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Biomedical subjects

F Hu

Publications and source records attributed to F Hu.

At least 37 records · Page 2Linked to original sources

Distribution of three HIV-1 resistance-conferring polymorphisms (SDF1-3'A, CCR2-641, and CCR5-delta32) in global populations.

Chemokine receptors (CCR5, CXCR4 and CCR2) have been shown to be important co-receptors for HIV infection. Mutations at CCR5 (CCR5-delta2), CCR2 (CCR2-641), and stromal-derived factor SDF1 (SDF1-3'A), a primary ligand for CXCR4, are known to have protective effects against HIV-1 infection and the onset of AIDS symptoms. We studied the three-locus genotype frequency distributions in 70worldwide populations from a sample of 2341 individuals without any known history of HIV-1 infection and AIDS symptoms. From these data, we estimated the risk of AIDS onset (relative hazard, RH) of each population. This survey shows that the substantial allele frequency differences of each of these mutations translate into an extensive variation in relative hazards for AIDS in worldwide populations. However, no evidence of natural selection against the mutant gene carriers is detected. Finally, the combined three-locus genotype data predict the highest relative hazard (RH) in South-East Asia and Africa where AIDS is known to be more prevalent.

Chemokine CXCL12↗

Altered reactivity of pulmonary vessels in postobstructive pulmonary vasculopathy.

Chronic ligation of one pulmonary artery results in pulmonary vascular remodeling and bronchial angiogenesis, collectively known as postobstructive pulmonary vasculopathy (POPV). To investigate pulmonary vascular reactivity in POPV, we ligated the left main pulmonary artery of guinea pigs and, after 1-10 mo, prepared explants by inflating lungs with agarose and sectioning them into approximately 1-mm-thick slices; we measured areas of pulmonary vessels and determined contractile responses to histamine and serotonin (5-HT) and relaxant responses to ACh and sodium nitroprusside. We found maximal contractions of arteries to 5-HT (24. 4 +/- 2.6%) and of veins to histamine (53.9 +/- 4.7%) were significantly increased in POPV of 3-mo duration compared with those of controls (16.8 +/- 1.5 and 40.8 +/- 5.0%, respectively). Relaxation of arteries with ACh was enhanced at 10 mo but not at 1 mo after ligation. Relaxation with sodium nitroprusside was increased in veins at 1 mo after ligation but was not altered in arteries. Morphometry revealed reduced diameters of arteries and veins without increased medial thickness. Our data suggest that the enhanced contractile responses of pulmonary vessels to histamine and 5-HT in POPV were not a result of endothelial dysfunction or of structural alterations but might be caused by as-yet-undiscovered mechanisms.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Cloning of a T-type Ca2+ channel isoform in insulin-secreting cells.

The T-type Ca2+ channel is an important determinant of electrical activity and of Ca2+ influx in rat and human pancreatic beta-cells. We have identified and sequenced a cDNA encoding a T-type Ca2+ channel alpha1-subunit derived from INS-1, the rat insulin-secreting cell line. The sequence of the cDNA indicates a protein composed of 2,288 amino acids that shares 96.3% identity to alpha1G, the neuronal T-type Ca2+ channel subunit. The transmembrane domains of the protein are highly conserved, but the isoform contains three distinct regions and 10 single amino acid substitutions in other regions. Sequencing rat genomic DNA revealed that the alpha1-subunit we cloned is an alternative splice isoform of alpha1G. By using specific primers and reverse transcription-polymerase chain reaction, we demonstrated that both splice variants are expressed in rat islets. The isoform deduced from INS-1 was also expressed in brain, neonatal heart, and kidney. Functional expression of this alpha1G isoform in Xenopus oocytes generated low voltage-activated Ba2+ currents. These results provide the molecular biological basis for studies of function of T-type Ca2+ channels in beta-cells, which is where these channels may play critical roles in diabetes.

Alternative Splicing↗

[Evaluation and comparison of the Helicobacter pylori stool antigen test and the gastric mucosal antigen test].

OBJECTIVE: To evaluate the reliability of an enzyme-linked immunosorbent assay by the Helicobacter pylori (H. pylori) stool antigen test for the detection of H. pylori infection. METHODS: Stool specimens were collected from 224 patients who received upper gastrointestinal endoscopic examination for gastrointestinal symptoms. H. pylori status was evaluated by five different tests: culture, histology, biopsy rapid urease test, H. pylori stool antigen test, and H. pylori gastric active mucosal antigen test (parts of the patients). A commercial kit using an enzyme-linked immunosorbent assay was used to examined H. pylori antigen in the stool or in the gastric active mucosa. H. pylori status was defined as positive when two of the three tests (culture, histology and biopsy rapid urease test) were positive. RESULTS: 137 patients were diagnosed as H. pylori-positive. The H. pylori stool antigen test was positive in 143 patients and negative in 81 patients. The sensitivity and specificity were 96.4% and 87.4%, respectively. The overall accuracy was 92.9%. 39 patients were examined H. pylori antigen in the gastric active mucosa, and 27/39 were diagnosed as H. pylori-positive. The H. pylori gastric active mucosal antigen test was positive in 28 patients and negative in 11 patients. The H. pylori stool antigen test was positive in 30 patients and negative in 9 patients. The corresponding rate between gastric active mucosa and stool was 94.9%. CONCLUSION: The H. pylori stool antigen test is a simple, non-invasive method for accurate diagnosis of H. pylori infection.

Adolescent↗

[Geographic information systems spatial analysis on transmission of schistosomiasis in China].

OBJECTIVE: To understand the epidemiologic status and geographical distribution of schistosomiasis in China. METHODS: Relevant detabases were set up after collection of data from two National Sampling Surveys on Schistosomiasis, in 1989 and 1995. Spatial analysis was undertaken after the database linked to the GIS software which was supported by Arc View 3.0a. Correlation analysis was performed to understand the relationship between rates of human infection and cattle infection. RESULTS: The epidemic areas of schistosomiasis with high risk are mainly distributed in the marshland along the Yangtze River and can be identified as five spatial distribution regions based on the results of spatial analysis. Both epidemic areas and positive rates of stool examination in cattle and water buffalo are much wider and higher than that in humans. The positive correlation was seen between infection rate in human and in cattle from data of both sampling surveys. CONCLUSION: The relevant strategy for schistosomiasis control in different spatial regions should be performed accordingly and the measures of control for cattle and water buffalo should be strengthened in the endemic areas.

Adolescent↗

[Studies on risk factors for liver fibrosis of schistosomiasis japonica].

OBJECTIVE: To explore the risk factors for schistosomal liver fibrosis. METHODS: 192 hepatitis-negative patients with schistosomiasis were selected and divided into 3 groups according to the result of B ultrasound examination, that is, grade 2 and 3 fibrosis group(81 patients), grade 1 fibrosis group (61 patients) and control group (non-fibrosis, 50 patiets). The univariate and multivariate ordinal regression model was made to analyse the possibly harmful factors influencing the liver damages of these patients. RESULTS: Four factors were found to be positively associated with schistosomal liver fibrosis. They were: number of treatments of schistosomiasis (OR = 1.75), interval of schistosomal infection(OR = 1.40), history of drinking wine (OR = 1.95) and familial history of advanced schistosomiasis (OR = 2.11). CONCLUSION: Patients with repeated schistosome infection, long duration of schistosomal infection, long history of drinking and familial history of advanced schistosomiasis had higher risk for liver fibrosis than schistosomiasis patients without these factors.

Adult↗

Procedural and late outcomes following MULTI-LINK DUET coronary stent deployment.

The MULTI-LINK DUET is the next generation MULTI-LINK stent with modified strut geometry. Safety and efficacy of the MULTI-LINK DUET were evaluated in a prospective multicenter registry and were compared with prior MULTI-LINK stent experience from the ASCENT randomized trial. A total of 270 patients received 302 MULTI-LINK DUET stents and were evaluated using a composite primary end point of major cardiac events (death, Q-wave and non-Q-wave myocardial infarction, and requirement for coronary revascularization) attributable to the target stenosis cumulative to 30 days following enrollment. Quantitative coronary angiography was performed at a mean follow-up of 6 +/- 2 (+/-SD) months. No difference in primary end point or in angiographic restenosis to 6 months was observed between MULTI-LINK DUET and MULTI-LINK experiences. The MULTI-LINK DUET demonstrated improved device and procedural success, less postprocedural in-stent stenosis, larger postprocedural minimal lumen diameter, and fewer postprocedural marginal dissections compared with the MULTI-LINK stent. Multivariate regression modeling identified stent length, diabetes mellitus, poststent minimal lumen diameter, lesion eccentricity, and current smoking as independent predictors of in-stent restenosis. Thus, the MULTI-LINK DUET Registry demonstrates enhanced procedural performance with clinical and angiographic outcomes similar to those previously observed for the MULTI-LINK stent in the ASCENT randomized trial.

Aged↗

Control of the DNA damage checkpoint by chk1 and rad53 protein kinases through distinct mechanisms.

In response to DNA damage, cells activate checkpoint pathways that prevent cell cycle progression. In fission yeast and mammals, mitotic arrest in response to DNA damage requires inhibitory Cdk phosphorylation regulated by Chk1. This study indicates that Chk1 is required for function of the DNA damage checkpoint in Saccharomyces cerevisiae but acts through a distinct mechanism maintaining the abundance of Pds1, an anaphase inhibitor. Unlike other checkpoint mutants, chk1 mutants were only mildly sensitive to DNA damage, indicating that checkpoint functions besides cell cycle arrest influence damage sensitivity. Another kinase, Rad53, was required to both maintain active cyclin-dependent kinase 1, Cdk1(Cdc28), and prevent anaphase entry after checkpoint activation. Evidence suggests that Rad53 exerts its role in checkpoint control through regulation of the Polo kinase Cdc5. These results support a model in which Chk1 and Rad53 function in parallel through Pds1 and Cdc5, respectively, to prevent anaphase entry and mitotic exit after DNA damage. This model provides a possible explanation for the role of Cdc5 in DNA damage checkpoint adaptation.

Anaphase↗

Bootstrap methods for adaptive designs.

Adaptive designs generate dependent sequences of random variables that are not exchangeable. Therefore, it is not obvious how to employ a resampling scheme for confidence interval estimation. We propose a simple procedure where observed response rates from an adaptive experiment are input to a simulation program. The program then generates sequences from the adaptive sampling scheme. We compare, via simulation, three bootstrap confidence intervals with the asymptotic confidence interval for two adaptive designs useful for clinical trials. A simple ranking of simulated response rates yields a confidence interval approximation with coverage close to 1-alpha in most cases. The method allows us to incorporate such complexities as staggered entry and delayed response. We give an example of its utility on a clinical trial of fluoxetine in depression.

Antidepressive Agents, Second-Generation↗

Distribution of two HIV-1-resistant polymorphisms (SDF1-3'A and CCR2-64I) in East Asian and world populations and its implication in AIDS epidemiology.

Chemokine receptor CCR2 and stromal-derived factor (SDF-1) are involved in HIV infection and AIDS symptom onset. Recent cohort studies showed that point mutations in these two genes, CCR2-64I and SDF1-3'A, can delay AIDS onset > or = 16 years after seroconversions. The protective effect of CCR2-64I is dominant, whereas that of SDF1-3'A is recessive. SDF1-3'A homozygotes also showed possible protection against HIV-1 infection. In this study, we surveyed the frequency distributions of the two alleles at both loci in world populations, with emphasis on those in east Asia. The CCR2-64I frequencies do not vary significantly in the different continents, having a range of 0.1-0.2 in most populations. A decreasing cline of the CCR2-64I frequency from north to south was observed in east Asia. In contrast, the distribution of SDF1-3'A in world populations varies substantially, and the highest frequency was observed in Oceanian populations. Moreover, an increasing cline of the SDF1-3'A frequency from north to south was observed in east Asia. The relative hazard values were computed to evaluate the risk of AIDS onset on the basis of two-locus genotypes in the east Asian and world populations.

Acquired Immunodeficiency Syndrome↗

Mechanisms for the diminished neutrophil exudation to secondary inflammatory sites in infected patients with a systemic inflammatory response (sepsis).

OBJECTIVE: To determine the mechanism for the reduced polymorphonuclear neutrophil exudation to secondary inflammatory sites in critically ill patients with infection and systemic inflammatory response (sepsis). DESIGN: Prospective cohort study. SETTING: Research laboratory and integrated intensive care unit of a tertiary care university-affiliated teaching hospital. PATIENTS: Healthy subjects or critically ill patients with confirmed infection and a systemic inflammatory response (septic patients). MEASUREMENTS AND MAIN RESULTS: We found that polymorphonuclear neutrophil delivery to a secondary inflammatory site (skin window blisters) is reduced by >70% in humans with sepsis, defined as serious infection and a systemic inflammatory response compared with healthy controls. The expression of the endothelial adhesion molecules intercellular adhesion molecule-1, E-selectin and P-selectin in microvessels from skin biopsies was comparable in the two study groups. Also, CD11a and CD11b levels were equal in circulating polymorphonuclear neutrophils (PMNs) from both study groups. Both adhesion molecules were markedly and equally up-regulated during exudation. Circulating PMNs from septic patients showed marked shedding of L-selectin compared to those of healthy controls, with a corresponding increase in their plasma L-selectin levels. An increased concentration gradient between plasma and exudate fluid was found for tumor necrosis factor-alpha and interleukin-8 in septic patients, but not for C5a. The phagocytic and bactericidal capacity of septic patient circulating PMNs was higher then in healthy control patients, but these differences were lost after exudation. There were no major differences in oxidative burst or intracellular calcium flux of circulating PMNs from the two study groups. Polymorphonuclear neutrophil exudation primed both responses to different extents. CONCLUSIONS: Septic patients deliver fewer PMNs to secondary inflammatory sites. In addition, neutrophil exudation results in loss of the small priming effect for phagocytosis and bactericidal function induced by sepsis. Failure to produce a gradient to C5a and intravascular shedding of L-selectin may be responsible for this sepsis-induced reduction in neutrophil exudation to secondary inflammatory sites.

Biomarkers↗

Rickettsia prowazekii transports UMP and GMP, but not CMP, as building blocks for RNA synthesis.

Rickettsia prowazekii, the etiological agent of epidemic typhus, is an obligate intracellular bacterium and is apparently unable to synthesize ribonucleotides de novo. Here, we show that as an alternative, isolated, purified R. prowazekii organisms transported exogenous uridyl- and guanylribonucleotides and incorporated these labeled precursors into their RNA in a rifampin-sensitive manner. Transport systems for nucleotides, which we have shown previously and show here are present in rickettsiae, have never been reported in free-living bacteria, and the usual nucleobase and nucleoside transport systems are absent in rickettsiae. There was a clear preference for the monophosphate form of ribonucleotides as the transported substrate. In contrast, rickettsiae did not transport cytidylribonucleotides. The source of rickettsial CTP appears to be the transport of UMP followed by its phosphorylation and the amination of intrarickettsial UTP to CTP by CTP synthetase. A complete schema of nucleotide metabolism in rickettsiae is presented that is based on a combination of biochemical, physiological, and genetic information.

Binding, Competitive↗

A low voltage-activated Ca2+ current mediates cytokine-induced pancreatic beta-cell death.

Insulin-dependent diabetes mellitus is characterized by the selective destruction of pancreatic beta-cells. Chronic treatment with cytokines induced a low voltage-activated (LVA) Ca2+ current in mouse beta-cells. The concomitant increase in the basal cytoplasmic free Ca2+ concentration ([Ca2+]i) was associated with DNA fragmentation and cell death. Antagonists of LVA Ca2+ channels prevented this elevation of basal [Ca2+]i and DNA fragmentation and reduced the percentage of cell death. Exposure to cytokines did not affect the profile of Ca2+ currents or basal [Ca2+]i in glucagon-secreting alpha-cells. An increased Ca2+ signal through LVA Ca2+ channels may thus be a key feature in cytokine-induced beta-cell destruction.

Animals↗

[Experiment and clinical application of targeting treatment with adriamycin magnetic albumin microspheres in human gastric carcinoma].

OBJECTIVE: To study the pharmacokinetics in experimental animals and observe the concurrent anticancer effects in human advanced gastric cancer as an adjuvant chemotherapy, when adriamycin magnetic albumin microspheres (ADM-MAM) were combined with external static magnetic fields. METHODS: The drug concentration of targeting tissues in the animals and the stability of ADM-MAM in human gastric juices were determined. Clinical and histopathological changes were observed in 55 cases of advanced gastric carcinomas after targeting treatment. RESULTS: The peak concentrations of the targeting tissue were highest after ADM-MAMs were administered for 2 hours and remained at the high level for a long time. ADM-MAM maintained its stability in human gastric juices. Targeting treatment improved the patients' symptoms, raised the rated of tumor resection, prolonged patients' lifetime, and enhanced histopathological effects (P < 0.01). CONCLUSIONS: The administration of ADM-MAM combined with the external static magnetic fields is effective for targeting location and is of clinical value as a preoperative adjuvant chemotherapy for human advanced gastric carcinoma.

Adolescent↗

[Effects and applications of ascorbic acid on the proliferation of Chlamydia trachomatis].

Two hundred and eighty-eight samples of patients with nongonococcal urethritis (NGU) and prostatitis were detected by cell culture and immunofluorescence assay for Chlamydia trachomatis (CT) and the effects of ascorbic acid(vitC) on the formation rate of inclusion of CT in positive samples were also studied. The results showed that the formation rate of inclusion of CT was 29.5% when the concentration of vitC was 5 micrograms.ml-1. The difference between test group and control group which contained cycloheximide in the media was insignificant (P > 0.05). The results suggested that vitC was a kind of nutrient needed for CT. The proliferation of CT in the cell can be promoted by vitC. We can replace cycloheximide by vitC in McCoy cell culture to detect clinic samples with CT.

Adult↗

[Study on family aggregation of cases of advanced schistosomiasis japonica].

AIM: To explore the family aggregation of advanced schistosomiasis japonica. METHODS: Eighty-one cases of advanced schistosomiasis(AS) and 67 cases of non-advanced schistosomiasis with history of infections in Yushan County, Jiangxi Province were chosen as proband groups and control groups respectively, then grades 1 and 2 relatives of them were investigated on AS. Family aggregation of AS was analyzed through comparing the prevalence rate between the close and distant relatives of probands and controls and fitting the observed distribution of AS cases among the population by zero-truncated Poisson distribution and zero-truncated negative binomial distribution. RESULTS: The prevalence rate was higher in the close relatives (Group I relatives) of the probands than in the distant relatives(Group II relatives) of the probands and in the controls' relatives. The observed distribution of AS was beyond the probability of the zero-truncated Poisson distribution, but consistent with the zero-truncated negative binomial distribution. CONCLUSION: Family aggregation of advanced schistosomiasis does exist.

Adult↗

Pilot study of schistosomiasis control in Poyang lake region.

AIM: To perform a longitudinal survey of the control of schistosomiasis in Fanhu Village hyperendemic for schistosomiasis, Poyang Lake region of Jiangxi Province from 1992 to 1996. METHODS: Annual mass chemotherapy and health education were implemented in all investigated individuals, in 1996, artesunate was used in high risk population in transmission season as a prophylactic measure. RESULTS: The prevalence of S. japonicum infection reduced from 26.0% in 1992 to 10.7% in 1994, the intensity of infection (geometric mean of EPG of feces) in residents decreased from 1.92 in 1992 to 0.55 in 1994, and the morbidity indicators such as hepatomegaly and splenomegaly in the cases also have been improved significantly after chemotherapy. In 1995, both the infection rate and intensity of infection of schistosomiasis were recurred from 10.7% and 0.55 in 1994 to 18.4% and 1.04 respectively due to the floods. In 1996, the infection rate reduced to 5.0% and the intensity of infection also decreased to 0.25 due to the additional measure. CONCLUSION: A mass chemotherapy in conjunction with health education and oral artesunate for preventing reinfection in transmission season is effective for the control of schistosomiasis in lake regions.

Adolescent↗

Northern blot identification of mRNA containing sequence for protein allergen, Alt a1, in eight strains of Alternaria alternata.

BACKGROUND: Concentrations of Alt a1, a major allergen from Alternaria alternata extracts, exhibit significant batch-to-batch variability. This variability may result from basic strain-related genetic differences or from environmental influences such as growth conditions or extraction methods. OBJECTIVE: The objective of this work is to determine if strain-to-strain allergen variability in Alternaria alternata, Alt a1 allergen occurs at the nucleic acid level. METHODS: We compared the content of mRNA for a segment known to contain sequence coding for the reported N-termini of this allergen in eight strains of Alternaria obtained from three individual sources grown under identical conditions. RNA was extracted from rapidly growing mycelia and analyzed by northern blot analysis for the content of a specific segment containing sequence for the Alt a1 allergen. Blots were also analyzed for the content of a specific 5.8S rRNA segment. RESULTS: The size of the mRNA for this protein was about 700 bases. Sequence for the specific segment was found in all of the eight strains tested. When normalized for extraction variabilities using the content of 5.8S rRNA, the calculated concentrations of Alt a1 mRNA of seven of the eight strains were similar. CONCLUSIONS: The results of these experiments suggest that this Alt a1 related allergen sequence is found in many strains of Alternaria and that variabilities in allergen protein content noted previously result from posttranslational events.

Allergens↗