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Biomedical subjects

Z Fang

Publications and source records attributed to Z Fang.

At least 19 recordsLinked to original sources

Change of electronic structure in Ca2RuO4 induced by orbital ordering.

Optical conductivity spectra sigma(omega) were used to investigate the effect of orbital ordering on the electronic structure of Ca2RuO4. Our LDA+U calculation predicts Ru 4d(xy) ferro-orbital ordering at the ground state, and well explains the present sigma(omega) as well as the reported O 1s x-ray absorption spectra. Variation of temperature (T) causes a large change of spectral weight over several eV as well as collapse of a charge gap accompanied by elongation of the c-axis Ru-O bond length. These results clearly indicate that the d(xy) orbital ordering plays a crucial role in the metal-insulator transition and the T-dependent electronic structure on a large energy scale.

Journal Article↗

cMap: the comparative genetic map viewer.

UNLABELLED: cMap, a www comparative genetic map graphical utility, has a search capability and provides comparison of two genetic maps within or between species with dynamic links to data resources and text lists of the shared loci, running in a relational database environment. Currently, maps from three species (maize 'Zea mays L.', rice 'Oryza sativa L.', and sorghum 'Sorghum bicolor L.'), representing over 13,800 distinct loci, are available for comparison at http://www.agron.missouri.edu/cMapDB/cMap.html. AVAILABILITY: cMap source code is available without cost on request for non-commercial use.

Database Management Systems↗

Rates of weight change for black and white Americans over a twenty year period.

OBJECTIVE: To examine the rate of weight gain over time among Americans by age, gender, and race. PARTICIPANTS: Scientific sample of 5117 Americans, ages 25-74 y in 1971 followed for 20 y. RESULTS: Rates of weight gain estimated by mixed effects models are highest among young adults and rates of weight loss are greatest among older adults. The overall shape of the growth curves are similar for men and women, black and white, in terms of both weight gain and weight loss. Rates are also affected by baseline body mass index (BMI=wt in kg/height in m(2)). CONCLUSIONS: Americans gain weight until middle age, stabilize, and begin to lose weight near age 60. Weight loss during old age is especially evident for obese Americans. The ability to accurately identify groups with increased risk and target them for obesity prevention will help combat the steady rise of overweight and obesity in America.

Adult↗

Induction of cyclooxygenase-2 in human endometrial stromal cells by malignant endometrial epithelial cells: evidence for the involvement of extracellularly regulated kinases and CCAAT/enhancer binding proteins.

We previously reported that human malignant endometrial epithelial cell conditioned medium (MECM) up-regulated cyclooxygenase (COX)-2 mRNA and protein levels in human normal endometrial stromal cells (ESC). Here we showed that pretreatment with a selective inhibitor of the extracellularly regulated kinase (ERK)1/2 signaling pathway blocked the MECM-induced COX-2 expression in ESC. Transient transfection assays indicated critical roles of a cAMP response element (CRE,-59/-53 bp) and a nuclear factor for interleukin (IL)-6 expression (NF-IL6) site (-132/-124 bp) in the regulation of basal and MECM-induced activity of COX-2 gene promoter in ESC. Employing electrophoretic mobility shift assays, we demonstrated that increased functional binding of CCAAT/enhancer binding protein (C/EBP)alpha, C/EBPbeta and upstream stimulatory factor-2 to the CRE and C/EBPalpha and C/EBPbeta to the NF-IL6 site were, at least in part, responsible for MECM-induced COX-2 expression in ESC. Moreover, overexpression of C/EBPalpha and C/EBPbeta significantly induced COX-2 promoter activity in ESC. Collectively, these results suggest that the basal and MECM-induced transcription of the COX-2 gene in ESC is regulated through a combination of the CRE and the NF-IL6 site by functional interactions of C/EBPalpha and C/EBPbeta.

Base Sequence↗

The humoral immune responses elicited in mice by inoculations with a recombinant protein or DNA based on the circumsporozoite-protein gene of Plasmodium falciparum.

The humoral responses elicited in mice by inoculation, in various doses and by several routes, with plasmid DNA containing the gene coding for the circumsporozoite protein (CSP) of Plasmodium falciparum FCC1/HN were compared with those evoked by inoculation with a recombinant expressed protein based on the CSP. With the DNA vaccine, intramuscular inoculations appeared the most effective, followed by intravenous and then subcutaneous injections, the responses in each case being dose-dependent. In both standard ELISA and dot-ELISA, sera from the mice immunized with the DNA were found to have much lower titres of antimalarial antibodies than the corresponding sera from mice immunized with the recombinant protein. Although both 'vaccines' elicited humoral immune responses in BALB/c mice, that based on plasmid DNA took much longer than the recombinant protein to induce high-titre antibody responses.

Animals↗

Identification of dipeptidyl nitriles as potent and selective inhibitors of cathepsin B through structure-based drug design.

Cathepsin B is a member of the papain superfamily of cysteine proteases and has been implicated in the pathology of numerous diseases, including arthritis and cancer. As part of an effort to identify potent, reversible inhibitors of this protease, we examined a series of dipeptidyl nitriles, starting with the previously reported Cbz-Phe-NH-CH(2)CN (19, IC(50) = 62 microM). High-resolution X-ray crystallographic data and molecular modeling were used to optimize the P(1), P(2), and P(3) substituents of this template. Cathepsin B is unique in its class in that it contains a carboxylate recognition site in the S(2)' pocket of the active site. Inhibitor potency and selectivity were enhanced by tethering a carboxylate functionality from the carbon alpha to the nitrile to interact with this region of the enzyme. This resulted in the identification of compound 10, a 7 nM inhibitor of cathepsin B, with excellent selectivity over other cysteine cathepsins.

Animals↗

Body mass index and asthma in adults in families of subjects with asthma in Anqing, China.

We conducted a cross-sectional study of 7,109 adults from families of subjects with asthma in the province of Anhui, China. Asthma was defined either as a combination of physician-diagnosed asthma, airway responsiveness to methacholine at < or = 25 mg/ml and two or more respiratory symptoms or asthma attacks ("asthma"); or as a combination of airway responsiveness to methacholine at < or = 8 mg/ml and two or more respiratory symptoms or asthma attacks ("symptomatic airway hyperresponsiveness [AHR]"). After adjusting for intensity of cigarette smoking and other variables, both extremes of the body mass index (BMI) distribution were associated with symptomatic AHR in men and women (p < 0.01). In the multivariate analysis, both under- and overweight were associated with asthma in women, and underweight was associated with asthma in men. Among men, those with BMIs of 16 and 30 kg/m(2) had 2.5 and 2.3 times higher odds of symptomatic AHR, respectively, than those whose BMI was 21 kg/m(2) (95% CI for OR(16 vs. 21 kg/m)(2) = 1.4 to 3.8; 95% CI for OR(30) (vs.) (21) (kg/m)(2) = 1.2 to 5.0). Among women, those with BMIs of 16 and 30 kg/m(2) had 2.0 and 2.3 times higher odds of symptomatic AHR than those whose BMI was 21 kg/m(2) (95% CI for OR(16) (vs.) (21) (kg/m)(2) = 1.3 to 3.1; 95% CI(30) (vs.) (21) (kg/m)(2) = 1.2 to 4.5). Among adults in families of subjects with asthma living in rural China, both underweight and overweight are associated with an increased risk of asthma.

Adult↗

A genomewide search for quantitative-trait loci underlying asthma.

A genomewide screen for quantitative-trait loci (QTLs) that underlie asthma was performed on 533 Chinese families with asthma, by the unified Haseman-Elston method. Nine asthma-related phenotypes were studied, including forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), airway responsiveness as indicated by methacholine (MTCH)-challenge test, serum total immunoglobulin E (TIgE), serum-specific immunoglobulin E, eosinophil count in peripheral blood, and skin-prick tests with three different allergens (cockroach, Dermatophagoides pteronyssinus, and D. farinae). Our study showed significant linkage between airway responsiveness to MTCH and D2S1780 on chromosome 2 (P<.00002) and provided suggestive evidence (P<.002) for six additional possible QTLs: D10S1435 and D22S685, for FEV1; D16S412, for FVC; D19S433, for airway responsiveness to MTCH; D1S518, for TIgE; and D4S1647, for skin reactivity to cockroach. No significant or suggestive evidence of linkage for the other four traits was found.

Adult↗

Establishment and characterization of a cell line from a malignant fibrous histiocytoma of bone developing in a patient with multiple fibrous dysplasia.

PURPOSE AND METHODS: In order to provide material for genetic analysis of fibrous dysplasia (FD), a cell line designated GBS-1 was established from a secondary bone malignant fibrous histiocytoma (MFH) developing in a rib of a 44-year-old male polyostotic FD patient. RESULTS: The GBS-1 cells are characterized by a pleomorphic spindle cell morphology with abundant mucus production. On transplantation to nude mouse subcutis the cell line forms myxoid-spindle cell sarcomas with giant cells, the myxoid product being positive for periodic acid-Schiff (PAS) and alcian blue (Al-B) stains and completely digested by hyaluronidase, mimicking the original tumor. Chromosome and genetic analyses revealed multiple structural and numerical abnormalities of chromosomes with a large number of unidentifiable chromosomes and p53 mutation in exon 7 with LOH in the counterpart. CONCLUSIONS: Since cell lines for FD have hitherto not been available, the GBS-1 cells should prove useful for genetic analyses of FD and also MFH of bone origin.

Adult↗

Exposure-response relationship between paternal smoking and children's pulmonary function.

We conducted a cross-sectional study to investigate paternal smoking and children's pulmonary function in rural communities of Anqing, China. Our analysis included 1,718 children 8 to 15 yr of age whose mothers were never-smokers. Multiple linear regression models were used to estimate the effect of paternal smoking on children's pulmonary function, with adjustment for children's age, sex, weight, height, square of height, asthma, and father's education. When compared with children of never-smoking fathers, children of smoking fathers had small, but detectable deficits in FEV(1) (-36 ml, SE = 20) and FVC (-37 ml, SE = 22). When children of smoking fathers were subdivided into two subgroups, father smoked < 30 cigarettes/day and >/= 30 cigarettes/day, we found that children whose fathers smoked >/= 30 cigarettes/day had the largest deficits in both FEV(1) (-79 ml, SE = 30) and FVC (-71 ml, SE = 34). This monotonic exposure-response relationship remained in all strata when we further stratified our analysis by children's sex and asthma status. Our data also suggested that the relationship was greatest among nonasthmatic girls, although neither sex nor asthma interaction terms were statistically significant. We conclude that there is a monotonic exposure-response relationship between paternal smoking and decline of pulmonary function in children in this rural Chinese population.

Adolescent↗

Anterior approach to the second thoracic vertebral body for surgical treatment (vertebrectomy, bone grafting, and titanium alloy plate fixation).

The surgical approach to the second thoracic vertebral body is difficult from the anterior side. A 38-year-old woman suffering from plasmacytoma in the second thoracic vertebra showed paraplegia for 2 weeks prior to surgery. X-ray, computed tomography (CT), and magnetic resonance imaging (MRI) examinations indicated breakdown of the second thoracic vertebral body and arch, associated with spinal cord compression. A 99mTc bone scintigram showed accumulation only in the second thoracic vertebra. After one course of chemotherapy with cyclophosphamide and prednisone (CP protocol), surgery was carried out. The incision was made on the right side of the anterior of the neck, from the middle half of the sternocleidomastoideus along the anterior edge to the jugular notch of the sternum. After cutting the platysma, severing the sternohyoideus, splitting the sternothyroid muscle, and forming a compartment between the esophagus and vagina carotica, we extended the incision to the sternum. Without wedging the sternum, we separated tissue from the posterior of the sternum to the second and third thoracic vertebrae, excised the second thoracic vertebra to expose the hard spinal meninges, and removed the tumor in the vertebral canal to release the compression on the spinal cord. An autogeneous bone graft, taken from the right ilium (1.5 x 1.5 x 3 cm in size), was implanted between the first and third thoracic vertebrae, and a spinal titanium alloy plate was used to increase fixation between the first and third thoracic vertebrae from the front. During the surgery, 800 ml of blood was transfused. On the fifth postsurgical day, the patient could walk normally with a neck collar, and the paraplegia was completely alleviated, with no complications.

Adult↗

A hypothesis on the metabolism of glyceryl trinitrate in vascular endothelial cells.

BACKGROUND: Extensive research has been conducted regarding the mechanism of action of glyceryl trinitrate (GTN). It is currently believed that GTN undergoes a thiol-dependent metabolic pathway and releases its active metabolite, nitric oxide (NO) and/or S-nitrosothiols (R-SNO). This activates guanylyl cyclase (GC) leading to the formation of cGMP, which is responsible for the relaxation of vascular smooth muscles and the inhibition of platelet aggregation. The lack of knowledge as to the precise mechanism of GTN action and the modulation of its formation has limited the prevention of tolerance to GTN. RESULTS: With cultured human vascular endothelial cells (EC), we showed that nitrite was first formed in endothelial cells whose concentration was dependent on reduced thiols. Cells preexposed to GTN significantly decreased the production of nitrite compared with cells that were not preexposed. Furthermore, we showed that thiols in cultured cells were oxidized during interaction with GTN, which correlated with the time of exposure to GTN. CONCLUSION: Nitrite is the first active intermediate of GTN metabolism in endothelial cells. The analysis of the changes of the blood nitrite and reduced thiols concentration is helpful for evaluating the vasodilatation activity of GTN during therapeutic treatments.

Buffers↗

Role of aromatase in endometrial disease.

Aromatase is the key enzyme for estrogen biosynthesis. It is normally expressed in the human ovary, skin, adipose tissue and brain. Aromatase activity is not detectable in normal endometrium. In contrast, aromatase is expressed aberrantly in endometriosis and is stimulated by PGE2. This results in local production of estrogen, which induces PGE2 formation and establishes a positive feedback cycle. Another abnormality in endometriosis, i.e. deficient 17beta-hydroxysteroid dehydrogenase (17beta-HSD) type 2 expression, impairs the inactivation of estradiol to estrone. These molecular aberrations collectively favor accumulation of increasing quantities of estradiol and PGE2 in endometriosis. The clinical relevance of these findings was exemplified by the successful treatment of an unusually aggressive case of post-menopausal endometriosis using an aromatase inhibitor.

Aromatase↗

Molecular evidence for independent occurrence of IS6110 insertions at the same sites of the genome of Mycobacterium tuberculosis in different clinical isolates.

Several characteristics of Mycobacterium tuberculosis (e.g., conserved genome and low growth rate) have severely restricted the study of the microorganism. The discovery of IS6110 raised hopes of overcoming these obstacles. However, our knowledge of this IS element is relatively limited; even its two basic characteristics (transposition mechanism and target site selection) are far from well understood. In this study, IS6110 insertions in ipl loci (iplA and iplB) in two collections of clinical isolates of M. tuberculosis from different geographic locations, one from Scotland and the other from Thailand, were investigated. Five different IS6110 insertions in the loci were identified: ipl-4::IS6110, ipl-5::IS6110, ipl-11::IS6110, ipl-12::IS6110, and ipl-13::IS6110. An attempt to establish the phylogenetic relationship of the isolates containing these insertions was unsuccessful, suggesting that some of these insertions may have arisen from more than one event. This possibility is further supported by the observation that IS6110 copies existed in the same site but with different orientations in different isolates, and the insertion site of ipl-1::IS6110 harbored IS6110 copies in both iplA and iplB in different strains. All these suggest the independent occurrence of IS6110 insertions at the same sites of the genome of M. tuberculosis in different clinical isolates. The implications of this finding are discussed.

Base Sequence↗

Estrogen depletion induces NaCl-sensitive hypertension in female spontaneously hypertensive rats.

In women, arterial pressure generally increases after menopause, but several studies suggest that women who eat large amounts of plant estrogens (phytoestrogens) experience a slower rise in the incidence of postmenopausal hypertension. This suggests that both ovarian hormones (principally estrogen) and phytoestrogens may protect at least some women from hypertension. The present study tests the hypothesis that phytoestrogens blunt hypertension in estrogen-depleted female spontaneously hypertensive rats (SHR). Three-week-old ovariectomized SHR were fed one of four diets that contained basal (0.6%) or high (8%) NaCl with or without dietary phytoestrogens for 9 wk. In SHR on the basal NaCl diet, arterial pressure was unaffected by the removal of dietary phytoestrogens. In contrast, in SHR on the high-NaCl diet, arterial pressure was significantly higher in rats on the phytoestrogen-free (204 +/- 4 mmHg) compared with the phytoestrogen-replete (153 +/- 4 mmHg) diet. Ganglionic blockade resulted in reductions in arterial pressure that were directly related to the dietary NaCl-induced increases in arterial pressure. Together, these data indicate that dietary phytoestrogens protect ovariectomized female SHR from dietary NaCl-sensitive hypertension and that the sympathetic nervous system plays an important role in this effect. Furthermore, these results demonstrate that dietary phytoestrogens can have a major impact on the interpretation of studies into the physiological role of estrogen in females.

Animals↗

Asthma, rhinitis, and skin test reactivity to aeroallergens in families of asthmatic subjects in Anqing, China.

In industrialized countries with a Western lifestyle, sensitization to perennial aeroallergens is strongly associated with asthma, whereas sensitization to seasonal aeroallergens is closely related to allergic rhinitis. Little is known, however, about the relation between skin test reactivity to aeroallergens and either asthma or rhinitis in mainland China. We studied 10,009 members of 2,544 families in Anqing (China) that were selected on the basis of physician-diagnosed asthma in at least two siblings. Generalized estimating equations were employed to study the association between skin test reactivity to aeroallergens and either asthma or rhinitis. After adjustment for age, sex, intensity of smoking, skin test reactivity to other aeroallergens, and household correlations, sensitization to dust mite was an independent predictor of both asthma (OR = 1.3, 95% CI = 1.1 to 1.5, p = 0.008) and rhinitis (OR = 1.3, 95% CI = 1.0 to 1.8, p = 0.04). Sensitization to mold was significantly associated with asthma (OR = 1.6, 95% CI = 1.1 to 2.3, p = 0.008), and sensitization to silk was an independent predictor of rhinitis (OR = 1.5, 95% CI = 1.1 to 2.2, p = 0.02). Although 46.9% of the study participants were sensitized to at least one allergen, only 3.5% of study subjects reported nasal symptoms consistent with rhinitis. Among asthmatic subjects, 6.2% reported nasal symptoms. Whereas sensitization to perennial aeroallergens was associated with asthma among families of asthmatic subjects in rural China, sensitization to silk was the strongest predictor of rhinitis in this population. Our findings also suggest that allergic rhinitis is far less common among asthmatic subjects in rural China than in asthmatic subjects in industrialized countries with a Western lifestyle.

Adolescent↗

Association of asthma with beta(2)-adrenergic receptor gene polymorphism and cigarette smoking.

Recent studies have suggested that two polymorphisms of the beta(2)-adrenergic receptor (beta(2)AR) gene at codons 16 (arginine to glycine) and 27 (glutamine to glutamate) affect an individual's airway responsiveness, or response to acute or chronic beta(2)-agonist therapy but are not risk factors for asthma. We hypothesize that there is an interaction effect on asthma between the beta(2)AR gene polymorphisms and cigarette smoking. A case-control study was conducted in 128 asthma cases and 136 control individuals identified from 10,014 studied subjects in rural Anqing, China. Allele-specific polymerase chain reaction (PCR) was used to genotype beta(2)AR gene polymorphisms. Multiple logistic regression was used to adjust for potential confounding factors. We found a marginally significant interaction between cigarette smoking and beta(2)AR-16 genotype after adjusting for important confounding factors (p = 0.06). Specifically, we found that compared with never-smoking Gly-16 homozygotes, those ever-smokers who are Arg-16 homozygotes had a significantly increased risk of asthma (odds ratio [OR] = 7.81; 95% confidence interval [CI]: 2.07 to 29.5). This association showed a clear dose-response relationship with the number of cigarettes smoked. However, there was no significant association of asthma with polymorphisms of the beta(2)AR at position 27 (OR = 1.38; 95% CI: 0.69 to 2.73). Our study suggests a gene-environment interaction between the Arg-16 genotype and ever cigarette smoking with respect to the susceptibility of an individual to asthma.

Adult↗

Stromal PRs mediate induction of 17beta-hydroxysteroid dehydrogenase type 2 expression in human endometrial epithelium: a paracrine mechanism for inactivation of E2.

Progesterone stimulates the expression of 17beta-hydroxysteroid dehydrogenase (HSD) type 2, which catalyzes the conversion of the potent estrogen, E2, to an inactive form, estrone, in epithelial cells of human endometrial tissue. Various effects of progesterone on uterine epithelium have recently been shown to be mediated by stromal PRs in mice. We describe herein a critical paracrine mechanism whereby progesterone induction of 17beta-HSD type 2 enzyme activity, transcript levels, and promoter activity in human endometrial epithelial cells are mediated primarily by PR in endometrial stromal cells. Medium conditioned with progestin-pretreated human endometrial stromal cells robustly increased 17beta-HSD type 2 enzyme activity (2-fold) and mRNA levels (13.2-fold) in Ishikawa malignant endometrial epithelial cells. In contrast, direct progestin treatment of Ishikawa epithelial cells gave rise to much smaller increases in enzyme activity (1.2-fold) and mRNA levels (4-fold). These results suggest that progesterone- dependent paracrine factors arising from stromal cells are primarily responsible for the induction of epithelial 17beta-HSD type 2 expression in the endometrium. We transfected serial deletion mutants of the -1,244 bp 5'-flanking region of the 17beta-HSD type 2 gene into Ishikawa cells. No progesterone response elements could be identified upstream of the 17beta-HSD type 2 promoter. Stromal PR-dependent induction of the 17beta-HSD type 2 promoter was mediated by a critical regulatory region mapped to the -200/-100 bp sequence. Direct treatment of Ishikawa cells with progestin gave rise to a maximal increase in the activity of -200 bp/Luciferase construct only by 1.2-fold, whereas medium conditioned by progestin-pretreated endometrial stromal cells increased promoter activity up to 2.4-fold in a time- and concentration-dependent manner. The stimulatory effect of medium conditioned by progestin-pretreated stromal cells was enhanced strikingly by increasing stromal cell PR levels with the addition of estrogen. This epithelial-stromal interaction was specific for endometrial epithelial cells, since 17beta-HSD type 2 could not be induced in malignant breast epithelial cells by media conditioned with progestin-treated breast or endometrial stromal cells. In conclusion, progesterone regulates the conversion of biologically active E2 to estrone by inducing the 17beta-HSD type 2 enzyme in human endometrial epithelium primarily via PR in stromal cells, which secrete factors that induce transcription mediated primarily by the -200/-100 bp 5'-regulatory region of the 17beta-HSD type 2 promoter.

17-Hydroxysteroid Dehydrogenases↗