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Biomedical subjects

Jian Huang

Publications and source records attributed to Jian Huang.

At least 109 records · Page 6Linked to original sources
PubMed2004

Estrogen regulates neprilysin activity in rat brain.

Neprilysin is a zinc metalloendopeptidase that regulates the activity of a number of physiological peptides through hydrolytic inactivation. Most recently, evidence has accumulated that neprilysin is involved in the clearance of amyloid beta peptides in the brain. Previous studies have shown that the neprilysin gene responds to progesterone, androgen, and glucocorticoids. We now show that estrogen regulates neprilysin activity in rat brain. Ovariectomy leads to a 30% decrease in neprilysin activity at 45 or 85 days, but not 21 days, post surgery. Estrogen replacement restores neprilysin levels back to control values. These changes in neprilysin activity suggest that in women estrogen is required to maintain basal levels of neprilysin.

Analysis of Variance↗
PubMed2004

A Role for the RSC chromatin remodeler in regulating cohesion of sister chromatid arms.

The precise segregation of chromosomes is critical for the proliferation and development of living organisms. Defects in this process can result in tumorigenesis and hereditary diseases. The four-subunit cohesin complex plays an essential role in chromosome segregation and genome integrity. Recently, we reported that the association of cohesin with centromeres and chromosome arms is differentially regulated by the ATP-dependent RSC chromatin-remodeling complex. Here, we propose two models to explain why the cell should have evolved special mechanisms for centromeric and sister arm cohesion and why RSC differentially regulates these processes.

Animals↗
PubMed2004

Real-time evaluation of myosin light chain kinase activation in smooth muscle tissues from a transgenic calmodulin-biosensor mouse.

Ca(2+)/calmodulin (CaM)-dependent phosphorylation of myosin regulatory light chain (RLC) by myosin light chain kinase (MLCK) initiates smooth muscle contraction and regulates actomyosin-based cytoskeletal functions in nonmuscle cells. The net extent of RLC phosphorylation is controlled by MLCK activity relative to myosin light chain phosphatase activity. We have constructed a CaM-sensor MLCK where Ca(2+)-dependent CaM binding increases the catalytic activity of the kinase domain, whereas coincident binding to the biosensor domain decreases fluorescence resonance energy transfer between two fluorescent proteins. We have created transgenic mice expressing this construct specifically in smooth muscle cells to perform real-time evaluations of the relationship between smooth muscle contractility and MLCK activation in intact tissues and organs. Measurements in intact bladder smooth muscle demonstrate that MLCK activation increases rapidly during KCl-induced contractions but is not maximal, consistent with a limiting amount of cellular CaM. Carbachol treatment produces the same amount of force development and RLC phosphorylation, with much smaller increases in [Ca(2+)](i) and MLCK activation. A Rho kinase inhibitor suppresses RLC phosphorylation and force but not MLCK activation in carbachol-treated tissues. These observations are consistent with a model in which the magnitude of an agonist-mediated smooth muscle contraction depends on a rapid but limited Ca(2+)/CaM-dependent activation of MLCK and Rho kinase-mediated inhibition of myosin light chain phosphatase activity. These studies demonstrate the feasibility of producing transgenic biosensor mice for investigations of signaling processes in intact systems.

Animals↗
PubMed2004

Somatic mutations of APC gene in carcinomas from hereditary non-polyposis colorectal cancer patients.

AIM: To investigate the mutational features of adenomatous polyposis coli (APC) gene and its possible arising mechanism in hereditary non-polyposis colorectal cancers (HNPCC). METHODS: PCR-based In Vitro Synthesized Protein Test (IVSP) assay and sequencing analysis were used to confirm somatic mutations of whole APC gene in 19 HNPCC cases. RESULTS: Eleven cases with 13 mutations were determined to harbor APC mutations. The prevalence of APC mutation was 58%(11/19). The mutations consisted of 9 frameshift and 4 nonsense ones, indicating that there were more frameshift mutations (69%). The frameshift mutations all exhibited deletion or insertion of 1-2 bp and most of them (7/9) happened at simple nucleotide repeat sequences, particularly within (A)n tracts (5/9). All point mutations presented C-to-T transitions at CpG sites. CONCLUSION: Mutations of APC gene were detected in more than half of HNPCC, indicating that its mutation was a common molecular event and might play an important role in the tumorigenesis of HNPCC. Locations of frameshift mutations at simple nucleotide repeat sequences and point mutations at CpG sites suggested that many mutations probably derived from endogenous processes including mismatch repair (MMR) deficiency. Defective MMR might affect the nature of APC mutations in HNPCC and likely occur earlier than APC mutational inactivation in some patients.

Carcinoma↗
PubMed2004

The RSC nucleosome-remodeling complex is required for Cohesin's association with chromosome arms.

The fidelity of chromosome segregation requires that the cohesin protein complex bind together newly replicated sister chromatids both at centromeres and at discrete sites along chromosome arms. Segregation of the yeast 2 micro plasmid also requires cohesin, which is recruited to the plasmid partitioning locus. Here we report that the RSC chromatin-remodeling complex regulates the differential association of cohesin with centromeres and chromosome arms. RSC cycles on and off chromosomal arm and plasmid cohesin binding sites in a cell cycle-regulated manner 15 min preceding Mcd1p, the central cohesin subunit. We show that in rsc mutants Mcd1p fails to associate with chromosome arms but still binds to centromeres, and that consequently, the arm regions of mitotic sister chromosomes separate precociously while cohesion at centromeres is unaffected. Our data suggest a role for RSC in facilitating the loading of cohesin specifically onto chromosome arms, thereby ensuring sister chromatid cohesion and proper chromosome segregation.

Binding Sites↗
PubMed2004

Wnt1-Cre-mediated deletion of AP-2alpha causes multiple neural crest-related defects.

The AP-2alpha transcription factor is required for multiple aspects of vertebrate development and mice lacking the AP-2alpha gene (tcfap2a) die at birth from severe defects affecting the head and trunk. Several of the defects associated with the tcfap2a-null mutation affect neural crest cell (NCC) derivatives including the craniofacial skeleton, cranial ganglia, and heart outflow tract. Consequently, there is considerable interest in the role of AP-2alpha in neural crest cell function in development and evolution. In addition, the expression of the AP-2alpha gene is utilized as a marker for premigratory and migratory neural crest cells in many vertebrate species. Here, we have specifically addressed how the presence of AP-2alpha in neural crest cells affects development by creating a conditional (floxed) version of tcfap2a which has subsequently been intercrossed with mice expressing Cre recombinase under the control of Wnt1 cis-regulatory sequences. Neural crest-specific disruption of tcfap2a results in frequent perinatal lethality associated with neural tube closure defects and cleft secondary palate. A small but significant fraction of mutant mice can survive into adulthood, but have retarded craniofacial growth, abnormal middle ear development, and defects in pigmentation. The phenotypes obtained confirm that AP-2alpha directs important aspects of neural crest cell function. At the same time, we did not observe several neurocristopathies affecting the head and heart that might be expected based on the phenotype of the AP-2alpha-null mouse. These results have important implications for the evolution and function of the AP-2 gene family in both the neural crest and the vertebrate embryo.

Animals↗
PubMed2004

Protective effect of pentoxifylline on volume-induced lung injury in newborn piglets.

To evaluate the efficacy of pentoxifylline (PTXF) in the attenuation of lung inflammation during volume-induced lung injury (VILI) in newborn piglets, 17 newborn piglets were mechanically ventilated with a large tidal volume (50 ml/kg) for a period of 8 h. They were randomly assigned to a placebo (PL, n = 9) or a treatment group (PTXF, n = 8) that received PTXF (20 mg/kg as a bolus, followed by a continuous infusion of 5 mg/kg/h). Hemodynamics, lung mechanics and arterial blood gases were measured during the 8 h of study. Serum and tracheoalveolar fluid (TAF) platelet-activating factor (PAF) and thromboxane (TXB(2)) levels were obtained at baseline and at 8 h, while lung tissue myeloperoxidase (MPO) and wet to dry weight were assessed after the completion of the study. In the PL group, a marked increase in TAF PAF and TXB(2) levels was observed only in TAF, suggesting that the inflammatory process was localized within the lungs. A significant decrease in lung tissue MPO activity (p < 0.005) and lung wet to dry weight ratio (p < 0.04) was observed in the PTXF group. There were no differences in hemodynamics, arterial blood gases or lung mechanics measurements between groups. A significant reduction in pulmonary inflammatory response was observed during VILI in the PTXF pretreated animals. These results suggest that PTXF may be effective in modulating lung inflammation associated with mechanical ventilation in neonates.

Animals↗
PubMed2004

The F-box protein AhSLF-S2 physically interacts with S-RNases that may be inhibited by the ubiquitin/26S proteasome pathway of protein degradation during compatible pollination in Antirrhinum.

Self-incompatibility S-locus-encoded F-box (SLF) proteins have been identified in Antirrhinum and several Prunus species. Although they appear to play an important role in self-incompatible reaction, functional evidence is lacking. Here, we provide several lines of evidence directly implicating a role of AhSLF-S(2) in self-incompatibility in Antirrhinum. First, a nonallelic physical interaction between AhSLF-S(2) and S-RNases was demonstrated by both coimmunoprecipitation and yeast two-hybrid assays. Second, AhSLF-S(2) interacts with ASK1- and CULLIN1-like proteins in Antirrhinum, and together, they likely form an Skp1/Cullin or CDC53/F-box (SCF) complex. Third, compatible pollination was specifically blocked after the treatment of the proteasomal inhibitors MG115 and MG132, but they had little effect on incompatible pollination both in vitro and in vivo, indicating that the ubiquitin/26S proteasome activity is involved in compatible pollination. Fourth, the ubiquitination level of style proteins was increased substantially after compatible pollination compared with incompatible pollination, and coimmunoprecipitation revealed that S-RNases were ubiquitinated after incubating pollen proteins with compatible but not with incompatible style proteins, suggesting that non-self S-RNases are possibly degraded by the ubiquitin/26S proteasome pathway. Fifth, the S-RNase level appeared to be reduced after 36 h of compatible pollination. Taken together, these results show that AhSLF-S(2) interacts with S-RNases likely through a proposed SCF(AhSLF-S2) complex that targets S-RNase destruction during compatible rather than incompatible pollination, thus providing a biochemical basis for the inhibition of pollen tube growth as observed in self-incompatible response in Antirrhinum.

Antirrhinum↗
PubMed2004

Identification and functional analysis of a novel human KRAB/C2H2 zinc finger gene ZNF300.

A novel human zinc finger gene, ZNF300, was isolated from human embryos on the base of the enrichment of C2H2-specific mRNAs. The ZNF300 cDNA is 3104 bp long and encodes a 604-amino acid protein with an amino-terminal KRAB domain, and 12 carboxyl-terminal C2H2 zinc finger motifs. According to the genome database, ZNF300 is assigned to chromosome 5q33.1. Northern blot analysis revealed that the ZNF300 transcripts are expressed mostly in heart, skeletal muscle and brain. ZNF300 is localized to the nucleus and the KRAB domain of ZNF300 protein exhibits transcription repressor activity. These results suggest that ZNF300 is a ubiquitous transcription repressor in the nucleus.

Amino Acid Sequence↗
PubMed2004

Activation sequences following failed atrial defibrillation.

OBJECTIVES: The purposes of this study were to examine the first activations following atrial defibrillation shocks to help understand how and where atrial fibrillation (AF) relapsed following failed shocks and to assess the difference in postshock activation between failed and successful shocks. BACKGROUND: While many studies have investigated the mechanism of ventricular defibrillation, much less is known about the mechanisms of AF. METHODS: Sustained AF was induced electrically after pericardial infusion of methylcholine in 10 sheep. Biphasic subthreshold shocks were delivered to three configurations: right atrium to distal coronary sinus (RA-CS), sequential shocks with RA-CS as the first pathway followed by proximal CS to superior vena cava as the second pathway (Sequential), and right ventricle to superior vena cava plus can (V-triad). In eight sheep, global atrial mapping was performed with 504 electrodes spaced 3 to 4 mm apart. RESULTS: Earliest postshock activations mostly arose from the left atrium for V-triad but arose from either atrium for RA-CS and Sequential. Preshock AF cycle lengths were significantly shorter at the earliest activation sites than at seven of eight other sites globally distributed over both atria. In all type B successful episodes in which one or more rapid activations occurred after the shock and in 50 of the 72 failed episodes analyzed, activation fronts spread away from the earliest site in a focal pattern, and discrete nonfragmented activation complexes were present in the first derivatives of the electrograms. In the other 22 failed episodes, earliest activation fronts spread in a nonfocal pattern, and earliest postshock electrogram derivatives were fractionated. To better interpret the activation pattern in the fragmented regions, a 504 electrode plaque with 1.5-mm electrode spacing was placed on the right atrial appendage in two additional sheep. In 11 of 108 failed episodes, earliest postshock activation appeared inside the plaque and spread in a focal pattern with nonfragmented electrogram derivatives in 10 episodes and in a reentrant pattern with fragmented electrogram derivatives in the other. CONCLUSIONS: (1) The electrode configuration influenced the location of earliest postshock activation. (2) Earliest postshock activation occurred where the preshock AF cycle length was short. (3) Earliest activations following all type B successful and most failed episodes were not fragmented and spread in a focal pattern. (4) The region of earliest postshock activation in the failed episodes without a focal postshock activation pattern exhibited regions of fragmented electrogram derivatives that may represent conduction block and possibly reentry.

Animals↗
PubMed2004

Hepatitis B virus (HBV) vaccine-induced escape mutants of HBV S gene among children from Qidong area, China.

Hepatitis B virus (HBV) infection is the main factor, which induces hepatocellular carcinoma (HCC) in Qidong high-risk area, China. To prevent HBV infection is the most important strategy to inhibit the HCC carcinogenesis. A large project was performed in Qidong area to protect newborn babies from the HBV infection that 80,000 children born between 1984 and 1990 were vaccinated. After three times of follow-up studies, 15 screened children were found to have symptoms of illness showing persistent elevation of serum glutamic-pyruvic transaminase (ALT). From these previously collected data, we found that the ALT levels of five vaccinees with negative hepatitis B surface antigen (HBsAg) were significantly higher than those of 10 vaccinees with positive HBsAg. Furthermore, with the passage of time, the difference of ALT levels between the two groups (HBsAg negative and positive groups) diminishes. After cloning and sequencing of the HBsAg "a" epitope coding sequences, we found that mutations in "a" epitope were correlated with the absence of detectable anti-HBsAg, while no mutations were seen in the anti-HBsAg positive infections. We also found that majority of point mutations were occurred in the coding sequences of the first loop structure in "a" epitope. The structure of double loop conformation in "a" epitope was conservative, and important for HBV antigenicity. These changes in a double loop conformation would escape neutralization by vaccine-induced antibody.

Alanine Transaminase↗
PubMed2004

Functional analysis of multiple transcription factor sites in a regulatory element of human epsilon-globin gene.

The developmental control of the human epsilon-globin gene expression is mediated by transcriptional regulatory elements in the 5' flanking DNA of this gene. A previously identified negative regulatory element (-3028 to -2902 bp, termed epsilon-NRAII) was analyzed and one putative NF-kappaB site and two GATA sites locate at -3004 bp, -2975 bp and -2948 bp were characterized. Electrophoresis mobility shift assay (EMSA) showed that the putative NF-kappaB site was specifically bound by nuclear proteins of K562 cells. Data obtained from transient transfection showed that the expression of reporter gene could be upregulated about 50% or 100% respectively when epsilon-NRAII was inserted upstream of the SV40 promoter or epsilon-globin gene proximal promoter (-177 bp to +1 bp), suggesting that epsilon-NRAII might not be a classic silencer. Mutation in the putative NF-kappaB site or in the GATA site (at -2975 bp) slightly reduced the expression of reporter gene driven by SV40 promoter or epsilon-globin gene proximal promoter. However, the mutation of GATA site at -2948 bp remarkably reduced the reporter gene activity driven by SV40 promoter, but not by epsilon-globin gene proximal promoter. Further mutation analysis showed that the negative effect of mutation in GATA site at -2948 bp on SV40 promoter was not affected by the mutation of the putative NF-kappaB site, whereas it could be abolished by the mutation of GATA site at -2975 bp. Furthermore, the mutation of both GATA sites could synergistically reduce the reporter gene activity driven by epsilon-globin gene proximal promoter. Those results suggested that epsilon-NRAII might function differently on the SV40 promoter and epsilon-globin gene proximal promoter.

Binding Sites↗
PubMed2004

Rhabdomyolysis in response to weight-loss herbal medicine.

The authors report rhabdomyolysis following the ingestion of weight-loss herbal medicine in an otherwise healthy 54-year-old woman. Three hours after ingestion of the herbal medicine, the patient suffered chest pain that continued for 2 hours and resolved gradually. Laboratory investigation showed the presence of rhabdomyolysis with peak serum creatine kinase (CK) of 1028 IU/L, which gradually decreased and normalized after the herbal medicine was discontinued. The pharmacological effects of the active ingredients of the herbal medicine, ma huang (ephedrine), guarana (active alkaloid caffeine), chitosan, Gymnena sylvestre, Garcinia cambogia (50% hydroxycitric acid), and chromium, are discussed, and similar case reports are reviewed. The elevation of CK in this case is of concern, as it may denote that muscle breakdown may be one of the mechanisms of weight loss in these herbal remedies. Further studies are needed to investigate their effects on muscle bulk or CK. Physicians should be aware of the potential side effects of many herbal medicines. It may be advisable to measure serum CK enzyme for patients who admit using weight-loss herbs.

Anti-Obesity Agents↗
PubMed2004

Physicians' weight loss counseling in two public hospital primary care clinics.

PURPOSE: Primary care physicians are an important source of information on weight management. Nevertheless, weight loss counseling by these physicians remains inadequate. This study sought to determine physicians' barriers to providing weight loss counseling in a public hospital, patients' recall of physicians' weight loss recommendations, and the influence of physicians' counseling on patients' understanding, motivation, and behavior regarding weight loss. METHOD: In 2001, four focus groups of faculty and residents were held at two primary care clinics affiliated with the Louisiana State University Health Sciences Center-Shreveport to determine the barriers to providing weight loss counseling. Scripted probes were used to uncover consensus norms. In 2001-02, structured exit interviews were conducted with 210 overweight or obese patients recruited from the clinics to determine patients' recall of physicians' weight loss recommendations, and patients' understanding of the relationship between weight and health, and their stages of readiness for weight loss. RESULTS: Physicians identified major barriers to providing weight loss counseling, including insufficient confidence, knowledge, and skills. Obesity was underdocumented as a distinct clinical diagnosis. Only 5% of the patients recalled being given the combined weight loss strategy of diet and exercise. However, patients who recalled being counseled to lose weight were more likely to understand the risks of obesity, the benefits of weight loss, and were at a higher stage of readiness for weight loss. CONCLUSIONS: Physicians' weight loss counseling had a significant effect on patients' understanding of and motivation for weight loss. However, physicians provided insufficient guidance on weight management strategies, possibly because of inadequate counseling skills and confidence.

Adolescent↗
PubMed2004

Evolution of activation patterns during long-duration ventricular fibrillation in dogs.

Although resuscitation for sudden cardiac arrest attempts are frequently not instituted for several minutes after the onset of ventricular fibrillation (VF), previous mapping studies have examined only the first 40 s of VF or have involved isolated perfused hearts that did not become ischemic during VF. We applied quantitative pattern analysis to mapping data throughout the first 10 min of VF acquired from a 21 x 24 unipolar electrode array located on the ventricular epicardium of six open-chest dogs. The following twelve descriptors were continuously quantified: 1) number of wavefronts, 2) incidence of reentry, 3) wavefront propagation velocity, 4) incidence of breakthrough/focus, 5) incidence of block, 6) mean area activated by the wavefronts, 7) wavefront fractionations, 8) wavefront collisions, 9) multiplicity index, 10) repeatability, 11) negative peak rate of voltage change, and 12) peak frequency of activation. Cluster analysis of these descriptors divided VF into five stages (stages i-v). The values of most descriptors (except block and breakthrough incidence) increased during stage i (1-11 s after VF induction) and maintained high values with rapid dynamic fluctuations during stage ii (12-62 s). Descriptors changed quickly to values indicating greater organization during stage iii (63-86 s), decreased steadily during stage iv (87-310 s), and approached zero during stage v (311-600 s). There was a high incidence of reentry just before, during, and after stage iii. In conclusion, during the first 10 min, VF can be divided into five stages according to the evolution of electrophysiological characteristics. All of the parameters show a rapid deterioration during VF, except for a temporary reversal approximately 1 min after induction when activation briefly became more organized. Thus a quantitative description of activation does not uniformly decrease as VF progresses, but undergo rapid changes and exhibit a brief interval of increased organization after approximately 1 min of VF. Further studies are warranted to determine whether these changes, particularly the increased organization of stage iii, have clinical consequences, such as an alteration in defibrillation efficacy.

Action Potentials↗
PubMed2004

[Dowel and composite resin as the post-core of long ceramic bridge for repair of dentition defect].

OBJECTIVE: To explore a new method for repairing the dentition defect involving multiple teeth. METHODS: Forty patients who had severe dentition defect were enrolled in this study. The defects were repaired by reserving the residual roots and the application of dowels and light-cure composite resin as the post-core of the long ceramic bridge. RESULTS: The patients were followed up for 2-4 years, and a success rate of 92.5% was achieved. CONCLUSION: Reserving the residual root, application of dowel and light-cure composite resin as the post-core of long ceramic bridge is effective for repairing severe dentition defect.

Adult↗
PubMed2004

Ginsenoside Rg1-induced alterations in gene expression in TNF-alpha stimulated endothelial cells.

BACKGROUND: In China the ginseng root began to be used in medicine over 2000 years ago. Ginsenosides are the most important component isolated from ginseng. The authors investigated the effect of ginsenoside Rg1 on the spectrum of gene expression in the endothelial cells stimulated by TNF-alpha and further explored the potential molecular mechanism of endothelial protection by ginsenoside Rg1. METHODS: Nitric oxide (NO) production in the cultured human umbilical vein endothelial cells (HUVECs) was measured by using an NO assay kit. A home-made oligonucleotide microarray containing approximately 400 cardiovascular disease-related genes was constructed. The alteration of the spectrum of gene expression induced by ginsenoside Rg1 in HUVECs which were activated by TNF-alpha were detected by oligonucleotide microarray analysis. RESULTS: NO production in HUVECs was decreased significantly after TNF-alpha treatment, while pretreatment with ginsenoside Rg1 enhanced NO production in TNF-alphastimulated HUVECs. Ginsenoside Rg1 affected the expression levels of genes involved in vascular constriction, cell adherence, coagulation, cell growth and signal transduction in TNF-alphastimulated HUVECs. CONCLUSIONS: Ginsenoside Rg1 could enhance NO production and the expression of eNOS mRNA in TNF-alpha stimulated HUVECs. Ginsenoside Rg1 regulated sets of genes in endothelial cells and protected endothelial cells from TNF-alpha activation. Microarray analysis provided us with valuable insights into the atheroprotective mechanism by gingsenoside Rg1.

Endothelial Cells↗