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Biomedical subjects

H Chen

Publications and source records attributed to H Chen.

At least 109 records · Page 6Linked to original sources

X-ray spectral measurements and collisional radiative modeling of Ni- to Kr-like Au ions in electron beam ion trap plasmas.

The line emission of n=7-->3, 6-->3, 5-->3, and 4-->3 transitions in Ni- to Kr-like gold ions produced in the Livermore electron beam ion traps EBIT-I and EBIT-II has been recorded with an x-ray crystal spectrometer and a photometrically calibrated microcalorimeter. The plasmas had either monoenergetic electron beams with E(beam)=2.66, 3.53, or 4.54 keV or an experimentally simulated thermal electron distributions with T(e)=2.5 keV. The electron densities were approximately 10(12)cm(-3). The measured spectra have been compared to atomic structure calculations and synthetic spectra provided by the Hebrew University Lawrence Livermore Atomic Code atomic data package. Line identifications and accurate photon energy measurements have been made for many collisionally excited transitions. Approximately 140 lines have been identified in nine charge states. Agreement within 20-30 % exists between the measured and modeled line intensities for most lines excited by the monoenergetic electron beam plasmas, although some larger discrepancies can be found for some weaker features.

Journal Article↗

Self-modulation of light in piezoelectric crystals.

Spectroscopic measurements were used to monitor the optical interference of ordinary (o-ray) waves with extraordinary (e-ray) waves by incidence of plane-polarized light and transmission through piezoelectriccrystals (alpha-quartz, LiNbO3, and LiTaO3). This observation confirms that the rotations of the vibration planes of the o- and e-ray waves originate from the dynamic gratings induced by the electric field of the incident light. This is a self-modulation process of the polarized incident light in piezoelectric crystals.

Journal Article↗

Mechanical force regulation of myofibroblast differentiation in cardiac fibroblasts.

The myocardium responds to chronic pressure or volume overload by activation and proliferation of cardiac fibroblasts and their differentiation into myofibroblasts. Because alpha-smooth muscle actin (SMA) expression is the classical marker for myofibroblast differentiation, we examined force-induced SMA expression and regulation by specific MAPK pathways. Rat cardiac fibroblasts were separated from myocytes and smooth muscle cells, cultured, and phenotyped by using the presence of SMA, vimentin, and ED-A fibronectin and the absence of desmin as myofibroblast markers. Static tensile forces (0.65 pN/microm2) were applied to fibroblasts via collagen-coated magnetite beads. In neonatal cardiac fibroblasts cultured for 1 day, immunostaining and Western and Northern blotting showed very low basal levels of SMA. After the application of force, there were 1.5- to 2-fold increases of SMA protein and mRNA within 4 h. Force-induced SMA expression was dependent on ERK phosphorylation and on intact actin filaments. In contrast to cells cultured for 1 day, cells grown for 3 days on rigid substrates showed prominent stress fibers and high basal levels of SMA, which were reduced by 32% within 4 h after force application. ERK was not activated by force, but p38 phosphorylation was required for force-induced inhibition of SMA expression. These results indicate that mechanical force-induced regulation of SMA content is dependent on myofibroblast differentiation and by selective activation of MAPKs.

Actins↗

Laboratory simulation of charge exchange-produced X-ray emission from comets.

In laboratory experiments using the engineering spare microcalorimeter detector from the ASTRO-E satellite mission, we recorded the x-ray emission of highly charged ions of carbon, nitrogen, and oxygen, which simulates charge exchange reactions between heavy ions in the solar wind and neutral gases in cometary comae. The spectra are complex and do not readily match predictions. We developed a charge exchange emission model that successfully reproduces the soft x-ray spectrum of comet Linear C/1999 S4, observed with the Chandra X-ray Observatory.

Journal Article↗

Genomic distribution and characterization of EST-derived resistance gene analogs (RGAs) in sugarcane.

A large sugarcane EST (expressed sequence tag) project recently gave us access to 261,609 EST sequences from sugarcane, assembled into 81,223 clusters. Among these, we identified 88 resistance gene analogs (RGAs) based on their homology to typical pathogen resistance genes, using a stringent BLAST search with a threshold e-value of e(-50). They included representatives of the three major groups of resistance genes with NBS/LRR, LRR or S/T KINASE domains. Fifty RGAs showed a total of 148 single-dose polymorphic RFLP markers, which could be located on the sugarcane reference genetic map (constructed in cultivar R570, 2n=approximately 115). Fifty-five SSR loci corresponding to 134 markers in R570 were also mapped to enable the classification of the various haplotypes into homology groups. Several RGA clusters were found. One cluster of two LRR-like loci mapped close to the only disease resistance gene known so far in sugarcane, which confers resistance to common rust. Detailed sequence comparison between two NBS/LRR RGA clusters in relation to their orthologs in rice and maize suggests their polyphyletic origins, and indicates that the degree of divergence between paralogous RGAs in sugarcane can be larger than that from an ortholog in a distant species.

Amino Acid Sequence↗

Caffeine, postmenopausal estrogen, and risk of Parkinson's disease.

BACKGROUND: Men who regularly consume caffeinated drinks have a lower risk of PD than do nondrinkers, but this relation has not been found in women. Because this sex difference could be due to hormonal effects, the authors examined prospectively the risk of PD according to use of postmenopausal hormones and caffeine intake among participants in the Nurses' Health Study. METHODS: The study population comprised 77,713 women free of PD, stroke, or cancer at baseline, who were postmenopausal at baseline or reached menopause before the end of the study. During 18 years of follow-up the authors documented 154 cases of PD. RESULTS: Overall, the risk of PD was similar in women using hormones and women who never used hormones (relative risk 1.02, 95% CI 0.69 to 1.52). Use of hormones, however, was associated with a reduced risk of PD among women with low caffeine consumption (RR 0.39, 95% CI 0.13 to 1.17), and with increased risk among women with high caffeine consumption (RR 2.44, 95% CI 0.75 to 7.86; p for interaction = 0.01). Among hormone users, women consuming six or more cups of coffee per day had a fourfold higher risk of PD (RR 3.92, 95% CI 1.49 to 10.34; p = 0.006) than did women who never drink coffee. CONCLUSION: These results suggest that caffeine reduces the risk of PD among women who do not use postmenopausal hormones, but increases risk among hormone users. Clinical trials of caffeine or estrogens in women should avoid the combined use of these agents.

Adult↗

Alternating layer and island growth of Pb on Si by spontaneous quantum phase separation.

Real-time in situ x-ray studies of continuous Pb deposition on Si(111)-(7x7) at 180 K reveal an unusual growth behavior. A wetting layer forms first to cover the entire surface. Then islands of a fairly uniform height of about five monolayers form on top of the wetting layer and grow to fill the surface. The growth then switches to a layer-by-layer mode upon further deposition. This behavior of alternating layer and island growth can be attributed to spontaneous quantum phase separation based on a first-principles calculation of the system energy.

Journal Article↗

Novel regulators of vitamin D action and metabolism: Lessons learned at the Los Angeles zoo.

We undertook an investigation of an outbreak of rachitic bone disease in the Emperor Tamarin New World primate colony at the Los Angeles Zoo in the mid-1980s. The disease phenotype resembled that observed in humans with an inactivating mutation of the vitamin D receptor (VDR), hypocalcemia, high 1,25-dihydroxyvitamin D (1,25-(OH)(2)D) levels, and rickets in rapidly growing adolescent primates. In contrast to the human disease, the New World primate VDR was functionally normal in all respects. The proximate cause of vitamin D hormone resistance in New World primates was determined to be the constitutive overexpression of a heterogeneous nuclear ribonucleoprotein in the A family which we coined the vitamin D response element binding protein (VDRE-BP). VDRE-BP competed in trans with the VDR-retinoid X receptor (RXR) for binding to the vitamin D response element. VDRE-BP-legislated resistance to 1,25-(OH)(2)D was antagonized (i.e., compensated) by another set of constitutively overexpressed proteins, the hsp-70-related intracellular vitamin D binding proteins (IDBPs). IDBPs, present but expressed at much lower levels in Old World primates including man, exhibited a high capacity for 25-hydroxylated vitamin D metabolites and functioned to traffic vitamin Ds to specific intracellular destinations to promote their action and metabolism.

Animals↗

Molecular characterization of a distinct potyvirus from whitegrass in China.

Apotyvirus isolated from perennial whitegrass ( Pennisetum centrasiaticum Tzvel.) in North China was characterized at the molecular level. The 3' terminal nucleotide (nt) sequence of 1669 nt of the viral RNA genome has been determined, which covered the coding region of the C-terminal part of the large nuclear inclusion protein (NIb, RNA polymerase), capsid protein (CP) gene and the 3' nontranslated region (NTR). The CP gene consisted of 909 nt (including the stop codon) encoding 302 amino acid residues, and the 3' NTR was 241 nt in length excluding the polyadenylated tract. Sequence comparison of the amino acids of CPs showed that this virus was most closely related to Sorghum mosaic virus and Maize dwarf mosaic virus with percent identities of 77% to 78% while that of the 3' NTRs suggested that it was most closely related to Zea mosaic virus with identity of 72%. This virus isolate was to some extent closely related to other members of the Sugarcane mosaic virus subgroup of potyviruses for the CP amino acid sequences. Phylogenetic analyses of the sequences indicated that this virus isolate represented a distinct potyvirus, and the name Pennisetum mosaic virus (PenMV) is proposed.

Capsid Proteins↗

Generation of expression constructs that secrete bioactive alphaMSH and their use in the treatment of experimental autoimmune encephalomyelitis.

alpha Melanocyte-stimulating hormone (alphaMSH) is a 13 amino acid peptide with potent anti-inflammatory effects. We created two DNA expression constructs (miniPOMC and pACTH1-17) that encode bioactive versions of the alphaMSH peptide, and tested these constructs for therapeutic effects in experimental autoimmune encephalomyelitis (EAE). Each construct contained the sequences for alphaMSH, as well as the sequences that are involved in the secretion and processing of the POMC gene with the assumption that these sequences would promote processing and release of the encoded alphaMSH peptide. The differences between the two constructs lie at the C-terminal end where amino acids necessary for amidation of alphaMSH were included in only the pACTH1-17 construct. These two constructs were tested in vitro in bioassays, and in vivo in a mouse model of EAE. The results show that although bioactive peptides are secreted from cells transfected with either construct, there appears to be a significant therapeutic effect only with the pACTH1-17 construct which contains the extra C-terminal amino acids. The data suggest that it is possible to engineer DNA expression vectors encoding small secreted peptides such as alphaMSH, and that similar type constructs may be useful as therapeutics for the treatment of inflammatory diseases.

Adrenocorticotropic Hormone↗

Genome-wide scan of bipolar disorder in 65 pedigrees: supportive evidence for linkage at 8q24, 18q22, 4q32, 2p12, and 13q12.

The purpose of this study was to assess 65 pedigrees ascertained through a Bipolar I (BPI) proband for evidence of linkage, using nonparametric methods in a genome-wide scan and for possible parent of origin effect using several analytical methods. We identified 15 loci with nominally significant evidence for increased allele sharing among affected relative pairs. Eight of these regions, at 8q24, 18q22, 4q32, 13q12, 4q35, 10q26, 2p12, and 12q24, directly overlap with previously reported evidence of linkage to bipolar disorder. Five regions at 20p13, 2p22, 14q23, 9p13, and 1q41 are within several Mb of previously reported regions. We report our findings in rank order and the top five markers had an NPL>2.5. The peak finding in these regions were D8S256 at 8q24, NPL 3.13; D18S878 at 18q22, NPL 2.90; D4S1629 at 4q32, NPL 2.80; D2S99 at 2p12, NPL 2.54; and D13S1493 at 13q12, NPL 2.53. No locus produced statistically significant evidence for linkage at the genome-wide level. The parent of origin effect was studied and consistent with our previous findings, evidence for a locus on 18q22 was predominantly from families wherein the father or paternal lineage was affected. There was evidence consistent with paternal imprinting at the loci on 13q12 and 1q41.

Adolescent↗

Trapping and sequence analysis of 1138 putative exons from human chromosome 18.

In a search for novel genes on chromosome 18 (HC18), on which several regions have been linked to bipolar disorder, we applied exon trapping to HC18-specific cosmids. Among the 1138 exons trapped, 1052 of them have been mapped to HC18, and the remaining 86 have not been localized. No exons were localized to genomic regions other than HC18. BLAST database search revealed that 190 exons were identical to 98 Unigenes on HC18; 98 identical to additional 82 clusters of ESTs not present in the HC18 Unigene set; 39 homologous to genes from human and other species (e<10(-3)); and the remaining 811 exons had no significant homology to transcripts in public databases. The mapped exons were compared to the 867 annotated genes on HC18 in the Celera databases; 216 exons were identical to 104 Celera 'genes' and the remaining 836 exons were not found in the Celera databases. On average, there were two exons for a matched transcript (known genes and ESTs). Therefore, the 850 novel exons may represent hundreds of novel genes on chromosome 18.

Bipolar Disorder↗

Combination of local and systemic parathyroid hormone enhances bone regeneration.

Parathyroid hormone is one of the most promising therapeutic agents for osteoporosis, but its use to facilitate bone regeneration in osseous defects is less clear. The purpose of the current study was to determine the effects of combining systematic parathyroid hormone and a local parathyroid hormone gene therapy in a critical-sized osteotomy model. Rats received bilateral femoral osteotomies followed by implantation of a gene-activated matrix encoding parathyroid hormone (1-34) on one side and a control gene-activated matrix on te opposite side. Systematic parathyroid hormone (1-34) or vehicle was injected daily and rats were sacrificed 6 weeks later. Systematic parathyroid hormone increased bone mineral density and bone mineral content measured by dual-energy xray absorptiometry analysis of tibias and vertebrae, and increased serum osteocalcin levels during healing of osteotomies. Furthermore, comparing osteotomy sites that received the same gene-activated matrices as vehicle-injected rats, parathyroid hormone-injected rats showed trends of greater bone areas via histomorphometric and microradiographic analyses and higher osteocalcin messenger ribonucleic acid expression via Northern blot analyses. The combination of systemic and local parathyroid hormone led to higher bone mineral density, bone mineral content, and bone area, a trend for greater radiographic-detected bone area and higher expression of osteocalcin in osteotomy sites when compared with the individual treatment or control groups. Local parathyroid hormone gene therapy enhanced the anabolic effect of systemic parathyroid hormone during osteotomy healing. This study supports the concept of a combined local and systemic approach for enhancing the repair of a fracture at risk for nonunion.

Absorptiometry, Photon↗

Lytic viral replication as a contributor to the detection of Epstein-Barr virus in breast cancer.

Epstein-Barr virus (EBV) has an accepted association with the epithelial malignancy nasopharyngeal carcinoma and has also been reported in other more controversial carcinoma settings. Evaluation of EBV association with epithelial carcinomas such as breast cancer would benefit from a better understanding of the outcome of EBV infection of these cells. Cell-free preparations of a green fluorescent protein-expressing virus, BX1, were used to infect breast cancer cell lines, which were then examined for EBV gene expression and viral genome copy number. Reverse transcription-PCR analyses revealed that the cells supported a mixture of latency II and lytic EBV gene expression. Lytic Zta and BMRF1 protein expression was detected by immunohistochemistry, and DNA PCR analyses estimated an EBV copy number of 300 to 600 genomes per infected cell. Evidence for lytic EBV expression was also found in breast tissue, where reverse transcription-PCR analyses detected lytic Zta transcripts in 7 of 10 breast carcinoma tissues and 4 of 10 normal tissues from the same patients. Scattered cells immunoreactive for Zta protein were also detectable in breast carcinoma. Quantitative real-time PCR analysis of EBV-positive breast carcinoma tissues suggested that less than 0.1% of the cells contained viral genomes. We suggest that sporadic lytic EBV infection may contribute to PCR-based detection of EBV in traditionally nonvirally associated epithelial malignancies.

Antigens, Viral↗

Interaction of dendrimers (artificial proteins) with biological hydroxyapatite crystals.

This investigation sets out to mimic protein-crystal interaction during biomineralization with the use of artificial proteins (dendrimers). It is hypothesized that these interactions depend on the surface charge of hydroxyapatite crystals. This was investigated with the use of dendrimers with capped surfaces of different charges to probe the surface. We used AFM images of crystal-bound dendrimers to determine the distribution of the surface charge, and its magnitude was correlated to the binding capacity of the dendrimers to the surface. The binding capacity of the dendrimers in ascending order at pH 7.4 was: acetamide-capped, -NHC(O)CH3, neutral charge; carboxylic-acid-capped, -COOH, negative charge; and amine-capped, -NH2, positive charge. AFM images of the crystals showed dendrimers spaced equally along the crystal. The results suggest that the crystal surface has alternating bands of positive and negative charge or a differential charge array, i.e., alternating bands of either more or less positive or negative charge.

Acetamides↗

Generation and characterization of an H9N2 cold-adapted reassortant as a vaccine candidate.

H9N2 subtype avian influenza viruses have been identified in avian species worldwide, and infections in pigs were confirmed in Hong Kong in 1998. Subsequently, H9N2 viruses were isolated from two children in Hong Kong in 1999, and five human infections were reported from China, raising the possibility that H9N2 viruses pose a potential pandemic threat for humans. These events prompted us to develop a vaccine candidate to protect humans against this subtype of influenza A viruses. Reassortant H1N1 and H3N2 human influenza A viruses with the six internal gene segments of A/Ann Arbor/6/60 (H2N2)(AA) cold-adapted (ca) virus have been tested extensively in humans and have proved to be attenuated and safe as live virus vaccines. Using classical genetic reassortment, we generated a reassortant that contains the hemagglutinin and neuraminidase genes from A/chicken/Hong Kong/G9/97 (H9N2) and six internal gene segments from the AAca virus. The G9/AAca reassortant virus exhibits the ca phenotype and the temperature-sensitive phenotypes of the AAca virus and was attenuated in mice. The reassortant virus was immunogenic and protected mice from wild-type H9N2 virus challenge. The G9/AAca virus bears the in vitro and in vivo phenotypes specified by the AAca virus and will be evaluated as a potential vaccine candidate in humans.

Acclimatization↗

Safety evaluation in chickens of candidate human vaccines against potential pandemic strains of influenza.

Two candidate formalin-inactivated vaccines, made from high-growth reassortant viruses with the HA and NA genes from avian viruses in a background of genes derived from A/Puerto Rico/8/34 (PR8), were prepared against H5N1 and H9N2 subtypes (designated as H5N1/PR8 and H9N2/PR8, respectively). These viruses bear the genotypes, antigenicity, and attenuation in mouse models that are desirable in candidate vaccines. The pathogenicity of the newly generated avian-human reassortant vaccine viruses was also evaluated in chickens. Neither H5N1/PR8 nor H9N2/PR8 were highly pathogenic for chickens. No clinical signs, gross legions, or histological lesions were observed in chickens that were administered H5N1/PR8 either intranasally (i.n.) or intravenously (i.v.), and virus was not detected in oropharyngeal or cloacal swabs. When H9N2/PR8 was administered i.n., no clinical signs, gross lesions, or histological lesions were observed and no virus was detected in cloacal swabs. However, virus was isolated at low titer from oropharyngeal swabs of all eight chickens. Although no clinical signs were observed when H9N2/PR8 was administered i.v., mild tracheitis was seen in one of two chickens. Moderate amounts of antigen were observed in tracheal respiratory epithelium, and low titers of virus were recovered from oropharyngeal and cloacal swabs of some chickens. In summary, both reassortant vaccine viruses replicated poorly in chickens. These studies suggest that these candidate vaccine viruses carry a low risk of transmission to chickens.

Animals↗