroid malignancy.

Goiter↗