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Biomedical subjects

H Chen

Publications and source records attributed to H Chen.

At least 91 records · Page 5Linked to original sources
PubMed2004

The evolution of H5N1 influenza viruses in ducks in southern China.

The pathogenicity of avian H5N1 influenza viruses to mammals has been evolving since the mid-1980s. Here, we demonstrate that H5N1 influenza viruses, isolated from apparently healthy domestic ducks in mainland China from 1999 through 2002, were becoming progressively more pathogenic for mammals, and we present a hypothesis explaining the mechanism of this evolutionary direction. Twenty-one viruses isolated from apparently healthy ducks in southern China from 1999 through 2002 were confirmed to be H5N1 subtype influenza A viruses. These isolates are antigenically similar to A/Goose/Guangdong/1/96 (H5N1) virus, which was the source of the 1997 Hong Kong "bird flu" hemagglutinin gene, and all are highly pathogenic in chickens. The viruses form four pathotypes on the basis of their replication and lethality in mice. There is a clear temporal pattern in the progressively increasing pathogenicity of these isolates in the mammalian model. Five of six H5N1 isolates tested replicated in inoculated ducks and were shed from trachea or cloaca, but none caused disease signs or death. Phylogenetic analysis of the full genome indicated that most of the viruses are reassortants containing the A/Goose/Guangdong/1/96-like hemagglutinin gene and the other genes from unknown Eurasian avian influenza viruses. This study is a characterization of the H5N1 avian influenza viruses recently circulating in ducks in mainland China. Our findings suggest that immediate action is needed to prevent the transmission of highly pathogenic avian influenza viruses from the apparently healthy ducks into chickens or mammalian hosts.

Animals↗
PubMed2004

Oral anti-pneumococcal activity and pharmacokinetic profiling of a novel peptide deformylase inhibitor.

OBJECTIVE: BB-81384, a novel peptide deformylase (PDF) inhibitor, was characterized in terms of enzyme inhibition profile, antibacterial activity, rodent pharmacokinetics and oral efficacy in murine infection models. METHODS: MICs were determined by standard NCCLS broth microdilution. Selectivity of metalloenzyme inhibition was determined with a limited panel of enzymes via standard biochemical assays. Profiling of the pharmacokinetics and select tissue disposition in mice was determined and compared with that of the macrolide, azithromycin. In vivo murine efficacy studies using Streptococcus pneumoniae were conducted using a peritonitis model, as well as lung and thigh burden models of infection. RESULTS: BB-81384 selectively inhibited PDF with an IC(50) approximately 10 nM and with MICs < 0.5 mg/L against most S. pneumoniae pathogens. Pharmacokinetic analysis revealed good oral bioavailability and moderate clearance and volume of distribution. BB-81384 partitioning to lung tissue was similar in terms of magnitude and kinetics to that of the plasma compartment. Single-administration oral efficacy in a mouse peritonitis model was evident with an ED(50) of 30 mg/kg. BB-81384 reduced the bacterial load by approximately 5 and 3 log units in organ-burden models of lung and thigh infection, respectively. CONCLUSION: BB-81384, a novel PDF inhibitor with good activity against S. pneumoniae in vitro, was the first compound of this class to be profiled for oral pharmacokinetics and tissue disposition and to demonstrate oral anti-pneumococcal efficacy in mice.

Amidohydrolases↗
PubMed2004

Hereditary prostate cancer in African American families: linkage analysis using markers that map to five candidate susceptibility loci.

African American men have the highest incidence of prostate cancer in the world. Despite this statistic, linkage studies designed to localise prostate cancer susceptibility alleles have included primarily men of Caucasian descent. In this report, we performed a linkage analysis using 33 African American prostate cancer families from two independent research groups. In total, 126 individuals (including 89 men with prostate cancer) were genotyped using markers that map to five prostate cancer susceptibility loci, namely HPC1 at 1q24-25, PCAP at 1q42.2-43, CAPB at 1p36, HPC20 on chromosome 20, and HPCX at Xq27-28. Multipoint mode-of-inheritance-free linkage analyses were performed using the GENEHUNTER software. Some evidence of prostate cancer was detected to HPC1 using all families with a maximum NPL Z score of 1.12 near marker D1S413 (P=0.13). Increased evidence of linkage was observed in the 24 families with prostate cancer diagnosis prior to age 65 years and in the 20 families with male-to-male transmission. Some evidence of prostate cancer linkage was also detected at markers mapping to PCAP, HPC20, and HPCX. Continued collection and analysis of African American prostate cancer families will lead to an improved understanding of inherited susceptibility in this high-risk group.

Black or African American↗
PubMed2004

Depressive symptomatology in pregnancy - a Singaporean perspective.

This is a two-part study looking at depressive symptomatology in pregnancy in Singaporean women, and the associated demographic, and bio-psychosocial characteristics of women at risk of depressive illness. We validated the 10-item Centre for Epidemiological Studies-Depression scale amongst pregnant women, and then used this tool to identify depressive states in an antenatal cohort from the national maternity hospital. Amongst the sample population, the rate of depressive disorders is as high as one in five in the antepartum. The risk factors in the antepartum include being young, history of smoking, having past and current obstetric complications, frequent alcohol use and having medical problems.

Adolescent↗
PubMed2004

Interleukin-7 and suppression of local peritoneal immunity in ovarian carcinoma.

OBJECTIVES: To investigate the epithelial ovarian carcinoma (EOC) secretion of interleukin-7 (IL-7). METHODS: Levels of IL-7 were assayed by enzyme-linked immunoadsorbent assay and IL-7 mRNA, and protein expression in tissues and cell lines were detected by RT-PCR and immunohistochemistry. RESULTS: The median serum IL-7 level in patients with EOC (32 cases; 32.49 pg/ml) was significantly higher than that of patients with benign tumors (16 cases; 7.59 pg/ml) and healthy women (16 cases; 10.64 pg/ml) (P<0.05). The median peritoneal fluid IL-7 level in patients with EOC (17.39 pg/ml) was slightly higher than that of patients with benign tumors (14.09 pg/ml), but not significantly so (P>0.05). There were positive correlations between the serum and peritoneal fluid IL-7 levels in both ovarian cancer and benign group (P<0.05, both). Only two EOC specimens expressed IL-7 mRNA, and no IL-7 protein positive was found in any specimens. CONCLUSIONS: Epithelial ovarian carcinoma cells rarely express IL-7, and IL-7 levels are decreased in the ascitic fluid of patients with EOC.

Adolescent↗
PubMed2004

Decreased placental GCM1 (glial cells missing) gene expression in pre-eclampsia.

Pre-eclampsia is a multisystem disorder of pregnancy associated with elevated blood pressure, proteinuria, and complex biochemical disturbances. The mammalian homologue of the glial cells missing (GCM) gene, GCM1, is selectively expressed in the placenta. GCM1 expression has been shown to affect placental branching and vasculogenesis, abnormalities of which may result in the development of pre-eclampsia. In this study immunohistochemistry, Western blot, and quantitative real-time PCR were used to investigate GCM1 expression at different gestational ages and in pre-eclampsia. Of 36 placentae without pre-eclampsia (ranged from 5-40 weeks of gestation), the level of GCM1 expression was relatively constant before late third trimester. The immunoreactivity of GCM1 protein and the level of GCM1 mRNA were not significantly different during normal pregnancy until 37 weeks of gestation, when the level of GCM1 expression was reduced significantly. Furthermore, significant reductions in GCM1 protein and mRNA were observed in pre-eclamptic placentae compared with gestational age-matched controls. Our results suggest that GCM1 is a distinct transcription factor involved in placental disease and altered expression of the GCM1 gene may contribute to the etiology of pre-eclampsia.

Adult↗
PubMed2004

Morphological study of the parathyroid gland and thyroid C cell in senescence-accelerated mouse (SAMP6), a murine model for senile osteoporosis.

SAMP6, a substrain of senescence-accelerated mouse, was developed as an animal model for senile osteoporosis. We investigated the morphology of the parathyroid gland and thyroid C cell, together with the serum parathyroid hormone (PTH) and calcitonin (CT) in SAMP6 and age-matched normal mice SAMR1. We did not find any significant differences between SAMR1 and SAMP6 at 1 month of age with regard to the serum PTH level and the morphology of the parathyroid glands. As compared with SAMR1, the serum PTH level was significantly higher in SAMP6 at 2, 5 and 12 months of age. In the parathyroid chief cells of SAMP6 at 2, 5 and 12 months of age, the Golgi complexes and the cisternae of the granular endoplasmic reticulum were well developed. Numerous secretory granules were located near the plasma membranes and mitoses were sometimes observed. There was no marked difference between SAMR1 and SAMP6 regarding the morphology of the thyroid C cells and the serum CT level. These findings suggest that the secretory activity of the parathyroid gland is stimulated in SAMP6 at 2, 5 and 12 months of age. The parathyroid follicle was sometimes found in SAMP6, and the significance of this structure was also discussed.

Aging↗
PubMed2004

Determination of a misfit dislocation complex in SiGe/Si heterostructures by image deconvolution technique in HREM.

The core structure of a dislocation complex in SiGe/Si system composed of a perfect 60 degrees dislocation and an extended 60 degrees dislocation has been revealed at atomic level. This is attained by applying the image deconvolution technique in combination with dynamical diffraction effect correction to an image taken with a 200kV field-emission high-resolution electron microscope. The possible configuration of the dislocation complex is analyzed and their Burgers vectors are determined.

Journal Article↗
PubMed2004

Adaptive, integrated sensor processing to compensate for drift and uncertainty: a stochastic 'neural' approach.

An adaptive stochastic classifier based on a simple, novel neural architecture--the Continuous Restricted Boltzmann Machine (CRBM) is demonstrated. Together with sensors and signal conditioning circuits, the classifier is capable of measuring and classifying (with high accuracy) the H+ ion concentration, in the presence of both random noise and sensor drift. Training on-line, the stochastic classifier is able to overcome significant drift of real incomplete sensor data dynamically. As analogue hardware, this signal-level sensor fusion scheme is therefore suitable for real-time analysis in a miniaturised multisensor microsystem such as a Lab-in-a-Pill (LIAP).

Journal Article↗
PubMed2004

Determinants of perioperative morbidity and mortality after pneumonectomy.

BACKGROUND: Pneumonectomy remains a relatively high-risk procedure. However, the underlying mechanism is still unknown. Thus, the effort to find out predisposing factors for surgical risks continues. We investigated the effect of both water-load control and sampling lymphadenectomy technique on perioperative morbidity and mortality after pneumonectomy. MATERIAL AND METHODS: A hundred and three consecutive patients undergoing simple pneumonectomy were included in the prospective study. Pneumonectomy was performed for lung cancer in 92 patients and for benign diseases in 11 cases; 81 patients were male and 22 female, and the mean age was 53.4 +/- 11.4 years. Both sampling and completion lymphadenectomy techniques were used randomly. Water-load was carefully limited to values as low as possible, depending on stable hemodynamics during and after operation. RESULTS: There were no deaths, and none of the patients needed postoperative mechanical ventilation. Major complications included dyspnea in 9 patients and supraventricular arrhythmias in 13 patients. Completion lymphadenectomy increased morbidity in both right and left pneumonectomy. CONCLUSIONS: Both water-load limitation and sampling lymphadenectomy technique may decrease morbidity and mortality after pneumonectomy.

Adult↗
PubMed2004

A phase I trial of a Bcl-2 antisense (G3139) and weekly docetaxel in patients with advanced breast cancer and other solid tumors.

PURPOSE: Expression of the Bcl-2 protein confers resistance to various apoptotic signals. G3139 [oblimersen sodium (Genasense)] is a phosphorothioate antisense oligodeoxynucleotide that targets Bcl-2 mRNA, downregulates Bcl-2 protein translation, and enhances the antitumor effects of subtherapeutic doses of docetaxel (Taxotere). PATIENTS AND METHODS: We performed a phase I trial to determine the maximum tolerated dose (MTD) and safety profile of combined therapy with G3139 and weekly docetaxel in patients with advanced Bcl-2-positive solid tumors. Cohorts of three to six patients were enrolled to escalating doses of G3139 and a fixed dose of weekly docetaxel using either of two schedules. In part I, G3139 was administered by continuous infusion for 21 days (D1-22), and docetaxel (35 mg/m2) was given weekly on days 8, 15 and 22. In part II, G3139 was given by continuous infusion for 5 days before the first weekly dose of docetaxel, and for 48 h before the second and third weekly docetaxel doses. For both schedules, cycles were repeated every 4 weeks. RESULTS: Twenty-two patients were enrolled. Thirteen patients were treated on the part I schedule with doses of G3139 escalated from 1 to 4 mg/kg/day. Nine patients were on the part II schedule of shorter G3139 infusion at G3139 doses of 5-9 mg/kg/day. Hematologic toxicities were mild, except for one case of persistent grade 3 thrombocytopenia in part I. The most common adverse events were cumulative fatigue and transaminase elevation, which prevented further dose escalation beyond 4 mg/kg/day for 21 days with the part I schedule. In part II of the study, using the abbreviated G3139 schedule, even the highest daily doses were tolerated without dose-limiting toxicity or the need for dose modification. Objective tumor response was observed in two patients with breast cancer, including one whose cancer previously progressed on trastuzumab plus paclitaxel. Four patients had stable disease. Pharmacokinetic results for G3139 were similar to those of other trials. CONCLUSIONS: G3139 in combination with standard-dose weekly docetaxel was well tolerated. The shortened and intermittent G3139 infusion had less cumulative toxicities and still allowed similar total G3139 delivery as the longer infusion. Further studies should examine the molecular effect of the regimen, as well as clinical activities in malignancies for which taxanes are indicated.

Adult↗
PubMed2004

A novel mutation of keratin 9 in a large Chinese family with epidermolytic palmoplantar keratoderma.

BACKGROUND: Epidermolytic palmoplantar keratoderma (EPPK) is an autosomal dominant inherited skin disorder characterized by diffuse yellow thickening of the skin of the palms and soles, sharply bordered with erythematous margins. Histologically and ultrastructurally, EPPK presents cytolysis of keratinocytes and abnormal aggregation of tonofilaments in the suprabasal layers of the epidermis. To date, 15 different mutations of the keratin 9 gene (KRT9) have been demonstrated to cause most cases of EPPK. OBJECTIVES: To identify the KRT9 mutation in a large Chinese family with EPPK. METHODS: Denaturing high-performance liquid chromatography (DHPLC), DNA sequencing and allele-specific polymerase chain reaction (AS-PCR) were used to screen exon 1 of the KRT9 gene for sequence variations. RESULTS: The DHPLC elution profiles of the DNA fragments amplified from the affected samples differed from those obtained from unaffected individuals, indicating that a sequence variation existed within the analysed fragment of KRT9. DNA sequencing revealed a novel insertion-deletion mutation in the exon 1 of KRT9, 497delAinsGGCT, resulting in the change of tyrosine(166) to tryptophan and leucine (Y166delinsWL). AS-PCR confirmed the mutation was not a common polymorphism. CONCLUSIONS: The results suggest the molecular basis of EPPK in this Chinese family and provide further evidence that mutations in the helix initiation motif of keratin 9 underlie Chinese EPPK.

Alleles↗
PubMed2004

Phosphorylation of critical serine residues in Gem separates cytoskeletal reorganization from down-regulation of calcium channel activity.

Gem is a small GTP-binding protein that has a ras-like core and extended chains at each terminus. The primary structure of Gem and other RGK family members (Rad, Rem, and Rem2) predicts a GTPase deficiency, leading to the question of how Gem functional activity is regulated. Two functions for Gem have been demonstrated, including inhibition of voltage-gated calcium channel activity and inhibition of Rho kinase-mediated cytoskeletal reorganization, such as stress fiber formation and neurite retraction. These functions for Gem have been ascribed to its interaction with the calcium channel beta subunit and Rho kinase beta, respectively. We show here that these functions are separable and regulated by distinct structural modifications to Gem. Phosphorylation of serines 261 and 289, located in the C-terminal extension, is required for Gem-mediated cytoskeletal reorganization, while GTP and possibly calmodulin binding are required for calcium channel inhibition. In addition to regulating cytoskeletal reorganization, phosphorylation of serine 289 in conjunction with serine 23 results in bidentate 14-3-3 binding, leading to increased Gem protein half-life. Evidence presented shows that phosphorylation of serine 261 is mediated via a cdc42/protein kinase Czeta-dependent pathway. These data demonstrate that phosphorylation of serines 261 and 289, outside the GTP-binding region of Gem, controls its inhibition of Rho kinase beta and associated changes in the cytoskeleton.

14-3-3 Proteins↗
PubMed2004

Mislocalisation of hephaestin, a multicopper ferroxidase involved in basolateral intestinal iron transport, in the sex linked anaemia mouse.

BACKGROUND: Hephaestin is a multicopper ferroxidase required for basolateral transport of iron from enterocytes. Sex linked anaemia (sla) mice have a defect in the release of iron from intestinal enterocytes into the circulation due to an interstitial deletion in the hephaestin gene (heph). RESULTS: We have demonstrated that hephaestin is primarily localised to a supranuclear compartment in both intestinal enterocytes and in cultured cells. In normal intestinal enterocytes, hephaestin was also present on the basolateral surface. In sla mice, hephaestin was present only in the supranuclear compartment. In contrast, the iron permease Ireg1 localised to the basolateral membrane in both control and sla mice. CONCLUSION: We suggest that mislocalisation of hephaestin likely contributes to the functional defect in sla intestinal epithelium.

Anemia, Iron-Deficiency↗
PubMed2004

Ultrastructural changes in bones of the senescence-accelerated mouse (SAMP6): a murine model for senile osteoporosis.

SAMP6, a substrain of senescence-accelerated mice, was developed as an animal model for senile osteoporosis. In the present study, we investigated the bone morphology, together with serum calcium and bone mineral density (BMD) in SAMP6 and age-matched normal mice SAMR1. We did not find any significant differences between SAMR1 and SAMP6 at 1 month of age with regard to the serum compositions and bone morphology. As compared with SAMR1, BMD, the femoral weight, femoral calcium and phosphorus levels were significantly reduced in SAMP6 at 2 and 5 months of age. The number of osteoblasts in trabecular bones was also significantly reduced. Swollen mitochondria and myelin-like structures were found in osteoblasts and osteocytes of SAMP6 mice at 2 and 5 months of age. There was a greater proportion of resting surface and less forming surface in the femoral endosteal surfaces of SAMP6 mice. The amount of trabecular bone in the lumbar vertebra and the distal metaphysis of the femur was reduced. The number of the mast cells in bone marrow of the tibia significantly increased in SAMP6 mice. These findings indicate that the lower bone mass in SAMP6 was due to the reduction in osteoblast formation and suggested that mast cells in bone marrows play a role in the pathogenesis of senile osteoporosis.

Aging, Premature↗
PubMed2003

RAPD markers linked to eastern filbert blight resistance in Corylus avellana.

A total of 1,110 decamer primers were screened for RAPD markers linked to a dominant allele in hazelnut ( Corylus avellana) that confers resistance to eastern filbert blight caused by Anisogramma anomala. Twenty RAPD markers linked in coupling, and five markers linked in repulsion, were found. A seedling population was used to construct a linkage map of the region flanking the resistance locus. The map spans 46.6 cM, with 14 markers on one side of the resistance locus and eight on the other side. Eleven markers showed less than 3% recombination with resistance, including three that showed no recombination. Seven of these 11 markers are sufficiently robust to allow their use in marker-assisted selection. These include AA12(850) which shows no recombination, and six markers on one side of the resistance locus: 173(500), 152(800), 122(825), 275(1130), H19(650) and O16(1250). Marker 268(580), which flanks the resistance locus on the other side, is also suitable for use in marker-assisted selection, but shows 5.8% recombination with resistance. Other markers are less suitable for marker-assisted selection because of sensitivity to changes in primer or MgCl(2) concentration, or the long time required for electrophoresis to separate bands of similar size. The 16 markers closest to the resistance locus were cloned and sequenced. The W07(365) marker, which showed no recombination with the resistance locus but is difficult to score, includes a CT microsatellite repeat. The sequence information will allow the design of SCAR primers and eventual map-based cloning of the resistance allele.

Base Sequence↗
PubMed2003

Generation and characterization of a cold-adapted influenza A H9N2 reassortant as a live pandemic influenza virus vaccine candidate.

H9N2 subtype influenza A viruses have been identified in avian species worldwide and were isolated from humans in 1999, raising concerns about their pandemic potential and prompting the development of candidate vaccines to protect humans against this subtype of influenza A virus. Reassortant H1N1 and H3N2 human influenza A viruses with the internal genes of the influenza A/Ann Arbor/6/60 (H2N2) (AA) cold-adapted (ca) virus have proven to be attenuated and safe as live virus vaccines in humans. Using classical genetic reassortment, we generated a reassortant virus (G9/AA ca) that contains the hemagglutinin and neuraminidase genes from influenza A/chicken/Hong Kong/G9/97 (H9N2) (G9) and six internal gene segments from the AA ca virus. When administered intranasally, the reassortant virus was immunogenic and protected mice from subsequent challenge with wild-type H9N2 viruses, although it was restricted in replication in the respiratory tract of mice. The G9/AA ca virus bears properties that are desirable in a vaccine for humans and is available for clinical evaluation and use, should the need arise.

Adaptation, Physiological↗