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J P Williams

Publications and source records attributed to J P Williams.

At least 19 recordsLinked to original sources
PubMed2006

Influence of the parathyroid glands on bone metabolism.

Bone is a classic target tissue for parathyroid hormone (PTH), whose calciotropic effect is mediated largely via catabolic actions on this tissue. Paradoxically, PTH also exerts anabolic actions, with intermittent injections of PTH or its amino-terminal fragments causing an increase in bone formation and bone mass, actions that form the basis for the use of PTH in the treatment of osteoporosis. Besides vitamin D, PTH is the only other known bone anabolic agent. High-affinity PTH receptors (PTH-1R) have been detected on osteoblasts and osteoclasts (albeit in lower numbers). Bone turnover, which includes activation of osteoclasts and osteoblasts, appears to be best reflected not by absolute concentrations of PTH (which can vary based on the assay and antibody used) but by a balance of circulating full-length PTH-(1-84) and amino-terminally truncated C-PTH fragments. When PTH-(1-84) is predominant, bone turnover is promoted. Among PTH fragments, PTH-(7-84) appears to be the most potent antagonist of PTH-(1-84). The mechanisms involved in these effects are unclear although mediation via unique C-terminal receptors has been suggested. We propose that, within the range of total PTH (100-1000 pg mL(-1)), the ratio of PTH-(1-84)/C-PTH fragment is a valuable tool for diagnosis of bone turnover. Data indicate that at PTH levels < 100-150 pg mL(-1) and > 1000 pg mL(-1), the ratio looses its predictive power. Assay type, patient characteristics (race, underlying renal disease) and treatment attributes (vitamin D, corticosteroids, phosphate binders) have an impact on the PTH ratio, and care should be used in interpreting assay results and making subsequent treatment decisions.

Bone and Bones↗
PubMed2005

Impairment of sustained attention after major gynaecological surgery.

BACKGROUND AND OBJECTIVES: The sustained attention to response task (SART) test is a sensitive indicator of deficits in sustained attention and is simple to perform. Sustained attention is impaired for a short period after minor surgery under general anaesthesia but the magnitude and duration of this effect after major surgery is unknown. We used the SART test to investigate deficits in sustained attention in patients undergoing major surgery under general anaesthesia. METHODS: The SART test was completed before surgery and at 24, 48 and 72 h postoperatively by 20 ASA I-II female patients (mean age 48.6 yr) undergoing total abdominal hysterectomy under general anaesthesia. It was also completed by 20 age-matched female controls at similar time intervals to evaluate the effect of repeated test performance. RESULTS: There was a significant (P < 0.05) interaction between the groups in number of errors made (a measure of sustained attention deficit). The number of errors decreased in control subjects on repeated performance of the SART test but remained unchanged in patients undergoing total abdominal hysterectomy. The differences between groups remained significant after 72 h (P < 0.05). Patients' overall response times slowed significantly at 24-48 h (P < 0.05), but this recovered by 72 h after surgery. In contrast, overall response times in the control group tended to accelerate on repeated performance of the SART. CONCLUSIONS: The results of this study suggest that 72 h following major surgery patients have deficits in sustained attention compared with controls. Control subjects demonstrated a marked learning effect on repeated test performance compared with patients.

Anesthesia Recovery Period↗
PubMed2003

Differential effects of calmodulin and protein kinase C antagonists on bone resorption and acid transport activity.

Tamoxifen inhibits bone resorption by disrupting calmodulin-dependent processes. Since tamoxifen inhibits protein kinase C in other cells, we compared the effects of tamoxifen and the PKC inhibitor, bis indolylmaleimide II (bIM), on bone resorption and acid transport activity in isolated membrane vesicles. Bis indolylmaleimide inhibited bone resorption 50% with an IC50 approximately 3 microM, as well as acid transport activity in a concentration -dependent manner with an IC50 of approximately 0.4 IM. The IC50 of bIM for inhibiting acid transport activity was similar to that of calmodulin antagonists. The potassium ionophore, valinomycin, failed to restore bIM or tamoxifen-dependent inhibition of acid transport, suggesting that bIM and tamoxifen both inhibit H(+)-ATPase activity. Half maximal inhibitory concentrations of tamoxifen and bIM were not additive in acid transport assays, suggesting different sites of action. Furthermore, exogenous calmodulin blocked tamoxifen, but not bIM, -dependent inhibition of acid transport. We also compared the effects of tamoxifen and bIM on phosphorylation of proteins in isolated membrane fractions as determined by 32P incorporation and autoradiography. Tamoxifen had no effect on protein phosphorylation in contrast to bIM, which inhibited phosphorylation of eight proteins with different apparent kinetics. The data suggest that, while tamoxifen and bIM both affect H(+)-ATPase activity, the mechanisms of action are different.

Acridine Orange↗
PubMed2002

Increasing Plasmodium falciparum malaria in southwest London: a 25 year observational study.

AIMS: To identify changes in the presenting number and species of imported malaria in children in southwest London. METHODS: A prospective single observer study over 25 years (1975-99) of all cases of paediatric malaria seen at St George's Hospital. RESULTS: A confirmed diagnosis was made in 249 children (56% boys; 44% girls; median age 8.0 years). Of these, 53% were UK residents and 44% were children travelling to the UK. A significant increase was noted in the number of cases over the 25 years (1975-79: mean 4.8 cases/year; 1990-99: mean 13.7 cases/year). Over the 25 years Plasmodium falciparum was seen in 77%, P vivax in 14%, P ovale in 6%, and P malariae in 3% of cases. P falciparum had increased in frequency (1975-79: P falciparum 50%, P vivax 50%; 1990-99: P falciparum 82%, P vivax 6%), associated with an increase in the proportion of children acquiring their infection in sub-Saharan Africa. Median time between arrival in the UK to the onset of fever was: P falciparum, 5 days; P ovale, 25 days; P malariae, 37 days; and P vivax, 62 days. Median time interval between the onset of fever to commencement of treatment was 4 days. This had not improved over the 25 year period. Only 41% of UK resident children presenting to hospital had taken prophylaxis and the overall number of symptomatic children taking no prophylaxis was increasing. CONCLUSION: Imported childhood P falciparum malaria is increasing in southwest London associated with increasing travel from sub-Saharan Africa. Over the 25 year period there has been no improvement in chemoprophylaxis rates or time to diagnosis.

Adolescent↗
PubMed2001

Dielectrophoretic assembly of electrically functional microwires from nanoparticle suspensions.

A new class of microwires can be assembled by dielectrophoresis from suspensions of metallic nanoparticles. The wires are formed in the gaps between planar electrodes and can grow faster than 50 micrometers per second to lengths exceeding 5 millimeters. They have good ohmic conductance and automatically form electrical connections to conductive islands or particles. The thickness and the fractal dimension of the wires can be controlled, and composite wires with a metallic core surrounded by a latex shell can be assembled. The simple assembly process and their high surface-to-volume ratio make these structures promising for wet electronic and bioelectronic circuits.

Journal Article↗
PubMed2001

Engineering salt-tolerant Brassica plants: characterization of yield and seed oil quality in transgenic plants with increased vacuolar sodium accumulation.

Transgenic Brassica napus plants overexpressing AtNHX1, a vacuolar Na(+)/H(+) antiport from Arabidopsis thaliana, were able to grow, flower, and produce seeds in the presence of 200 mM sodium chloride. Although the transgenic plants grown in high salinity accumulated sodium up to 6% of their dry weight, growth of the these plants was only marginally affected by the high salt concentration. Moreover, seed yields and the seed oil quality were not affected by the high salinity of the soil. Our results demonstrate the potential use of these transgenic plants for agricultural use in saline soils. Our findings, showing that the modification of a single trait significantly improved the salinity tolerance of this crop plant, suggest that with a combination of breeding and transgenic plants it could be possible to produce salt-tolerant crops with far fewer target traits than had been anticipated.

Journal Article↗
PubMed2001

The nitric oxide-induced reduction in cardiac energy supply is not due to inhibition of creatine kinase.

OBJECTIVES: While nitric oxide (NO) is a potent vasodilator already in the nM range, a cGMP-independent negative inotropic effect is observed at higher concentrations. Since inhibition of creatine kinase (CK) by NO-induced nitrosylation has been proposed as a possible mechanism of action, we measured the flux through CK in the intact heart. METHODS: In saline perfused, paced guinea pig hearts 31P NMR spectroscopy was employed to directly assess the cardiac energy status, i.e. free energy of ATP hydrolysis (DeltaG(ATP)) and flux through CK using magnetization transfer in absence and presence of NO. RESULTS: NO (50 microM) doubled coronary flow and induced a rapid drop in left ventricular developed pressure (39+/-10 vs. 81+/-10 mmHg) and MVO(2) (1.3+/-0.8 vs. 3.7+/-0.5 micromol/min/g) (n=7). This effect was associated with an immediate decrease in phosphocreatine (PCr) (-69%) and DeltaG(ATP). During the subsequent 35 min of NO infusion cardiac function and MVO(2) remained depressed, while PCr partially recovered. NO had no effect on the unidirectional forward flux through CK (98 +/- 21 vs. 99 +/- 20 micromol/min/g, n=7) which was 5- to 10-fold greater than the rate of ATP turnover. Upon cessation of NO infusion both cardiac function and PCr rapidly returned to baseline values. The NO-induced fall in the myocardial energy status was associated with an increase in mitochondrial NADH (n=7) as assessed by surface fluorescence. The observed change in fluorescence was similar to that observed with short term ischemia. CONCLUSION: The NO-mediated depression of myocardial function, MVO(2) and energy status is not mediated by changes in CK flux. Most likely a partial blockade of mitochondrial oxidative phosphorylation at the level of cytochrome c oxidase is responsible for this effect.

Animals↗
PubMed2001

Osteoclasts secrete the chemotactic cytokine mim-1.

Osteoclasts are terminally differentiated, multinucleated cells of monocytic origin. In this study, we report that osteoclasts secrete a 35 kD protein and that phorbol myristate acetate treatment stimulates secretion dramatically. Peptide digests of the protein were analyzed by mass spectroscopy. The protein was identified as myb induced myeloid protein-1 precursor (mim-1 protein). Mim-1 is expressed specifically by hematopoietic cells and has no known function. It is homologous with the neutrophil chemokine, chondromodulin II, which stimulates proliferation of osteoblasts and chondrocytes. Western analysis showed that osteoclasts secrete mim-1 into culture media. Immunofluorescence studies demonstrated a cytoplasmic and perinuclear distribution of mim-1 in both avian osteoclasts and human osteoclast-like cells. Expression and secretion of a chemokine-like protein by osteoclasts suggests a novel signaling pathway in the bone microenvironment that may be involved in coordinating bone remodeling.

Acetyltransferases↗
PubMed2001

External beam irradiation for inhibition of intimal hyperplasia following prosthetic bypass: preliminary results.

To determine whether external beam irradiation delivered immediately after graft implantation can inhibit anastomotic intimal hyperplasia (IH) 1 month following polytetrafluoroethylene (PTFE) bypass in a sheep carotid artery model, 23 sheep underwent bilateral bypass of the ligated common carotid artery with 8-mm PTFE immediately followed by a single dose of irradiation (15, 21, or 30 Gy) to one side. The 15 animals with bilaterally patent grafts were euthanized at 1 month and graft-arterial anastomoses harvested. Using computer-aided image analysis, IH areas and thicknesses were measured. Graft patency in this model was 83% at 1 month and did not differ according to treatment administered. In the control animals, IH was greatest at mid-anastomosis, but minimal within the native vessel. All three radiation doses markedly inhibited mid-anastomotic IH area and thickness. At the proximal anastomosis, 30 Gy reduced the IH area 20-fold, from 2.06 to 0.14 mm2 (p < 0.0001 by ANOVA), and IH thickness 70-fold, from 29.0 to 0.4 micron (p < 0.0002); similar effects were seen at the distal anastomosis. No adverse effects of radiation treatment were observed. External beam irradiation in doses of 15 to 30 Gy delivered in a single fraction immediately after operation markedly inhibits development of intimal hyperplasia 1 month following end-to-side anastomosis with PTFE in sheep.

Animals↗
PubMed2001

Minimally invasive coronary bypass without general endotracheal anesthesia.

This report describes the case of a 51-year-old man with myocardial ischemia resulting from in-stent restenosis of the left anterior descending coronary artery who underwent a minimally invasive direct coronary artery bypass using thoracic epidural analgesia while awake, without general endotracheal anesthesia.

Anesthesia, Endotracheal↗
PubMed2001

Effect of energy restriction and exercise on vitamin B-6 status of women during lactation.

PURPOSE: Lactation increases vitamin B-6 requirements because its concentration in breast milk is related to maternal intake and it is essential for infants. Exercise may also increase the requirement because it increases utilization and excretion of vitamin B-6. Therefore, the purpose of this study was to determine whether energy restriction and exercise affected vitamin B-6 status of lactating women. METHODS: Breastfeeding women with a body mass index > or = 25 and < or = 30 kg x m(-2) were randomly assigned at 4 wk postpartum to either restrict energy intake by 500 kcal x d(-1) and exercise for 45 min x d(-1), 4 d x wk(-1) (weight loss group, WG) or maintain usual diet and not exercise (control group, CG) for 10 wk. Women were given a supplement containing 2.0 mg of vitamin B-6. Measurements included vitamin B-6 concentrations in breast milk and plasma, plasma pyridoxal 5'-phosphate, and erythrocyte alanine aminotransferase activity. RESULTS: The WG lost more weight (-4.4 +/- 0.4 vs -0.9 +/- 0.5 kg, P < 0.01) than the CG. Cardiovascular fitness increased by 12% in the WG, compared to 3% in the CG (P = 0.09). Milk vitamin B-6 concentrations increased in both groups (161 +/- 107 and 191 +/- 85 nmol x L(-1), WG and CG, respectively, P = 0.05). There were no significant differences in other vitamin B-6 parameters. Weight and length gain (2.06 +/- 0.21 and 1.83 +/- 0.17 kg; 8.6 +/- 0.6 and 7.2 +/- 0.5 cm; WG and CG, respectively) of infants was not significantly different between groups. CONCLUSIONS: Energy restriction and exercise from 4 to 14 wk postpartum in overweight, breastfeeding women consuming adequate dietary intakes and 2.0 mg of supplemental vitamin B-6 does not adversely affect vitamin B-6 status or infant growth.

Adult↗
PubMed2000

Effect of a neuronal sodium channel blocker on magnetic resonance derived indices of brain water content during global cerebral ischemia.

Diffusion-weighted magnetic resonance imaging (DWI) with calculation of the apparent diffusion coefficient (ADC) of water is a widely used noninvasive method to measure movement of water from the extracellular to the intracellular compartment during cerebral ischemia. Lamotrigine, a neuronal Na(+) channel blocker, has been shown to attenuate the increase in extracellular concentrations of excitatory amino acids (EAA) during ischemia and to improve neurological and histological outcome. Because of its proven ability to reduce EAA levels during ischemia, lamotrigine should also minimize excitotoxic-induced increases in intracellular water content and therefore attenuate changes in the ADC. In this study, we sought to determine the effect of lamotrigine on intra- and extracellular water shifts during transient global cerebral ischemia. Fifteen New Zealand white rabbits were anesthetized and randomized to one of three groups: a control group, a lamotrigine-treated group, or a sham group. After being positioned in the bore of the magnet, a 12-min 50-s period of global cerebral ischemia was induced by inflating a neck tourniquet. During ischemia and early reperfusion there was a similar and significant decrease of the ADC in both the lamotrigine and control group. The ADC in the sham ischemia group remained at baseline throughout the experiment. Lamotrigine-mediated blockade of voltage-gated sodium channels did not prevent the intracellular movement of water during 12 min 50 s of global ischemia, as measured by the ADC, suggesting that the ADC decline may not be mediated by voltage-gated sodium influx and glutamate release.

Animals↗
PubMed2000

Calmodulin and HIV type 1: interactions with Gag and Gag products.

The level of calmodulin increases in cells expressing HIV-1 envelope glycoprotein. Although a calmodulin increase is bound to alter many cellular metabolic and signaling pathways, the benefits to the virus of these alterations must be indirect. However, the possibility exists that increased cellular calmodulin benefits the virus by directly associating with nonenvelope viral proteins. We have, therefore, investigated whether calmodulin can interact with HIV structural proteins Gag, p17, and p24. Calmodulin binds Gag and p17 but not p24 in (125)I-labeled calmodulin overlays of SDS-polyacrylamide gels. Removal of calcium by addition of EGTA eliminates this binding. A computer algorithm for predicting helical regions that should bind calmodulin predicts that there are two calmodulin-binding regions near the N terminus of p17. Intrinsic tryptophan fluorimetry shows that two peptides, each of which includes one of the predicted regions, bind calmodulin: p17(11-25) binds calmodulin with a 2-to-1 stoichiometry and dissociation constant of approximately 10(-9) M(2), and p17(31-46) also binds calmodulin with a dissociation constant of about 10(-9) M. These binding sites are nearly contiguous, forming an extended calmodulin-binding domain p17(11-46). In H-9 cells, Gag and calmodulin colocalize within the resolution of confocal light microscopy.

Amino Acid Sequence↗
PubMed2000

The role of phosphatidylcholine in fatty acid exchange and desaturation in Brassica napus L. leaves.

The role of phosphatidylcholine (PC) in fatty acid exchange and desaturation was examined and compared with that of monogalactosyldiacylglycerol (MGDG) in Brassica napus leaves using (14)C-labelling in vivo. Data are presented which indicate that in the chloroplast newly formed saturated (palmitic acid, 16:0) and monounsaturated (oleic acid, 18:1) fatty acid is incorporated into MGDG and desaturated in situ. In the non-plastidic compartments, however, newly formed fatty acid is exchanged with polyunsaturated fatty acid in PC, the probable major site of subsequent desaturation. The unsaturated fatty acid is released to the acyl-CoA pool, which is then used to synthesize diacylglycerol (DAG) containing a high level of unsaturated fatty acid. This highly unsaturated DAG may be the source for the biosynthesis of other cellular glycerolipids. The generally accepted pathway in which PC is synthesized from molecular species of DAG containing 16:0 and 18:1 followed by desaturation of the 18:1 to linoleic (18:2) and linolenic (18:3) acids is questioned.

Brassica↗
PubMed2000

The effect of weight loss in overweight, lactating women on the growth of their infants.

BACKGROUND: The retention of weight gained during pregnancy may contribute to obesity. Lactation should promote weight loss, but weight loss is highly variable among lactating women. The risks associated with the restriction of energy intake during lactation have not been adequately evaluated. The purpose of this study was to determine whether weight loss by women during lactation affects the growth of their infants. METHODS: We randomly assigned 40 breast-feeding women who were overweight (defined as a body-mass index [the weight in kilograms divided by the square of the height in meters] of 25 to 30) at 4 weeks post partum either to restrict their energy intake by 500 kcal per day and to exercise for 45 minutes per day for 4 days per week (the diet-and-exercise group) or to maintain their usual dietary intake and not exercise more than once per week for 10 weeks (the control group). We measured the weight and fat mass of the women and the weight and length of the infants before, during, and at the end of the study period. RESULTS: The mean (+/-SD) energy intake decreased by 544+/-471 kcal per day in the diet-and-exercise group. As compared with the control group, the women in the diet-and-exercise group lost more weight (4.8+/-1.7 kg vs. 0.8+/-2.3 kg, P<0.001) and fat mass (4.0+/-2.0 kg vs. 0.3+/-1.8 kg, P<0.001). The gains in weight and length of the infants whose mothers were in the diet-and-exercise group (1925+/-500 g and 7.8+/-2.0 cm, respectively) were not significantly different from those of the infants whose mothers were in the control group (1861+/-576 g and 7.3+/-1.7 cm). CONCLUSIONS: Weight loss of approximately 0.5 kg per week between 4 and 14 weeks post partum in overweight women who are exclusively breast-feeding does not affect the growth of their infants.

Adult↗