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Biomedical subjects

H Wang

Publications and source records attributed to H Wang.

At least 73 records · Page 4Linked to original sources

The lipid second messenger diacylglycerol as a negative regulator of Rac signalling.

We have established a novel role for the second messenger DAG (diacylglycerol), a product of PtdIns(4,5)P2 hydrolysis by PLC (phospholipase C). In addition to its well-known function as a protein kinase C activator, DAG produced by stimulation of the epidermal growth factor receptor causes the redistribution of the Rac-GAP (GTPase-activating protein) beta2-chimaerin to the plasma membrane, where it associates with the active form of Rac1 and promotes the inactivation of this small G-protein. This represents the first example of a Rac-GAP regulated directly by DAG in response to the activation of a tyrosine kinase receptor, and suggests a previously unappreciated role for this lipid as a negative modulator of Rac signalling.

Animals↗

Nanofluidic channels fabrication and manipulation of DNA molecules.

Nanofluidic channel arrays, which have a width of about 40 nm, depth of 60 nm and length of 50 mum, were created using a focused-ion-beam milling instrument on a silicon nitride film swiftly and exactly, as is necessary. Stained -DNA molecules were put inside these sub-100 nm conduits by capillary force and they were stretched and transferred along these conduits, which were dealt with activating reagent Brij aqueous solution in advance. The movements of DNA molecules in these channels were discussed. These nano-structure channels may be useful in the study and analysis of the statics as well as the dynamics of single biomolecules.

DNA↗

Atopic dermatitis and cancer risk.

BACKGROUND: Epidemiological studies have provided growing evidence of a link between atopy and cancer risk. OBJECTIVES: To review the evidence from case-control studies and cohort studies on a possible association between atopic dermatitis (AD) and cancer risk, with particular attention to the case definition of AD. METHODS: Studies with quantitative data on the association between AD (eczematous disease) and cancer risk were obtained from MEDLINE in combination with a review of cited references. RESULTS: In 23 publications, AD was implicated in the risk of haematological [childhood leukaemia (n = 3), adult leukaemia (n = 3), non-Hodgkin lymphoma (NHL; n = 4) and different haematological cancers (n = 1)], pancreatic (n = 5), skin (n = 2) and brain malignancies (n = 5). The overall picture of the results of these studies shows that a history of AD may be associated with a decreased risk of pancreatic cancer, brain tumour and childhood leukaemia, although in most instances the findings were not statistically significant. No consistent associations were observed for skin cancer or NHL. The definition of AD had varying quality, and was imprecise in the majority of publications. CONCLUSIONS: The findings of the epidemiological studies tend to support a lower risk of cancer among persons with a history of AD. Although a more careful definition of AD is needed, these epidemiological studies could provide an estimate of the background cancer risk in patients with AD when the long-term effects of treatments for AD are assessed.

Brain Neoplasms↗

Increased expression of Toll like receptor 4 on peripheral-blood mononuclear cells in patients with coronary arteriosclerosis disease.

The family of Toll-like receptors (TLRs) initiates innate immune responses, and Toll-like receptor 4 (TLR4) was considered to be an important player in the initiation and progression of atherosclerotic disease. The aim of the study was to investigate the expression of TLR4 on peripheral-blood mononuclear cells (PBMCs) in patients with coronary arteriosclerosis disease (CAD). We have examined the expression of TLR4 protein and mRNA by flow cytometry (FCM) and real-time quantitative reverse transcription polymerase chain reaction (RT-PCR). In addition, the levels of plasma lipids were determined by automatic biochemistry analyzer. The results showed that the positive rates and the mean mRNA copy number of TLR4 in CAD group were significantly higher than that in controls. But no significant difference was found in the positive rate and the mean mRNA copy number of TLR4 between CAD group with normal level of plasma lipids and the CAD group with abnormal level of plasma lipids. We suggest that expression level of TLR4 on peripheral-blood mononuclear cells is increased in atherosclerotic, but the differential expression of TLR4 has no correlation with the level of plasma lipids.

Aged↗

Night-to-night alterations in sleep apnea type in patients with heart failure.

In patients with heart failure, apnea type can shift overnight from mainly obstructive to mainly central in association with reductions in PCO(2) and increases in periodic breathing cycle length, indicative of a fall in cardiac output. We hypothesized that the predominant apnea type could also vary from one night to another in association with alterations in PCO(2) and cycle length. We studied 12 men with heart failure in whom the predominant apnea type changed from one night to the next over periods of at least 1 month, and two groups with either predominantly obstructive or central sleep apnea (OSA or CSA) in whom apnea type remained stable over time. In patients with unstable apnea type (n = 12, duration between sleep studies 9.0 +/- 4.4 months), PCO(2) was significantly lower (37.6 +/- 1.6 mmHg versus 41.7 +/- 1.9 mmHg, P < 0.01), and cycle length significantly longer (61.9 +/- 3.4 s versus 51.0 +/- 1.9 s, P < 0.001) during nights with predominantly central than nights with predominantly obstructive apnea. In contrast, in both the stable central (n = 8, duration between sleep studies 11.9 +/- 5.3 months) and the stable obstructive (n = 8, duration between studies 6.9 +/- 5.2 months) sleep apnea groups, neither PCO(2) nor cycle length changed significantly between the baseline and follow-up sleep studies. We conclude that in some patients with heart failure, OSA and CSA are part of a spectrum of periodic breathing that can shift over time in association with alterations in PCO(2), cycle length and probably cardiac function.

Aged↗

Induction of interleukin-6 release from monocytes by serine proteinases and its potential mechanisms.

Serine proteinases have been recognized playing an important role in inflammation via proteinase-activated receptors (PAR). However, little is known of the influence of serine proteinases and PAR on interleukin-6 (IL-6) secretion from highly purified monocytes. We challenged monocytes from human peripheral blood with serine proteinases and agonist peptides of PAR and measured the levels of IL-6, IL-1beta and IL-12 in culture supernatants by enzyme-linked immunosorbent assay. The results showed that thrombin, trypsin, tryptase and elastase stimulated approximately up to 2.9-, 2.0-, 1.8- and 2.1-fold increase in IL-6 release from monocytes following 16 h of incubation, respectively. Proteinase inhibitors inhibited the actions of proteinases on monocytes. Agonist peptides of PAR-1 (SFLLR-NH(3)) and PAR-4 (GYPGQV-NH(2)), but not PAR-3 (TFRGAP-NH(2)), also induced IL-6 release from monocytes. The proteinases and agonists of PAR failed to stimulate IL-1beta and IL-12 secretion. In conclusion, the induction of IL-6 secretion by serine proteinases may be through the activation of PAR.

Blood Cells↗

Chimaeric protein improved immunogenicity compared with fusion protein of Ag85B and ESAT-6 antigens of Mycobacterium tuberculosis.

Antigen 85B (Ag85B) and ESAT-6 are important immunodominant antigens of Mycobacterium tuberculosis, and both are very promising vaccine candidate molecules. In this study, we relied on the T-cell epitopes of Ag85B and ESAT-6 to design a chimaeric protein by inserting ESAT-6 into Ag85B from the amino acids 167-182. We found the ratio of IgG2b/IgG1 and the secretion of interferon (IFN)-gamma in the mice vaccinated with the new protein with adjuvant MPL and TDM were higher than the mice immunized with fusion protein Ag85B-ESAT-6, which have been reported and could induce levels of protective immunity similar to BCG in the mouse model of tuberculosis (TB) infection. These results suggest that the chimaeric protein Ag85B(N)-ESAT-6-Ag85B(C) is a strong candidate for further study and the T-cell epitopes of the antigens should be considered when we design the subunit vaccine.

Acyltransferases↗

A double-blind, placebo-controlled study of house dust mite immunotherapy in Chinese asthmatic patients.

BACKGROUND: The purpose of this study was to determine if house dust mite immunotherapy with Alutard SQ is effective in improving symptom control and reducing rescue medication use in Chinese patients with mild to moderate allergic asthma. METHODS: This is a double-blind, placebo-controlled study involving 132 asthmatic subjects aged 6-45 years recruited from three different regions of Mainland China. Subjects were given a 52-week course of immunotherapy with Dermatophagoides pteronyssinus extract (Alutard Der p, ALK-Abelló, Hørsholm, Denmark) or placebo while their dose of inhaled corticosteroids (ICS) was maintained. RESULTS: 129 subjects (64 in active group) completed the study. The symptom scores began to diverge at week 29 with the immunotherapy group showing a significantly lower score until week 48 (P = 0.018). Immunotherapy resulted in a significant decline in symptom (P = 0.002) and medication (P = 0.007) scores during the second half of the treatment period. Both groups showed significant improvement in peak flow rate and bronchial hyperresponsiveness. Serum eosinophil cationic protein (ECP) also decreased in both groups of subjects, but peripheral blood eosinophil count remained unchanged. Skin test response decreased in actively treated subjects only, but Der p-specific immunoglobulin E (IgE) remained unchanged. Immunotherapy resulted in a significantly greater improvement in self-evaluation scores (P < 0.01). CONCLUSIONS: One year treatment with Alutard SQ house dust mite immunotherapy significantly reduced symptoms and medication use in asthmatic subjects. This was associated with a greater subjective improvement in asthma control.

Adolescent↗

Low abundance of Escherichia coli microsatellites is associated with an extremely low mutation rate.

It is widely assumed that microsatellites are generated by replication slippage, a mutation process specific to repetitive DNA. Consistent with their high mutation rate, microsatellites are highly abundant in most eukaryotic genomes. In Escherichia coli, however, microsatellites are rare and short despite the fact that a high microsatellite mutation rate was described. We show that this high microsatellite instability depends on the presence of the F-plasmid. E. coli cells lacking the F-plasmid have extremely low microsatellite mutation rates. This result provides a possible explanation for the genome-wide low density of microsatellites in E. coli. Furthermore, we show that the F-plasmid induced microsatellite instability is independent of the mismatch repair pathway.

Conjugation, Genetic↗

Genomic organization, localization and polymorphism of porcine PSMB10, a gene encoding the third beta-type proteasome subunit of 26S proteasome complex.

The proteasome subunit, beta type 10 (PSMB10) gene regulated by interferon-gamma is a core part of the 26S proteasome complex, which is an important protein degrading system. Isolation and characterization of swine PSMB10 revealed a conserved structure with other mammalian PSMB10 genes. An A/G nucleotide polymorphism in PSMB10 intron 2 and a C/T single nucleotide polymorphism in exon 5 were detected by polymerase chain reaction restriction fragment length polymorphism. The allele frequencies were significantly different among Tongcheng, Landrace, Large White and Duroc. The porcine PSMB10 was mapped by somatic cell hybrid panel and radiation hybrid mapping on SSC6p14-p15, which is in good agreement with human-pig comparative maps.

Animals↗

Increased calcium deposits and decreased Ca2+-ATPase in right ventricular myocardium of ascitic broiler chickens.

Right ventricular hypertrophy and failure is an important step in the development of ascites syndrome (AS) in broiler chickens. Cytoplasmic calcium concentration is a major regulator of cardiac contractile function and various physiological processes in cardiac muscle cells. The purpose of this study was to measure the right ventricular pressure and investigate the precise ultrastructural location of Ca(2+) and Ca(2+)-ATPase in the right ventricular myocardium of chickens with AS induced by low ambient temperature. The results showed that the right ventricular diastolic pressure of ascitic broilers was significantly higher than that of control broilers (P < 0.01), and the maximum change ratio of right intraventricular pressure (RV +/- dp/dt(max)) of ascitic broilers was significantly lower than that of the controls (P < 0.01). Extensively increased calcium deposits were observed in the right ventricular myocardium of ascitic broilers, whereas in the age-matched control broilers, calcium deposits were much less. The Ca(2+)-ATPase reactive products were obviously found on the sarcoplasmic reticulum and mitochondrial membrane of the control right ventricular myocardium, but rarely observed in the ascitic broilers. The data suggest that in ascitic broilers there is the right ventricular diastolic dysfunction, in which the overload of intracellular calcium and the decreased Ca(2+)-ATPase activity might be the important factors.

Animals↗

Association of intercellular adhesion molecule 1 polymorphisms with retinopathy in Chinese patients with Type 2 diabetes.

AIMS: To investigate the relationship of the K469E and G241R polymorphisms of the intercellular adhesion molecule 1 (ICAM-1) gene with diabetic retinopathy in Chinese patients with Type 2 diabetes mellitus. PATIENTS AND METHODS: One hundred and seventy-two Chinese patients with Type 2 diabetes and 80 normal control subjects were recruited. Patients with diabetes were placed into two groups: the diabetic retinopathy (DR) group and the non-diabetic retinopathy (NDR) group. The DR group was subdivided into those with proliferative retinopathy (PDR) and non-proliferative retinopathy (NPDR). Genomic DNA was prepared using the hydroxybenzene-chloroform extraction method. Genotypes and alleles were detected by polymerase chain reaction-heteroduplex-single-strand conformation polymorphism (PCR-HA-SSCP) analysis combined with gene sequencing. RESULTS: The patients with retinopathy had an increased frequency of the K469K genotype compared with both the patients without retinopathy and the control subjects (61.4 vs. 40.0 and 35.0%, respectively; chi(2) = 8.280 and 13.952, respectively; P < 0.05). The frequency of the K allele in the DR group was higher than in the NDR group and control subjects (75.4 vs. 58.8 and 61.3%, respectively; chi(2) = 9.693 and 11.219, respectively; P < 0.05). Genotype and allele frequencies were similar in the NDR group and control subjects, and in the PDR and NPDR groups. CONCLUSION: The ICAM-1 gene K469E polymorphism is associated with diabetic retinopathy in Chinese patients with Type 2 diabetes. Patients with the K469K genotype were more likely to have diabetic retinopathy than patients with the K469E or E469E genotype.

Adult↗

OmpC and OmpF are required for growth under hyperosmotic stress above pH 8 in Escherichia coli.

AIMS: To investigate the requirement of outer membrane porins for osmotic adaptation at alkaline pH in Escherichia coli. METHODS AND RESULTS: Escherichia coli mutants deficient in ompC, ompF and both genes were constructed and the growth of these mutants was observed at alkaline pH. The growth rate of the mutant deficient in both ompC and ompF was slower than that of the wild type and mutants deficient in one of these genes under hyperosmotic stress at pHs above 8.0. The decreased rate was recovered when a cloned ompC was introduced to the mutant, but the growth recovery with a cloned ompF was partial. Such growth diminution was not observed at pHs below 8.0. CONCLUSION: OmpC and OmpF were shown to participate in hyperosmotic adaptation at alkaline pH in E. coli. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first report to demonstrate that OmpC and OmpF are required for hyperosmotic adaptation at pHs above 8.0, but not below 8.0.

Adaptation, Physiological↗

Neck pain and associated head pain: persistent neck complaint with subsequent, transient, posterior headache.

BACKGROUND: During the Vågå headache epidemiology study, there were indications that various types of work, such as carpentry and hairdressing, frequently seemed to be linked to a combination of neckache and headache. OBJECTIVES: A post hoc study was conducted among 1838, 18- to 65-year-old Vågå citizens, looking for patients with combined neck/headache. DESIGN: Face-to-face interview was conducted. RESULTS: Combined neckache and headache were detected in 121 (6.6%) individuals. The bilateral headache originated in the neck; it was mild/moderate, symptom-poor, and frequently provoked by awkward neck positions. No such headache occurred without a neckache. Headache in this group of patients resembles tractor drivers' headache, except for the provoking factor itself. CONCLUSIONS: This headache is not listed in headache classification systems/textbooks on headache. This headache must be distinguished from the unilateral cervicogenic headache proper because of the different treatment perspectives.

Adult↗

Presence of functional mouse regulatory CD4+CD25+T cells in xenogeneic neonatal porcine thymus-grafted athymic mice.

Xenotransplantation with porcine thymus is emerging as a possible means to reconstitute host cellular immunity and to induce immune tolerance in rodents and large animals. However, the presence of regulatory T cells (Treg cells) in this model needs to be determined. We herein demonstrated that efficient repopulation of mouse CD4+CD25+Treg cells was achieved in Balb/c nude mice by grafting neonatal porcine thymic tissue (NP THY). Mouse CD4+CD25+T cells expressed normal levels of Foxp3 in NP THY-grafted nude mice. Furthermore, these CD4+CD25+Treg cells showed significant inhibitory effects on the cell proliferation or interleukin-2 products of syngeneic T cells to alloantigens, Con A or a peptide antigen, although the potent immunosuppressive function might be lower than CD4+CD25+Treg cells in Balb/c mice. CD4+CD25+T cells in NP THY-grafted nude mice showed significantly stronger inhibition on the response to donor porcine antigens of CD4+CD25(-)T cells than CD4+CD25+Treg cells in Balb/c mice. Both CD4+CD25+Treg cells in NP THY-grafted nude and Balb/c mice prevented the development of autoimmune disease mediated by syngeneic CD4+CD25(-)T cells in a similar efficient way in the secondary recipients. These findings provide evidence for the potential involvement of CD4+CD25+Treg cells in keeping self-tolerance and transplant tolerance in this xeno-thymus transplantation model.

Animals↗

Application of Gleason analogous grading system and flow cytometry DNA analysis in a novel knock-in mouse prostate cancer model.

OBJECTIVE: A new knock-in mouse adenocarcinoma prostate model (KIMAP) was established, which showed a close to human kinetics of tumour development. This study used a new mouse histological grading system similar to the human Gleason grading system and flow cytometry DNA analysis to measure and compare the new KIMAP model with human CaP and transgenic mouse adenocarcinoma prostate (TGMAP) model. METHODS: According to heterogeneity of the clinical standard for prostate cancer diagnosis, a close to human mouse standard for histological grading and scoring system, Gleason analogous grading system, was established in this study. Sixty KIMAP and 48 TGMAP prostate cancer samples were measured and compared with human CaP. Flow cytometry DNA analysis was performed on malignant prostate tissues obtained from both TGMAP and KIMAP models. RESULTS: Mice with CaP from KIMAP (n = 60) and TGMAP (n = 48) models showed a different distribution of histological scores (p = 0.000). KIMAP mice showed higher percentage (53.3%) of compound histological score rate than TGMAP (25%), but closer to the human clinical average (50%), which showed significant correlation with age (p = 0.001), while TGMAP mice showed unbalanced and random score distribution in all age groups. Flow cytometry analyses showed that most tumour tissues in KIMAP were diploid, analogous to the human condition, while all the TGMAP mice showed aneuploid tumours. CONCLUSIONS: Results of this study further show that KIMAP, a new generation of murine prostate cancer model, could be used as a supplementary model in addition to the currently widely used transgenic models.

Adenocarcinoma↗