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Biomedical subjects

W Wang

Publications and source records attributed to W Wang.

At least 127 records · Page 7Linked to original sources

Blood transfusion for preventing stroke in people with sickle cell disease.

BACKGROUND: Sickle cell disease is a common inherited haemoglobin disorder. The abnormal haemoglobin causes distortion of red blood cells, anaemia, vaso-occlusion and dysfunction in virtually any organ system in the body. Stroke occurs in around 10% of children with sickle cell anaemia, and recurrences after a first stroke are likely. Chronic blood transfusion regimes are often used in an attempt to dilute the sickled red blood cells, thus reducing the risk of vaso-occlusion and stroke. However, the side-effects of such regimens can be severe. OBJECTIVES: To assess the relative risks and benefits of chronic blood transfusion regimes in patients with sickle cell disease to prevent a first stroke or further strokes. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group specialist register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings. Date of the most recent search of the Group's specialised register: July 2001 SELECTION CRITERIA: All those randomised or quasi-randomised controlled trials in which blood transfusion as a preventative measure for stroke in patients with sickle cell disease are compared to an alternative treatment or to no treatment. DATA COLLECTION AND ANALYSIS: Both reviewers independently assessed trial quality and extracted data from the study included. MAIN RESULTS: One trial was identified by the initial search and this met the inclusion criteria for the review. The trial compared a chronic transfusion regime to maintain sickle haemoglobin at less than 30% with standard care in 130 children with sickle cell disease who were judged to be at high risk of a first stroke through transcranial doppler ultrasonography. Eleven children in the standard care group suffered a stroke during the trial, compared to only one in the transfusion group. Because of this 92% relative risk reduction, the trial was terminated 16 months early. It had been planned that all patients would be treated for 30 months, but median follow-up only 21.1 months. However, a high rate of complications such as iron overload, alloimmunisation and transfusion reactions were seen in the children who were receiving transfusions. No randomised controlled trials were identified which investigated use of transfusion for preventing recurrence of stroke. REVIEWER'S CONCLUSIONS: While the included study demonstrated a significantly reduced risk of stroke in patients receiving regular blood transfusions, the degree of risk must be balanced against the burden of a chronic transfusion regime. Further research is required to establish the use of transfusion in preventing secondary stroke, the age, or length of time after an event, at which transfusion can safely be stopped, and to further define risk factors for stroke in order to reduce the chance of unnecessarily putting children onto a chronic transfusion regime.

Anemia, Sickle Cell↗

Alternative transcripts of the GABA(A) receptor epsilon subunit in human and rat.

In both human and rat tissues, complex patterns of transcripts are derived from the genes that encode the gamma-aminobutyric acid (GABA)(A) receptor epsilon subunit. An epsilon subunit transcript (approximately 3.6 kb) is expressed at relatively high levels in regions of the human brain and heart, but is not detected in most other major tissues. The encoded human epsilon subunit (epsilon (h)) confers distinctive properties to receptors into which it assembles. A distinct transcript of the gene (6.2 kb) is expressed abundantly in a variety of human tissues. This alternative transcript (ET2) appears to originate from within the epsilon subunit gene. It is possible that this transcript encodes a truncated subunit (epsilon (hS)), containing all of the transmembrane and intracellular domains. However, a combination of biochemical and electrophysiological analyses does not support this hypothesis. A distinct transcript of the epsilon subunit gene, encoding a large extracellular pro/glx domain, is expressed abundantly in rat and mouse brain. Functional analyses also failed to provide evidence for incorporation of this subunit (epsilon (rL)) into recombinant receptors. However, a shorter rat epsilon subunit (epsilon (r)), which lacks the pro/glx domain, conferred epsilon (h)-like properties to recombinant receptors, providing evidence for a functional rat epsilon subunit. In common with its human orthologue, incorporation of the epsilon (r) subunit into recombinant GABA(A) receptors confers several distinctive properties, including a reduced modulation by the anesthetic propofol and the appearance of spontaneous current.

Animals↗

Research on the microstructure of insect cuticle and the strength of a biomimetic preformed hole composite.

The insect cuticle is a typical natural composite with excellent strength, stiffness, and fracture toughness. Scanning electron microscope observation of the microstructure of Hydrophilidae (an insect) cuticle showed several unique plies and structural characteristics, which may provide available information to the design of advanced composites. The microstructure found in the vicinity of pore canals in the insect cuticle was used for the design of the composite laminate with a hole. Compared with the composite laminate with a normally drilled hole, it was found that the strength of the specially designed composite laminate increases markedly, which is of important significance to the design of high-performance composites.

Animals↗

Power of a simplified multivariate test for genetic linkage.

In this paper we compare the power of the multivariate Haseman-Elston (MHE) test proposed earlier by Amos et al. (1990) and a computationally rapid new version of the multivariate Haseman-Elston test (NMHE) (Elston et al. 2000). We show that the power of NMHE was, for different simulation setups, identical or higher than that of MHE. In the bivariate case, the power of the NMHE method was somewhat less than that of the computationally intensive maximum likelihood variance components method (Amos et al. 2001). We present comparisons of the empirical distributions of the NMHE test to its limiting distributions for a range of numbers of traits. The distribution of the NMHE test appeared to conform satisfactorily to its limiting asymptotic distribution in large samples. Otherwise, empirical critical values for NMHE are somewhat higher than predicted, i.e. the test proposed by Elston et al. (2000) is non-conservative. The use of empirical critical values is therefore recommended for limited sample sizes (less than several hundred families). We also present the results of a linkage analysis performed by the NMHE method on a set of 4 body size-related traits. The method identified meaningful combinations of traits that showed significant linkage on chromosome 2 and suggestive linkage to regions on chromosomes 16 and 17.

Body Constitution↗

Chemosensitive serotonergic neurons are closely associated with large medullary arteries.

We have previously shown that serotonergic neurons of the medulla are strongly stimulated by an increase in CO(2), suggesting that they are central respiratory chemoreceptors. Here we used confocal imaging and electron microscopy to show that neurons immunoreactive for tryptophan hydroxylase (TpOH) are tightly apposed to large arteries in the rat medulla. We used patch-clamp recordings from brain slices to confirm that neurons with this anatomical specialization are chemosensitive. Serotonergic neurons are ideally situated for sensing arterial blood CO(2), and may help maintain pH homeostasis via wide-ranging effects on brain function. The results reported here support a recent proposal that sudden infant death syndrome (SIDS) results from a developmental abnormality of medullary serotonergic neurons.

Animals↗

Rate-dependency of calcitonin secretion in response to increased plasma Ca2+.

BACKGROUND: Calcitonin (CT) is a polypeptide hormone secreted from C-cells of the thyroid gland in response to hypercalcemia. The physiological contribution of CT to calcium homeostasis has not been completely clarified. The present study therefore further characterized the sigmoidal relationship between plasma ionized calcium (P-Ca2+) and CT in normal rats, and examined the possibility of rate-dependency of CT secretion in response to changes in P-Ca2+. DESIGN: Hypercalcaemia was induced by an infusion of calcium gluconate at rate of 4.5 x 10(-2) mmol h-1 rat-1 i.v. (n = 8) and hypocalcaemia was induced by an EGTA infusion at a rate of 4.5 x 10(-2) mmol h-1 rat-1 (n = 7) in one protocol: the 'slow' protocol. In another protocol an increased rate of infusion of calcium gluconate or EGTA was used to induce a more rapid change in P-Ca2+. Calcium gluconate was infused at a rate of 6.0 x 10(-2) mmol h-1 rat-1 (n = 6) and EGTA infused at a rate of 7.5 x 10(-2) mmol h-1 rat-1 (n = 7): the 'rapid' protocol. RESULTS: The infusions of both the 'slow' and 'rapid' protocols resulted in linear changes in P-Ca2+, but with significantly different slopes (P < 0.01). The Ca2+/CT curves of both protocols were represented by sigmoidal curves. The 'rapid' increase of P-Ca2+ resulted in a higher maximal CT secretion (2032 +/- 215 pg mL-1) than the 'slow' increase of P-Ca2+ (1213 +/- 85 pg mL-1; P < 0.001), despite similar minimal and maximal levels being obtained in P-Ca2+ in the two protocols. Thus, a significantly greater CT response was obtained with a more rapid increment in P-Ca2+. CONCLUSION: The relationship between P-Ca2+ and CT is represented by a sigmoidal curve, as previously shown. The CT response depended, however, not only upon the concentration of P-Ca2+ obtained but also upon the rate of increase in P-Ca2+, demonstrating rate-dependency as another significant physiological relation between Ca2+ and CT.

Animals↗

Role of calcitonin in the rapid minute-to-minute regulation of plasma Ca2+ homeostasis in the rat.

BACKGROUND: Plasma ionized calcium (Ca2+) is maintained at a very stable concentration in mammals. The hormones or factors involved in the very rapid regulation of calcium homeostasis are still debated. Thus, previous results from our laboratory have clearly shown that parathyroid hormone (PTH) and 1,25(OH)2D3 are not responsible for the rapid up-regulation of plasma Ca2+ after a brief induction of hypocalcaemia. The present investigation therefore examined in vivo the possible role of calcitonin (CT) in the very rapid, minute-to-minute regulation of plasma Ca2+ in rats. STUDY DESIGN: The rapid calcaemic response to acute thyroparathyroidectomy (TPTX) and to acute selective thyroidectomy (TX) (n = 10), as well as the possible effect of CT on the very rapid recovery of plasma Ca2+ after termination of a brief induction of hypocalcaemia were studied. Hypocalcaemia was induced by a 30-min EGTA infusion in ras in three different protocols: 1 h after TPTX (n = 9) compared with control TPTX rats not given EGTA (n = 13); 1 h after TX (n = 7); and 1 h after TPTX, but during supplementation with exogenous CT (n = 8) and compared with the response in TPTX rats infused with vehicle (n = 8). RESULTS: An immediate and significant increase of plasma Ca2+ was found after TPTX (P < 0.01) as well as after selective TX (P < 0.01) in the nonfasting rats. Significant hypercalcaemia (P < 0.05) was still present in rats fasting for 2 days before these procedures, but the increase in plasma Ca2+ was considerably less (P < 0.01). After induction of a brief period of hypocalcaemia by infusion of EGTA a significant (P < 0.01) and rapid recovery of plasma Ca2+ took place within 10 min and a further increase within the next 60 min (P < 0.01), whether or not the rats were normal, TPTX, TX or were supplemented by CT during the experiments. The plasma Ca2+ recovery curves after termination of a brief induction of hypocalcaemia all had similar appearances, indicating that presence or absence of CT had no influence on this very rapid Ca2+ recovery after induction of hypocalcaemia. CONCLUSIONS: Acute removal of the tonus of CT results in an acute increase in plasma Ca2+ for up to 3 h. This effect of CT is probably mainly related to the postprandial maintenance of normocalcaemia, but is also seen in fasting rats, although to a lesser degree. The very rapid calcaemic recovery after discontinuation of a brief induction of hypocalcaemia is, however, not a result of suppressed plasma calcitonin levels.

Animals↗

Effect of cage vs. floor litter environments on the pulmonary hypertensive response to intravenous endotoxin and on blood-gas values in broilers.

Intravenous endotoxin has been shown to trigger a delayed pulmonary hypertensive response that varies widely in magnitude and duration among individual broilers. It was proposed that this individual variability may reflect immunological differences acquired during previous respiratory challenges that might have subsequently altered the endotoxin-initiated biochemical cascade. In Experiment 1, we tested the hypothesis that, when compared with broilers reared in clean stainless steel cages (Cage group), broilers reared on floor litter (Floor group) should experience a greater respiratory challenge and therefore may consistently exhibit a more enhanced pulmonary hypertensive response to intravenous endotoxin. Birds in the Cage group were grown in stainless steel cages at a low density (72 birds/8 m2 chamber), and fecal and dander materials were removed daily. Birds in the Floor group were reared on wood-shavings litter at a higher density (110 birds/8 m2 chamber). Pulmonary and systemic mean arterial pressures and blood-gas values were evaluated prior to and following the intravenous administration of 1 mg Salmonella typhimurium endotoxin. Broilers in the Floor and Cage groups exhibited pulmonary hypertensive responses to endotoxin that were very similar in terms of time of onset, duration, and magnitude, as well as variability in the response among individuals. Systemic hypotension also developed similarly in both groups following endotoxin injection. Blood-gas values indicated that the partial pressure of CO2 and the HCO3- concentration in arterial blood were higher (P < 0.05) in the Floor group than in the Cage group prior to and subsequent to the endotoxin injection. In Experiment 2, we reevaluated the effect of a dirty vs. a clean environment on blood-gas values using a different strain of broilers, and confirmed the negative impact of floor rearing on blood-gas values. We conclude that broilers reared on the floor inhaled litter dust and noxious fumes, which impaired pulmonary gas exchange and increased the arterial partial pressure of CO2 when compared with broilers reared in clean stainless steel cages. Nevertheless, the pulmonary hypertensive response to endotoxin did not differ between broilers reared on the floor and those in cages.

Animal Husbandry↗

Intravenous micro-particle injections and pulmonary hypertension in broiler chickens: acute post-injection mortality and ascites susceptibility.

Intravenously injected micro-particles become trapped within the pulmonary vasculature where they increase the resistance to blood flow and trigger pulmonary hypertension. We tested the hypothesis that i.v. micro-particle injections can be used to trigger acute (24 to 48 h) post-injection mortality in broilers having the most limited pulmonary vascular capacity, or ascites in broilers whose marginal cardiopulmonary capacity renders them susceptible to pulmonary hypertension syndrome (PHS). Progressive inflammation-associated responses were initiated within the lung parenchyma by 10 to 80 microm diameter dextran polymer (Sephadex) and 30 microm diameter cellulose micro-particles, leading to the scavenging of Sephadex micro-particles from the pulmonary vasculature by <5 d post-injection, whereas the cellulose micro-particles persisted for >7 d post-injection. The persistency and size of the cellulose apparently facilitated chronic occlusion of blood flow through precapillary arterioles, thereby triggering appreciable post-injection mortality and PHS at relatively low injection volumes (0.3 to 0.6 mL at 0.02 g/mL). In contrast, the small size of the polystyrene microspheres (15 microm), and the lack of persistency of the Sephadex micro-particles, apparently precluded the reliable occurrence of post-injection mortality or PHS until higher volumes (>0.8 mL at 0.02 g/mL) were injected. Values for the total susceptibility index (TSI: 24 to 48 h post-injection mortality + PHS mortality) following cellulose injections were higher for broilers reared at cool temperatures than at thermoneutral temperatures. The incidences of PHS induced by exposing broilers from different genetic lines to constant cool temperatures qualitatively paralleled the respective post-injection mortalities elicited by injecting the cellulose micro-particle suspension into the same lines. These observations indicate the micro-particle injection methodology potentially can replace unilateral pulmonary artery occlusion as the technique of choice for genetically selecting broilers that have a sufficiently robust pulmonary vascular capacity to resist the onset of pulmonary hypertension and PHS. The functional importance of the relative antigenicity of different micro-particle types, and the extent to which key immune-mediated responses, either beneficial or detrimental, might be co-selected by the micro-particle injection technology, remain to be clarified.

Animals↗

Pulmonary hypertensive response to endotoxin in cellulose-primed and unprimed broiler chickens.

Previous studies indicate that individual broilers vary widely in their pulmonary vascular responsiveness to i.v. injections of endotoxin. This individual variability may reflect differences acquired during previous respiratory challenges or genetic variability that may be associated with susceptibility to pulmonary hypertension syndrome (ascites). In the present study, we compared the endotoxin responses of 4- to 5- wk-old control broilers (unprimed) and broilers in which the pulmonary vasculature had been immunologically challenged 48 h previously by an i.v. injection of cellulose micro-particles (primed). The injected cellulose micro-particles are carried in the venous blood to the lungs, where they become trapped in the pulmonary vasculature and initiate acute focal inflammatory responses within the surrounding lung parenchyma. Physiological variables (respiratory rate, heart rate, pulmonary and systemic arterial pressures) were evaluated prior to and following the i.v. administration of 1 mg of Salmonella typhimurium endotoxin. Prior to endotoxin injection, the respiratory rate was higher in primed than in unprimed broilers; however, the heart rate, pulmonary arterial pressure, and systemic arterial pressure did not differ between groups. Broilers in both groups exhibited similar ranges of individual variability in their endotoxin responses. The overall time of onset, magnitude, and duration of the pulmonary hypertensive responses were similar for both groups. Accordingly, the initiation of a preexisting inflammatory response within the lung parenchyma did not alter the timing, amplitude, or variability of the subsequent pulmonary hypertensive response to endotoxin in broilers.

Animals↗

Molecular wires, switches, and memories.

Design and measurements of molecular wires, switches, and memories offer an increased device capability with reduced elements. We report: Measurements on through-bond electronic transport properties of nanoscale metal-1,4-phenylene diisocyanide-metal junctions are reported, where nonohmic thermionic emission is the dominant process, with isocyanide-Pd showing the lowest thermionic barrier of 0.22 eV; robust and large reversible switching behavior in an electronic device that utilizes molecules containing redox centers as the active component, exhibiting negative differential resistance (NDR) and large on-off peak-to-valley ratio (PVR) are realized; erasable storage of higher conductivity states in these redox-center-containing molecular devices are observed; and a two-terminal electronically programmable and erasable molecular memory cell with long bit retention time is demonstrated.

Cyanides↗

Spatial organization and magnitude of orientation contrast interactions in primate V1.

We have explored the spatial organization of orientation contrast effects in primate V1. Our stimuli were either concentric patches of drifting grating of varying orientation and diameter or grating patches displaced in x-y coordinates around a central patch overlying the classical receptive field (CRF). All cells in the sample exhibited response suppression to iso-oriented stimuli exceeding the CRF. Changing the outer stimulus orientation revealed five response patterns: 1) orientation alignment suppression (17% of cells)-a suppressive component tuned to the same orientation as the cell's optimal, 2) orientation contrast facilitation (63%)-responses to orientation contrast stimuli exceeded those to the center stimulus alone, 3) nonorientation specific suppression (3%), 4) mixed general suppression and alignment suppression (14%), and 5) orientation contrast suppression (14%)-cross-oriented stimuli evoked stronger suppression than iso-oriented stimuli. Thus most cells (94%) showed larger responses to orientation contrast stimuli than to iso-oriented stimuli, and over one-half showed orientation contrast facilitation. There appeared to be a spatially structured organization of the zones driving the different response patterns with respect to the CRF. Nonorientation-specific suppression and orientation contrast suppression were predominantly evoked by orientation contrast borders located within the CRF, and orientation contrast facilitation was mainly driven by surround stimuli lying outside the CRF. This led to different response patterns according to border location. Zones driving orientation contrast facilitation were not necessarily contiguous to, nor uniformly distributed around, the CRF. Our data support two processes underlying orientation contrast enhancement effects: a simple variation in the strength of surround suppression drawing on the fact that surround suppression is tuned to the same orientation as the CRF and a second process driven by orientation contrast that enhanced cells' responses to CRF stimulation by either dis-inhibition or orientation contrast facilitation. We suggest these processes may serve to enhance response levels to salient image features such as junctions and corners and may contribute to orientation pop-out.

Algorithms↗

Predicting caries in permanent teeth from caries in primary teeth: an eight-year cohort study.

Several cross-sectional studies report that caries in primary teeth is correlated with caries in permanent teeth. This eight-year cohort study sought to determine if caries in the primary dentition can predict caries in the permanent dentition of the same individuals and, if so, with what degree of prediction accuracy. A total of 362 Chinese children, from 3 to 5 years old at the time of the 1992 baseline study, were re-examined in 2000. The study found statistically significant associations between caries prevalence in primary and permanent dentitions (p < 0.01). Children having caries in their primary teeth were three times more likely to develop caries in their permanent teeth (relative ratio = 2.6, 95% CI = 1.4-4.7; p < 0.001). Caries on primary molars had the highest predictive value (85.4%). This study demonstrates that caries status in the primary teeth can be used as a risk indicator for predicting caries in the permanent teeth.

Adolescent↗