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Biomedical subjects

H Zhang

Publications and source records attributed to H Zhang.

At least 163 records · Page 9Linked to original sources
PubMed2002

Sonic hedgehog regulates otic capsule chondrogenesis and inner ear development in the mouse embryo.

Development of the cartilaginous capsule of the inner ear is dependent on interactions between otic epithelium and its surrounding periotic mesenchyme. During these tissue interactions, factors endogenous to the otic epithelium influence the differentiation of the underlying periotic mesenchyme to form a chondrified otic capsule. We report the localization of Sonic hedgehog (Shh) protein and expression of the Shh gene in the tissues of the developing mouse inner ear. We demonstrate in cultures of periotic mesenchyme that Shh alone cannot initiate otic capsule chondrogenesis. However, when Shh is added to cultured periotic mesenchyme either in combination with otic epithelium or otic epithelial-derived fibroblast growth factor (FGF2), a significant enhancement of chondrogenesis occurs. Addition of Shh antisense oligonucleotide (AS) to cultured periotic mesenchyme with added otic epithelium decreases levels of endogenous Shh and suppresses the chondrogenic response of the mesenchyme cells, while supplementation of Shh AS-treated cultures with Shh rescues cultures from chondrogenic inhibition. We demonstrate that inactivation of Shh by targeted mutation produces anomalies in the developing inner ear and its surrounding capsule. Our results support a role for Shh as a regulator of otic capsule formation and inner ear development during mammalian embryogenesis.

Animals↗
PubMed2002

Determination of chromium speciation in natural systems using DGT.

The techniques of diffusive gradients (DGT) and equilibration (DET) in thin-films have been combined in a single probe that can determine Cr(III) and Cr(VI) simultaneously in solution. The assembly has a layer of polyacrylamide hydrogel overlying a separate layer of resin embedded in gel. Cr(III) species accumulate exclusively and quantitatively in the resin layer, while Cr(VI) species equilibrate with both hydrogel and resin layers. The species are separated by peeling the two layers apart. Chromium is then eluted from each of the two layers. Cr(III) and Cr(VI) were determined quantitatively in standard, mixed solutions by in situ separation with DGT and detection by GF-AAS. With this method, Cr(III) is typically preconcentrated by a factor of 10 over a 24 h deployment, and limits of detection of 8 ng/L Cr(III) and 0.3 micro g/L Cr(VI) were achieved. Due to the inbuilt preconcentration of Cr(III), the technique is particularly good at measuring low concentrations of Cr(III) in the presence of an excess of Cr(VI). Measurements were performed in three soils with various levels of chromium contamination. A concentration of 3 micro g/L of labile Cr(III) was measured reproducibly in the presence of 290 micro g/L of unreactive Cr species and 0.2 micro g/L of labile Cr(III) was measured in the presence of 24 micro g/L of unreactive Cr. The unique feature of the method is that the separation of Cr(III) from Cr(VI) occurs in situ. The Cr species are then stable in the resin and gel prior to analysis, eliminating the artefacts associated with sampling and storage, which are particularly prevalent for redox-sensitive elements. Therefore, it has great potential for assessing Cr(III) and Cr(VI) concentrations in situ in environments near redox boundaries where possible dynamic changes in Cr(III) and Cr(VI) concentrations are occurring.

Journal Article↗
PubMed2002

Effects of cigarette smoking on quinine pharmacokinetics in malaria.

OBJECTIVE: Quinine is an important antimalarial drug that is metabolised mainly by the hepatic mixed-function microsomal enzyme cytochrome P(450). Cigarette smoking in healthy volunteers has been reported to enhance quinine clearance. The present study evaluated the effects of smoking on quinine pharmacokinetics in patients with uncomplicated falciparum malaria treated with a 7-day course of oral quinine. Of 22 studied male patients, 10 were regular smokers and 12 were non-smokers. METHODS: All patients were treated with a 7-day oral regimen of quinine sulfate (10 mg salt/kg three times a day). Serial venous blood samples were taken for quinine levels before and during treatment at 12 h and 24 h and then daily until day 7. Plasma quinine and 3-hydroxyquinine concentrations were assayed using high-performance liquid chromatography. Quinine pharmacokinetics were evaluated using non-compartmental modelling. RESULTS: All patients recovered, and there were no significant differences in clinical responses or cure rates between the two studied groups ( P> or =0.32). The median (range) fever clearance time was 51 h (4-152 h) and mean (SD) parasite clearance time was 74+/-28 h. The overall median times to maximum concentrations of quinine and its main metabolite 3-hydroxyquinine were 1.5 days and 4.0 days, respectively. The maximum concentrations of quinine were approximately tenfold higher than 3-hydroxyquinine. There were no significant differences in any pharmacokinetic variables for the parent compound or metabolite between the two groups. The median area under the plasma drug concentration-time curve to day 7 (AUC(0-7)) of quinine in non-smokers was 67.0 micro g/ml/day and in smokers was 51.3 micro g/ml/day, and AUC(0-7) values of 3-hydroxyquinine were 6.2 micro g/ml/day and 4.8 micro g/ml/day, respectively. CONCLUSION: These results indicated that cigarette smoking has no significant effects on quinine pharmacokinetics or the therapeutic response in patients with falciparum malaria.

Acute Disease↗
PubMed2002

Predicting arsenic solubility in contaminated soils using isotopic dilution techniques.

An isotopic dilution assay was developed to measure radiolabile As concentration in a diverse range of soils (pH 3.30-7.62; % C = 1.00-6.55). Soils amended with 50 mg of As kg(-1) (as Na2HAsO4 x 7H2O) were incubated for over 800 d in an aerated "microcosm" experiment. After 818 d, radiolabile As ranged from 27 to 57% of total applied As and showed a pH-dependent increase above pH 6. The radiolabile assay was also applied to three sets of soils historically contaminated with sewage sludge or mine-spoil. Results reflected the various geochemical forms in which the arsenic was present. On soils from a sewage disposal facility, radiolabile arsenate ranged from 3 to 60% of total As; mean lability was lower than in the equivalent pH range of the microcosm soils, suggesting occlusion of As into calcium phosphate compounds in the sludge-amended soils. In soils from mining areas in the U.K. and Malaysia, radiolabile As accounted for 0.44-19% of total As. The lowest levels of lability were associated with extremely large As concentrations, up to 17,000 mg kg(-1), from arsenopyrite. Soil pore water was extracted from the microcosm experiment and speciated using "GEOCHEM". The solid<==>solution equilibria of As in the microcosm soils was described by a simple model based on competition between HAsO4(2-) and HPO4(2-) for "labile" adsorption sites.

Arsenic↗
PubMed2002

Selection of in vitro mutants of pyrazinamide-resistant Mycobacterium tuberculosis.

Mutations within the pncA gene coding for pyrazinamidase of Mycobacterium tuberculosis can cause pyrazinamide (PZA) resistance. The effect of drug concentrations on PZA resistance in a clinical isolate of M. tuberculosis was studied in vitro. Serial passage at gradually increased concentrations of PZA from 200 to 500 microg/ml was performed using BACTEC radiometric method. Thirteen in vitro-selected variant strains were assembled and sequence analysis showed that 12 of the 13 variants had a novel single point mutation within the pncA gene by deletion at nucleotide 381 (G), codon 127. This lead to a frameshift that affected the function of the pyrazinamidase resulting in PZA resistance regardless of different PZA concentrations used. One variant had a silent mutation at nucleotide 6 (G-->A) and remains PZA sensitive. We conclude that the mutation location found is an important position for full resistance, at least in this strain. The lack of further mutations even after exposure to higher PZA concentrations implies a critical value for development of resistance-a level exceeded in tissues in clinical treatment regimes.

Antitubercular Agents↗
PubMed2002

Age- and gender-related differences in bone mineral status and biochemical markers of bone metabolism in Northern Chinese men and women.

The aim of this study was to provide insight into the bone mineral status and biochemical markers of bone metabolism in a Chinese population from Shenyang, in the north of China, where hip fracture incidence is low. A total of 194 healthy men and women, aged 25-35 years and 65-75 years, were studied. Bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN) was measured using dual-energy X-ray absorptiometry. Fasting blood and 24 h urine samples were collected for bone alkaline phosphatase (bAP), osteocalcin, calcium, phosphate, and free deoxypyridinoline (Dpd). Both older women and men had lower BMD compared with younger women and men by 27.2 +/- 3.0% (mean +/- SE) and 9.8 +/- 3.0% at the LS and 22.0 +/- 3.4% and 12.8 +/- 3.4% at the FN, respectively, after adjusting for bone and body size (p < 0.01). BMD at the two sites was lower in older women than in older men by 10.7 +/- 4.1% and 10.2 +/- 4.2%, respectively, after size correction (p < 0.05). Plasma bAP, osteocalcin, calcium, and phosphate concentrations were higher in older women than younger women by 69.3 +/- 9.7%, 77.2 +/- 11.1%, 7.5 +/- 2.3%, and 8.0 +/- 3.8%, respectively, and older men by 67.6 +/- 11.1%, 72.1 +/- 11.0%, 7.7 +/- 2.3%, and 23.8 +/- 3.8%, respectively (p < 0.01). However, plasma osteocalcin, calcium, and phosphate concentrations were lower in older men compared with their younger counterparts by 35.6 +/- 11.0%, 8.7 +/- 2.3%, and 14.1 +/- 3.8%, respectively (p < 0.05). Urinary calcium and phosphate output were lower in older men compared with younger men by 48.0 plus minus 10.3% and 27.6 +/- 6.9%, respectively (p < 0.01), whereas there were no differences between older and younger women. No differences in Dpd between older and younger groups were found. This study demonstrates that bone mineral status is lower in older people in Shenyang, as has been shown in populations elsewhere. The pronounced low bone mineral status in older women may be associated with increased bone turnover, which was not observed in older men.

Adult↗
PubMed2002

Reelin gene alleles and susceptibility to autism spectrum disorders.

A polymorphic trinucleotide repeat (CGG/GCC) within the human Reelin gene (RELN) was examined as a candidate gene for autism spectrum disorders (ASDs). This gene encodes a large extracellular matrix protein that orchestrates neuronal positioning during corticogenesis. The CGG-repeat within the 5' untranslated region of RELN exon 1 was examined in 126 multiple-incidence families. The number of CGG repeats varied from three to 16 in affected individuals and controls, with no expansion or contraction observed during maternal (n = 291) or paternal (n = 287) transmissions in families with autistic probands. Although the frequencies of the RELN alleles and genotypes in affected children were not different from those in the comparison group, a family-based association test (FBAT) showed that the larger RELN alleles (> or = 11 repeats) were transmitted more often than expected to affected children (S = 43, E(S) = 34.5, P = 0.035); this was particularly the case for the 13-repeat RELN allele (S = 22, E(S) = 16, P = 0.034). Affected sib-pair (ASP) analysis found no evidence of excess sharing of RELN alleles in affected siblings. The impact of genotypes with large alleles (> or = 11 repeats) on the phenotypes in individuals with ASD was analyzed by ANOVA in a subset of the families for which results of the Autism Diagnostic Interview-Revised were available. Children with large RELN alleles did not show any difference in scores for questions related to the core symptoms of autistic disorder, but there was a tendency for children with at least one large RELN allele to have an earlier age at first phrase (chi(2) = 3.538, P = 0.06). Thus, although the case-control and affected sib-pair findings did not support a role for RELN in susceptibility to ASD, the more powerful family-based association study demonstrated that RELN alleles with larger numbers of CGG repeats may play a role in the etiology of some cases of ASD, especially in children without delayed phrase speech.

Autistic Disorder↗
PubMed2002

Survival-promoting functions of 14-3-3 proteins.

The 14-3-3 proteins are a family of phosphoserine/phosphothreonine-binding molecules that control the function of a wide array of cellular proteins. We suggest that one function of 14-3-3 is to support cell survival. 14-3-3 proteins promote survival in part by antagonizing the activity of associated proapoptotic proteins, including Bad and apoptosis signal-regulating kinase 1 (ASK1). Indeed, expression of 14-3-3 inhibitor peptides in cells is sufficient to induce apoptosis. Interestingly, these 14-3-3 antagonist peptides can sensitize cells for effective killing by anticancer agents such as cisplatin. Thus, 14-3-3 may be part of the cellular machinery that maintains cell survival, and targeting 14-3-3-ligand interactions may be a useful strategy to enhance the efficacy of conventional anticancer agents.

14-3-3 Proteins↗
PubMed2002

Identifying patient and physician characteristics that affect compliance with antihypertensive medications.

BACKGROUND: Compliance with antihypertensive medications is essential to the clinical management of hypertension. Poor compliance with antihypertensive medications has often been associated with treatment failure and disease progression. OBJECTIVE: To identify patient and prescriber characteristics that may influence compliance with antihypertensive medications. METHOD: We used pharmacy records within the Veterans Health Administration, a database which included 1292 patients and 656 physicians over a 2-year time period from April 1, 1996, to April 1, 1998. The level of compliance with antihypertensive medications was assessed using a measure developed for this purpose within the Administration. Three separate ordinary least squares regression models were conducted to ascertain the effects of patient and physician characteristics on compliance. RESULTS: Despite the importance of compliance in the clinical management of hypertension, poor compliance with antihypertensive drug treatment was still widespread. Patients who were younger and less active in their treatment decisions tended to be less compliant (P < 0.05 and 0.05, respectively). Health care providers who were older, residents in speciality care, and physicians (as compared with non-physicians) had patients who were also less likely to be compliant (P < 0.01, 0.01, and 0.05, respectively). CONCLUSION: These findings suggest that in order to increase the effectiveness of medical care for hypertension, it is important to improve compliance with antihypertensive agents.

Adult↗
PubMed2002

Enterovirus replication in valvular tissue from patients with chronic rheumatic heart disease.

AIMS: To investigate the involvement of enterovirus infection in chronic, rheumatic heart disease. METHODS AND RESULTS: Formalin-fixed, paraffin-embedded, surgical samples of valve tissue were examined for the presence of enteroviral RNA and virus capsid protein VP1 by in situ hybridization and immunostaining. Of 53 cases, 33 were patients with chronic rheumatic heart disease and 20 had Marfan's syndrome or degenerative valve disease. Enterovirus RNA was detected in 8 (24.2%) of 33 patients with chronic rheumatic heart disease by in situ hybridization using strand-specific oligonucleotide probes, complementary to conserved sequences in enterovirus genomic (positive strand) RNA. The replication template (negative strand) RNA also was found in seven of these eight cases. The viral capsid protein VP1 was detected in 16 (48.5%) of 33 patients with chronic rheumatic heart disease by immunohistochemistry and correlated with viral RNA detection. Virus was localized generally to valvular tissue. Neither viral RNA nor capsid protein VP1 were found in valvular tissue from any of the 20 comparison cases. CONCLUSIONS: This is the first demonstration of detection and localization of both enterovirus RNA and capsid protein in chronic rheumatic heart disease. The presence of negative strand RNA and VP1 indicates enteroviral RNA replication and protein synthesis and suggests an aetiological role of enterovirus in the pathogenesis of chronic rheumatic heart disease.

Adult↗
PubMed2002

Microarray analysis reveals the involvement of beta-2 microglobulin (B2M) in human osteoarthritis.

OBJECTIVE: To assess whether beta-2 microglobulin (B2M) has effects on articular chondrocytes that would implicate B2M involvement in osteoarthritis (OA) pathogenesis. METHODS: The mRNA levels of B2M in fetal and osteoarthritic chondrocytes were detected by RT-PCR. B2M levels in synovial fluid and tissue cultured media from cartilage explants were tested using B2M ELISA kit. Primary cultured chondrocytes were used for proliferation and microarray experiments. RESULTS: The average B2M level in OA synovial fluid is significantly higher than that found in normal synovial fluid. However, there was no significant difference in B2M synovial fluid levels amongst differing OA stages. The release of B2M by osteoarthritic cartilage was detectable after 24h in culture and continued to increase during the 72 h study period. B2M had an inhibitory effect on chondrocyte growth at 1.0 microg/ml, and became significantly inhibitory at 10.0 microg/ml. Genes regulated by B2M were detected through microarray technology. Twenty genes were found to be up-regulated by B2M, including collagen type III which is known to be up-regulated in OA. Eleven genes were found to be down-regulated at least two-fold by B2M. CONCLUSION: These results indicate that B2M is highly expressed in OA cartilage and synovial fluid compared to normal, and suggest that B2M may have effects on chondrocyte function that could contribute to OA pathogenesis. Published by Elsevier Science Ltd.

Cartilage, Articular↗
PubMed2002

Human-bacteria nitric oxide cycles in HIV-1 infection.

The human intestinal tract harbors a complex microbiotic environment containing commensal bacteria and immunocompetent mucosal cells. There is considerable communication between the bacteria and host cells through dietary constituents and metabolic cycles. We propose that in the pathogenesis of acquired immunodeficiency syndrome (AIDS), the human immunodeficiency virus-1 (HIV-1) triggers a change in a coupled transorganism (human-bacteria) nitric oxide interchange cycle, that may influence the biosynthesis and recycling of nitric oxide (NO) in AIDS patients. Normally, nitric oxide (NO) is produced from arginine through nitrate NO(3)(-), which is ultimately eliminated in the urine and feces. In HIV infection, however, the NO(3)(-) is converted into NO and nitrite NO(2)(-) and recirculated in the body, perhaps as a result of concomitant opportunistic bacterial infections and cellular hypoxia. Due to the efficient coupling of the human-bacteria nitric oxide cycles, persistently high levels of nitrite and the free radicals peroxynitrite (ONOO(-)) may occur in AIDS patients, contributing to the etiology of AIDS-related dementia, persistent immunosuppression and Kaposi's sarcoma.

Bacterial Physiological Phenomena↗
PubMed2002

Quantitative oculographic characterisation of internuclear ophthalmoparesis in multiple sclerosis: the versional dysconjugacy index Z score.

BACKGROUND: There is a poor correlation between multiple sclerosis disease activity, as measured by magnetic resonance imaging, and clinical disability. OBJECTIVE: To establish oculographic criteria for the diagnosis and severity of internuclear ophthalmoparesis (INO), so that future studies can link the severity of ocular dysconjugacy with neuroradiological abnormalities within the dorsomedial brain stem tegmentum. METHODS: The study involved 58 patients with multiple sclerosis and chronic INO and 40 normal subjects. Two dimensional infrared oculography was used to derive the versional dysconjugacy index (VDI)-the ratio of abducting to adducting eye movements for peak velocity and acceleration. Diagnostic criteria for the diagnosis and severity of INO were derived using a Z score and histogram analysis, which allowed comparisons of the VDI from multiple sclerosis patients and from a control population. RESULTS: For a given saccade, the VDI was typically higher for acceleration v velocity, whereas the Z scores for velocity measures were always higher than values derived from comparable acceleration VDI measures; this was related to the greater variability of acceleration measures. Thus velocity was a more reliable measure from which to determine Z scores and thereby the criteria for INO and its level of severity. The mean (SD) value of the VDI velocity derived from 40 control subjects was 0.922 (0.072). The highest VDI for velocity from a normal control subject was 1.09, which was 2.33 SD above the normal control mean VDI. We therefore chose 2 SD beyond this value (that is, a Z score of 4.33) as the minimum criterion for the oculographic confirmation of INO. Of patients thought to have unilateral INO on clinical grounds, 70% (16/23) were found to have bilateral INO on oculographic assessment. CONCLUSIONS: INO can be confirmed and characterised by level of severity using Z score analysis of quantitative oculography. Such assessments may be useful for linking the level of severity of a specific clinical disability with neuroradiological measures of brain tissue pathology in multiple sclerosis.

Case-Control Studies↗
PubMed2002

Oncological diagnosis using positron coincidence gamma camera with fluorodeoxyglucose in comparison with dedicated PET.

The purpose of this study was to compare the utility of a dual-head positron coincidence detection gamma camera (PCD) with that of dedicated positron emission tomography (PET) in the imaging of various malignancies using (18)F-fluorodeoxyglucose (FDG). 25 patients with known or suspected malignancies at various sites underwent imaging with both methods, and diagnostic performance on a lesion basis was compared. Tumour lesions were analyzed visually and semi-quantitatively using the ratio of tumour-to-background counts (T/B ratio). FDG PCD and FDG PET visually detected 34 (72.3%) lesions and 37 (78.7%) lesions, respectively. The mean T/B ratio and standard deviation (SD) of FDG PCD was 3.5+/-3.3, significantly lower than that of FDG PET (8.4+/-7.1, p<0.001). When tumour lesions were less than 2.0 cm in diameter, the sensitivity of FDG PCD was 37.5%, significantly inferior to that of FDG PET (50.0%, p<0.01). Sensitivity between FDG PCD and FDG PET in lesions of more than 2.0 cm diameter showed no statistically significant difference. This study indicates that FDG imaging with a dual-head coincidence detection gamma camera can provide suitable diagnostic performance for lesions greater than 2.0 cm diameter, but performed significantly worse than dedicated PET for lesions smaller than this.

Adult↗
PubMed2002

The effects of cigarette smoke extract on the endothelial production of soluble intercellular adhesion molecule-1 are mediated through macrophages, possibly by inducing TNF-alpha release.

Cigarette smoke (CS) is a major risk factor for many human diseases, although the underlying mechanisms are not clearly understood. This study was undertaken to investigate the effect of a water-soluble CS extract (CSE) on soluble intercellular adhesion molecule-1 (sICAM-1) production by human umbilical vein endothelial cells (HUVEC) mediated through ANA-1 macrophages. First, macrophages were incubated with or without CSE, and the supernatants collected at different time points were used to measure the levels of tumor necrosis factor-alpha (TNF-alpha) and sICAM-1 by enzyme-linked immunosorbent assay (ELISA); and second, HUVEC were cultured with CSE, a vehicle, or ANA-1 supernatants (collected at different time points) and the sICAM-1 levels in the supernatants were measured by ELISA at 24 h. The results showed that: i) CSE showed no effect on the production of sICAM-1 by HUVEC; ii) sICAM-1, in unstimulated or CSE-stimulated ANA-1 supernatants collected at different time points, was under the detectable level; iii) CSE-stimulated ANA-1 supernatants collected at 3 or 6 h showed no effect on sICAM-1 production in HUVEC, while those collected at 12 and 24 h significantly increased sICAM-1 production (p < 0.02 and p < 0.005, respectively); iv) no significant difference in TNF-alpha levels was detected between unstimulated and CSE-stimulated macrophage supernatants collected at 3 and 6 h, however, higher levels of TNF-alpha were found in CSE-stimulated supernatants collected at 12 and 24 h (p < 0.05 and p < 0.002, respectively); and v) a significant correlation (r = 0.9693, p < 0.001) was found between the levels of TNF-alpha in CSE-stimulated ANA-1 supernatants and those of related sICAM-1 production in HUVEC. These findings indicate that CSE indirectly increases the production of sICAM-1 in HUVEC by activating macrophages, which possibly induces the release of TNF-alpha from them, which in turn enhances the production of sICAM-1 from HUVEC.

Cells, Cultured↗