Temperature sensitive oculocutaneous albinism associated with missense changes in the tyrosinase gene.
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Adult↗
Biomedical subjects
T Wang
Publications and source records attributed to T Wang.
Physical activity staging distribution: establishing a heuristic using multiple studies.
The purpose of this study was to identify the population prevalence across the stages of change (SoC) for regular physical activity and to establish the prevalence of people at risk. With support from the National Institutes of Health, the American Heart Association, and the Robert Wood Johnson Foundation, nine Behavior Change Consortium studies with a common physical activity SoC measure agreed to collaborate and share data. The distribution pattern identified in these predominantly reactively recruited studies was Precontemplation (PC) = 5% (+/- 10), Contemplation (C) = 10% (+/- 10), Preparation (P) = 40% (+/- 10), Action = 10% (+/- 10), and Maintenance = 35% (+/- 10). With reactively recruited studies, it can be anticipated that there will be a higher percentage of the sample that is ready to change and a greater percentage of currently active people compared to random representative samples. The at-risk stage distribution (i.e., those not at criteria or PC, C, and P) was approximately 10% PC, 20% C, and 70% P in specific samples and approximately 20% PC, 10% C, and 70% P in the clinical samples. Knowing SoC heuristics can inform public health practitioners and policymakers about the population's motivation for physical activity, help track changes over time, and assist in the allocation of resources.
Behavioral Research↗
The role of peritoneal dialysis in renal replacement therapy: an update on medical aspects.
In this brief review, we discuss various medical factors that are of importance for the role of peritoneal dialysis (PD) in renal replacement therapy (RRT), whereas the complex role of non medical factors will only be mentioned briefly. The aim of any RRT, including hemodialysis, PD and renal transplantation, is to normalize the volume and composition of the body fluids, to remove uremic toxins, and to improve clinical outcome. In the following, we will focus on adequacy, preservation of residual renal function, fluid balance, infections, nutrition, cardiovascular disease and systemic inflammation in PD as these factors are strong predictors of clinical outcome in end stage renal disease patients.
Humans↗
Factorial scopes of cardio-metabolic variables remain constant with changes in body temperature in the varanid lizard, Varanus rosenbergi.
The majority of information concerning the cardio-metabolic performance of varanids during exercise is limited to a few species at their preferred body temperature (T(b)) even though, being ectotherms, varanids naturally experience rather large changes in T(b). Although it is well established that absolute aerobic scope declines with decreasing T(b), it is not known whether changes in cardiac output (V(b)) and/or tissue oxygen extraction, (Ca(O2) - Cv(O2)), are in proportion to the rate of oxygen consumption (Vo(2)). To test this, we studied six Rosenberg's goannas (Varanus rosenbergi) while at rest and while maximally exercising on a treadmill both at 25 and 36 degrees C. During maximum exercise both at 25 and 36 degrees C, mass-specific rate of oxygen consumption (Vo(2kg)) increased with an absolute scope of 8.5 ml min(-1) kg(-1) and 15.7 ml min(-1) kg(-1), respectively. Interestingly, the factorial aerobic scope was temperature-independent and remained at 7.0 which, at each T(b), was primarily the result of an increase in V(bkg), governed by approximate twofold increases both in heart rate (f(H)) and cardiac stroke volume (V(Skg)). Both at 25 degrees C and 36 degrees C, the increase in V(bkg) alone was not sufficient to provide all of the additional oxygen required to attain maximal Vo(2kg), as indicated by a decrease in the blood convection requirement V(bkg)/Vo(2kg); hence, there was a compensatory twofold increase in (Ca(O2) - Cv(O2)). Although associated with an increase in hemoglobin-oxygen affinity, a decrease in T(b) did not impair unloading of oxygen at the tissues and act to reduce (Ca(O2) - Cv(O2)); both Ca(O2)) and Cv(O2)) were maintained across T(b). The change in Vo(2kg) with T(b), therefore, is solely reliant on the thermal dependence of V(bkg). Maintaining a high factorial aerobic scope across a range of T(b) confers an advantage in that cooler animals can achieve higher absolute aerobic scopes and presumably improved aerobic performance than would otherwise be achievable.
Aerobiosis↗
Inhibition of microglial activation by the herbal flavonoid baicalein attenuates inflammation-mediated degeneration of dopaminergic neurons.
Accumulating evidence has suggested that inflammation in the brain participates in the pathogenesis of Parkinson's disease (PD). Therefore, anti-inflammatory therapy has attracted much attention as novel interference to neurodegenerative diseases. Baicalein, a major flavonoid extracted from a traditional Chinese herb Scutellaria baicalensis Georgi (Huangqin), possesses potent anti-inflammatory and antioxidant properties. To test the potential neuroprotective effect of baicalein on dopaminergic neurons, primary midbrain neuron-glia cultures from E-14 rat embryos were used. Cultures were pretreated with baicalein for 30 min prior to stimulation with lipopolysaccharide (LPS, 10 ng/ml). LPS leads to massive activation of microglial cells revealed by OX-42 immunostaining, and produced excessive quantities of NO. Excessive elevation of superoxide level was also observed in enriched-microglia after stimulating with LPS. LPS-induced damage to dopaminergic neurons was evaluated by uptake capacity for [3H]dopamine and tyrosine hydroxylase (TH)-immunocytochemistry. Pretreatment with baicalein concentration-dependently attenuated LPS-induced decrease in [3H]dopamine uptake and loss of TH-immunoreactive (TH-ir) neurons, which the maximum protective effect was observed at the concentration of 5 microM. Post-treatment with baicalein (5 microM) was also shown to be effective even if baicalein administered up to 2 h later than LPS application. Morphological study shows that baicalein (5 microM) almost completely blocked LPS-induced activation of microglia. Excessive production of TNF(alpha) and free radicals such as NO and superoxide by LPS stimulation were also attenuated by baicalein at a concentration-dependent pattern. The present study indicates that baicalein exerts potent neuroprotective effect on LPS-induced injury of dopaminergic neurons. We hypothesize that the inhibition of LPS-induced production of NO and free radicals from microglia may underlie the mechanism of baicalein's neuroprotection.
Animals↗
Differential expression of adenylyl cyclase subtypes in human cardiovascular system.
In human myocardium, beta1-adrenoceptor stimulation achieves maximal inotropic response but less than 50% of maximal adenylyl cyclase activation, whereas the reverse is true of the beta2-adrenoceptor. Four types of adenylyl cyclase, type IV-VII, have been described in mammalian heart, but their expression and relative distribution in human heart and blood vessels is not known. We found that type IV, V, VI and VII adenylyl cyclases were all expressed in cardiomyocytes. Whereas types IV and VII RNA were more abundant in extra-cardiac than cardiac tissues, both absolute and relative expression of type VI was greatest in heart, and lower in tissues lacking a beta1-adrenoceptor. Type V expression was virtually confined to atrium. In situ mRNA hybridisation showed that the beta1-adrenoceptor co-localised with type VI adenylyl cyclase but not other subtypes in juxtoglomerular cells of human kidney. The tissue specific expression of these adenylyl cyclase subtypes may favour its coupling to corresponding receptors expressed in the given tissue type.
Adenylyl Cyclases↗
Nanometer size diesel exhaust particles are selectively toxic to dopaminergic neurons: the role of microglia, phagocytosis, and NADPH oxidase.
The contributing role of environmental factors to the development of Parkinson's disease has become increasingly evident. We report that mesencephalic neuron-glia cultures treated with diesel exhaust particles (DEP; 0.22 microM) (5-50 microg/ml) resulted in a dose-dependent decrease in dopaminergic (DA) neurons, as determined by DA-uptake assay and tyrosine-hydroxylase immunocytochemistry (ICC). The selective toxicity of DEP for DA neurons was demonstrated by the lack of DEP effect on both GABA uptake and Neu-N immunoreactive cell number. The critical role of microglia was demonstrated by the failure of neuron-enriched cultures to exhibit DEP-induced DA neurotoxicity, where DEP-induced DA neuron death was reinstated with the addition of microglia to neuron-enriched cultures. OX-42 ICC staining of DEP treated neuron-glia cultures revealed changes in microglia morphology indicative of activation. Intracellular reactive oxygen species and superoxide were produced from enriched-microglia cultures in response to DEP. Neuron-glia cultures from NADPH oxidase deficient (PHOX-/-) mice were insensitive to DEP neurotoxicity when compared with control mice (PHOX+/+). Cytochalasin D inhibited DEP-induced superoxide production in enriched-microglia cultures, implying that DEP must be phagocytized by microglia to produce superoxide. Together, these in vitro data indicate that DEP selectively damages DA neurons through the phagocytic activation of microglial NADPH oxidase and consequent oxidative insult.
Animals↗
C3-C12 non-methane hydrocarbons in subtropical Hong Kong: spatial-temporal variations, source-receptor relationships and photochemical reactivity.
Annual data on C3-C12 non-methane hydrocarbons (NMHCs) from different areas in Hong Kong are analyzed to examine the spatial distribution, seasonal variation, source-receptor relationships, and photochemical reactivity of NMHCs in subtropical Hong Kong. As expected, the highest levels of NMHCs were found at roadsides, and the lowest levels were observed at a rural site. For seasonal variations, the rural site showed the lowest NMHCs levels in summer, but the roadside site gave a different picture, with the highest NMHCs levels in summer. This was believed to be due to the strong evaporation of alkanes in the hot season. With the exception of isoprene, NMHCs levels in Hong Kong were generally low compared to those of other overseas cities. Principal component analysis suggested that while the isoprene at the rural site mainly came from biogenic emissions, vehicular emissions were the major source in the urban areas, especially at roadsides. Ratios of hydrocarbons with different reactivities were also analyzed to evaluate the ages of air masses and emission ratios. A high toluene-to-benzene ratio at roadsides was due to the widespread use of aromatic-rich unleaded fuels in Hong Kong. The ratios of total NMHCs to nitrogen oxides were found to be 2 to 10 (ppbC/ppbv) indicating that the formation of photochemical ozone (O3) in Hong Kong is controlled by the levels of NMHCs. The reactivity of hydroxyl radicals (OH) and O3 formation potential of NMHCs were evaluated using the propene-equivalent concentration and maximum incremental reactivity. Isoprene was found to have the highest OH-reactivity and O3 formation potential at the rural site, while toluene was the most important contributor to the two parameters at the roadside site. These results are valuable for the understanding of O3 pollution in Hong Kong and the formulation of an effective strategy to manage O3.
Air Pollutants↗
Interactive effects of mechano- and chemo-receptor inputs on cardiorespiratory outputs in the toad.
Arterial blood pressure (P(b)), pulmocutaneous blood flow (Q(pc)), heart rate (f(H)), and fictive ventilation (motor activity in the Vth cranial nerve, V(int)), were recorded from decerebrated, paralysed toads receiving unidirectional ventilation with experimental gas mixtures over a range of lung inflation. At the onset of spontaneous bouts of fictive ventilation, (Q(pc)) and P(b) increased immediately, often with changes in heart rate, implying central cardiorespiratory interactions. Inflation of the lungs with different gas mixtures revealed that the effect of hypercarbia on V(int) was reduced by lung inflation and that feedback from pulmonary stretch receptors may summate with central feedforward control of f(H) and (Q(pc)) in an interactive fashion. The results of bolus injections of cyanide into the carotid or the pulmonary circulations suggest there are oxygen sensitive receptors in both circuits that affect the cardiovascular system directly and respiratory activity by complex central interactions with inputs from central chemoreceptors and pulmonary stretch receptors.
Afferent Pathways↗
Imaging lung function using rapid dynamic acquisition of T1-maps during oxygen enhancement.
This paper describes imaging of lung function with oxygen-enhanced MRI using dynamically acquired T1 parameter maps, which allows an accurate, quantitative assessment of time constants of T1-enhancement and therefore lung function. Eight healthy volunteers were examined on a 1.5-T whole-body scanner. Lung T1-maps based on an IR Snapshot FLASH technique (TE = 1.4 ms, TR = 3.5 ms, FA = 7 (composite function )) were dynamically acquired from each subject. Without waiting for full relaxation between subsequent acquisition of T1-maps, one T1-map was acquired every 6.7 s. For comparison, all subjects underwent a standard pulmonary function test (PFT). Oxygen wash-in and wash-out time course curves of T1 relaxation rate (R1)-enhancement were obtained and time constants of oxygen wash-in (w(in)) and wash-out (w(out)) were calculated. Averaged over the whole right lung, the mean w(out) was 43.90 +/- 10.47 s and the mean (w(in)) was 51.20 +/- 15.53 s, thus about 17% higher in magnitude. Wash-in time constants correlated strongly with forced expired volume in one second in percentage of the vital capacity (FEV1 % VC) and with maximum expiratory flow at 25% vital capacity (MEF25), whereas wash-out time constants showed only weak correlation. Using oxygen-enhanced rapid dynamic acquisition of T1-maps, time course curves of R1-enhancement can be obtained. With w(in) and w(out) two new parameters for assessing lung function are available. Therefore, the proposed method has the potential to provide regional information of pulmonary function in various lung diseases.
Administration, Inhalation↗
Relationship between osteopenia and lumbar intervertebral disc degeneration in ovariectomized rats.
Ovariectomy (OVX) can cause bone loss in rats, but little is known about how it also induces lumbar intervertebral disc degeneration (LVD). This study investigated how estrogen deficiency affected intervertebral discs in OVX rats. Thirty 3-month-old female Sprague-Dawley rats were divided randomly into three equal groups. The baseline control group (BL) was killed at the beginning of the experiment. An ovariectomy was performed in 10 rats (OVX group) and another group of 10 rats was subjected to a sham surgery (Sham group). The OVX rats were untreated after the surgery to allow for the development of moderate osteopenia. Bone mineral density (BMD) measurement and bone histomorphometric analysis were applied to the segments of lumbar spines in all rats killed 6 months after surgery. The pathological changes of intervertebral discs were observed and the degree of LVD was scored by a histological scoring system. The BMD of the spines (L3-L5) in the OVX group decreased significantly compared with the Sham group. The bone volume indices in the OVX group were significantly lower, but the bone turnover rate parameters were significantly higher than those in the Sham group (P < 0.01). The histological scores for LVD in the OVX group were significantly higher than those in the Sham group (P < 0.01). There was a significant negative correlation between the BMD and Grade II discs in the OVX rats (P = 0.042). In conclusion, LVD occurs in the OVX rats and the degeneration of cartilage end plates may be a pathogenic factor in disc degeneration.
Animals↗
Source apportionment of ambient non-methane hydrocarbons in Hong Kong: application of a principal component analysis/absolute principal component scores (PCA/APCS) receptor model.
Receptor-oriented source apportionment models are often used to identify sources of ambient air pollutants and to estimate source contributions to air pollutant concentrations. In this study, a PCA/APCS model was applied to the data on non-methane hydrocarbons (NMHCs) measured from January to December 2001 at two sampling sites: Tsuen Wan (TW) and Central & Western (CW) Toxic Air Pollutants Monitoring Stations in Hong Kong. This multivariate method enables the identification of major air pollution sources along with the quantitative apportionment of each source to pollutant species. The PCA analysis identified four major pollution sources at TW site and five major sources at CW site. The extracted pollution sources included vehicular internal engine combustion with unburned fuel emissions, use of solvent particularly paints, liquefied petroleum gas (LPG) or natural gas leakage, and industrial, commercial and domestic sources such as solvents, decoration, fuel combustion, chemical factories and power plants. The results of APCS receptor model indicated that 39% and 48% of the total NMHCs mass concentrations measured at CW and TW were originated from vehicle emissions, respectively. 32% and 36.4% of the total NMHCs were emitted from the use of solvent and 11% and 19.4% were apportioned to the LPG or natural gas leakage, respectively. 5.2% and 9% of the total NMHCs mass concentrations were attributed to other industrial, commercial and domestic sources, respectively. It was also found that vehicle emissions and LPG or natural gas leakage were the main sources of C(3)-C(5) alkanes and C(3)-C(5) alkenes while aromatics were predominantly released from paints. Comparison of source contributions to ambient NMHCs at the two sites indicated that the contribution of LPG or natural gas at CW site was almost twice that at TW site. High correlation coefficients (R(2) > 0.8) between the measured and predicted values suggested that the PCA/APCS model was applicable for estimation of sources of NMHCs in ambient air.
Air Pollutants↗
Tau epitope display in progressive supranuclear palsy and corticobasal degeneration.
Filamentous aggregates of the protein tau are a prominent feature of Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). However, the extent to which the molecular structure of the tau in these aggregates is similar or differs between these diseases is unclear. We approached this question by examining these disorders with a panel of antibodies that represent different structural, conformational, and cleavage-specific tau epitopes. Although each of these antibodies reveals AD pathology, they resolved into three classes with respect to PSP and CBD: AD2 and Tau-46.1 stained the most tau pathology in all cases; Tau-1, 2, 5, and 12 exhibited variable reactivity; and Tau-66 and MN423 did not reveal any tau pathology. In addition, hippocampal neurofibrillary tangles in these cases showed a predominantly PSP/CBD-like, rather than AD-like, staining pattern. These results indicate that the patterns of the tau epitopes represented by this panel that reside in the pathological aggregates of PSP and CBD are similar to each other but distinct from that of AD.
Aged↗
Recombinant adeno-associated virus-mediated kallikrein gene therapy reduces hypertension and attenuates its cardiovascular injuries.
Gene therapy of hypertension requires long-term expression of a therapeutic gene to achieve stable reduction of blood pressure. Human tissue kallikrein (HK) cleaves kininogen to produce a potent vasoactive peptide kinin, which plays an important role in the regulation of the cardiovascular and renal functions. In the present study, we have delivered human kallikrein cDNA with an rAAV vector to explore the potential therapeutic effects of kallikrein on hypertension and related secondary complications. A single tail vein injection of the rAAV-HK vector into the adult spontaneously hypertensive rats resulted in a significant reduction (12.0+/-2.55 mmHg, P<0.05, n=6, ANOVA) of the systolic blood pressure from 2 weeks after vector injection, when compared with the control rAAV-lacZ vector-injected rats. Weekly blood pressure monitoring showed stable hypertension-reduction effect throughout the course of the 20-week experiments. In addition, total urine microalbumin contents decreased as a result of rAAV-HK treatment. Histological analysis of various tissues showed remarkable amelioration of cardiovascular hypertrophy, renal injury and collagen depositions in the rAAV-treated group. Finally, persistent expression of the transgene product HK was confirmed by the enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction. We conclude that rAAV-mediated HK delivery rendered a long-term and stable reduction of hypertension and protected against renal injury, cardiac remodeling in the spontaneously hypertensive rat model. Further studies are warranted for the development of a gene therapy strategy for human hypertension.
Animals↗
Alterations in angiogenic growth factors and neuronal nitric oxide synthase expression in chronic cavernosal ischemia.
Our aim was to study anatomical and molecular changes at varying time points after the induction of cavernosal ischemia (CI) in a rabbit model of arteriogenic erectile dysfunction. Tissue structure and the expression of angiogenic and neurogenic genes were examined using immunostaining and reverse transcription-polymerase chain reaction (RT-PCR) analyses. We found a progressive increase of erectile connective tissue together with a decrease in smooth muscle cell content as the duration of CI increased. Immunohistochemical staining showed an increase in vascular endothelial growth factor (VEGF) levels at the early stages and a decrease at the later stages of ischemia. RT-PCR analysis of VEGF and neuronal nitric oxide synthase (nNOS) confirmed these results and showed nearly a two-fold increase in VEGF and nNOS mRNA levels in the early stages of CI with a decrease at the later stages of CI. On the other hand, mRNA levels of VEGF receptor, KDR, decreased approximately by 50% over the course of CI. Our studies showed that the cellular and molecular responses of the erectile tissue to short-term ischemia are different than those seen after long-term ischemia. The dramatic reduction in KDR expression suggests that the cavernosal endothelium is very sensitive to ischemia. The similar changes in VEGF and nNOS expression over the course of CI suggest a tissue-defensive mechanism to CI via the VEGF and NO pathways. Taken together, this study suggests that supplementation of VEGF at earlier stages of ischemia may restore the damaged endothelial cells of the corpus cavernosum and support tissue perfusion.
Aging↗
Assessing health-related quality-of-life in individuals with haemophilia in China.
Haemophilia is a group of inherited, congenital diseases present all through the life. Those disorders are associated with a chronic burden of morbidity punctuated by episodes of acute deterioration in health-related quality-of-life (HR-QL). The significances of assessing HR-QL in individuals with haemophilia as an important component of the clinical database have gained increasing recognition in recent years. To the best of our knowledge, reports on the HR-QL of Chinese patients with haemophilia are not available. The purpose of this paper was to assess the HR-QL of patients with haemophilia in China. In order to do this, 179 patients with haemophilia (age 16-70) were mailed China quality-of-life questionnaire, which was designed specially for this study taking into account the culture characters of Chinese. Compared with the normal male general population, individuals with haemophilia experienced significantly lower levels of HR-QL and within the subgroups of patients, there was a gradation of HR-QL from mild < moderate < severe haemophilia patients. Age, clinical severity, degree of arthropathy, hepatitis status, salary and mean annual expenditure for replacement therapy were predictors of HR-QL. Clinical severity of the disease manifestation rather than the severity of the disease based on molecular classification was a factor that negatively influenced the HR-QL of patients with haemophilia. Arthropathies of patients with haemophilia in China were more severe than that in western countries because of the poorer medical care and were associated with their lower income and therapy cost. A large number of patients never had hepatitis or HIV serological examination. The exact prevalence of hepatitis and HIV was difficult to obtain and the HR-QL of hepatitis and HIV positive patients required further study.
Adolescent↗
Effects of several Chinese herbal aqueous extracts on human sperm motility in vitro.
The effects of six kinds of aqueous extracts of Chinese herbal medicine (Astragalus membranaceus, Acanthopanacis senticosi, Panax genseng and Ophiopogon japonicus, P. genseng and Aconitum carmichaeli, Salviae miltiorrhiae, Polyporus umbellatus polysaccharide) on sperm motility characteristics of 30 infertile male volunteers were studied in vitro with a computer-assisted sperm analysis at 15, 60 and 180 min after incubated with the drugs. The results showed that per cent viability, number of progressive motile spermatozoa, curvilinear velocity, average path velocity and amplitude of lateral head displacement were significantly enhanced by A. membranaceus (P < 0.05 or < 0.01), per cent viability, average path velocity and amplitude of lateral head displacement were significantly enhanced by A. senticosi (P < 0.05), but all the above were not affected by P. genseng and O. japonicus, P. genseng and A. carmichaeli, S. miltiorrhiae and P. umbellatus polysaccharide. It is suggested that A. membranaceus and A. senticosi can enhance the motility of human spermatozoa in vitro.
Drugs, Chinese Herbal↗
Complete genome sequence of the genetically tractable hydrogenotrophic methanogen Methanococcus maripaludis.
The genome sequence of the genetically tractable, mesophilic, hydrogenotrophic methanogen Methanococcus maripaludis contains 1,722 protein-coding genes in a single circular chromosome of 1,661,137 bp. Of the protein-coding genes (open reading frames [ORFs]), 44% were assigned a function, 48% were conserved but had unknown or uncertain functions, and 7.5% (129 ORFs) were unique to M. maripaludis. Of the unique ORFs, 27 were confirmed to encode proteins by the mass spectrometric identification of unique peptides. Genes for most known functions and pathways were identified. For example, a full complement of hydrogenases and methanogenesis enzymes was identified, including eight selenocysteine-containing proteins, with each being paralogous to a cysteine-containing counterpart. At least 59 proteins were predicted to contain iron-sulfur centers, including ferredoxins, polyferredoxins, and subunits of enzymes with various redox functions. Unusual features included the absence of a Cdc6 homolog, implying a variation in replication initiation, and the presence of a bacterial-like RNase HI as well as an RNase HII typical of the Archaea. The presence of alanine dehydrogenase and alanine racemase, which are uniquely present among the Archaea, explained the ability of the organism to use L- and D-alanine as nitrogen sources. Features that contrasted with the related organism Methanocaldococcus jannaschii included the absence of inteins, even though close homologs of most intein-containing proteins were encoded. Although two-thirds of the ORFs had their highest Blastp hits in Methanocaldococcus jannaschii, lateral gene transfer or gene loss has apparently resulted in genes, which are often clustered, with top Blastp hits in more distantly related groups.
Archaeal Proteins↗