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Biomedical subjects

P White

Publications and source records attributed to P White.

At least 145 records · Page 8Linked to original sources
PubMed1996

Outcome of mechanical ventilation for adults with hematologic malignancy.

BACKGROUND: Patients with hematologic malignancy who develop respiratory failure generally have a very poor prognosis. A few such patients, however, enjoy long-term survival. The objective of this study was to identify clinical characteristics of patients with hematologic malignancy and respiratory failure that are predictive of outcome. METHODS: We performed a retrospective chart review of all patients who required mechanical ventilation for acute respiratory failure while on the leukemia or bone marrow transplantation units at the Johns Hopkins Oncology Center between January 1985 and October 1991 (n = 157). RESULTS: Overall hospital mortality was 83%. Major organ system dysfunction, as measured by the acute physiology score (APS) of the APACHE III prognostic system, was significantly (P < 0.05) related to hospital mortality. Three disease-specific clinical characteristics were predictive of mortality: 1) stage beyond first complete remission, 2) duration of neutropenia greater than 30 days, and 3) treatment with bone marrow transplantation, especially if HLA-mismatched. None of the 15 (10%) patients with neutropenia greater than 30 days or the four patients who underwent HLA-mismatched transplantation survived to discharge. Age was also a significant predictor of hospital mortality. CONCLUSIONS: Overall outcome of patients with hematologic malignancy and acute respiratory failure is poor. A larger prospective study will be required to confirm the relative value of disease-specific variables identified in this study when combined with established predictive variables. In the future, it may be possible to develop a predictive instrument that is specifically tailored for patients with hematologic malignancy who develop respiratory failure.

APACHE↗
PubMed1995

Construction and characterization of a humanized anti-gamma-Ig receptor type I (Fc gamma RI) monoclonal antibody.

The murine mAb 22 (M22) binds to the human high affinity receptor for the Fc portion of IgG (Fc gamma RI). This mAb recognizes an epitope on Fc gamma RI that is distinct from the natural ligand (Fc) binding site, and, therefore, can bind to Fc gamma RI in the presence of saturating levels of IgG found in vivo. Fc gamma RI is expressed only on cytotoxic effector cells and it acts as an efficient mediator (trigger molecule) of effector functions. Directing tumor cells or other pathogens to Fc gamma RI utilizing M22 conjugated to an anti-tumor- or to an anti-pathogen-specific mAb may represent an effective method to enhance their removal and destruction under physiologic conditions. Humanization of M22 may improve the therapeutic potential of the mAb since murine mAbs normally elicit a human anti-mouse Ab response. In this report we describe the humanization of M22 by CDR-grafting onto human V region frameworks based on KOL VH and REI V kappa attached to human IgG1 and kappa constant domains. This humanized mAb, H22, displays equivalent binding specificity and affinity as its murine counterpart. In addition, H22 is able to trigger superoxide release from Fc gamma RI-bearing cells, a finding that demonstrates that H22 triggers Fc gamma RI functions. The successful humanization of mAb 22 is an important step in the development of Fc gamma RI-directed immunotherapy.

Amino Acid Sequence↗
PubMed1995

Using information from asthma patients: a trial of information feedback in primary care.

OBJECTIVE: To test the effects of feedback of information about patients' asthma to primary care teams. DESIGN: Patients' reports of morbidity, use of health services, and drug use on questionnaire was given to primary care teams. Randomised controlled trial with general practices as the subject of the intervention was used to test effectiveness of supplying information. SETTING: Primary care in district health authority, London. SUBJECTS: 23 general practices, each of which notified at least 20 asthmatic patients aged 15-60 years for each principal. Practices were randomly allocated to an invention group (receiving feedback of information on control of asthma) or a control group (no feedback). INTERVENTION: Information on cards inserted in patients' medical records; booklet copies of information for team members; formal presentation to primary care teams; poster displays of data on patients in each practice. MAIN OUTCOME MEASURES: Type and frequency of asthma symptoms, use of health services, use of asthma drugs. RESULTS: Reported morbidity at entry to the study was substantial: 45% (818) patients reported breathlessness at least once a week. Less than half these patients were using inhaled steroids regularly. Intervention and control groups did not differ in practice or patient characteristics on entry to the study. In spite of the potential for improvement no differences were observed between the two practice groups at the end of the study--for example, breathlessness at least once a week in last six months was experienced by 36% in intervention group v 35% in control group (t = -0.27, P < 0.79); surgery attendance in last six months by 48% v 48% (t = -0.05, P < 0.96); regular use of inhaled steroids by 60% v 58% (t = 0.51, P < 0.62). CONCLUSION: Feedback to general practitioners of information about patients' asthma does not on its own lead to change in the outcome of clinical care.

Adolescent↗
PubMed1995

Plasma cholesterol esterase level is a determinant for an atherogenic lipoprotein profile in normolipidemic human subjects.

Plasma cholesterol level is controlled by various factors. In the present study, high plasma activity of cholesterol esterase was found to correlate with plasma total cholesterol and low density lipoprotein (LDL) cholesterol levels in normolipidemic human subjects. However, the cholesterol esterase is not elevated in plasma of patients with familial hypercholesterolemia. These observations suggest that cholesterol esterase level is not determined by plasma cholesterol level, but elevated cholesterol esterase may be causative in increasing plasma cholesterol and LDL. Additional experiments further demonstrated that cholesterol esterase can convert the larger and less-atherogenic LDL to the smaller and more atherogenic LDL subspecies in vitro. These results suggest that plasma cholesterol esterase contributes to the formation and accumulation of atherogenic lipoproteins, and thus is a major risk factor for premature atherosclerosis in normal human subjects.

Adult↗
PubMed1995

Musculoskeletal problems among Ontario dental hygienists.

Two U.S. surveys suggested that dental hygienists (DHs) may suffer from carpal tunnel syndrome (CTS), but these studies did not use validated questionnaires, adjust for confounders, or include external controls. We conducted a questionnaire survey of all 2,142 DHs belonging to the Ontario Dental Hygienists' Association, and a referent group of 305 dental assistants (DAs), who do not scale teeth. The Standardized Nordic Questionnaire was used as the basis for asking about musculoskeletal symptoms. The response rates in the two groups were identical. Of the DHs, 7.0% had been told by a physician since starting work that they had CTS, but only 1 of 65 had received workers' compensation. Compared to the DAs, after adjusting for age the DHs were 5.2 times (95% confidence interval [CI] 0.9-32) more likely to have been told they had CTS and 3.7 times (95% CI 1.1-11.9) more likely to meet a CTS case definition. The DHs were also 2.5 (95% CI 1.6-3.9), 2.8 (95% CI 1.8-4.4), and 1.8 (95% CI 1.2-2.7) times more likely to report hand/wrist, shoulder, and neck problems in the past 12 months, respectively, but were less likely to report low back trouble. In internal analyses among DHs using logistic regression models, the number of heavy calculus patients per day, "clock" position around the dental chair, and years in practice were significant predictors of CTS. Days worked per week (but not heavy calculus patients), time with the trunk rotated, and years of practice were significant predictors of reported shoulder trouble in the past 12 months. Given that there are more than 9,000 DHs in Canada and about 100,000 in the United States, these findings suggest an important public health problem. They highlight the need to inform DHs during training and continuing education about musculoskeletal problems in general and CTS in particular. Attention should be directed to areas such as work station design, posture, treating patients with heavy calculus, and scheduling rest periods.

Adult↗
PubMed1995

(Re)theorising population geography.

"Population geography has become separated from other branches of human geography by not engaging strongly with recent debates in social theory. The reasons for this partly lie in the wealth of data that population geographers have available to them concerning their major interest--demographic events....A case is made here for population geographers to consider in particular three areas of social theoretic debate--social construction theories, realist ideas on extensive and intensive research, and the politics of position. Suggestions are made as to what a (re)theorised population geography might look like."

Demography↗
PubMed1995

Identification of framework residues required to restore antigen binding during reshaping of a monoclonal antibody against the glycoprotein gB of human cytomegalovirus.

Introduction of the complementary determining regions (CDRs) from a murine antibody to a human monoclonal antibody is an important technique (humanization) in the development of human immunotherapeutics. We have humanized murine monoclonal antibody HCMV37 which binds to the gB envelope glycoprotein of human cytomegalovirus. Simple transfer of the murine HCMV37 CDRs into heavy- and light-chain framework regions (FRs) based on human NEW and REI, respectively, together with human IgGI and K constant regions, abolished antigen binding because of a suboptimal heavy chain. Replacement of human VH amino acids Leu70, Val71 and Arg94 with murine residues Thr70, Arg71 and Asn94 was insufficient to improve affinity. However, significant restoration of binding was obtained by substitution of human VH amino acids Thr28, Phe29, Ser30 with murine residues Ser28, Ile29, Thr30, in conjunction with the position 94 change. Residue 71, often regarded as critical for antigen binding, was not a major factor.

Amino Acid Sequence↗
PubMed1995

Preparation of a novel monoclonal antibody specific for myelin basic protein phosphorylated on Thr98.

Phosphorylation is one of a number of post-translational modifications resulting in charge microheterogeneity of myelin basic protein (MBP). This phosphorylation is claimed to destabilise the compact myelin sheath by decreasing the interaction of membrane bilayers, thereby creating or maintaining pockets of cytoplasm. To further investigate and localise MBP phosphorylation to discrete regions of the myelin sheath we raised a monoclonal antibody with specificity for a known phosphorylation site in MBP. A synthetic peptide was made by Fmoc peptide chemistry and phosphorylation of Thr98 was achieved on the resin by the global phosphorylation methodology, utilising dibenzyl-N,N-diethylphosphoramidite phosphitylation and t-butylhydroperoxide oxidation. The peptide coupled to tuberculin was used to immunise mice for monoclonal antibody production. The selected hybridoma (Clone P12) secreted an IgG2a antibody which reacted strongly with the phosphorylated immunogen and with phosphorylated fractions of bovine MBP obtained by ion exchange chromatography. The antibody had minimal reactivity with the unphosphorylated peptide; the same peptide phosphorylated at another site Ser102; a preparation of unphosphorylated MBP obtained by ion exchange chromatography; and with an irrelevant phosphorylated protein (histone). Similar phosphorylation state-specific monoclonal antibodies could be made to recognise other specific phosphorylation sites in MBP or other proteins. It is planned to use these antibodies to quantify and locate the extent of MBP phosphorylation in normal and multiple sclerosis myelin.

Amino Acid Sequence↗
PubMed1995

Endoscopic balloon sphincteroplasty (papillary dilation) for bile duct stones: efficacy, safety, and follow-up in 100 patients.

BACKGROUND: Because sphincterotomy accounts for a major portion of the morbidity and mortality associated with ERCP, we have proposed endoscopic balloon papillary dilation or sphincteroplasty as an alternative. METHODS: We report the outcome in a series of 100 patients in whom balloon sphincteroplasty was attempted for bile duct stones up to 20 mm in diameter, with a median follow-up of 16 months (range 6 to 30). RESULTS: During one ERCP session using sphincteroplasty alone, the bile duct was cleared in 78%, mechanical lithotripsy being required in 10% for stones greater than 12 mm in diameter. Incomplete duct clearance was achieved in a further 4%, all of whom underwent repeat ERCP with successful duct clearance without recourse to sphincterotomy. Failure to clear the bile duct with sphincteroplasty in the remaining 18% was primarily related to large stone size ( > 15 mm). Sphincterotomy was required to clear the duct in 7%. Another 6% comprised elderly high-risk patients with multiple large stones greater than 15 mm who were treated by stent insertion plus ursodeoxycholic acid. No papillary hemorrhage was observed; uncomplicated pancreatitis occurred in 5%. During a median follow-up of 16 months, 2% had recurrent symptomatic bile duct stones considered to have been unrecognized following the initial ERCP: these were removed after repeat sphincteroplasty. No clinical evidence of papillary stenosis was observed during follow-up. CONCLUSIONS: Endoscopic balloon papillary dilation or sphincteroplasty is a safe and effective alternative to sphincterotomy in the management of bile duct stones less than 12 mm; larger stones may require mechanical lithotripsy to facilitate duct clearance.

Ampulla of Vater↗
PubMed1995

You are not alone. Advocacy for children and young adults with rheumatic diseases.

The goal of this article is to assist individuals with an interest in childhood rheumatic diseases to gain the knowledge and the skills necessary to become a strong advocate for their own, or someone else's, needs. Seeking information and help, as demonstrated by Jeremy's mother, shows how rewarding the process of becoming an advocate can be.

Adult↗
PubMed1995

The potent bone-resorbing mediator of Actinobacillus actinomycetemcomitans is homologous to the molecular chaperone GroEL.

Actinobacillus actinomycetemcomitans is a Gram-negative bacterium implicated in the pathology of localized juvenile periodontitis, a condition involving rapid destruction of alveolar bone. We have established that gentle extraction of this bacterium in saline releases a proteinaceous fraction (which we have termed surface-associated material [SAM] which has potent osteolytic activity in the murine calvarial bone resorption assay. Fractionation of the SAM has now revealed that activity is associated with a 62-kD protein. This bone-resorbing activity can be blocked by a monoclonal antibody (raised to the whole bacterium) that is claimed to recognize a protein homologous to the Escherichia coli molecular chaperone GroEL. Purification of this bone-resorbing protein to homogeneity has been achieved by a combination of anion exchange, gel filtration, and ATP-affinity chromatography and the NH2-terminal sequence shows > 95% homology to E. coli GroEL. This GroEL homologue is found in the SAM of A. actinomycetemcomitans but is not found in the osteolytically active SAM from other Gram-negative or Gram-positive bacteria. The GroEL protein from E. coli, but not from Mycobacterium tuberculosis and Mycobacterium leprae, also showed activity in the bone resorption assay. We believe this to be the first observation that a molecular chaperone has the capacity to stimulate the breakdown of connective tissue.

Aggregatibacter actinomycetemcomitans↗
PubMed1995

Actin's view of actomyosin interface.

Actomyosin interactions were examined by using yeast actin mutants with alanines replacing charged amino acid pairs D24/D25, E99/E100, D80/D81, and E83/K84. In the in vitro motility experiments, actin filaments of D24A/D25A or E99A/E100A mutants moved in the presence of 0.7% methylcellulose at the velocities of wild-type actin. Without methylcellulose, these mutant filaments, but not the D80/D81 or E83/K84 filaments, dissociated from the assay surface upon addition of ATP. Measurements of myosin subfragment-1 (S1) binding to D24A/D25A- and E99A/E100A-polymerized actins in the presence of ATP revealed a three- and twofold decrease in their binding constant, respectively, compared with wild-type actin. In contrast to this, all monomeric actins had the same binding affinity for S1. The rates and extents of polymerization of D24A/D25A and E99A/E100A actins by S1 were reduced in comparison to wild-type actin. The local structure of subdomain-2 on actin, as probed by subtilisin cleavage, was not altered for either mutant. A twofold decrease in nucleotide exchange was detected for the D24A/D25A mutant actin. These results demonstrate the involvement of the D24/D25 and E99/E100 residues in the weak binding of myosin to actin and reveal that residues D80/D81 and E83/K84 do not modulate actomyosin interactions.

Actins↗
PubMed1994

Role of the interdomain hinge of flavocytochrome b2 in intra- and inter-protein electron transfer.

The two distinct domains of flavocytochrome b2 (L-lactate:cytochrome c oxidoreductase, EC 1.1.2.3) are connected by a hinge peptide. Kinetics experiments [White, P., Manson, F. D. C., Brunt, C. E., Chapman, S. K., & Reid, GA. (1993) Biochem. J. 291, 89-94] have illustrated the importance for efficient interdomain electron transfer of maintaining the structural integrity of the hinge. To probe the role of the hinge in a more subtle manner, we have constructed a mutant enzyme, H delta 3, which has a three amino acid deletion in the hinge region. Intra- and inter-protein electron transfer within H delta 3 flavocytochrome b2 and the H delta 3:cytochrome c redox complex was investigated by steady-state and stopped-flow kinetics analysis. The H delta 3 mutant enzyme remains a good L-lactate dehydrogenase, as is evident from steady-state experiments with ferricyanide as electron acceptor (40% less active than wild-type enzyme) and stopped-flow experiments monitoring flavin reduction (15% less active than wild-type enzyme). The global effect of the deletion is to lower the enzyme's effectiveness as a cytochrome c reductase. This property of the H delta 3 enzyme is manifested at two electron-transfer steps on the catalytic cycle of flavocytochrome b2. First, the rate of heme reduction has fallen 5-fold in H delta 3 compared with the wild-type enzyme (from 445 to 91 s-1), due to poor interdomain electron transfer from flavin to heme.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Schizophrenics have fewer and smaller P300s: a single-trial analysis.

Because P300 is typically measured from an average of single trials, variations among individual trials may account for P300 amplitude reduction so often seen in patients with schizophrenia. We tested three hypotheses regarding single-trial contribution to small average P300s in schizophrenics: normal P300s are elicited on some trials and no P300s on others, all trials have consistently small P300s, or P300 latency varies over trials. Nineteen schizophrenics and 35 controls were tested on a two-tone auditory oddball event-related potential (ERP) paradigm. ERPs recorded from the parietal electrode (Pz) were subjected to a P300-screening procedure in which a 2 Hz half-sine wave template was moved across the electroencephalogram (EEG) to find the point of best fit. If, for the point of best fit, the EEG:Template covariance was greater in the signal epoch (280-600 msec) than in the noise epoch (610-930 msec), and if the EEG:Template correlation was statistically significant, the trial passed the P300-screen and was deemed to have a P300. Three types of average ERPs were constructed: Traditional Average from all good (artifact-free, correct response) trials, P300-Screen Average from all good trials that also passed the P300-screen, and Latency Adjusted Average by aligning the P300-screen trials at the latency of maximum covariance. Traditional average ERPs were significantly smaller in schizophrenics than in controls. The results of the P300-screen confirmed all three hypotheses: schizophrenics had fewer trials passing the P300-screen, smaller P300s on each trial, and P300s that were more variable in latency across trials.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗