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Biomedical subjects

W Zhang

Publications and source records attributed to W Zhang.

At least 289 records · Page 16Linked to original sources

Effect of long-acting isosorbide-5-mononitrate administration on large artery distensibility in patients with essential hypertension.

To evaluate the clinical efficacy of long-acting nitrates, isosorbide-5-mononitrate (IS-5-MN), on large artery distensibility in patients with essential hypertension. Large arterial distensibility was assessed by automatic noninvasive measurement of the carotid-femoral pulse wave velocity (PWV). Seventeen patients aged 62.53+/-7.94 years (mean+/-SD) with essential hypertension undering long-term antihypertensive therapy were studied in this trial. PWV was measured 2 weeks and 4 weeks after oral administration of IS-5-MN (30 mg once daily) with previous therapy. There was no significant difference in systolic blood pressure, diastolic blood pressure, pulse pressure or heart rate at 2 weeks and 4 weeks after treatment compared with baseline. The carotid-femoral PWV decreased significantly at 2 and 4 weeks after treatment (p<0.05, p< 0.05, respectively). Long-acting nitrates have potential value in improving large arterial distensibility in patients with essential hypertension independent of blood pressure alteration. It might be used as an effectively additive drug in hypertension control.

Administration, Oral↗

Effect of long-term exposure to fluoride in drinking water on risks of bone fractures.

Findings on the risk of bone fractures associated with long-term fluoride exposure from drinking water have been contradictory. The purpose of this study was to determine the prevalence of bone fracture, including hip fracture, in six Chinese populations with water fluoride concentrations ranging from 0.25 to 7.97 parts per million (ppm). A total of 8266 male and female subjects > or =50 years of age were enrolled. Parameters evaluated included fluoride exposure, prevalence of bone fractures, demographics, medical history, physical activity, cigarette smoking, and alcohol consumption. The results confirmed that drinking water was the only major source of fluoride exposure in the study populations. A U-shaped pattern was detected for the relationship between the prevalence of bone fracture and water fluoride level. The prevalence of overall bone fracture was lowest in the population of 1.00-1.06 ppm fluoride in drinking water, which was significantly lower (p < 0.05) than that of the groups exposed to water fluoride levels > or =4.32 and < or =0.34 ppm. The prevalence of hip fractures was highest in the group with the highest water fluoride (4.32-7.97 ppm). The value is significantly higher than the population with 1.00-1.06 ppm water fluoride, which had the lowest prevalence rate. It is concluded that long-term fluoride exposure from drinking water containing > or =4.32 ppm increases the risk of overall fractures as well as hip fractures. Water fluoride levels at 1.00-1.06 ppm decrease the risk of overall fractures relative to negligible fluoride in water; however, there does not appear to be similar protective benefits for the risk of hip fractures.

Aged↗

Maternal and infant factors associated with failure to thrive in children with vertically transmitted human immunodeficiency virus-1 infection: the prospective, P2C2 human immunodeficiency virus multicenter study.

OBJECTIVE: Many children with human immunodeficiency virus-1 (HIV-1) have chronic problems with growth and nutrition, yet limited information is available to identify infected children at high risk for growth abnormalities. Using data from the prospective, multicenter P2C2 HIV study, we evaluated the relationships between maternal and infant clinical and laboratory factors and impaired growth in this cohort. METHODS: Children of HIV-1-infected women were enrolled prenatally or within the first 28 days of life. Failure to thrive (FTT) was defined as an age- and sex-adjusted weight z score < or =-2.0 SD. Maternal baseline covariates included age, race, illicit drug use, zidovudine use, CD4+ T-cell count, and smoking. Infant baseline predictors included sex, race, CD4+ T-cell count, Centers for Disease Control stage, HIV-1 RNA, antiretroviral therapy, pneumonia, heart rate, cytomegalovirus, and Epstein-Barr virus infection status. RESULTS: The study cohort included 92 HIV-1-infected and 439 uninfected children. Infected children had a lower mean gestational age, but birth weights, lengths, and head circumferences in the 2 groups were similar. Mothers of growth-delayed infants were more likely to have smoked tobacco and used illicit drugs during pregnancy. In repeated-measures analyses of weight and length or height z scores, the means of the HIV-1-infected group were significantly lower at 6 months of age (P <.001) and remained lower throughout the first 5 years of life. In a multivariable Cox regression analysis, FTT was associated with a history of pneumonia (relative risk [RR] = 8.78; 95% confidence interval [CI]: 3.59-21.44), maternal use of cocaine, crack, or heroin during pregnancy (RR = 3.17; 95% CI: 1.51-6.66), infant CD4+ T-cell count z score (RR = 2.13 per 1 SD decrease; 95% CI: 1.25-3.57), and any antiretroviral therapy by 3 months of age (RR = 2.77; 95% CI: 1.16-6.65). After adjustment for pneumonia and antiretroviral therapy, HIV-1 RNA load remained associated with FTT in the subset of children whose serum was available for viral load analysis. CONCLUSIONS: Clinical and laboratory factors associated with FTT among HIV-1-infected children include history of pneumonia, maternal illicit drug use during pregnancy, lower infant CD4+ T-cell count, exposure to antiretroviral therapy by 3 months of age (non-protease inhibitor), and HIV-1 RNA viral load.

Adult↗

Sequence verification as quality-control step for production of cDNA microarrays.

To generate cDNA arrays in our core laboratory, we amplified about 2300 PCR products from a human, sequence-verified cDNA clone library. As a quality-control step, we sequenced the PCR products immediately before printing. The sequence information was used to search the GenBank database to confirm the identities. Although these clones were previously sequence verified by the company, we found that only 79% of the clones matched the original database after handling. Our experience strongly indicates the necessity to sequence verify the clones at the final stage before printing on microarray slides and to modify the gene list accordingly.

Gene Library↗

Comparative evaluation of laser-based microarray scanners.

Laboratories use different laser-based scanners to scan microarray images. To assess whether results from different scanners are comparable, and thus whether data from different laboratories can be compared, we scanned the same microarray slide with three commercial scanners that use different imaging techniques. After the acquisition of the microarray images produced by the three scanners, the images were quantified using a single imaging software package and protocol. The results were compared, and we found that the data obtained from the three scanners were comparable and that the variations caused by the use of different instruments were negligible, in spite of the fact that the scanners were based on different optical imaging techniques.

Carbocyanines↗

A build-it-yourself inexpensive lock-out device.

This paper describes a low-cost easily constructed and readily portable "lock-out system" suitable for college bowl and related quiz games. Suggestions on how to use the device are presented.

Competitive Behavior↗

Enhancement of the antiproliferative function of p53 by phosphorylation at serine 20: an inference from site-directed mutagenesis studies.

Recent studies have shown that Ser20 of p53 is phosphorylated in vivo in response to DNA damage caused by ionizing radiation (IR) or ultraviolet radiation (UV), treatments that also result in the induction of p21WAF1/Cip1 (p21) expression. We hypothesized that Ser20 phosphorylation enhances the transactivation function of p53. To test this, we generated two p53 mutants, changing the Ser residue to either Ala, an uncharged form that may mimic unphosphorylated p53, or to Asp, a negatively charged form that may mimic constitutively phosphorylated p53. p53-null cells transfected with the Ser20 phosphorylation-mimicking mutant p53Asp20 demonstrated heightened p21 expression and reduced cell proliferation relative to wild-type p53-transfected cells. Moreover, p53Asp20 exhibited reduced capacity to interact with the Mdm-2 protein in vitro. This abridged interaction had no effect, however, on p53 protein stability. These results suggest that the phosphorylation of p53 at Ser20 is an important mechanism in the activation of the p53/p21 cell-growth inhibitory pathways in response to DNA damage by IR and UV.

Amino Acid Substitution↗

Statistical pattern analysis of gene expression profiles for glioblastoma tissues and cell lines.

The recent development and refinement of cDNA array and genechip techniques allows for large-scale parallel screening of gene expression and thereby provides a global assessment of molecular events transpiring in cell populations. We hypothesized that such an approach might help illuminate current issues in glioma research. To what degree are glioblastoma multiforme (GBM) cell lines representative of primary GBM tumors? We carried out a gene expression profiling study using cDNA array technology on 10 GBM primary tissues and 3 GBM cell lines. The gene expression levels were quantified, and the within-subject ranks of the gene expression levels were subsequently evaluated by hierarchical clustering analysis, multidimensional scaling analysis, and principal component analysis. Hierarchical cluster analysis shows that the 3 cell lines form one main cluster and the 10 tissue samples form a separate cluster. Multidimensional scaling and principal components analysis provided further graphical demonstration that the cell lines are clearly different from the tissue samples and that the cell lines are more different between themselves than are the tissues.

Central Nervous System Neoplasms↗

Identification and spatial analysis of metallothioneins expressed by the adult human lens.

PURPOSE: Metallothioneins (MTs) are a large family of proteins involved in multiple protective pathways including binding of toxic metals, free radical scavenging, and oxidative stress. Increased expression of the MT IIA gene in age-related cataractous relative to normal human lenses, suggesting a role for MTs in the maintenance of lens transparency, has previously been detected. The MT family consists of many closely related isoforms grouped into four classes (I-IV). As a first step toward defining the function of MTs in the lens, the range and expression patterns of those MT isoforms expressed by the adult human lens were established. METHODS: Normal human lenses were microdissected into epithelia and fiber cells. Primers specific for individual MT isoforms were designed. MT transcripts were monitored in whole lenses, epithelia, and fibers by RT-PCR and confirmed to be authentic by sequencing. MT protein levels were evaluated by immunoblotting and by immunostaining. RESULTS: Transcripts encoding MT classes I and II but not III or IV were detected in adult human lenses. In addition to MT IIA, five other MT transcripts were identified including IE, IF, IG, IH, and IL. MT IIA was detected almost exclusively in the lens epithelium, whereas the class I isoforms were detected at high levels in both lens epithelia and fibers. MT protein was detected almost exclusively in the lens epithelium. CONCLUSIONS: The present report establishes the spectrum of MTs expressed by the adult human lens, defines their spatial expression patterns in lens epithelia and fibers, and demonstrates that MT protein is abundantly present in the lens epithelium.

Adolescent↗

[Gene mapping on Blepharophimosis Epicanthus Inversus and Ptosis syndrome type I in Chinese family].

OBJECTIVE: To map the gene responsible for Blepharophimosis Epicanthus Inversus and Ptosis syndrome(BPES) type I in a Chinese family. METHODS: Polymorphisms of 4 satellite markers of 3q were analyzed and linkage analysis was performed using linkage software (MLINK, Version 5.2). RESULTS: No deletion was detected for the four markers. The maximum lod scores were: 0.77 (theta = 0.00) at D3S3045; 3.61 (theta = 0.00) at D3S1764; 0.11 (theta = 0.3) at D3S3053 and -0.03 (theta = 0.4) at D3S2436. CONCLUSION: The gene responsible for BPES in the Chinese family was tightly linked to D3S1764.

Abnormalities, Multiple↗

[An acceptor-splice-site mutation responsible for complete androgen insensitivity syndrome].

OBJECTIVE: To study the molecular mechanism of androgen insensitivity syndrome (AIS) and the relationship among androgen receptor's molecular structure, function and clinical manifestation. METHODS: PCR-SSCP analysis was carried out to screen exons from B to H of androgen receptor(AR) gene in a cAIS patient for AR gene mutation; direct DNA sequencing of PCR product was performed to find out the location and the pattern of the mutation. RESULTS: A newly found point mutation G(3346) to T, which is located at intron 5-exon F acceptor splice site in the AR gene, was identified. CONCLUSION: Highly conserved GU-AG structure at splice site plays a crucial role in maintaining normal function of AR.

Adult↗

Ectopic expression of MyD118/Gadd45/CR6 (Gadd45beta/alpha/gamma) sensitizes neoplastic cells to genotoxic stress-induced apoptosis.

The MyD118/Gadd45/CR6 gene family (also termed Gadd45beta/alpha/gamma) has been identified as genes which are rapidly induced by genotoxic agents, during terminal differentiation, as well as by apoptotic cytokines. In recent years, evidence has emerged that the proteins encoded by these genes play pivotal roles in negative growth control, including growth suppression and apoptotic cell death. However, under what physiological condition these proteins mediate either cell cycle arrest or apoptosis, and the molecular nature of apoptotic pathways involved are currently unclear. Thus, to further explore the effects of these genes on cell growth and cell viability, either in the presence or absence of extrinsic stress, we have established M1 myeloblastic leukemia and H1299 lung carcinoma cell lines, where high level ectopic expression of MyD118, Gadd45, or CR6 can be induced by isopropyl beta-D-thiogalactopyranoside (IPTG). By taking advantage of these cell lines, it was observed that in the absence of genotoxic stress, inducible expression of MyD118, Gadd45 and/or CR6 resulted in retardation of cellular proliferation and accumulation of cells in the G1 phase of the cell cycle. Ectopic expression of these proteins also was found to sensitize the cells to apoptosis induced by genotoxic agents such as UV, MMS, gamma-irradiation and VP16. Finally, evidence has been obtained that in the absence of stress, ectopic expression of MyD118/Gadd45/CR6 is insufficient to activate the MTKl/JNK/p38 stress cascade, and that enhancement of genotoxic stress induced apoptosis by these proteins may involve apoptotic pathways other than the JNK/p38 pathways.

Antigens, Differentiation↗

[Identification of mutation of the X-linked juvenile retinoschisis gene].

OBJECTIVE: To elucidate the pathogeny of X-linked retinoschisis(XLRS) and evaluate its value in direct gene diagnosis. METHODS: Polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP) assay was performed to examine exons of XLRS1 gene in six unrelated retinoschisis cases (3 families and 3 sporadic cases), and fragments with a mobility shift were sequenced to identify the mutation. The deletion mutations were further identified by Southern blotting analysis. RESULTS: Three deletions that eliminate exon 1, exon 2, and exon 3 were found in 4 patients of one family. There was severe effect of the mutation in the coding region. Three kinds of mutations were found in exon 4: Glu72Lys, Glu72Gln, Gly70Ser. CONCLUSION: XLRS is caused by mutation of the XLRS1 gene. The finding helps establish a fast and effective direct diagnosis.

Adolescent↗

Genetic approach to insight into the immunobiology of human dendritic cells and identification of CD84-H1, a novel CD84 homologue.

To better understand the immunobiology of dendritic cells (DCs), we took the expressed sequence tag (EST) approach to describe their transcript profile and discovered novel genes. ESTs (n = 25,668) were generated from monocyte-derived DCs, and 15,863 ESTs (61.8%) represented unique genes in GenBank. Integration of ESTs allowed for the generation of a profile of 4,367 known genes and identification of > 100 novel genes. HLA-DR invariant chain p33, cathepsin D, HLA-DR alpha chain, beta2-microglobulin, HLA-DP beta chain, CD11a, and mannose receptor were in the top 30 transcripts, and 451 known genes were potentially associated with the immunobiology of DCs. This transcript profile was consistent with the unique antigen-presenting capacity of DCs and provided invaluable information to better understand the immunobiology of DCs. On the basis of the EST database, a full-length novel gene was identified that exhibited close homology with CD84; it was designated CD84-H1. The full-length cDNA of CD84-H1 contained an open reading frame of 870 bp encoding a type I transmembrane protein of 289 amino acids. Consistent with the structural feature of the CD2 family, the predicted 270-amino acid mature protein of CD84-H1 contained two extracellular immunoglobulin-like domains that shared homology with CD2 family members, e.g., CD84, Ly-9, CD48, and signaling lymphocyte activation molecule. Its intracellular domain was short and contained no putative signaling structure. Northern blot analysis revealed that CD84-H1 expression was predominantly restricted in hematopoietic tissues. Reverse transcription-PCR analysis showed that it was widely expressed in the immune cells, including monocytes, DCs, B cells, and T cells. These data indicate that CD84-H1 may be relevant to immune responses.

Adult↗

[Research on fibrotic effect of Ni-Ti and 317L alloys in esophagus].

This study was conducted to examiune the fibrotic effect of Ni-Ti and 317L alloys in esophagus. The extract fluid from Ni-Ti, 317L alloys was made according to the ASTM standards of U.S.A. The Fb of esophageal scar was cultured primarily, then incubated with alloy abstract fluid. The proliferating activity of Fb was measured by MTT at 4, 24, 48, 72 hours in the course of culturing. The esophagus embedding test of Ni-Ti, 317L alloys was made according to ASTM standards of U.S.A. The tissue around the alloys was taken at weeks 2 and 12, and the pathologic changes were analysed. The results showed that Ni-Ti, 317L extract could depress the proliferating function of Fb gently, and the depressing action increased gradually with the culturing time. The result of embedding test was in accord with the ASTM standards of U.S.A. completely; the fibrotic membrane around the NiTi, 317L alloys became thinner with embedding time. These findings suggested that the scattering composition of Ni-Ti, 317L in body fluid might not activate the proliferating and secreting function of Fb, and the two alloys could not lead to fibrosis of esophagus aroun them.

Alloys↗

Determination of nucleic acids with crystal violet by a resonance light-scattering technique.

For the first time, Crystal Violet (CV) was used to determine nucleic acid concentrations using the resonance light-scattering (RLS) technique. Based on the enhancement of the RLS of CV by nucleic acids, a new quantitative determination method for nucleic acids in aqueous solutions has been developed. At pH 5.03 and ionic strength 0.005 mol kg-1, the interaction of CV with nucleic acids results in three characteristic RLS peaks at 344.0, 483.0 and 666.0 nm. With 4.0 x 10(-5) mol l-1 of CV, linear relationships were found between the enhanced intensity of RLS at 666.0 nm and the concentration of nucleic acids in the range 0-2.5 micrograms ml-1 for herring sperm DNA, 0-4.0 micrograms ml-1 for calf thymus DNA and 0-4.5 micrograms ml-1 for yeast RNA. The limits of determination were 13.8 ng ml-1 for herring sperm DNA, 36.8 ng ml-1 for calf thymus DNA and 69.0 ng ml-1 for yeast RNA. The assay is convenient, rapid, inexpensive and simple.

Animals↗

[Overexpression of heat shock protein 70 and spontaneous cancer cell apoptosis in hepatocellular carcinoma].

OBJECTIVE: To evaluate the expression of heat shock protein 70 (HSP70) and its relation to spontaneous cancer cell apoptosis in hepatocellular carcinoma (HCC). METHODS: A series of 68 resected HCC tissues from untreated patients and 68 adjacent normal liver tissues were analyzed for HSP70 expression and apoptosis by immunohistochemical SP and TUNEL methods. RESULTS: HSP70 was detected positive in 48/68(71%) cases of HCC and 19/68(28%) cases of the adjacent liver tissues. Overexpression of HSP70 was found in 36/68(53%) cases of HCC and 14/68(21%) cases of the liver tissues. The positive rate and overexpression of HSP70 were significantly higher in HCC than in the liver tissues (P<0.01). Apoptosis index was 8.9 in HCC and 1.9 in the liver tissues, showing significant different between the two groups (P<0.01). The positive rate of HSP70 was correlated with apoptosis index (r=0.8765, P<0.05) and both of them correlated with HCC histological grades. CONCLUSIONS: These results suggest that there is an overexpression of HSP70 and spontaneous cancer cell apoptosis in HCC. They seem to be markers of poor proliferation.

Apoptosis↗

Evaluation of methoxsalen, tranylcypromine, and tryptamine as specific and selective CYP2A6 inhibitors in vitro.

CYP2A6 is the principle enzyme metabolizing nicotine to its inactive metabolite cotinine. In this study, the selective probe reactions for each major cytochrome P450 (P450) were used to evaluate the specificity and selectivity of the CYP2A6 inhibitors methoxsalen, tranylcypromine, and tryptamine in cDNA-expressing and human liver microsomes. Phenacetin O-deethylation (CYP1A2), coumarin 7-hydroxylation (CYP2A6), diclofenac 4'-hydroxylation (CYP2C9), omeprazole 5-hydroxylation (CYP2C19), dextromethorphan O-demethylation (CYP2D6), 7-ethoxy-4-trifluoromethylcoumarin deethylation (CYP2B6), p-nitrophenol hydroxylation (CYP2E1), and omeprazole sulfonation (CYP3A4) were used as index reactions. Apparent K(i) values for inhibition of P450s' (1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, and 3A4) activities showed that tranylcypromine, methoxsalen, and tryptamine have high specificity and relative selectivity for CYP2A6. In cDNA-expressing microsomes, tranylcypromine inhibited CYP2A6 (K(i) = 0.08 microM) with about 60- to 5000-fold greater potency relative to other P450s. Methoxsalen inhibited CYP2A6 (K(i) = 0.8 microM) with about 3.5- 94-fold greater potency than other P450s, except for CYP1A2 (K(i) = 0.2 microM). Tryptamine inhibited CYP2A6 (K(i) = 1.7 microM) with about 6.5- 213-fold greater potency relative to other P450s, except for CYP1A2 (K(i) = 1.7 microM). Similar results were also obtained with methoxsalen and tranylcypromine in human liver microsomes. R-(+)-Tranylcypromine, (+/-)-tranylcypromine, and S-(-)-tranylcypromine competitively inhibited CYP2A6-mediated metabolism of nicotine with apparent K(i) values of 0.05, 0.08, and 2.0 microM, respectively. Tranylcypromine [particularly R-(+) isomer], tryptamine, and methoxsalen are specific and relatively selective for CYP2A6 and may be useful in vivo to decrease smoking by inhibiting nicotine metabolism with a low risk of metabolic drug interactions.

Aryl Hydrocarbon Hydroxylases↗