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Biomedical subjects

G He

Publications and source records attributed to G He.

At least 19 recordsLinked to original sources
PubMed2006

Upregulation of p27 and its inhibition of CDK2/cyclin E activity following DNA damage by a novel platinum agent are dependent on the expression of p21.

The cisplatin analogue 1R,2R-diaminocyclohexane(trans-diacetato)(dichloro)platinum(IV) (DAP) is a DNA-damaging agent that will be entering clinical trials for its potent cytotoxic effects against cisplatin-resistant tumour cells. This cytotoxicity may reside in its ability to selectively activate G1-phase checkpoint response by inhibiting CDKs via the p53/p21 pathway. We have now evaluated the role of another CDK inhibitor p27 as a contributor to DAP-mediated inhibition of G1-phase CDK2 activity. Our studies in ovarian A2780 tumour cells demonstrate that p27 levels induced by DAP are comparable to or greater than those seen for p21. The induction of p27 is not through a transcriptional mechanism, but rather is due to a four-fold increase in protein stabilisation through a mechanism dependent on p21. Moreover, DAP-induced p21 promoted the selective increase of p27 in the CDK2 complex, but not in CDK4 complex, and this selective increase contributed to inhibition of the CDK2 kinase activity. The inhibited complex contained either p27 or p21, but not both, with the relative levels of cyclin E associated with p27 and p21 indicating that about 25% of the inhibition of CDK2 activity was due to p27 and 75% due to p21. This study provides the first evidence that p27 upregulation is directly attributable to activation of the p53/p21 pathway by a DNA-damaging agent, and promulgates p53/p21/p27 axis as a significant component of checkpoint response.

Antineoplastic Agents↗
PubMed2006

MPZL1/PZR, a novel candidate predisposing schizophrenia in Han Chinese.

The MPZL1/PZR gene has been mapped to 1q23.3, located in close proximity to a recognized schizophrenia susceptibility locus. Recently, the MPZL1/PZR gene has been found to be significantly upregulated in schizophrenia brain tissue and to play an important role in cell signaling, thus indicating that MPZL1/PZR could be a potential schizophrenia marker. To test this hypothesis, we selected three single nucleotide polymorphisms (SNPs) for genotyping in 523 Han Chinese trios. We found that two individual SNPs were significant at the Bonferroni's corrected significance level P<0.017: rs3767444 (chi2=6.299, P=0.0121) and rs2051656 (chi2=9.856, P=0.0017). Haplotype transmission/disequilibrium tests revealed a significant association with the disease (global P-value=1.064 x 10(-6)), but no specific transmission distortions. Thus, we propose that the MPZL1/PZR gene may be important in the predisposition to schizophrenia among Han Chinese.

Adult↗
PubMed2006

Overexpression of the prostaglandin E2 receptor EP2 results in enhanced skin tumor development.

We previously showed that the EP2 knockout mice were resistant to chemically induced skin carcinogenesis. The purpose of this study was to investigate the role of the overexpression of the EP2 receptor in mouse skin carcinogenesis. To determine the effect of overexpression of EP2, we used EP2 transgenic (TG) mice and wild-type (WT) mice in a DMBA (7,12-dimethylbenz[alpha]anthracene)/TPA (12-O-tetradecanoylphorbol-13-acetate) two-stage carcinogenesis protocol. EP2 TG mice developed significantly more tumors compared with WT mice. Overexpression of the EP2 receptor increased TPA-induced keratinocyte proliferation both in vivo and in vitro. In addition, the epidermis of EP2 TG mice 48 h after topical TPA treatment was significantly thicker compared to that of WT mice. EP2 TG mice showed significantly increased cyclic adenosine monophosphate levels in the epidermis after prostaglandin E2 (PGE2) treatment. The inflammatory response to TPA was increased in EP2 TG mice, as demonstrated by an increased number of macrophages in the dermis. Tumors and 7 x TPA-treated and DMBA-TPA-treated (6 weeks) skins from EP2 TG mice produced more blood vessels than those of WT mice as determined by CD-31 immunostaining. Vascular endothelial growth factor (VEGF) protein expression was significantly increased in squamous cell carcinoma (SCC) samples from EP2 TG mice compared that of WT mice. There was, however, no difference in the number of apoptotic cells in tumors from WT and EP2 TG mice. Together, our results suggest that the overexpression of the EP2 receptor plays a significant role in the protumorigenic action of PGE2 in mouse skin.

Animals↗
PubMed2006

Family-based association studies of the TCP1 gene and schizophrenia in the Chinese Han population.

A previous case-control study by Yang et al. indicated that the TCP1 gene in 6q25 was associated with schizophrenia in the Han population. To replicate this result, we selected eight SNPs (rs2273828, rs3818298, rs1547094, rs1547093, rs2295898, rs2295899, rs4832, rs15982) spanning the whole gene and performed a family-based study using 325 trios samples. Our transmission disequilibrium test showed neither allele nor haplotype association with schizophrenia, and suggests that the TCP1 locus is not associated with schizophrenia in the Chinese population. Since 6q25 has consistently been found to be a susceptible region for schizophrenia, we suggest that other genes within this region should be the focus of attention.

Adult↗
PubMed2006

Association of TPH1 with suicidal behaviour and psychiatric disorders in the Chinese population.

Tryptophan hydroxylase (TPH), the rate limiting enzyme in serotonin biosynthesis, is one of the most important regulating factors in the serotonergic system. Recently, polymorphisms of the TPH gene have been identified as being associated with suicide, but the evidence is inconsistent. To investigate the role in suicide of one of the isoforms, TPH1, we examined the association of five single nucleotide polymorphisms (SNPs) in the promoter region and in intron 7 of the TPH1 gene based on a sample from the Chinese population of 810 subjects, of whom 329 had made no suicide attempts (NSA), 297 had made suicide attempts (SA), and 184 were healthy subjects (HS). In this study, we observed statistically significant differences between NSA and HS subjects in allele distributions on one marker, -6526A (p = 0.0329; odds ratio (OR) 1.36; 95% confidence interval (CI) 1.01 to 1.81). No significant difference in genotype distribution or allele frequencies of other polymorphisms was found between the suicide victims and the controls. The overall haplotype frequency was significantly different between cases and healthy controls (p = 0.000024 NSA v HS; p < 0.000001, SA v HS; p < 0.000001, cases v HS). We found the haplotype TCAAA of -7180/-7065/-6526/218/779 to be strongly associated with suicidal behaviour and psychiatric disorders (p = 0.00243; OR = 1.62; 95% CI 1.17 to 2.24 and p = 0.018; OR = 1.41; 95% CI 1.05 to 1.91), which suggests an association of TPH1 with suicidal behaviour and indicates that TPH1 may play a significant role in the aetiology of psychiatric disorders in the Han Chinese population.

Alleles↗
PubMed2005

Interleukin-10 -1082 promoter polymorphism is associated with schizophrenia in a Han Chinese sib-pair study.

The interleukin-10 (IL-10) gene has been identified as a susceptibility gene for schizophrenia in Caucasians. A previous case-control study conducted by our group revealed a weak association between polymorphism, -592C/A, of the IL-10 gene promoter and schizophrenia. Our present study was aimed at confirming the association of the IL-10 promoter with schizophrenia using 197 Han Chinese sib-pair families. A family-based association test (FBAT) and haplotype analysis was undertaken using the FBAT v1.5.5. The global TDT was significant for a different polymorphism, -1082G/A (chi2=13.16, P=0.000285) and that the allele -1082G was preferentially transmitted to schizophrenia-affected children. Furthermore, haplotype TDT analysis showed that haplotype "GCC" was significantly associated with the disease (chi2=8.1, P=0.00443). Our results also indicate that the IL-10 gene may play a significant role in the etiology of schizophrenia among Han Chinese.

Adult↗
PubMed2005

Possible association of the MAG locus with schizophrenia in a Chinese Han cohort of family trios.

Neurotransmitter-based hypotheses have so far led to only moderate success in predicting new pathogenetic findings in etiology of schizophrenia. On the other hand, the more recent oligodendroglia hypotheses of this disorder have been supported by an increasing body of evidence. For example, the expression level of the myelin associated glycoprotein (MAG) gene has been shown to be significantly lower in schizophrenia patient groups compared to control groups. Such an effect might be a result of genetic variations of the MAG gene. In order to test this hypothesis, we genotyped four markers within the MAG locus in 413 trios sample of the Han Chinese using allele-specific PCR. None of the four markers revealed noticeable allelic significance. However, the four-marker and two-marker haplotypes covering components rs720309 and rs720308 were observed to be significantly associated with schizophrenia (P < 0.0001) in this study. In addition, we identified one common risk haplotype TA (rs720309-rs720308, present in 78.5% of the general population) that showed increased evidence of overtransmission from parents to affected offspring (P = 0.0001). The results demonstrated MAG might play a role in genetic susceptibility to schizophrenia. Furthermore, our finding of a possible association between the MAG locus and schizophrenia is in agreement with the hypotheses of oligodendrltic and myelination dysfunction.

Adult↗
PubMed2005

Plasminogen activator inhibitor type 1 (PAI-1) in plasma and adipose tissue in HIV-associated lipodystrophy syndrome. Implications of adipokines.

BACKGROUND: PAI-1, an important inhibitor of fibrinolysis, is increased in obese subjects and has been shown to be an independent risk factor for cardiovascular disease. In the present study, we investigated the association between circulating levels of PAI-1 and locally produced PAI-1 in adipose tissue and body fat distribution and adipokines (TNF-alpha, TNF receptors, IL-6, IL-8) in patients with and without HIV-associated lipodystrophy syndrome (HALS). MATERIALS AND METHODS: Eighteen men with HALS and 18 men with HIV but without HALS were investigated. DEXA and computed tomography scan were performed to determine total body fat and visceral adipose tissue mass. Insulin sensitivity was determined by the euglycaemic clamp technique. Plasma levels of PAI-1 and cytokines were determined. In addition, PAI-1, TNF-alpha, IL-6 and IL-8 mRNA levels in subcutaneous adipose tissue were measured by real-time reverse transcriptase polymerase chain reaction. RESULTS: HALS patients were characterized by a 3-fold increased visceral adipose tissue (P < 0.001) and reduced limb fat (P < 0.01) as compared with non-HALS patients but with no difference in total fat mass between the groups. Plasma PAI-1 was increased in HALS patients (16.7 ng mL(-1) vs. 8.2 ng mL(-1), P < 0.05). Plasma PAI-1 was positively correlated with BMI (r = 0.74, P < 0.01), plasma TNF-alpha level (r = 0.64, P < 0.01), sTNFR-I (r = 0.38, P < 0.05), and visceral fat (r = 0.67, P < 0.01). Moreover, plasma PAI-1 was negatively associated with insulin sensitivity (r = -0.57, P < 0.01) and the percentage of limb fat (r = -0.57, P < 0.01). A positive correlation was found between plasma PAI-1 and TNF-alpha mRNA level. No association was, however, found between plasma PAI-1 and PAI-1 mRNA level in adipose tissue. CONCLUSION: Plasma PAI-1 is increased in HALS patients and it is suggested that dysregulation of the TNF-system (high TNFalpha and high sTNFR1) may play a role in up-regulating PAI-1 in HALS.

Adipose Tissue↗
PubMed2005

Removal of contaminants released from room surfaces by displacement and mixing ventilation: modeling and validation.

UNLABELLED: This paper presents the experimental and numerical modeling of contaminant dispersion in a full-scale environmental chamber with different room air distribution systems. For the experimental modeling, an area source with uniform emissions of a hypothetical contaminant (SF6) from the entire floor surface is designed and constructed. Two different types of ventilation are studied: displacement and mixing ventilation. A computer model for predicting the contaminant dispersion in indoor spaces was validated with experimental data. The validated model is used to study the effects of airflow and the area-source location on contaminant dispersion. Results show that the global airflow pattern has a strong impact on the distribution of the contaminants. In general, the personal exposure could be estimated by analyzing the relative source positions in the airflow pattern. Accordingly, the location of an exhaust diffuser may not greatly affect the airflow pattern, but can significantly affect the exposure level in the room. PRACTICAL IMPLICATIONS: When designing ventilation in addition to bringing fresh air to occupants, it is important to consider the removal of contaminants released in the off-gassing of building materials. Typical indoor off-gassing examples are emissions of volatile organic compounds from building enclosure surfaces such as flooring and painted walls. In this study, we conducted experimental and numerical modeling of different area sources in a mock-up office setup, with displacement or mixing ventilation. Displacement ventilation was as successful as mixing ventilation in removing the contaminant source from the floor area. Actually, the most important consideration in the removal of these contaminants is the relative position of the area source to the main airflow pattern and the occupied zone.

Air Pollutants↗
PubMed2004

Transmission disequilibrium analysis of the GSN gene in a cohort of family trios with schizophrenia.

Apoptosis is thought to play a role in neuronal pathology in schizophrenia. Recently, the GSN gene was reported to have anti-apoptotic properties. In a genome-wide expression analysis on schizophrenia, GSN was also found to be significantly down-regulated in schizophrenia. All the hints suggest that GSN is a novel candidate gene in occurrence of schizophrenia. In this work, we genotyped 3 SNPs around the GSN locus in 493 sets of the Han Chinese trio sample using allele-specific PCR. A weak association or a marginally positive result was detected (0.05 for P-value of the overtransmitted haplotype and 0.02 for a global P-value).

Adult↗
PubMed2004

Disgust and the insula: fMRI responses to pictures of mutilation and contamination.

Although previous functional brain imaging studies have found that the insula responds selectively to facial expressions of disgust, it remains unclear whether the insula responds selectively to disgust-inducing pictures. In this fMRI study, healthy volunteers viewed pictures of contamination, human mutilation, attacks and neutral scenes during scanning, and then rated pictures for the 'basic' emotions. The anterior insula responded to contamination and mutilation but not attacks, while the ventral visual areas responded to attacks and mutilations more strongly than contamination. The above activations were predicted by disgust and arousal ratings respectively. Additionally, mutilations uniquely activated the right superior parietal cortex. These results support selective disgust processing at the insula, and suggest distinct neural responses to contamination and mutilation.

Adult↗
PubMed2004

Increasing the capacity for treatment of chemical plant wastewater by replacing existing suspended carrier media with Kaldnes Moving Bed media at a plant in Singapore.

The Kaldnes biomedia K1, which is used in the patented Kaldnes Moving Bed biofilm process, has been tested along with other types of biofilm carriers for biological pretreatment of a complex chemical industry wastewater. The main objective of the test was to find a biofilm carrier that could replace the existing suspended carrier media and at the same time increase the capacity of the existing roughing filter-activated sludge plant by 20% or more. At volumetric organic loads of 7.1 kg COD/m3/d the Kaldnes Moving Bed process achieved much higher removal rates and much lower effluent concentrations than roughing filters using other carriers. The Kaldnes roughing stage achieved more than 85% removal of organic carbon and more than 90% removal of BOD5 at the tested organic load, which was equivalent to a specific biofilm surface area load of 24 g COD/m2/d. Even for the combined roughing filter-activated sludge process, the Kaldnes carriers outperformed the other carriers, with 98% removal of organic carbon and 99.6% removal of BOD5. The Kaldnes train final effluent concentrations were only 22 mg FOC/L and 7 mg BOD5/L. Based on the successful pilot testing, the full-scale plant was upgraded with Kaldnes Moving Bed roughing filters. During normal operation the upgraded plant has easily met the discharge limits of 100 mg COD/L and 50 mg SS/L. For the month of September 2002, with organic loads between 100 and 115% of the design load for the second half of the month, average effluent concentrations were as low as 9 mg FOC/L, 51 mg COD/L and 12 mg SS/L.

Biodegradation, Environmental↗
PubMed2003

Stimulation of PAI-1 and adipokines by glucose in human adipose tissue in vitro.

Adipokines such as Plasminogen activator inhibitor-1 (PAI-1), interleukin (IL)-8, and tumor necrosis factor (TNF)-alpha are elevated in patients with obesity, insulin resistance, and type 2 diabetes. In the present study, we investigated whether glucose affected the production of these adipokines in human adipose tissue in vitro. Glucose (up to 35mM) increased secretion of PAI-1 (p<0.01) and IL-8 (p<0.01), but not TNF-alpha, in a dose- and time-dependent manner. Half-maximal stimulatory concentration of glucose was about 1mM. Glucosamine (5mM) decreased production of PAI-1 (p<0.05) and IL-8 (p<0.05), indicating that the hexosamine biosynthesis pathway is not involved in the glucose-induced increment in adipokine secretion. The present data demonstrate that glucose increases PAI-1 and IL-8 secretion. However, glucose concentrations above 5mM had no additional effects on adipokine secretion, suggesting that mechanisms other than diabetes/insulin resistance-related hyperglycemia may be involved in the observed elevation of these adipokines.

Adipose Tissue↗
PubMed2003

Fracture mechanisms in bulk metallic glassy materials.

We find that the failure of bulk metallic glassy (BMG) materials follows three modes, i.e., shear fracture with a fracture plane significantly deviating from 45 degrees to the loading direction, normal tensile fracture with a fracture plane perpendicular to the loading direction, or distensile fracture in a break or splitting mode with a fracture plane parallel to the loading direction. The actually occurring type of failure strongly depends on the applied loading mode and the microstructure of the material. Extensive evidence indicates that the Tresca fracture criterion is invalid, and for the first time, three fracture criteria are developed for isotropic materials with high strength, such as advanced BMGs or the newly developed bulk nanostructural materials.

Journal Article↗
PubMed2003

Nanostructured Ti-based multi-component alloys with potential for biomedical applications.

A group of Ti(60)Cu(14)Ni(12)Sn(4)M(10) (M=Nb, Ta, Mo) alloys was prepared using arc melting and copper mold casting. The as-prepared alloys have a composite microstructure containing a micrometer-sized dendritic beta-Ti(M) phase dispersed in a nanocrystalline matrix. These new alloys exhibit a low Young's modulus in the range of 59-103 GPa, and a high yield strength of 1037-1755 MPa, together with large plastic strains. The combination of high strength and low elastic modulus offers potential advantages in biomedical applications.

Alloys↗
PubMed2003

Metformin, but not thiazolidinediones, inhibits plasminogen activator inhibitor-1 production in human adipose tissue in vitro.

Biguanides and thiazolidinediones (TZDs), which are primarily used as anti-diabetic drugs, are also associated with other beneficial effects on cardiovascular risk factors such as reduced plasma plasminogen activator inhibitor-1 (PAI-1) concentration in both diabetic and non-diabetic obese subjects. Since human adipose tissue is of importance for the production of PAI-1, the aim of the present study was to investigate the possible direct effects of these anti-diabetic agents on PAI-1 mRNA and secretion by human adipose tissue. Adipose tissue was obtained from biopsies taken from the subcutaneous abdominal depot. Adipose tissue fragments, isolated mature adipocytes, and preadipocytes were incubated in vitro with metformin and various TZDs. Metformin (0.1 - 10 mM) dose-dependently decreased PAI-1 production (and PAI-1 mRNA) under both basal (43 % inhibition at 10 mM, p < 0.05) and interleukin-1beta (IL-1beta)-stimulated conditions where the levels were inhibited by 47.8 % at 1 mM metformin (p < 0.05) and by 100 % at 10 mM (p < 0.01). None of the TZDs tested (PPAR-gamma agonists: troglitazone, pioglitazone, or ciglitazone) had any effects on PAI-1 production. Moreover, no effects on PAI-1 production were observed using various PPAR-alpha agonists such as 5, 8, 11, 14-eicosatetraynoic acid (ETYA), Wy14643 and fenofibrate. Our findings indicate no direct effects of TZDs on PAI-1 secretion, whereas metformin was able to directly inhibit PAI-1 production in human adipose tissue.

Adipocytes↗
PubMed2003

Differences in plasminogen activator inhibitor 1 in subcutaneous versus omental adipose tissue in non-obese and obese subjects.

Human adipose tissue can produce plasminogen activator inhibitor-1 (PAI-1). It has been suggested that high levels of PAI-1 are of importance in enhanced cardiovascular disease observed among obese subjects, especially abdominally obese individuals. In the present study, we investigated the level of mRNA and production of PAI-1 in adipose tissue from two adipose tissue depots (omental vs. subcutaneous). Adipose tissue from both depots was obtained from obese (mean BMI, 46.9 kg/m 2) and non-obese (mean BMI, 23.9 kg/m 2) women. PAI-1 mRNA was measured both in fresh adipose tissue obtained immediately after surgery and after the adipose tissue (fragments) had been incubated for up to 72 h. In immediately frozen adipose tissue, PAI-1 mRNA expression was similar in omental and subcutaneous adipose tissue. No differences between obese and non-obese women were found. However, when adipose tissue fragments were cultured, PAI-1 mRNA and PAI-1 production were significantly higher in omental than in subcutaneous adipose tissue (p < 0.05). In the culture system, the production of PAI-1 in obese subjects was higher than in non-obese subjects in both subcutaneous (p < 0.05) and in omental adipose tissue (p = 0.19). In order to test whether these regional differences observed after incubation of the adipose tissue were due to differences in local accumulation of cytokines that may stimulate PAI-1 by a paracrine or autocrine manner, we investigated the expression of transforming growth factor beta1 (TGF-beta1) mRNA and tumor necrosis factor alpha (TNF-alpha) mRNA and protein. No differences between the two fat depots were found. In conclusion, no differences in PAI-1 expression between omental and subcutaneous adipose tissue were observed in biopsies frozen immediately after removal, but after incubation of adipose tissue (which somehow stimulates PAI-1 production), higher levels of PAI-1 were found in omental adipose tissue than in subcutaneous adipose tissue. Finally, PAI-1 production in adipose tissue from obese women was higher in non-obese women after incubation for 72 h.

Adipose Tissue↗