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Biomedical subjects

H Y Wang

Publications and source records attributed to H Y Wang.

At least 19 recordsLinked to original sources

Screening and mutagenesis of a novel Bacillus pumilus strain producing alkaline protease for dehairing.

AIMS: To characterize and optimize a novel Bacillus pumilus strain isolated from biological waste which produces protease with excellent dehairing effect. This newly isolated strain could be utilized in the industrial leather dehairing process. METHODS AND RESULTS: Bacterial strains secreting proteases were screened from biological wastes. Positive clones were further characterized by analysing their efficacy in dehairing and effects on collagen integrity. Among 171 colonies tested, a strain BA06, identified as B. pumilus, was picked owing to its efficient dehairing capabilities with minimal impact on collagen. By combined mutagenesis using UV, N-methyl-N'-nitro-N-nitrosdguanidine and Co(60)-gamma-rays, this strain was further improved with regard to its alkaline protease production. The alkaline protease activity of the mutant strain SCU11was greatly improved up to 6000 U ml(-1), in comparison with its parent strain BA06 of 1200 U ml(-1). CONCLUSIONS: By using screening and mutagenesis methods, we have successfully created a B. pumilus strain that can produce high levels of alkaline proteases that are able to efficiently remove hair from skin with minimal damage on the collagen. SIGNIFICANCE AND IMPACT OF THE STUDY: This strain could be used in commercial alkaline protease production for leather dehairing.

Animals↗

Addressing Taiwan's high incidence of cervical cancer: factors associated with the Nation's low compliance with Papanicolaou screening in Taiwan.

BACKGROUND: Despite cervical cancer being the leading female cancer, women in Taiwan have received fewer screening examinations for this disease than populations in Western countries. METHODS: Randomly selected telephone questionnaire interviews with women aged 20 years and over were conducted to investigate the factors associated with the subject's cancer screening practices. RESULTS: Among 1021 respondents, 51.6% self-reported no Papanicolaou (Pap) examination received within their lifetime. The multivariate logistic regression analysis revealed that, in addition to marital status, cancer knowledge was the most significant factor associated with screening practice compliance. Compared with women with correct answers for 22-28 cancer knowledge questions, the odds ratios (OR) for non-compliance were 1.4 (95% confidence interval (CI)=1.0-2.0) for women with 17-21 correct answers and 2.3 (95% CI=1.6-3.4) for women with less than 17 correct answers. Women aged 40-49 years had the best cancer knowledge scores. Unmarried women were at an elevated risk for no Pap examination (OR=7.6, 95% CI=5.2-11.3). CONCLUSIONS: Women in Taiwan should be targeted for intervention to promote cancer knowledge and screening compliance.

Adult↗

Bioprocess monitoring and computer control: key roots of the current PAT initiative.

This review article has been written for the journal, Biotechnology and Bioengineering, to commemorate the 70th birthday of Daniel I.C. Wang, who served as doctoral thesis advisor to each of the co-authors, but a decade apart. Key roots of the current PAT initiative in bioprocess monitoring and control are described, focusing on the impact of Danny Wang's research as a professor at MIT. The history of computer control and monitoring in biochemical processing has been used to identify the areas that have already benefited and those that are most likely to benefit in the future from PAT applications. Past applications have included the use of indirect estimation methods for cell density, expansion of on-line/at-line and on-line/in situ measurement techniques, and development of models and expert systems for control and optimization. Future applications are likely to encompass additional novel measurement technologies, measurements for multi-scale and disposable bioreactors, real time batch release, and more efficient data utilization to achieve process validation and continuous improvement goals. Dan Wang's substantial contributions in this arena have been one key factor in steering the PAT initiative towards realistic and attainable industrial applications.

Bioreactors↗

Association between polymorphisms of vitamin D receptor gene ApaI, BsmI and TaqI and muscular strength in young Chinese women.

UNLABELLED: The association between the polymorphisms of vitamin D receptor gene ApaI, BsmI and TaqI and isokinetic muscular strength was examined in 109 healthy, young Chinese women. METHODS: Genomic DNA was extracted from mouthwash samples and vitamin D receptor genotypes were determined with the established methods. The peak torque of the dominant limb in concentric and eccentric knee extensors and flexors and elbow extensors and flexors was measured using Cybex-Norm-770 isokinetic dynamometer at slow and fast velocities. The distribution frequency of vitamin D receptor gene alleles was analyzed by chi-square test. The difference in muscular strength between VDR genotype groups was analyzed using one-way ANOVA. The ApaI, BsmI and TaqI alleles and genotype frequencies appeared to be in a Hardy-Weinberg equilibrium. Subjects with the vitamin D receptor ApaI null (A allele) mutation (AA) exhibited significantly lower knee and elbow concentric or eccentric peak torque than those with aa homozygous or Aa heterozygous. The BB & Bb group showed significantly higher peak torque in concentric knee flexors than bb group. No association was found between vitamin D receptor gene TaqI and muscular strength. The data indicated that vitamin D receptor gene ApaI and BsmI polymorphisms rather than TaqI polymorphism might be associated with muscular strength.

Adult↗

Wheezing in Chinese schoolchildren: disease severity distribution and management practices, a community-based study in Hong Kong and Guangzhou.

BACKGROUND: Asthma is a common chronic disease and information on its management practices at the community level is helpful in identifying problems and improving asthma care. OBJECTIVE: To assess the severity status and management of the asthma symptom of wheeze of children at the community level in Hong Kong (HK) and Guangzhou (GZ). METHODS: Cross-sectional study of children aged 10 years using the International Study of Asthma and Allergic disease in Childhood (ISAAC Phase II protocol). Asthma management and lung function were assessed in 178 (98 from HK and 80 from GZ) randomly selected children with wheeze over the past 12 months. RESULTS: Eighty-three percent, 11%, 6% and 0% of children suffered from intermittent, mild persistent, moderate persistent and severe persistent asthma, respectively, according to the frequency of their symptoms. Addition of spirometric parameter only changed the asthma severity classification in 2.8% of children. Medications were used by 30.6% and 71.3% of children for wheeze in HK and GZ, respectively. In HK, inhaled beta(2)-agonist (73.3% among the drug users) was the commonest medication used followed by inhaled corticosteroid (ICS) (23.3%). In GZ, inhaled beta(2)-agonist was used by 75.4% of children, but use of ICS (26.3%), oral beta(2)-agonist (26.3%), oral theophylline (45.6%), oral ketotifen (36.8%) and oral steroid (35.1%) were also common. ICS was only used by 11.4% of children with persistent asthma. Ten percent and 18.7% of children in HK and GZ, respectively, had emergency department visits, while 16.3% and 11.6% of children in HK and GZ, respectively, had missed school secondary to asthma over the past 1 year. CONCLUSIONS: Most children in the community had intermittent asthma and addition of lung function to symptoms did not significantly affect classification of asthma severity. Significant morbidity was seen even in this group of children with mostly intermittent and mild persistent asthma.

Administration, Inhalation↗

Refinement of a locus for Marie Unna hereditary hypotrichosis to a 1.1-cM interval at 8p21.3.

BACKGROUND: Marie Unna hereditary hypotrichosis (MUHH) is a rare autosomal congenital alopecia with progressive hair loss starting in early childhood and accelerating at puberty. A locus for MUHH has been mapped on chromosome 8p21 but no genes for MUHH have been identified to date. OBJECTIVES: To refine the MUHH locus to a narrow chromosome region to facilitate cloning of the gene. METHODS: We performed genotyping and linkage analysis in a multigeneration Chinese family with MUHH, using 18 high-density microsatellite markers spanning the previously mapped interval at 8p21. RESULTS: Significant evidence for linkage was observed in this region, with a maximum two-point LOD score of 3.01 (theta = 0). Haplotype analysis localized the MUHH locus within the region defined by D8S282 and D8S1839. This region overlaps by 1.1-cM with the previously reported MUHH region and represents a physical distance of about 380 kb. CONCLUSIONS: This study provides a refined map location (1.1 cM) for isolation of the gene causing MUHH. These data also indicate the existence of a common MUHH locus at 8p21.3 between affected caucasian and Chinese families.

Aged↗

The genetic epidemiology of alopecia areata in China.

BACKGROUND: Alopecia areata (AA) is hypothesized to be an organ-specific autoimmune disease with genetic predisposition and an environmental trigger. There are few clinical data in Asians. OBJECTIVES: To describe the genetic epidemiological features of AA patients in China and to determine the possible genetic model for AA. METHODS: Data for 1032 patients with AA were obtained by questionnaire in the Institute of Dermatology of Anhui Medical University in China from 2001 to 2003. Complex segregation analysis and heritability analysis were performed using Falconer's method, EPI INFO 6.0 and SAGE-REGTL programs. RESULTS: In total, 1032 AA patients (male/female ratio 1.1 : 1) were enrolled, representing 0.94% of the total number of cases seen in our outpatient clinic during that time. The mean +/- SD age of onset was 28.98 +/- 13.43 years. The difference between the mean age of onset in males and females was not significant. Most patients (82.6%) experienced their first episode of AA within the first four decades of life. A positive family history of AA was obtained in 87 patients (8.4%). The prevalence of AA in first-, second- and third-degree relatives of the proband with AA was 1.6%, 0.19% and 0.03%, respectively. These figures were higher than those in controls. A greater severity and longer duration of AA were seen in the early onset group than in the late-onset group. The early onset group also had more affected first- and second-degree relatives. The heritability of AA in first-, second- and third-degree relatives was 47.16%, 42.53% and 22.29%, respectively. Based on the REGTL results, the best model was a polygenic additive model for AA. CONCLUSIONS: The effect of genetic factors is strong in AA, but environmental factors such as infection and psychological stress may still play an important role. Our findings on the genetics of AA are consistent with a polygenic additive mode of inheritance.

Adolescent↗

Chlamydia pneumoniae infection associated with enhanced MRI spinal lesions in multiple sclerosis.

Cerebrospinal fluid (CSF) from 66 patients with multiple sclerosis (MS) and 25 patients with other neurological diseases (OND) were examined for the infection of Chlamydia pneumoniae by culture, polymerase chain reaction (PCR) assay, and determination of antibodies to C. pneumoniae. PCR was positive not only in 9 of 28 (32%) patients with MS but also in 2 patents with inflammatory disorders in 15 (13%) OND controls (p = 0.18). Viable C. pneumoniae was isolated from one patient with MS and one with paraneoplastic encephalomyelitis. C. pneumoniae could be detected only in cell-containing CSF. In MS, enhanced spinal magnetic resonance imaging (MRI) lesions were detected in all of four PCR-positive patents but none of five PCR-negative patients, and the difference was significant (p = 0.0079). However, no correlation was found between enhanced brain MRI lesions and CSF C. pneumoniae DNA. Elevated titers of anti-C. pneumoniae IgG were detected in CSF in 13 of 66 (20%) patients with MS and 1 of 25 (4%) OND controls (p = 0.064). CNS C. pneumoniae infection is not uncommon in MS as well as in other inflammatory disorders of the nervous system. The association of active spinal lesions with Chlamydia in CSF collected by lumber puncture suggests the detection of a recent infection. On the other hand, the lack of association of active MS brain lesions with CSF Chlamydia and the presence of PCR-positive patents who are clinically stable and have no enhancing MRI lesions imply the existence of a chronic infectious process.

Adult↗

Prenatal exposure to cocaine disrupts D1A dopamine receptor function via selective inhibition of protein phosphatase 1 pathway in rabbit frontal cortex.

Previous work has demonstrated that in utero cocaine exposure induces an uncoupling of brain D(1A) dopamine receptors (D(1A)DARs) from G(s)-protein. The present work is an attempt to define the mechanism underlying the uncoupling. We detected a significant elevation of phosphoserine in frontal cortical D(1A)DARs of rabbits that were exposed prenatally to cocaine compared with saline controls. This increase in phosphorylation is observed at gestational day 22 and persists to postnatal day 20. The hyperphosphorylation of the D(1A)DAR is accompanied by a 45% inhibition in frontal cortex (FCX) protein phsphatase-1 (PP1) activity that appears to be mediated via DARPP-32 (dopamine and cAMP-regulated phosphoprotein) as indicated by elevated FCX phospho-DARPP-32 (Thr(34)). Furthermore, we demonstrated in both FCX and in PC2 cells that express D(1A)DARs that PP1 is physically associated with D(1A)DARs. We also observed a dramatic decrease in D(1A)DAR-associated PP1 activity in FCX of prenatal cocaine-exposed rabbits, indicating that the reduction in PP1 activity may be responsible for the hyperphosphorylation of the receptor. Furthermore, pretreatment of cortical membranes obtained from cocaine-exposed animals with exogenous PP1 dephosphorylated the phosphorylated D(1A)DAR and significantly reversed the impaired receptor-G(alphas) coupling. This work indicates (1) that D(1A)DAR dephosphorylation via PP1 is essential for receptor resensitization or reactivation and (2) an alteration in the DARPP-32/PP1 cascade appears to be a primary event responsible for D(1A)DAR dysfunction in in utero cocaine-exposed rabbit progeny. The present finding of an altered DARPP-32/PP1 cascade in association with a dysfunction in D(1A)DAR signal transmission in the prenatal cocaine-exposed rabbit brain may implicate novel strategies for the prevention and treatment for in utero cocaine-induced developmental and behavioral abnormalities.

Aging↗

Lithium suppresses signaling and induces rapid sequestration of beta2-adrenergic receptors.

Lithium is a monovalent cation used therapeutically to treat a range of affective disorders (1), although the cellular mechanisms of lithium regulation that might contribute to its therapeutic effects at the level of neurotransmitter receptors are not known. Herein we report the ability of lithium to stimulate the internalization of beta2-adrenergic receptors. Lithium treatment of A431 human epidermoid carcinoma cells resulted in a rapid, prominent desensitization and internalization of beta2-adrenergic receptors. The ability of these receptors to generate a cyclic AMP response was strongly inhibited by lithium, at concentrations therapeutic in humans. Receptors for the serotonin (5HT1c) and for opiates (mu-opioid), in sharp contrast, resisted the effects of lithium on internalization. These data provide the first receptor-based mechanism to be described for lithium that could explain, in part, the therapeutic effects of lithium on affective disorders.

Adrenergic beta-2 Receptor Antagonists↗

Identification and characterization of a novel human hepatocellular carcinoma-associated gene.

To investigate liver cancer-associated genes and to explore the molecular basis of liver cancer genesis, we have cloned a novel hepatocellular carcinoma (HCC)-related gene with a transcript of 2520 base pairs in length named HCCA2 by mRNA differential display polymerase chain reaction (DDPCR) and screening a placenta cDNA library. No significant homologous protein with known genes was found. Western blot analysis showed that HCCA2 could be expressed in transfected 293 cells. Northern hybridization analysis showed that HCCA2 mRNA was expressed in 79% (34/43) patients with HCC, most of whom had significantly high expression in HCC tissues, while not expressed in corresponding noncancerous liver tissues. The clinical pathological data showed that the HCCA2 was significantly associated with the invasion of tumour capsule (P = 0.0007) and the expression of ki-67 protein (P = 0.0022). Immunohistochemical staining confirmed that the HCCA2 protein was localized in cytoplasm of liver cancer tissues. According to amino acid analysis of the protein and its localization, it may play a role in a cascade of intracellular signal transduction because the protein was characterized with two Src homology 3 (SH3) binding-domains and several functional motifs of phosphorylation.

Adult↗

Galpha(i2) enhances insulin signaling via suppression of protein-tyrosine phosphatase 1B.

Suppression of the expression of the heterotrimeric G-protein Galpha(i2) in vivo has been shown to provoke insulin resistance, whereas enhanced insulin signaling is observed when Galpha(i2) is overexpressed in vivo. The basis for Galpha(i2) regulation of insulin signaling was explored in transgenic mice with targeted expression of the GTPase-deficient, constitutively active Q205L Galpha(i2) in fat and skeletal muscle. Phosphorylation of insulin receptor and IRS-1 in response to insulin challenge in vivo was markedly amplified in fat and skeletal muscle expressing Q205L Galpha(i2). The expression and activity of the protein-tyrosine phosphatase 1B (PTP1B), but not protein-tyrosine phosphatases SHP-1, SHP-2, and LAR, were constitutively decreased in tissues expressing the Q205L Galpha(i2), providing a direct linkage between insulin signaling and Galpha(i2). The loss of PTP1B expression may explain, in part, the loss of PTP1B activity in the iQ205L transgenic mice. Activation of Galpha(i2) in mouse adipocytes with lysophosphatidic acid was shown to decrease PTP1B activity, whereas pertussis toxin inactivates Galpha(i2), blocks lysophosphatidic acid-stimulated inhibition of PTP1B activity, and blocks tonic suppression of PTP1B activity by Galpha(i2). Elevation of intracellular cAMP in fat cells is shown to increase PTP1B activity, whereas either depression of cAMP levels or direct activation of Galpha(i2) suppresses PTP1B. These data provide the first molecular basis for the interplay between Galpha(i2) and insulin signaling, i.e. activation of Galpha(i2) can suppress both the expression and activity of PTP1B in insulin-sensitive tissues.

Adipose Tissue↗

Insulin stimulates tyrosine phosphorylation and inactivation of protein-tyrosine phosphatase 1B in vivo.

Protein-tyrosine phosphatase (PTP) 1B has been implicated in negative regulation of insulin action, although little is known of the ability of insulin to regulate PTP1B itself. The ability of insulin to regulate phosphorylation and activation of PTP1B was probed in vivo. Challenge with insulin in vivo provoked a transient, sharp increase in the phosphotyrosine content of PTP1B in fat and skeletal muscle that peaked within 15 min. Insulin stimulated a decline of 60--70% in PTP1B activity. In mouse adipocytes, the inhibition of PTP1B activity and increased tyrosine phosphorylation of the enzyme were blocked by the insulin receptor tyrosine kinase inhibitor AG1024. Phosphoserine content of PTP1B declined in response to insulin stimulation. Elevation of intracellular cyclic AMP provokes a sharp increase in PTP1B activity and leads to increased phosphorylation of serine residues and decreased tyrosine phosphorylation. Suppression of cyclic AMP levels or inhibition of protein kinase A leads to a sharp decline in PTP1B activity, a decrease in phosphoserine content, and an increase in PTP1B phosphotyrosine content. PTP1B appears to be a critical point for insulin and catecholamine counter-regulation.

Adipocytes↗

Cbl promotes ubiquitination of the T cell receptor zeta through an adaptor function of Zap-70.

Triggering of the T cell antigen receptor (TCR).CD3 complex induces its ubiquitination. However, the molecular events that lead to ubiquitin conjugation to these cell surface molecules have not been defined. Here we report that Cbl, a RING-type E3 ubiquitin-protein ligase, promotes ubiquitination of TCR zeta chain, which requires its functional variant Src homology 2 domain and an intact RING finger. The tyrosine kinase Zap-70, which binds to both TCR zeta and Cbl, plays an adaptor role in these events. Mutations in TCR zeta, Zap-70, or Cbl that disrupt the interaction between TCR zeta and Zap-70 or between Zap-70 and Cbl reduce ubiquitination of TCR zeta. Our results suggest a novel mechanism by which Cbl negatively regulates T cell development and activation by inducing ubiquitination of the TCR.CD3 components.

Cell Line↗

Molecular phylogeny of gobioid fishes (Perciformes: Gobioidei) based on mitochondrial 12S rRNA sequences.

The molecular phylogeny of the gobioid fishes, comprising 33 genera and 43 valid species, was examined by use of complete mitochondrial 12S rRNA and tRNA(VAL)genes. Both parsimony and neighbor-joining analyses revealed comparable results and are generally congruent with those of morphological studies. The Odontobutis, which was always placed at the base of the phylogenetic trees, can be treated as a sister group of all other nonrhyacichthyid gobioids. Within eleotrid fishes, the monophyly of the Eleotrinae is strongly supported by molecular data. The Butinae is closer to fishes with five branchiostegal rays and should be treated as a sister group of the latter. The group with five branchiostegal rays, except for sicydiines, can be divided into two groups according to their epural counts. Fish with one epural, the Gobiinae of Pezold plus Microdesmidae, form a monophyletic group which is sister to those with two epurals, the Oxudercinae and Gobionellinae of Pezold. However, Sicydiinae, which have one epural, are closer to the Oxudercinae and Gobionellinae rather than to the Gobiinae. Since progressive reduction in epural number has been observed along this lineage, the sicydiines should be treated as a derived group within the groups with two epurals.

Animals↗