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Biomedical subjects

P White

Publications and source records attributed to P White.

At least 163 records · Page 9Linked to original sources

Sequences of heavy and light chain variable regions from four bovine immunoglobulins.

Oligodeoxyribonucleotide primers based on the 5' ends of bovine IgG1/2 and lambda constant (C) region genes, together with primers encoding conserved amino acids at the N-terminus of mature variable (V) regions from other species, have been used in cDNA and polymerase chain reactions (PCRs) to amplify heavy and light chain V region cDNA from bovine heterohybridomas. The amino acid sequences of VH and V lambda from four bovine immunoglobulins of different specificities are presented.

Amino Acid Sequence↗

Beliefs about menopause of general practitioners and mid-aged women.

Recent general population studies suggest that experience of the normal menopause transition is relatively unremarkable for the majority of women, but negative stereotyped beliefs about menopause remain pervasive. This study explored GPs' beliefs and opinions about menopause in general, and compared the GPs' beliefs with those of their mid-aged female patients. All GPs at five general practices (n = 24) and 101 45-year-old women registered at the same practices took part. Large proportions of both groups believed that most women experience somatic and psychological difficulties during menopause. GPs expressed more negative beliefs than patients but were also more likely to express positive/neutral beliefs. Some causal attributions of menopausal problems were shared by the two groups, but they differed on others. When both GPs and patients hold negative social stereotypes about menopause, problems of mid-aged women may be misattributed to menopause. Health information on menopause may be biased towards negative images of menopause and of aging women.

Aging↗

Efficient generation of a reshaped human mAb specific for the alpha toxin of Clostridium perfringens.

We have used the technique of antibody reshaping to produce a humanized antibody specific for the alpha toxin of Clostridium perfringens. The starting antibody was from a mouse hybridoma from which variable (V) region nucleotide sequences were determined. The complementarity-determining regions (CDRs) from these V regions were then inserted into human heavy and light chain V region genes with human constant region gene fragments subsequently added. The insertion of CDRs alone into human frameworks did not produce a functional reshaped antibody and modifications to the V region framework were required. With minor framework modifications, the affinity of the original murine mAb was restored and even exceeded. Where affinity was increased, an altered binding profile to overlapping peptides was observed. Computer modelling of the reshaped heavy chain V regions suggested that amino acids adjacent to CDRs can either contribute to, or distort, CDR loop conformation and must be adjusted to achieve high binding affinity.

Amino Acid Sequence↗

Nutritional regulation of growth hormone receptor gene expression.

The role of energy intake in regulating growth hormone receptor (GHR) gene expression has been assessed in young growing pigs living at thermal neutrality (26 degrees C) for a 4-wk period. To determine the importance of altering metabolic demand while maintaining food intake constant, littermates were also studied in a cold environment (10 degrees C). Results were tissue-specific: the level of GHR mRNA per unit total RNA in liver was greater on high than low (high = 2 x low) food intake (P < 0.001), whereas in muscle it was elevated on the low compared with the high intake diet (P < 0.02) and also at 10 degrees C compared with 26 degrees C (P < 0.04). When results for GHR mRNA were expressed per unit weight of tissue, only the effects of diet on liver and temperature on muscle remained significant. The changes in hepatic GHR mRNA may have been driven in part by nutritionally induced changes in thyroid status, because both plasma 3,5,3'-triiodothyronine concentration and liver 5'-deiodinase activity were greater on the high than the low intake diet (P < 0.001). Levels of liver GHR mRNA probably had a direct influence on growth of the animals, as they were positively correlated with plasma IGF-I and growth rate (P < 0.001), whereas muscle GHR mRNA may have had a metabolic role when energy supplies were limited.

Animal Nutritional Physiological Phenomena↗

Endoscopic sphincteroplasty: a novel and safe alternative to papillotomy in the management of bile duct stones.

Removal of bile duct stones during endoscopic retrograde cholangiopancreatography (ERCP) usually includes papillotomy. Papillotomy is associated with occasional complications and in addition, the longterm sequelae of papillotomy in young patients having laparoscopic cholecystectomy remain unclear. As an alternative to papillotomy, this study prospectively evaluated the efficacy and safety of endoscopic balloon sphincteroplasty to facilitate bile duct clearance. Of 32 patients with bile duct stones (diameter 3-30 mm) at ERCP, sphincteroplasty was considered inappropriate in four patients because of stone size (> 20 mm) necessitating papillotomy for bile duct clearance. Sphincteroplasty was performed in the remaining 28 patients to permit duct clearance by dormier basket, balloon or mechanical lithotripsy. The bile duct was cleared in 22 patients (79%) while additional measures including papillotomy or stent insertion were required in the remaining six patients (21%) because of stone size or technical difficulties. There was no associated papillary haemorrhage. Pancreatitis was seen in one patient (4%) but resolved within 24 hours. Our preliminary experience suggests that sphincteroplasty is a safe and effective sphincter preservation technique that significantly reduces the necessity for papillotomy in the management of bile duct stones.

Adult↗

Effect of hypoxia on lung fluid balance in ferrets.

To determine how hypoxia may alter determinants of pulmonary transvascular fluid flux, adult male ferrets were exposed to either room air (C) or hypoxia (H; FIO2 = 0.12) for 24 h. After anesthesia and ventilation with C or H, the mean pulmonary artery pressures were 18.4 +/- 2.2 (SEM) and 27.3 +/- 2.9 mm Hg, respectively (p < 0.025). The right lung was then removed for gravimetric analysis of lung water and the left lung was blood-perfused (approximately 142 ml/kg/min) and continuously weighed for 15 min at left atrial pressures of 20, 25, and 30 mm Hg. Filtration coefficient (Kf) was estimated from the slopes of the relationships of rate of weight gain versus change in vascular pressure over the last 5 min of each interval. Extravascular lung water/blood-free dry lung weight for C and H were 2.95 +/- 0.06 (SEM) and 3.53 +/- 0.09 ml/g, respectively (p < 0.01). Kf for C and H were 0.0645 +/- 0.0190 (SEM) and 0.0662 +/- 0.0085 ml/min/mm Hg/100 g, respectively (NS). In a second group of experiments, in which lungs were removed from ferrets after 24 h exposures to C or H, protein reflection coefficients (sigma) were estimated by comparing the increases in perfusate hematocrit and protein concentrations during edema formation. Reflection coefficients for albumin were 0.64 +/- 0.03 (SEM) and 0.39 +/- 0.07 with C and H, respectively (p < 0.01). The sigma values for IgG and IgM were not affected.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Enhancing faculty participation and interest in quality improvement in academic centers.

Continuous quality improvement (CQI) is necessary in maintaining and improving the quality of medical care delivered. However, quality assurance (QA) in the past was performed superficially to meet requirements of the Joint Commission on Accreditation of Health Care Organizations and other regulatory agencies. Academic faculty participation in QA activity was also limited. Faculty often assume that meaningful quality process demands excessive efforts and time unrewarded with career advancement, promotion, or monetary compensation. In addition, unstructured QA leads to duplication of data and loss of educational opportunity. We reorganized the QA process in internal medicine using the CQI concept to: (a) improve academic faculty participation, (b) incorporate educational concepts, (c) stimulate interest in outcome research and CQI, and (d) integrate cost containment. A reorganized CQI format has stimulated enthusiastic participation of faculty and residents, and has generated conferences and grand rounds pertinent to medical care, outcome research, and cost containment. We conclude that academic faculty should play leadership roles in the CQI process and include teaching models. Improved and increased academic faculty participation could be realized, when educational values, research activities, and cost analysis are incorporated into the CQI process.

Academic Medical Centers↗

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Data Collection↗

The importance of the interdomain hinge in intramolecular electron transfer in flavocytochrome b2.

The two distinct domains of flavocytochrome b2 (L-lactate:cytochrome c oxidoreductase) are connected by a typical hinge peptide. The amino acid sequence of this interdomain hinge is dramatically different in flavocytochromes b2 from Saccharomyces cerevisiae and Hansenula anomala. This difference in the hinge is believed to contribute to the difference in kinetic properties between the two enzymes. To probe the importance of the hinge, an interspecies hybrid enzyme has been constructed comprising the bulk of the S. cerevisiae enzyme but containing the H. anomala flavocytochrome b2 hinge. The kinetic properties of this 'hinge-swap' enzyme have been investigated by steady-state and stopped-flow methods. The hinge-swap enzyme remains a good lactate dehydrogenase as is evident from steady-state experiments with ferricyanide as acceptor (only 3-fold less active than wild-type enzyme) and stopped-flow experiments monitoring flavin reduction (2.5-fold slower than in wild-type enzyme). The major effect of the hinge-swap mutation is to lower dramatically the enzyme's effectiveness as a cytochrome c reductase; kcat. for cytochrome c reduction falls by more than 100-fold, from 207 +/- 10 s-1 (25 degrees C, pH 7.5) in the wild-type enzyme to 1.62 +/- 0.41 s-1 in the mutant enzyme. This fall in cytochrome c reductase activity results from poor interdomain electron transfer between the FMN and haem groups. This can be demonstrated by the fact that the kcat. for haem reduction in the hinge-swap enzyme (measured by the stopped-flow method) has a value of 1.61 +/- 0.42 s-1, identical with the value for cytochrome c reduction and some 300-fold lower than the value for the wild-type enzyme. From these and other kinetic parameters, including kinetic isotope effects with [2-2H]lactate, we conclude that the hinge plays a crucial role in allowing efficient electron transfer between the two domains of flavocytochrome b2.

Amino Acid Sequence↗

Chronic pancreatitis: a complication of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE), an autoimmune disease with multisystem involvement, has been reported to be associated with a number of gastrointestinal complications. Acute pancreatitis is an unusual manifestation of this disorder. This report presents two cases of patients with SLE who developed chronic pancreatitis with no other identifiable etiology.

Adult↗