Biomedical subjects

Y-T Chen

Publications and source records attributed to Y-T Chen.

6 recordsLinked to original sources

PubMed2003

Genetic epistasis of adiponectin and PPARgamma2 genotypes in modulation of insulin sensitivity: a family-based association study.

AIMS/HYPOTHESIS: Genetic interactions in modulating the phenotypes of a complex trait, such as insulin sensitivity, were usually taken for granted. However, this has not been commonly shown. Previous studies have suggested that both PPARgamma2 and adiponectin genes could influence insulin sensitivity. Therefore it is likely that they could modulate insulin sensitivity through gene to gene interactions. METHODS: We genotyped 1793 subjects of Chinese and Japanese descendents from 601 hypertensive families recruited in Sapphire study for a T94G in the adiponectin gene exon 2 and the PPARgamma2 Pro12Ala polymorphisms. Serum insulin concentrations and insulin resistance index (HOMA(IR)) were used as the markers of insulin sensitivity. RESULTS: We found that the T allele of adiponectin gene was associated with a higher Ins60 and higher area under curve of insulin (AUCi) in OGTT utilizing all subjects in a mixed model that corrected for family effects. Important interactions between adiponectin and PPARgamma2 genotypes were found in fasting insulin concentrations (Ins0), insulin concentrations at 2-h (Ins120) in OGTT and insulin resistance index (HOMA(IR)). The main effects of the PPARgamma2 genotypes were in the plasma glucose concentrations in OGTT. In contrast, the main effects of adiponectin genotypes were in every insulin variable, including Ins0, Ins60, Ins120, AUCi and HOMA(IR). The subjects carrying the adiponectin G allele and the PPARgamma2 Ala12 allele seemed to be more insulin sensitive. CONCLUSION/INTERPRETATION: These results showed that adiponectin is a genetic factor associated with insulin sensitivity. Interactions with PPARgamma2 genotypes modified this association.

Adiponectin↗

PubMed2003

Rare disorders of metabolism with elevated butyryl- and isobutyryl-carnitine detected by tandem mass spectrometry newborn screening.

Tandem mass spectrometry was adopted for newborn screening by North Carolina in April 1999. Since then, three infants with short-chain acyl-CoA dehydrogenase (SCAD) and one with isobutyryl-CoA dehydrogenase deficiency were detected on the basis of elevated butyrylcarnitine/isobutyrylcarnitine (C4-carnitine) concentrations in newborn blood spots analyzed by tandem mass spectrometry. For three SCAD-deficient infants, biochemical evaluation included a plasma acylcarnitine profile with markedly elevated C4-carnitine, urine organic acid analysis with markedly elevated ethylmalonic and 2-methylsuccinic acids, and markedly elevated [U-13C]butyrylcarnitine concentrations in medium from fibroblasts incubated with [U-13C]palmitic acid and excess l-carnitine, consistent with classic SCAD deficiency. Two of three infants diagnosed with classic SCAD deficiency remained asymptomatic; however, the third infant presented with seizures and a cerebral infarct at 10 wk of age. All three infants had putatively inactivating mutations in both alleles of the SCAD gene. The highly elevated plasma C4-carnitine levels in the three infants detected by newborn screening tandem mass spectrometry differentiated them from infants and children who were homozygous or compound heterozygous for one of two SCAD gene susceptibility variations; for the latter group the C4-carnitine levels were normal. Isobutyryl-CoA dehydrogenase deficiency in a fourth infant was confirmed after isolated elevation of C4-carnitine in the acylcarnitine profile.

Butyryl-CoA Dehydrogenase↗

PubMed2003

Long-term correction of glycogen storage disease type II with a hybrid Ad-AAV vector.

We administered an adenovirus-adeno-associated virus (Ad-AAV) vector encoding human acid alpha-glucosidase (hGAA) to acid alpha-glucosidase-knockout (GAA-KO) mice on day 3 of life by gastrocnemius injection. In contrast to previous results for muscle-targeted Ad vector in adult GAA-KO mice, the muscles of the hindlimb showed reduced glycogen content and persistent hGAA for as long as 6 months after neonatal Ad-AAV vector administration. Not only the injected gastrocnemius muscles, but also the hamstrings and quadriceps muscles produced therapeutic levels of hGAA as a result of widespread transduction with the Ad-AAV vector; moreover, hGAA activity was 50-fold elevated as compared to normal mice. Vector RNA was detected in the hindlimb muscles, the hearts, and the livers by northern blot analysis and/or by RT-PCR for as long as 6 months. The low levels of hGAA detected in the heart were attributable to transduction with the Ad-AAV vector, not to secretion of hGAA by the injected muscle and uptake by the heart. Finally, although an antibody response to hGAA was present, it did not prevent the correction of glycogen storage in the skeletal muscle of GAA-KO mice.

Adenoviridae↗

PubMed2003

Packaging of an AAV vector encoding human acid alpha-glucosidase for gene therapy in glycogen storage disease type II with a modified hybrid adenovirus-AAV vector.

We have developed an improved method for packaging adeno-associated virus (AAV) vectors with a replication-defective adenovirus-AAV (Ad-AAV) hybrid virus. The AAV vector encoding human acid alpha-glucosidase (hGAA) was cloned into an E1, polymerase/preterminal protein-deleted adenovirus, such that it is packaged as an Ad vector. Importantly, the Ad-AAV hybrid cannot replicate during AAV vector packaging in 293 cells, because of deletion of polymerase/preterminal protein. The residual Ad-AAV in the AAV vector stock was reduced to <1 infectious particle per 10(10) AAV vector particles. These modifications resulted in approximately 30-fold increased packaging of the AAV vector for the hybrid Ad-AAV vector method as compared with standard transfection-only methods. Similarly improved packaging was demonstrated for pseudotyping the AAV vector as AAV6, and for AAV vector packaging with a second Ad-AAV vector encoding canine glucose-6-phosphatase. Liver-targeted delivery of either the Ad-AAV hybrid or AAV vector particles in acid alpha-glucosidase-knockout (GAA-KO) mice revealed secretion of hGAA with the Ad-AAV vector, and sustained secretion of hGAA with an AAV vector in hGAA-tolerant GAA-KO mice. Further development of hybrid Ad-AAV vectors could offer distinct advantages for gene therapy in glycogen storage diseases.

Adenoviridae↗

PubMed2002

PALS db: Putative Alternative Splicing database.

PALS db is a collection of Putative Alternative Splicing information from 19 936 human UniGene clusters and 16 615 mouse UniGene clusters. Alternative splicing (AS) sites were predicted by using the longest messenger RNA (mRNA) sequence in each UniGene cluster as the reference sequence. This sequence was aligned with related sequences in UniGene and dbEST to reveal the AS. This information was presented with six features: (i) literature aliases were used to improve the result of a gene name search; (ii) the quality of a prediction can be easily judged from the color-coded similarity and the scaled length of an alignment; (iii) we have clustered those EST sequences that support the same AS site together to enhance the users' confidence on a prediction; (iv) the users can also set up the alignment criteria interactively to recover false negatives; (v) tissue distribution can be displayed by placing the mouse cursor over an alignment; (vi) gene features will be analyzed at foreign sites by submitting the selected mRNA or its encoded protein as a query. Using these features, the users cannot only discover putative AS sites in silico, but also make new observations by combining AS information with tissue distributions or with gene features. PALS db is available at http://palsdb.ym.edu.tw/.

Alternative Splicing↗

PubMed2002

Expression and roles of herpesvirus entry mediators A and C in cells of oral origin.

The roles of viral glycoprotein D (gD) and cellular herpesvirus entry mediators A (HveA) and C (HveC) in herpes simplex virus entry into oral cells were determined. Studies with purified truncated forms of gD-1, HveA and HveC indicated that these molecules may be involved in herpes simplex virus entry into oral cells. Moreover, HveA was expressed similarly in primary cultures of gingival keratinocytes and fibroblasts, whereas HveC was expressed at higher levels in gingival keratinocytes, as determined by RT-PCR and immunocytochemical staining. Further analysis using immunohistochemistry demonstrated that both HveA and HveC were expressed in epithelial cells, fibroblasts and vascular endothelial cells in gingival tissues. However, only HveC was detected in nerve fibers. Also, HveA was detected throughout the epidermis, whereas HveC was pronounced in the strata basale and spinosum. In conclusion, this study characterized HveA and HveC, molecules that may participate in entry of herpes simplex virus into oral cells.

Adult↗