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Biomedical subjects

N He

Publications and source records attributed to N He.

At least 19 recordsLinked to original sources
PubMed2007

Substance use and HIV risks among male heterosexual and 'money boy' migrants in Shanghai, China.

There is a growing awareness that internal migration in China might shift the HIV epidemic by broadening the social and sexual mixing of its population. However, little is known about how drug use/abuse might contribute to the spread of HIV. This qualitative study aims to elucidate factors for preventing substance abuse and HIV among two types of male migrants living in the Shanghai metropolitan area; the general migrant population and so-called 'money boys' (those who engaged in same-sex activities for money). Compared to most male migrants, the 'money boys' had a slightly better economic situation; rarely visited their hometowns; used alcohol less but drugs more; had more knowledge about HIV and sexually transmitted diseases; higher HIV/ STD testing rates and fewer HIV risk behaviors. The general male migrants had more misconceptions about HIV (e.g. the need to pay for HIV testing) than the 'money boys'. However, it was noted that 'money boys' who were new to the enterprise and men who have sex with men but did not engage in commercial sex often lacked HIV knowledge and protective skills. Given the needs of various sub-types of 'migrants', differential approaches to HIV prevention are needed.

Adolescent↗
PubMed2003

A novel polygalacturonic acid bioflocculant REA-11 produced by Corynebacterium glutamicum: a proposed biosynthetic pathway and experimental confirmation.

Corynebacterium glutamicum CCTCC M201005 produces a novel polygalacturonic acid bioflocculant, REA-11, consisting of galacturonic acid as the main structural unit. A biosynthetic pathway of REA-11 in C. glutamicum CCTCC M201005 was proposed. Evidence for the biosynthetic pathway was provided by: (1) analyzing the response upon addition of UDP-glucose to the culture medium; (2) detecting the presence of several key intermediates in the pathway; and (3) correlating the activities of several key enzymes involved in the pathway with the yields of polygalacturonic acid. The production of polygalacturonic acid was improved by 24%, while the activities of UDP-galactose epimerase and UDP-galactose dehydrogenase were improved by 200% and 50%, respectively, upon addition of 100 microM UDP-glucose. In addition, the key intermediates in the proposed biosynthetic pathway, such as UDP-glucose, UDP-galactose, and UDP-glucuronic acid, were detected in cell-free extracts. Furthermore, the activities of UDP-glucose pyrophosphorylase (R2=0.97), UDP-galactose epimerase (R2=0.75) and UDP-galactose dehydrogenase (R2=0.89) were well correlated with the yields of polygalacturonic acid when different sugars were used as sole carbon sources. Therefore, the biosynthetic pathway of REA-11 in C. glutamicum CCTCC M201005 starts from phosphate-1-glucose, which was then converted to UDP-glucose by UDP-pyrophosphorylase. Predominantly, the UDP-glucose was converted to UDP-galactose by UDP-galactose epimerase; the latter was further converted to UDP-galacturonic acid by UDP-galactose dehydrogenase, which was presumably polymerized to polygalacturonic acid bioflocculant REA-11 by an unknown glucosyltransferase and a polymerase.

Corynebacterium↗
PubMed2001

Bilineal disease and trans-heterozygotes in autosomal dominant polycystic kidney disease.

In searching for a putative third gene for autosomal dominant polycystic kidney disease (ADPKD), we studied the genetic inheritance of a large family (NFL10) previously excluded from linkage to both the PKD1 locus and the PKD2 locus. We screened 48 members of the NFL10 pedigree, by ultrasonography, and genotyped them, with informative markers, at both the PKD1 locus and the PKD2 locus. Twenty-eight of 48 individuals assessed were affected with ADPKD. Inspection of the haplotypes of these individuals suggested the possibility of bilineal disease from independently segregating PKD1 and PKD2 mutations. Using single-stranded conformational analysis, we screened for and found a PKD2 mutation (i.e., 2152delA; L736X) in 12 affected pedigree members. Additionally, when the disease status of these individuals was coded as "unknown" in linkage analysis, we also found, with markers at the PKD1 locus, significant LOD scores (i.e., >3.0). These findings strongly support the presence of a PKD1 mutation in 15 other affected pedigree members, who lack the PKD2 mutation. Two additional affected individuals had trans-heterozygous mutations involving both genes, and they had renal disease that was more severe than that in affected individuals who had either mutation alone. This is the first documentation of bilineal disease in ADPKD. In humans, trans-heterozygous mutations involving both PKD1 and PKD2 are not necessarily embryonically lethal. However, the disease associated with the presence of both mutations appears to be more severe than the disease associated with either mutation alone. The presence of bilineal disease as a confounder needs to be considered seriously in the search for the elusive PKD3 locus.

Amino Acid Sequence↗
PubMed2001

Pharmacokinetics of sertraline in relation to genetic polymorphism of CYP2C19.

OBJECTIVE: Our objective was to evaluate the relationship between the disposition of sertraline and the presence of the CYP2C19 gene and to define the contribution of cytochrome P450 2C19 (CYP2C19) to sertraline N-demethylation. METHODS: A single oral 100-mg dose of sertraline was administered to 6 subjects who were extensive metabolizers and 6 subjects who were poor metabolizers recruited from 77 healthy Chinese volunteers whose genotypes were predetermined by polymerase chain reaction-based amplification, followed by restriction fragment length polymorphism analysis. Phenotypes were determined by use of the omeprazole metabolic rate. The plasma concentrations of sertraline and desmethylsertraline were determined by gas chromatography with electron-capture detection. RESULTS: Six poor metabolizers with m1 mutation had area under the plasma concentration versus time curve (AUC(0-infinity)) values (983.6 +/- 199.3 microg x h/L versus 697.6 +/- 133.0 microg x h/L; P <.05) and terminal elimination half-life values of sertraline (35.5 +/- 5.6 hours versus 23.5 +/- 4.4 hours; P <.01) that were significantly higher than the values in 6 extensive metabolizers who were either homozygous or heterozygous for CYP2C19*1. The oral clearance of sertraline in poor metabolizers (105.3 +/- 19.4 L/h) was significantly lower than that of extensive metabolizers (148.4 +/- 28.6 L/h). The area under the concentration-time curve from 0 to 144 hours and the maximum plasma concentration of desmethylsertraline in poor metabolizers were significantly lower than the values of extensive metabolizers (627.6 +/- 203.8 microg x h/L versus 972.1 +/- 270.3 microg x h/L; P <.05; and 23.6 +/- 6.5 nmol/L versus 32.4 +/- 8.2 nmol/L; P <.01; respectively). CONCLUSIONS: The polymorphic CYP2C19 appears to be a major enzyme involved in the N-demethylation of sertraline, and both extensive and poor metabolizers had marked differences in the disposition of sertraline.

Administration, Oral↗
PubMed2001

Assessment of cytochrome P450 activity by a five-drug cocktail approach.

OBJECTIVES: Our goal was to establish and validate a modified cocktail approach including probe drugs caffeine, chlorzoxazone, mephenytoin, metoprolol, and midazolam for simultaneous phenotyping of CYP1A2, CYP2E1, CYP2C19, CYP2D6, and CYP3A. METHODS: The study was conducted in 14 healthy, nonsmoking male volunteers with a cocktail of 5 drugs consisting of 100 mg caffeine, 200 mg chlorzoxazone, 100 mg mephenytoin, 100 mg metoprolol, and 7.5 mg midazolam in a randomized manner with a 7 x 7 Latin square design. Plasma was obtained at 1, 4, and 6 hours, and urine was collected from 0 to 8 hours after oral drug administration. RESULTS: The phenotypic indexes determined for caffeine, chlorzoxazone, mephenytoin, metoprolol, and midazolam were not significantly different when the drugs were given in different combinations. There were no metabolic interactions or analytic interference of these probe drugs. CONCLUSIONS: This cocktail approach can simultaneously provide independent in vivo phenotypic measures for the cytochrome P450 (CYP) enzymes CYP1A2, CYP2E1, CYP2C19, CYP2D6, and CYP3A.

Adult↗
PubMed2001

Zinc-alpha(2)-glycoprotein hinders cell proliferation and reduces cdc2 expression.

Zinc-alpha(2)-glycoprotein (Znalpha(2)gp) is widely distributed in body fluids and epithelia. Its expression in stratified epithelia increases with differentiation. We previously showed that Zn alpha(2)gp has ribonuclease activity, and that squamous tumor cells grown on a matrix of Znalpha(2)gp were growth-inhibited. Here we demonstrate, both by adding Znalpha(2)gp to the culture medium and, more unequivocally, by stably transfecting SiHa cells with Znalpha(2)gp cDNA, that the introduction of Znalpha(2)gp into SiHa tumor cells reduces proliferation. In response to Znalpha(2)gp, we find an accumulation of the cell population in G(2)/M by flow cytometry, paralleling the reduction of proliferation. In order to distinguish growth inhibition by cell cycle arrest from that produced by apoptosis or differentiation, we examine by RT-PCR how Znalpha(2)gp affects the expression of genes commonly used as markers of these properties. No changes are observed for PCNA, p53, c-myc, or bcl-2. Only cdc2 expression responds to Znalpha(2)gp, with a reduction of up to over a factor of two. Cdc2 is the only cyclin-dependent kinase regulating the G(2)/M transition without redundancy and is required as a rate-limiting step in the cell cycle. Its increased expression has been directly linked to increased proliferation and decreased differentiation of advanced tumors; conversely, its downregulation by Znalpha(2)gp might hinder tumor progression. J. Cell. Biochem. Suppl. 36: 162-169, 2001.

Blotting, Western↗
PubMed2001

[Treatment of severe hepatitis with artificial liver support system and liver transplantation].

OBJECTIVE: To observe and investigate the efficacy of the hybrid artificial liver support system plus liver transplantation in the treatments of patients with severe viral hepatitis. METHODS: Eight severe viral hepatitis patients with metaphase and advanced stage liver failure received the artificial liver support using a self-command extracorporeal hybrid artificial liver support system and orthotopic liver transplantation after the artificial support for 3-14 days. RESULTS: The liver failure of the 8 patients was controlled by the hybrid artificial liver support effectively. All patients were successfully bridged to orthotopic liver transplantation. Four out of the eight patients survived after transplantation. Four patients died of pulmonary infection or hepatorenal syndrome. CONCLUSIONS: Artificial liver support system combined with liver transplantation can be regarded as an efficient measure for the treatment of metaphase and advanced stage patients of severe viral hepatitis.

Adult↗
PubMed2001

Effects of CYP2C19 genotype and CYP2C9 on fluoxetine N-demethylation in human liver microsomes.

AIM: The present study was designed to define the kinetic behavior of fluoxetine N-demethylation in human liver microsomes and to identify the isoforms of cytochrome P-450 (CYP) involved in this metabolic pathway. METHODS: The kinetics of Ne formation of norfluoxetine was determined in human liver microsomes from six genotyped CYP2C19 extensive metabolizers (EM). The correlation studies between the fluoxetine N-demethylase activity and various CYP enzyme activities were performed. Selective inhibitors or chemical probes of various cytochrome P-450 isoforms were also employed. RESULTS: The kinetics of norfluoxetine formation in all liver microsomes were fitted by a single-enzyme Michaelis-Menten equation (mean Km=32 micromol/L+/-7 micromol/L). Significant correlations were found between N-demethylation of fluoxetine at both 25 micromol/L and 100 micromol/L and 3-hydroxylation of tolbutamide at 250 micromol/L (r1=0.821, P1=0.001; r2=0.668, P2=0.013), respectively, and S-mephenytoin 4'-hydroxylase activity (r=0.717, P=0.006) at high substrate concentration of 100 micromol/L. S-mephenytoin (SMP) (a CYP2C19 substrate) at high concentration and sulfaphenazole (SUL) (a selective inhibitor of CYP2C9) substantially inhibited norfluoxetine formation. The reaction was minimally inhibited by coincubation with chemical probe, inhibitor of CYP3A4 (triacetyloleandomycin, TAO). The inhibition of fluoxetine N-demethylation at high substrate concentration (100 micromol/L) was greater in PM livers than in EM livers (73 % vs 45 %, P < 0.01) when the microsomes were precoincubated with SUL plus TAO. CONCLUSION: Cytochrome P-450 CYP2C9 is likely to be a major CYP isoform catalyzing fluoxetine N-demethylation in human liver microsomes at a substrate concentration close to the therapeutic level, while polymorphic CYP2C19 may play a more important role in this metabolic pathway at high substrate concentration.

Aryl Hydrocarbon Hydroxylases↗
PubMed2001

[The CPBC types used for clinical choice and observation on their microstructure].

UNLABELLED: According to the primary properties of calcium phosphate bone cement (CPBCs), we have chosen certain types of them for use in cranioplasty and have observed the microstructure of their set bodies by means of SEM. Five kinds of CPBCs powder have been prepared, including: octacalcium phosphate precipitated hydroxyapatite (OCP-PHA) type, octacalcium phosphate hydroxyapatite (OCP-HA) type, octacalcium phosphate (OCP) type, calcium deficient hydroxyapatite (CDHA) type and hydroxyapatite (HA) type. The mixing liquids were deionized water and 0.25 M Na2HPO4/NaH2PO4 buffer solution. The setting time was measured by Gillmore method. The compressive strengths were measured using the TS-14 automatically measured instrument-II of single granule's compressive strength. The CPBC types used for clinical cranioplasty were defined according to Ginebra's Criteria of the CPBCs, and the ultrastructure of the set-bodies of the defined CPBC type was observed by SEM before and after its immersion in Ringer's Solution. RESULT: Two out of five CPBCs, OCP-PHA-CPBC and CDHA-CPBC were selected for clinical cranioplasty. Before and after they were immersed in Ringer's Sol., the SEM found their set-bodies to be structurally porous and to dissolve with the increase of immension time. These data indicate that OCP-PHA-CPBC and CDHA-CPBC are sufficient for the reconstruction of non-stress-bearing bone, and the porous structure of their set-bodies is advantageous to fibroplasty or fibrovasculization in their set bodies.

Bone Cements↗
PubMed2001

[Morphological and ultrastructural observation of Blastocystis hominis].

OBJECTIVE: To observe the morphology and ultrastructure of Blastocystis hominis. METHODS: Morphological observation was made with 4-5 days cultured B. hominis by light microscopy, and similar material fixed with 4% glutaraldehyde was used for transmission electron microscopy. RESULTS: Several forms of B. hominis were observed including vacuolar, granular, amebic, multifission and cystic forms. The multiplication patterns of B. hominis included both binary fission and sporogony. Under transmission electron microscope, the nuclei, mitochondria, rough endoplasmic reticula and lysomes were observed in addition to lipid droplets in its cytoplasm, and glycogen in the central vacuole. CONCLUSION: The central vacuole of vacuolar form may be related to the storage of the excreta. The amebic form of B. hominis might be pathogenic.

Adult↗
PubMed2001

[Influences of age and gender on dose-response and recovery time-course of atracurium].

OBJECTIVES: To evaluate the influences of age and sex on dose-response and recovery time course of atracurium. METHODS: Seventy-two patients (38 men and 34 women), ASA grade I, aged 15-59 years, scheduled for elective surgery were included in the study. All patients were divided into three groups according to their ages: Group 1, 32 patients aged 15-29 years; Group 2, 21 patients aged 30-40 years, and Group 3, 19 patients aged 41-59 years. General anesthesia was maintained with 60% nitrous oxide in oxygen, thiopentone and fentanyl. Neuromuscular function was assessed by train-of-four(TOF) stimulation of accelerometry and the percentage depression of the first response (T1) of the TOF stimulus was used as the study parameter. The dose-response relations of atracurium were determined by the cumulative dose-response technique. RESULTS: As compared to older and female patients, dose-response curves of atracurium in young and male patients were shifted in a parallel fashion to the left. The dose-response relation of atracurium correlated closely with patients' ages and sexes by multiple linear regression analysis. There were significant differences of ED50, ED90 and ED95, and clinical duration and total duration of action following administration of atracurium of same doses between the three age groups as well as men and women. CONCLUSIONS: Age and gender could significantly affect the pharmacodynamics of atracurium.

Adolescent↗
PubMed2000

Mutations of PKD1 in ADPKD2 cysts suggest a pathogenic effect of trans-heterozygous mutations.

Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1 and PKD2. The products of these genes associate to form heteromeric complexes. Several models have been proposed to explain the mechanism of cyst formation. Here we find somatic mutations of PKD2 in 71% of ADPKD2 cysts analysed. Clonal somatic mutations of PKD1 were identified in a subset of cysts that lacked PKD2 mutations.

Base Sequence↗
PubMed2000

Experience with a yes-no single-interval maximum-likelihood procedure.

The report in 1993 by Green [J. Acoust. Soc. Am. 93, 2096-2105 (1993)] describing the application of a new psychophysical method requiring few trials and little time to measure auditory thresholds has generated considerable interest among experimentalists. The procedure uses a single-interval stimulus presentation, requests a yes-no decision by subjects, and implements a maximum-likelihood calculation to determine the next trial stimulus level within an adaptive track, as well as the final threshold estimate. Data are presented here describing separate experiences with this procedure in two laboratories in both detection and discrimination tasks. Issues addressed include comparisons with more traditional psychophysical methods, variability in threshold estimates, experimental time required, and possible minor modifications to improve the basic procedure. Results using this procedure are comparable in terms of variability of estimates to those emerging from more lengthy procedures. However, because it may be difficult for some listeners to maintain a consistent criterion and because attentional lapses may be costly, experimenters must be willing to monitor performance closely and repeat some tracks in cases where excessively high variability is noted. Further, this procedure may not be suitable for tasks for which the form of the psychometric function is not well-established. Modifications allowing a variable slope parameter in the maximum-likelihood evaluations of psychometric functions may be of benefit.

Attention↗
PubMed2000

[Effect of domestic glutathione on the alcoholic liver disease].

OBJECTIVE: To evaluate the effect and safety of domestic glutathione (GSH) on serum ALT, AST, SB levels in alcoholic liver disease (ALD) by multicenter, randomized and TAD controlled trial. METHODS: All the 110 patients with ALD enrolled had a history of drinking over 80g-120g daily for 5 years, and were randomized either into GSH (continuous infusion of 600g daily for 30d) or TAD (with the same dosage, course and route as GSH) group. The efficacy and safery were evaluated with clinical and biochemical (ALT, AST and GGT) parameters. RESULTS: After 8 weeks of treatment, the clinical signs were improved at a different degree in both groups. ALT, AST and SB showed no significant difference in the two groups (the efficacy rate of 93% vs 96%, P>0.05). CONCLUSION: The domestic GSH, with a good tolerance and safety, has a sound efficacy in the improvement of clinical signs and hepatic functions.

Adolescent↗
PubMed2000

5-hydroxylation of omeprazole by human liver microsomal fractions from Chinese populations related to CYP2C19 gene dose and individual ethnicity.

It has been previously reported that omeprazole (OP) oxidation is mediated by CYP2C19 and CYP3A4 in human livers. In this study, we assessed their relative contributions with human liver microsomal fractions from Chinese populations that were genotyped by CYP2C19 and recruited from two ethnic groups, Han and Zhuang. The kinetics of 5-hydroxyomeprazole (5-OH-OP) formation was best described by the two-enzyme and single-enzyme Michaelis-Menten equations for liver microsomes from CYP2C19 extensive (EMs) and poor metabolizers, respectively. At a low substrate concentration that may be encountered in vivo, the monoclonal antibody to CYP2C8/9/19 strongly inhibited 5-OH-OP formation in EM microsomes, whereas troleandomycin (TAO) eliminated most of the formation at a high substrate concentration. In poor metabolizer microsomes, either TAO or anti-CYP3A4 could alone abolish 5-OH-OP formation. Furthermore, there were differences between homozygous and heterozygous EMs in the percentage of inhibition by TAO and the antibodies. At the low substrate concentration, OP 5-hydroxyaltion was correlated well with S-mephenytoin 4'-hydroxylation and CYP2C19 contents in liver microsomes of 34 Chinese individuals. Moreover, in these individuals, obviously genetic and somewhat ethnic differences in OP 5-hydroxylation were observed between different CYP2C19 genotypes (wt/wt > wt/m1 > m1/m1) and between Han and Zhuang (Han > Zhuang), respectively. The results indicate that CYP2C19 is a high-affinity enzyme for OP 5-hydroxylation by liver microsomes from Chinese individuals and that its contribution is CYP2C19 gene dependent and ethnically related. Similar studies indicate that OP sulfoxidation is mediated mainly by CYP3A4 and independent of CYP2C19 genotype status.

Adult↗
PubMed2000

Interventional treatment of huge hepatic cavernous hemangioma.

OBJECTIVE: To study the methods of interventional treatment of huge hepatic cavernous hemangioma (HCH). METHOD: A total of 14 patients with HCH were treated with lipiodol-ultrafluid (10-15 ml), bleomycin A (PYM 16-32 mg), and gelatin-sponge particles. RESULTS: DSA hepatic arteriography showed multiple vascular lakes in the early arterial phase, so-called "to hang the fruits on the branches", which persisted for a long time. CT scan showed a significant reduction in tumor size in 8 of the 14 patients after the treatment. CONCLUSION: Embolization with lipiodol-ultrafluid, PYM and gelatin sponge particles is one of the best methods for the treatment of HCH.

Adult↗
PubMed1999

Role of glutathione S-transferase 8-8 in allylamine resistance of vascular smooth muscle cells in vitro.

Allylamine (AA) is a cardiovascular toxin that causes lesions resembling atherosclerosis in several mammalian species. AA's toxic effects are thought to be exerted through its conversion to acrolein (AC), a potent electrophilic alkylating agent and atherogen. Semicarbazide sensitive amine oxidase (SSAO) catalyzes the oxidation of AA to AC. Glutathione S-transferases (GST) can catalyze the first step of detoxification of AC to mercapturic acid. Our previous studies suggest that the isozyme rGST8-8 is a principal defense against electrophilic stress exerted by alpha,beta-unsaturated carbonyls such as AC. In the present studies, we use cultured rat vascular smooth muscle cells (VSMC) to examine the relative roles of SSAO and rGST8-8 in the cytotoxic effects of the atherogens, AA and AC. Exposure derived AA-resistant cells (VSMC-AA) were 3.5-fold more resistant to AA when compared to VSMC and 1.8-fold more resistant to acrolein. SSAO activity was 2-fold higher in VSMC-AA than in VSMC. Consistent with the role of SSAO in biotransformation of AA, the SSAO inhibitor semicarbazide (SC; 100 microM) provided nearly complete protection from AA to both VSMC-AA and VSMC. As expected, SC did not affect the cytotoxicity of AC. Pretreatment with 100 microM sulfasalazine (SS), a GST inhibitor, potentiated AA and AC toxicity in both VSMC-AA and VSMC, indicating a protective role of GST. Catalytic efficiency (K(cat)/K(m)) of GSTs was higher toward 4-hydroxynonenal (4-HNE) (0.65 mM(-1) s(-1)) than toward 1-chloro-2, 4-dinitrobenzene (CDNB) (0.14 mM(-1) s(-1)) for VSMC. In VSMC-AA, K(cat)/K(m) was increased 4.1-fold toward CDNB (0.58 mM(-1) s(-1)) and 6-fold toward 4HNE (3.9 mM(-1) s(-1)) when compared to VSMC, indicating a preferential increase in VSMC-AA of GST isozymes which utilize alpha,beta-unsaturated carbonyls. Western blots confirmed induction of rGST8-8 in VSMC-AA. Expression of recombinant mGSTA4 (the mouse homolog of rGST8-8) in VSMC caused a 1.6-fold increase in resistance to AA and AC. This resistance was fully reversed by 50 microM SS. Our results demonstrate that GSTs are an important defense against electrophilic atherogens and that isozymes with high activity toward alpha,beta-unsaturated carbonyls are particularly important in the vascular wall.

Acrolein↗