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Biomedical subjects

A Watts

Publications and source records attributed to A Watts.

At least 91 records · Page 5Linked to original sources

Measurement error and its impact on the estimated relationship between dust lead and children's blood lead: Members of the Rochester Lead-in-Dust Study Group.

OBJECTIVE: Lead-contaminated house dust is a major contributor to lead intake among urban children, but the reliabilities of various dust lead measurement methods and their impact on the estimated correlations between dust lead and children's blood lead levels are unknown. METHODS: Repeated field measurements of lead-contaminated dust from children's homes were taken from 16 housing units using five dust lead measurement methods. Estimates of measurement error were used to obtain reliability ratios for the dust lead measurements, which were then used to correct estimated correlations between lead-contaminated dust and children's blood lead. RESULTS: Reliability varied over methods and surface types (from 0.0 to 0.8), but wipe loading and the BRM vacuum loading methods generally had greater reliability. Technician effects, inadvertent field exposure to lead, contamination of collection equipment, and laboratory instrument error were found to contribute little to total measurement error. Corrected correlations between blood lead and wipe loading measurements were 7 to 104% higher than uncorrected correlations. The multiple R2 and partial R2 for a wipe composite measurement in a multivariate regression model increased from 0.43 to 0.64 and from 0.053 to 0.26, respectively, after correction for measurement error bias. CONCLUSIONS: Variation in lead deposition within small areas and variations in collection inherent to the devices are major contributors to measurement error. Measurement error causes dramatic underestimation of correlation between lead-contaminated house dust and children's blood lead.

Air Pollution, Indoor↗

Phospholipid headgroup dynamics in DOPG-d5-cytochrome c complexes as revealed by 2H and 31P NMR: the effects of a peripheral protein on collective lipid fluctuations.

The dynamics of the glycerol headgroup of dioleoylphosphatidylglycerol (DOPG) in hydrated bilayers were studied by 2H and 31P NMR spectroscopy, and the effects of binding a peripheral protein, cytochrome c, were evaluated. The fast headgroup segmental motions (tau c, 10(-10)-(-13) s) of DOPG in fully hydrated bilayers were not affected upon binding of cytochrome c, as evaluated by the spin-lattice (T1) relaxation of deuterons in the DOPG glycerol headgroup. In contrast, the spin-spin (T2e) relaxation is strongly affected, indicating that slow cooperative bilayer motions (tau c, 10(-3)-10(-6) s) are enhanced upon the interaction with cytochrome c, 2H and 31P NMR spectral lineshape analysis reveal details of the nature of these motions. The importance of these effects are discussed in terms of a possible mechanism for modulating membrane-associated processes.

Cytochrome c Group↗

Protein conformational distortions induced by membrane interfacial interactions.

It is clear that considerable conformational distortions may occur in peripheral proteins on interaction with anionic lipid bilayers. Specific lipid interactions do occur at least in the case of cytochrome c, and each perturbation and interaction may well take place before insertion into, or translocation across, a biomembrane.

Animals↗

The relationship between overnight GH levels and insulin concentrations in adolescents with insulin-dependent diabetes mellitus (IDDM) and the impact of recombinant human insulin-like growth factor I (rhIGF-I).

OBJECTIVE: We examined the relationship between GH concentrations and free insulin concentrations, used as an index of insulin sensitivity, before and after recombinant human insulin-like growth factor I (RhIGF-I) administration in adolescents with insulin-dependent diabetes mellitus (IDDM). DESIGN AND PATIENTS: Growth hormone concentrations were assessed by a peak detection programme (Pulsar) on a control night (2000 h-0800 h) and a night when rhIGF-I administered in a subcutaneous dose of 40 micrograms/kg at 1800 h to 16 adolescent subjects. Stable euglycaemia was maintained by a continuous intravenous insulin infusion and changes in free insulin levels on the two nights were compared with growth hormone data. RESULTS: Mean overnight GH concentrations (2000 h-0800 h) on the control night were positively related to glycated haemoglobin (Hba1) concentrations (r = 0.63; P < 0.01) and were reduced following rhIGF-I administration (24.9 +/- 3.6 mU/I on the control night versus 17.4 +/- 2.2 mU/I after administration, P = 0.01). The mean GH pulse amplitude on the control night was related to the change in GH levels after rhIGF-I (rs = -0.66, P < 0.001). Multiple regression analysis revealed that mean GH pulse amplitude was the only determinant of free insulin concentrations (0500 h-0700 h on both study nights (P < 0.01). The percentage change in mean growth hormone pulse amplitude between the two nights was related to the percentage reduction in free insulin concentrations (r = 0.53, P = 0.03). CONCLUSIONS: Growth hormone pulse amplitude is related to early morning insulin sensitivity in adolescents with IDDM on control nights and after rhIGF-I administration. The reduction in insulin levels following rhIGF-I may be linked to the change in GH pulse amplitude and not just to direct insulin-like actions. Individuals with the higher GH (and thus HbA1 levels) were most sensitive to the GH-suppressive effects of rhIGF-I.

Adolescent↗

Community-based post-operative follow-up visit after major surgery for benign gynaecological conditions: a prospective study.

The time from surgery to discharge after major procedures for benign gynaecological conditions continues to fall. This small prospective study was undertaken to assess the postoperative problems encountered by patients after gynaecological surgery for a variety of benign disorders, and the potential of the 6-week surgical follow-up to be performed by the patient's family doctor rather than the hospital. The patients' and doctors' satisfaction with such care was determined. The study showed that follow-up in the community was acceptable to both patient and doctor. When problems arose after discharge most patients ( 50%) contacted their family doctor. At the 6-week visit few had physical problems, though most (58-100% depending on the Group) felt that a 6-week follow-up was required. Six-week postoperative follow-up by the family doctor is acceptable, and could permit more effective use of hospital specialists, though would increase the workload of family doctors.

Journal Article↗

Effect of cholesterol on rhodopsin stability in disk membranes.

The effect of cholesterol on rhodopsin stability has been investigated in intact disk membranes. Because cholesterol readily equilibrates between membranes, the disk membrane cholesterol content can be altered by incubation with cholesterol/phospholipid vesicles. The effect of membrane cholesterol on rhodopsin was investigated using three independent techniques: thermal bleaching, differential scanning calorimetry (DSC) and activation of the cGMP cascade. Rhodopsin exhibited an increased resistance to thermally induced bleaching as the membrane cholesterol level was increased. DSC also indicated that the protein is stabilized by cholesterol in that the Tm increased in response to higher membrane cholesterol. A similar degree of stabilization was observed in both the unbleached and bleached states in the DSC experiments. These results suggest that cholesterol affects the disk membrane properties such that thermally induced unfolding is inhibited, thus stabilizing the rhodopsin structure. Furthermore, high membrane cholesterol inhibited the activation of the cGMP cascade. This is consistent with the stabilization of the metarhodopsin I photointermediate relative to the metarhodopsin II intermediate.

Animals↗

Asymmetric and functional reconstitution of band 3 into pre-formed phosphatidylcholine vesicles.

Human erythrocyte band 3 protein was purified in 0.1% Triton X-100 and reconstituted into pre-formed phosphatidylcholine vesicles by a Triton X-100-mediated procedure [1]. Band 3 (and its transmembrane domain) could be asymmetrically reconstituted into phosphatidylcholine vesicles with retention of sulfate transport activity which showed behaviour characteristic of red cell anion transport in response to pH, H2DIDS and temperature. Successful reconstitution was also possible using high mol ratios of band 3/phosphatidylcholine (1:200), which are not achieved by any other method.

Anion Exchange Protein 1, Erythrocyte↗

Spin label and 2H-NMR studies on the interaction of melanotropic peptides with lipid bilayers.

The interaction of the cationic tridecapeptide alpha-melanocyte stimulating hormone (alpha-MSH) and the biologically more active analog [Nle4, DPhe7]-alpha-MSH with lipid membranes was investigated by means of ESR of spin probes incorporated in the bilayer, and NMR of deuterated lipids. All spin labels used here, stearic acid and phospholipid derivatives labeled at the 5th and 12th position of the hydrocarbon chain, and the cholestane label, incorporated into anionic vesicles of DMPG (1,2-dimyristoyl-sn-glycero-3-phosphoglycerol) in the liquid-crystalline phase, indicated that both peptides decrease the motional freedom of the acyl chains. No peptide effect was detected with neutral lipid bilayers. Changes in the alpha-deuteron quadrupolar splittings and spin lattice relaxation time of DMPG deuterated at the glycerol headgroup paralleled the results obtained with ESR, showing that the peptides cause a better packing both at the headgroup and at the acyl chain bilayer regions. The stronger effect caused by the more potent analog in the membrane structure, when compared to the native hormone, is discussed in terms of its larger lipid association constant and/or its deeper penetration into the bilayer.

Amino Acid Sequence↗

Hydrodynamic examination of the dimeric cytoplasmic domain of the human erythrocyte anion transporter, band 3.

Solution studies of the cytoplasmic domain (molecular mass approximately 40kDa) of band 3, the anion exchanger from human erythrocyte membranes, previously suggested a dimeric molecule on the basis of the relative techniques of calibrated gel filtration and calibrated preparative ultracentrifugation. This dimeric behavior is firmly established on an absolute basis by a combination of calibrated gel chromatography and absolute ultracentrifugation techniques. Sedimentation velocity in the analytical ultracentrifuge combined with calibrated gel chromatography give a molecular mass M of (77 +/- 4) kDa, a value confirmed by low-speed sedimentation equilibrium. Velocity sedimentation in the analytical ultracentrifuge gave a single sedimenting species with an s o 20,w of (3.74 +/- 0.07)S. Sedimentation equilibrium analysis was also used to establish the strength of the binding via the dissociation constant Kd, with a value from direct fitting of the concentration distribution curves of (2.8 +/- 0.5) microM, confirmed by a value of approximately 3 microM obtained from fitting a plot of molecular weight Mw,app versus cell loading concentration. Hydrodynamic calculations based on the classical translational frictional ratio showed that the protein was highly asymmetric, with an axial ratio of approximately 10:1, consistent with observations from electron microscopy.

Anion Exchange Protein 1, Erythrocyte↗

Serum insulin-like growth factor II levels in normal adolescents and those with insulin dependent diabetes mellitus.

OBJECTIVE: Unlike IGF-I and its principal binding proteins, data regarding IGF-II levels have not been well defined in normal subjects and those with insulin-dependent diabetes mellitus (IDDM). We have therefore measured IGF-II, as well as IGF-I, and IGFBP-3, levels in a large cohort of subjects with IDDM and in age/sex matched controls. PATIENTS: One hundred and fourteen patients with IDDM (57 males, 57 females) and 89 control subjects (49 males, 40 females). MEASUREMENTS: Random blood samples were obtained from each subject for the measurement of IGF-II, IGF-I and IGFBP-3 levels. RESULTS: Mean values of IGF-II (+/- SEM) were 630 (+/- 27.8) micrograms/l and 646 (+/- 32.3) micrograms/l in female and male controls, compared to 569 (+/- 23.3) micrograms/l and 623.3 (+/- 28.1) micrograms/l in female and male diabetics respectively. IGF-II levels did not differ significantly between the sexes or show any change with transition through puberty in either control or diabetic groups. In contrast, IGF-I levels increased through puberty peaking at stages 3-5 in controls (P < 0.001) and G4-5 (P = 0.002) in diabetic males but not females. IGF-I levels in all diabetics were generally lower than in controls, differences reaching significance at G4-5 in males (P = 0.002) and B5 in females (P = 0.002). IGFBP-3 levels did not show any variation with puberty stage in diabetics, in contrast to controls where levels increased, peaking at G4-5 in males (P = 0.001) and B3 in females. IGFBP-3 levels were lower in diabetics of both sexes and at all stages compared to controls (P range 0.047 to < 0.001). Multiple regression analysis revealed significant correlations between IGF-II and IGFBP-3 (F = 20.1, P = < 0.001) and reaffirmed previously observed associations for IGF-I and IGFBP-3. The sum of IGF-I and IGF-II (expressed as nmol/l) correlated with IGFBP-3; r = 0.47 in controls and 0.60 in diabetics. CONCLUSIONS: Insulin-dependent diabetes mellitus is not associated with any significant changes in IGF-II levels during puberty. The binding of IGFBP-3 for both IGF-I and IGF-II is unaltered by insulin-dependent diabetes mellitus.

Adolescent↗

The conformations of a functional spin-labeled derivative of gastric H/K-ATPase investigated by EPR spectroscopy.

A spin-labeled derivative of porcine gastric H/K-ATPase with high ATP hydrolyzing activity (77 mumol of Pi/(mg.h)) has been prepared. Over 65% of initial ATPase activity (115 mumol of Pi/(mg.h)) was preserved after complete reaction of the enzyme with the lysine reactive nitroxide spin-labeled TEMPO isothiocyanate (TITC). In contrast, rapid and complete loss of ATPase activity occurred after reaction of the enzyme with the lysine directed fluorescent probe FITC. Conventional EPR spectra of TITC labeled H/K-ATPase reflected mainly the slow rotational diffusion of the enzyme in the membrane. An upper limit enzyme intramembranous radius of 108 A was calculated on the basis of rotational correlation times estimated from saturation transfer (ST) EPR spectral lineshapes. Conventional EPR spectra exhibited two major components corresponding to at least two populations of strongly constrained spin-labels. Difference spectroscopy revealed that the proportion of these two components changed markedly with temperature. Moreover, the proportion of the components was sensitive to the presence of the activating ionic ligands Mg2+ and ATP, which induce enzyme conformational transitions, and to the reversible inhibitor SCH 28080, which binds to the K+ sensitive form of the enzyme. These findings show that EPR spectroscopy is able to report functionally coupled conformational changes of gastric H/K-ATPase and imply that the spin-labels are attached to lysines within functionally important regions of the enzyme.

Animals↗

Effect of the C-terminal proline repeats on ordered packing of squid rhodopsin and its mobility in membranes.

Negative stain electron microscopy and saturation transfer electron spin resonance spectroscopy have been used to compare the lattice ordering and in-plane membrane mobility of full-length and C-terminally cleaved squid rhodopsin. The C-terminus of squid rhodopsin contains a negatively charged region followed by 9-10 repeats of a proline-rich sequence, not found in rhodopsins other than those of cephalopod invertebrates, but similar proline repeats are found in other, unrelated membrane proteins. We find that the proline repeats cluster the rhodopsins into small groups, interfering with two-dimensional crystallization and maintaining their mobility in the membrane.

Animals↗

Physiological changes after Delorme's procedure for full-thickness rectal prolapse.

Anal sphincter pressures, rectal compliance and sensation in 19 women of mean age 77 (range 57-94) years were studied before and after Delorme's procedure for full-thickness rectal prolapse. No patient had significant problems with defaecation after operation. There were no significant changes in anal sphincter pressures but the volume of first rectal sensation decreased from a median of 140 ml before surgery to 65 ml after the procedure (P = 0.01) and the maximum tolerated rectal volume declined from a median of 249 ml to 120 ml (P = 0.001). Rectal compliance was reduced from a median of 142.9 ml/kPa to 12.2 ml/kPa (P = 0.002). Improved rectal sensation and lowered compliance are associated with a reduced incidence of defaecatory problems after Delorme's procedure.

Aged↗

Initial stages in the development of valid criteria for the replacement of amalgam restorations.

OBJECTIVES: Replacement amalgam restorations account for the largest single cost in the General Dental Services in Scotland. There is little practical advice available to practitioners on the maintenance and replacement of amalgam restorations. A distance learning package is being prepared for distribution to general dental practitioners in Scotland and this paper describes the initial stages in the development of the policy statements for the proposed package. METHODS: In the first stage proposals are being developed by a panel of dental academics using a modified Delphi technique. This technique is designed to produce a consensus view. Seventeen statements have been set out by the expert group. RESULTS AND CONCLUSIONS: While agreement was rapidly reached that 'ditching' of amalgam restoration margins did not justify their replacement and that repair was preferable to total replacement, some difficulty was experienced in arriving at a consensus view on the correct management of 'white spot' lesions at restoration margins and dentinal staining adjacent to amalgam restorations. The next stage in the development will be to present these statements to a selected panel of general dental practitioners and to develop their consensus view of the proposals, again using the Delphi technique.

Delphi Technique↗