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Biomedical subjects

G Williams

Publications and source records attributed to G Williams.

At least 181 records · Page 10Linked to original sources
PubMed1999

Urinary excretion of pyridinium crosslinks in healthy 4-10 year olds.

Urinary pyridinoline and deoxypyridinoline, pyridinium crosslinks released during breakdown of mature collagen, might serve as useful markers of bone resorption. Before their role can be identified, reference values must be established. In this study, free pyridinoline (f-Pyr), free deoxypyridinoline (f-DPyr), and creatinine (Cr) were measured in first morning void urine samples from 250 girls and 265 boys between the ages of 4 and 10 years. Overall, there was a decrease in f-Pyr:Cr and f-DPyr:Cr ratios with increasing age in both sexes, but there was a wide range of values for individuals of similar ages. Further studies are required to assess whether urinary pyridinium crosslink excretion is sufficiently deranged in conditions affecting bone metabolism for the measurement of these compounds to be of clinical value.

Age Factors↗
PubMed1999

Growth factor staining patterns in the pig retina following retinal laser photocoagulation.

AIM: To identify changes in growth factor expression in miniature pig retinas following retinal laser photocoagulation. METHODS: Pigs were sacrificed at different times (15 minutes to 42 days) post-laser and the retinas were immunolabelled for basic fibroblast growth factor, insulin-like growth factor I, transforming growth factor beta, epidermal growth factor, transforming growth factor alpha, platelet derived growth factor, vascular endothelial growth factor, and epidermal growth factor receptor. Total mRNA levels were also determined. RESULTS: With the exception of vascular endothelial growth factor, immunoreactivity for all other growth factors studied and epidermal growth factor receptor was observed throughout normal non-lasered control retina, generally being high in the retinal pigment epithelium and low in the neural retina. Changes in growth factor expression following laser photocoagulation were observed only in burn areas and changes were mainly confined to the retinal pigment epithelium and outer nuclear layer. The immunoreactivity within retinal pigment epithelial cells in burn areas was either absent or decreased following laser treatment but returned to normal by 21 days. The immunoreactivity was increased within the outer nuclear layer of burn areas during the healing process but returned to normal by 42 days. Vascular endothelial growth factor immunoreactivity was weak/absent in the normal retina and remained unchanged following laser photocoagulation. Change of total mRNA levels in burn areas during time post-laser was confined to retinal pigment epithelial cells, being low immediately following photocoagulation and returning to normal by 42 days. CONCLUSIONS: These results demonstrate a temporal alteration in growth factor expression and transcriptional activity in the retina following laser photocoagulation.

Animals↗
PubMed1999

Hand vein responses to noradrenaline in normotensive patients with insulin-dependent diabetes mellitus and microalbuminuria: effects of alpha-adrenoceptor blockade with doxazosin.

Nephropathy commonly develops in patients with insulin-dependent (type 1) diabetes. Administration of an antihypertensive agent to type 1 diabetes patients with microalbuminuria, the first clinically detectable stage of nephropathy, can help slow renal deterioration. It is postulated that the exaggerated vasoconstrictor response to noradrenaline seen in these patients may be relevant in the development of microalbuminuria. This open, non-comparative pilot study was designed to investigate the effects of the alpha-adrenoceptor antagonist doxazosin on noradrenaline-induced hand vein vasoconstriction and on albumin excretion in 14 normotensive type 1 diabetes patients with microalbuminuria. After a three-week placebo run-in period, patients received doxazosin (1, 2, and then 4 mg once-daily, at two-week intervals) for six weeks, followed by a two-week placebo washout period. Vasoconstrictor responses to noradrenaline were measured in dorsal hand veins at the end of each two-week period. Hand vein vasoconstrictor responses to noradrenaline decreased significantly, compared with placebo, at 4 mg/day doxazosin (p = 0.006). The mean albumin excretion rate was lower than baseline at all doses of doxazosin, but changes did not reach statistical significance. Doxazosin was generally well-tolerated; four patients (29%) reported mild-to-moderate treatment-related adverse events. This study indicates that alpha 1-adrenoceptor blockade can blunt the exaggerated vascular reactivity to noradrenaline in normotensive type 1 diabetes patients with microalbuminuria, and supports further research into a potential role for doxazosin in preventing the development of diabetic nephropathy.

Adrenergic alpha-Antagonists↗
PubMed1999

Future systems for remote health care.

As the number of elderly people in society increases, the use of technology to support the care system is being examined. However, there is no agreed model of a technology-based health-care system that fully integrates the technical and social aspects to meet the needs of both clients and care providers. This paper examines a possible model from the perspective of both the client and the service provider, and estimates the costs, and hence the potential savings, associated with the introduction of a health-care system based on this model. Cost data are presented in the context of an installation as might be anticipated within a city such as Birmingham, UK. Installation costs of an advanced telecare system would be higher than the set-up costs of conventional systems. Expected savings in control centre costs and emergency services costs would be small. However, a reduction in the average annual length of hospital stay by one day and a reduction in the proportion of elderly people being treated in hospital from 32.4% to 32.0%, directly as a result of the use of advanced telecare, would produce significant savings. A financing scheme with a 5-year or 10-year repayment period would then be financially viable for a 10,000-home advanced telecare system.

Delivery of Health Care↗
PubMed1999

Hypothalamic orexin expression: modulation by blood glucose and feeding.

Orexins (hypocretins), novel peptides expressed in specific neurons of the lateral hypothalamic area (LHA), stimulate feeding when injected intracerebroventricularly. We investigated their role in feeding in the rat by measuring hypothalamic prepro-orexin mRNA levels under contrasting conditions of increased hunger. Prepro-orexin mRNA levels increased significantly after 48 h of fasting (by 90-170%; P < 0.05) and after acute (6 h) hypoglycemia when food was withheld (by 90%; P < 0.02). By contrast, levels were unchanged during chronic food restriction, streptozotocin-induced diabetes, hypoglycemia when food was available, voluntary overconsumption of palatable food, or glucoprivation induced by systemic 2-deoxy-D-glucose. Orexin expression was not obviously related to changes in body weight, insulin, or leptin, but was stimulated under conditions of low plasma glucose in the absence of food. Orexins may participate in the short-term regulation of energy homeostasis by initiating feeding in response to falls in glucose and terminating it after food ingestion. The LHA is known to contain neurons that are stimulated by falls in circulating glucose but inhibited by feeding-related signals from the viscera; orexin neurons may correspond to this neuronal population.

Animals↗
PubMed1999

Altered energy balance causes selective changes in melanocortin-4(MC4-R), but not melanocortin-3 (MC3-R), receptors in specific hypothalamic regions: further evidence that activation of MC4-R is a physiological inhibitor of feeding.

We have examined the effects of underfeeding and obesity on the density of hypothalamic melanocortin MC3 and MC4 receptors (MC3-R and MC4-R, respectively), which may mediate the hypophagic effects of alpha-melanocyte-stimulating hormone (MSH) in the rat. MC3-R and MC4-R were measured by quantitative autoradiography in brain sections using 125I-labeled Nle4-D-Phe7-alpha-MSH (125I-NDP-MSH) and discriminated by masking MC3-R with excess unlabelled gamma2-MSH. High densities of MC4-R occurred in the ventromedial (VMH) and arcuate (ARC) nuclei, median eminence (ME), and medial habenular nucleus (MHb), with lower densities in the dorsomedial hypothalamus (DMH) and forebrain regions. MC3-R were confined to the VMH, ARC, and MHb. After 10-days of food restriction (14% weight loss), density of MC4-R was significantly increased by 20-65% in the VMH, ARC, ME, and DMH, with no changes elsewhere. Similarly, obese (fa/fa) Zucker rats showed 43-98% increases in MC4-R in the same regions. By contrast, rats with diet-induced obesity (18% heavier than controls) showed significantly decreased binding to MC4-R, especially in the VMH, ARC, and ME. MC3-R showed no significant alterations in any model. We suggest that increased density of MC4-R with food restriction and in obese Zucker rats reflects receptor upregulation secondary to decreased release of alpha-MSH, consistent with increased hunger in these models. Conversely, downregulation of MC4-R in diet-induced obesity may indicate increased alpha-MSH secretion in an attempt to limit overeating. This alpha-MSH/MC4-R system may be inhibited by leptin and/or insulin. MC3-R are not apparently involved in regulating feeding.

Animals↗
PubMed1999

The thiazolidinedione rosiglitazone (BRL-49653) lowers blood pressure and protects against impairment of endothelial function in Zucker fatty rats.

Human obesity is associated with insulin resistance, hyperinsulinemia, and a predisposition to hypertension and vascular disease, the origin of which may lie in impairment of endothelial function. We tested the effects of the thiazolidinedione rosiglitazone on blood pressure and endothelial function in insulin-resistant fatty Zucker rats, which display hypertension and abnormal endothelial cell function. We studied fatty Zucker rats given rosiglitazone maleate (50 micromol/kg diet; n = 8) for 9-12 weeks (treated fatty), untreated fatty rats (n = 8), and lean rats (n = 8) given diet alone. At the end of the study, systolic blood pressure was significantly higher in untreated fatty (147 +/- 5 mmHg) than in lean rats (125 +/- 2 mmHg; P < 0.05), but rosiglitazone treatment prevented the development of hypertension in fatty rats (123 +/- 1 mmHg). Fasting hyperinsulinemia in untreated fatty rats (28.7 +/- 6.0 ng/ml) was significantly lowered by rosiglitazone (7.0 +/- 1.4 ng/ml; P < 0.05 vs. untreated fatty), but remained significantly higher than the levels seen in lean rats (1.5 +/- 0.4 ng/ml; P < 0.01). Mesenteric arteries were studied in a myograph. Maximal acetylcholine chloride (1.1 micromol/l)-induced relaxation of norepinephrine hydrochloride (NE)-induced constriction was impaired in untreated fatty (62.4 +/- 3.4%) vs. lean (74.3 +/- 3.5%; P = 0.01) rats; this defect was partially prevented by rosiglitazone (66.5 +/- 3.0%; P = 0.01 vs. untreated fatty). Insulin (50 mU/l) significantly attenuated the contractile response to NE in lean rats (14.7 +/- 3.3%; P = 0.02); this vasodilator effect of insulin was absent in untreated fatty rats at concentrations of 50-5,000 mU/l, but was partially restored by rosiglitazone (9.7 +/- 2.5% attenuation; P = 0.02 vs. no insulin). Thus, rosiglitazone prevents the development of hypertension and partially protects against impaired endothelial function associated with insulin resistance. These latter effects may contribute to the drug's antihypertensive properties.

Acetylcholine↗
PubMed1999

Purification of masked temperature data from humans: some preliminary observations on a comparison of the use of an activity diary, wrist actimetry, and heart rate monitoring.

Fourteen ambulatory subjects, varying in their amount of habitual physical activity, were studied for 24 h during a total of 25 "typical" days. Rectal temperature was recorded every 6 minutes, an activity diary was filled in every half hour, and wrist activity and heart rate were monitored every minute. Actimetry and heart rate data generally showed close parallelism with each other and with the masking effects on body temperature. Psychological stressors such as public speaking produced a greater effect on heart rate and body temperature than on wrist movement, while typing produced high values for wrist movement, but affected heart rate and temperature much less. When data for the circadian rhythm of body temperature were purified, the diary, actimetry, and measurement of heart rate were all useful in reducing masking effects, but the present evidence indicates that heart rate can be more successful than actimetry--as judged by the closeness of the purified data to a sinusoid. This superiority of heart rate monitoring over wrist activity as a method of purification might be because core temperature can be increased by stressor-induced thermogenesis, as well as by physical activity, and because wrist movement can, with some activities, give an inaccurate estimate of the factors that contribute to whole-body thermogenesis.

Adult↗
PubMed1999

Two male patients with ring Y: definition of an interval in Yq contributing to Turner syndrome.

Turner syndrome is thought to result from the haploinsufficiency of genes on the sex chromosomes, but these genes have not been identified yet. We describe two males with deleted ring Y chromosomes, one (TS) with full Turner syndrome and one (DM) without. TS has short stature, skeletal anomalies, lymphogenic obstruction, cardiovascular abnormalities, and miscellaneous features including pigmented naevi, antimongoloid slanting of the palpebral fissures, and widely spaced nipples. In contrast, DM has short stature but no other specific Turner stigmata except high arched palate and a few pigmented naevi. Since little chromosomal mosaicism was detected, the different segments of the Y chromosome retained by these two males identify the location of one or more "anti-Turner" genes. Most of the Yp pseudoautosomal region and Yq were deleted from both patients during the formation of the ring chromosome, while the Y specific portion of Yp and the centromere were retained. The major difference detected was an interval of proximal Yq present in DM and deleted in TS. None of the previously identified genes, DFFRY, DBY, UTY, or TB4Y, lies entirely within this interval, although DFFRY was truncated by DM's breakpoint. These data suggest that one or more additional "anti-Turner" gene(s) remains to be identified in the region of Yq proximal to DFFRY.

Adolescent↗
PubMed1999

Comparable vasorelaxant effects of 17alpha- and 17beta-oestradiol on rat mesenteric resistance arteries: an action independent of the oestrogen receptor.

17beta-Oestradiol (17betaE(2)) has vasorelaxant properties that may contribute to its beneficial cardiovascular effects. The mechanism of vasorelaxation remains controversial, but does not appear to involve interaction of 17betaE(2) with its nuclear receptor. The present study examined the effects on resistance arteries of 17betaE(2) and its isomer, 17alpha-oestradiol (17alphaE(2)), which does not bind to the classical oestrogen receptor. In arteries precontracted with either noradrenaline or KCl, 17betaE(2) and 17alphaE(2) caused comparable relaxation in a concentration-dependent manner over the concentration range 0.1-10 micromol/l, with no significant difference in the maximal effect obtained. Pre-incubation of the arteries with 17betaE(2) or 17alphaE(2) for 15 min reduced the magnitude and duration of the force generated with both noradrenaline and KCl to a comparable degree. Vasorelaxation induced by either 17betaE(2) or 17alphaE(2) was not blocked by an inhibitor of NO synthase or by protein synthesis inhibitors, indicating that vasodilatation is not dependent upon either NO generation or protein synthesis. In the absence of extracellular calcium, both oestradiols still relaxed arteries precontracted with NA, suggesting that they inhibit intracellular calcium release. Both 17betaE(2) and 17alphaE(2) therefore have important and comparable vasorelaxant properties that do not require interaction with the nuclear oestrogen receptor. Direct interactions with the cell membrane or with ion-channel proteins may be responsible.

Analysis of Variance↗
PubMed1998

Lactation suppresses diurnal rhythm of serum leptin.

Rats consume most of their daily food intake at night; serum leptin levels and adipose tissue leptin mRNA content are elevated at night in non-lactating rats fed ad libitum. Lactation induces massive hyperphagia with most food still consumed at night, but the nocturnal increase in leptin secretion was not observed in lactating rats. Thus the link between nocturnal food intake and increased serum leptin is broken during lactation and the hypoleptinaemia may be an important factor promoting the hyperphagia of lactation.

Adipocytes↗
PubMed1998

Genotoxicity of radiofrequency radiation. DNA/Genetox Expert Panel.

During the past several years, concerns have been raised regarding the potential adverse effects of exposures to nonionizing radiation, particularly in the extremely low frequency (ELF) range (50 to 60 MHz) and radiofrequency radiation (RFR) with frequencies ranging from 30 KHz to 30,000 MHz. One focus of concern has been potential DNA interactions. Publications reviewing the genotoxicity of ELF radiation [McCann et al. (1993): Mutat Res 297(1):61-95; Murphy et al. (1993): Mutat Res 296:221-240; NAS (1997)], have been uniform in concluding that the weight of evidence does not indicate any genotoxic risk from exposure to this type of radiation. Concern that RFR may be associated with adverse biological effects [WHO, 1993], including recent allegations that they may be involved in the production of brain tumors in humans [Elmer-Dewit (1993): Time, February 8:42], has resulted in the production of a large number of publications describing the effects of RFR on the integrity of nucleic acids. Data from studies conducted in a frequency range from 800 to 3,000 MHz were reviewed and subjected to a weight-of-evidence evaluation. The evaluation focused on direct toxicological effects of RFR as well as on studies addressing basic biological responses to RFR at the cellular and molecular level. The data from over 100 studies suggest that RFR is not directly mutagenic and that adverse effects from exposure of organisms to high frequencies and high power intensities of RFR are predominantly the result of hyperthermia; however, there may be some subtle indirect effects on the replication and/or transcription of genes under relatively restricted exposure conditions.

Animals↗
PubMed1998

Uclacyanins, stellacyanins, and plantacyanins are distinct subfamilies of phytocyanins: plant-specific mononuclear blue copper proteins.

The cDNAs encoding plantacyanin from spinach were isolated and characterized. In addition, four new cDNA sequences from Arabidopsis ESTs were identified that encode polypeptides resembling phytocyanins, plant-specific proteins constituting a distinct family of mononuclear blue copper proteins. One of them encodes plantacyanin from Arabidopsis, while three others, designated as uclacyanin 1, 2, and 3, encode protein precursors that are closely related to precursors of stellacyanins and a blue copper protein from pea pods. Comparative analyses with known phytocyanins allow further classification of these proteins into three distinct subfamilies designated as uclacyanins, stellacyanins, and plantacyanins. This specification is based on (1) their spectroscopic properties, (2) their glycosylation state, (3) the domain organization of their precursors, and (4) their copper-binding amino acids. The recombinant copper binding domain of Arabidopsis uclacyanin 1 was expressed, purified, and shown to bind a copper atom in a fashion known as "blue" or type 1. The mutant of cucumber stellacyanin in which the glutamine axial ligand was substituted by a methionine (Q99M) was purified and shown to possess spectroscopic properties similar to uclacyanin 1 rather than to plantacyanins. Its redox potential was determined by cyclic voltammetry to be +420 mV, a value that is significantly higher than that determined for the wild-type protein (+260 mV). The available structural data suggest that stellacyanins (and possibly other phytocyanins) might not be diffusible electron-transfer proteins participating in long-range electron-transfer processes. Conceivably, they are involved in redox reactions occurring during primary defense responses in plants and/or in lignin formation.

Amino Acid Sequence↗