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J Xia

Publications and source records attributed to J Xia.

At least 91 records · Page 5Linked to original sources
PubMed1999

Clustering of AMPA receptors by the synaptic PDZ domain-containing protein PICK1.

Synaptic clustering of neurotransmitter receptors is crucial for efficient signal transduction and integration in neurons. PDZ domain-containing proteins such as PSD-95/SAP90 interact with the intracellular C termini of a variety of receptors and are thought to be important in the targeting and anchoring of receptors to specific synapses. Here, we show that PICK1 (protein interacting with C kinase), a PDZ domain-containing protein, interacts with the C termini of alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) receptors in vitro and in vivo. In neurons, PICK1 specifically colocalizes with AMPA receptors at excitatory synapses. Furthermore, PICK1 induces clustering of AMPA receptors in heterologous expression systems. These results suggest that PICK1 may play an important role in the modulation of synaptic transmission by regulating the synaptic targeting of AMPA receptors.

Aging↗
PubMed1999

Skeletal muscle UCP2 and UCP3 expression in trained and untrained male subjects.

OBJECTIVE: The new uncoupling proteins, UCP2 and UCP3, are thought to play a role in energy efficiency in humans. Endurance training has been suggested to have effects on resting metabolic rate and energy efficiency. We therefore determined UCP2 and UCP3 mRNA levels in skeletal muscle of trained and untrained male subjects. METHODS: Using reverse transcription-polymerase chain reaction (RT-PCR), expression of UCP2, UCP3L and UCP3S mRNA were measured in muscle biopsies from the quadriceps femoris in eight trained (23.9+/-1.6 y; 70.6+/-3.1 kg; 14+/-3% body fat; maximal power output (Wmax): 5. 6+/-0.4 W/kg; mean+/-s.d.) and 10 lean, untrained (22.1+/-2.9 y; 72. 0+/-7.9 kg; 18+/-4% body fat; Wmax: 3.9+/-0.4 W/kg; mean+/-s.d.) subjects. In six of the trained subjects, UCP2 and UCP3 mRNA were measured before and after an exercise bout to exhaustion. To correct for differences in mitochondrial content, levels of UCP2 and UCP3 mRNA were expressed relative to cytochrome-b, a marker of mitochondrial content. RESULTS: Acute exercise had no effect on the expression of UCP3L or UCP3S, but in five out of six subjects UCP2 expression decreased after exercise, although the difference was not statistically significant (P=0.11). Trained subjects had significantly reduced mRNA levels of UCP3L (P=0.028) and UCP3S (P=0. 031). VO2max expressed per kg of fat-free mass was negatively correlated with UCP3L (r=-0.61, P=0.009) and UCP3S (r=-0.52, P=0. 028). Mechanical efficiency correlated negatively with UCP3L (r=-0. 56, P=0.019), UCP3S (r=-0.47, P=0.048) and tended to correlate with UCP2 (r=-0.46, P=0.06). CONCLUSION: The lower levels of UCP3 mRNA in trained subjects and the inverse relationship of UCP3 expression and mechanical efficiency suggest that exercise training produces an adaptive physiological response in skeletal muscle improving mechanical efficiency.

Adult↗
PubMed1999

A novel polymorphism in the proximal UCP3 promoter region: effect on skeletal muscle UCP3 mRNA expression and obesity in male non-diabetic Pima Indians.

OBJECTIVE: UCP2 and UCP3 are newly discovered uncoupling proteins, which are thought to underlie the variability in energy metabolism in humans. Mutations in the UCP2 and/or UCP3 gene have been associated with sleeping metabolic rate. Recently we reported that skeletal muscle UCP3 mRNA expression was positively correlated with sleeping metabolic rate in Pima Indians. To study whether genetic variation in the promoter region of UCP3 contributed to the variation in expression of UCP3, we screened part of the proximal promoter region for polymorphisms. METHODS: In the first part of the study, the proximal promoter region of UCP3 was screened by direct sequencing in 24 non-diabetic Pima Indians (range body mass index (BMI): 18-47 kg/m2) (Schrauwen et al. Diabetes 1999; 48: 146-149) and skeletal muscle UCP3 mRNA expression was measured by RT-PCR. In the second part of the study, we typed the polymorphism found in the first part of the study in 67 Pima Indians (32 males, 35 females) from the upper and lower extremes of the BMI distribution. RESULTS: We identified a novel C to T substitution in the UCP3 promoter, 6bp upstream of the putative TATA signal, and 55bp upstream of the transcription starting site. Among 18 male subjects, skeletal muscle UCP3 mRNA expression was significantly higher in the C/T & T/T group compared to the C/C homozygotes (P<0.02). However, in the group of 67 Pima Indians genotype frequencies were not different in the obese and lean groups. CONCLUSION: We identified a novel polymorphism in the proximal promoter region of UCP3, which was associated with increased skeletal muscle expression of UCP3 in male non-diabetic Pima Indians. Considering the suggested role of UCP3 in energy metabolism, this polymorphism might be of physiological importance in the regulation of energy balance.

Amino Acid Substitution↗
PubMed1999

Cytokine induction of iNOS and sPLA2 in immortalized astrocytes (DITNC): response to genistein and pyrrolidine dithiocarbamate.

Using an immortalized astrocyte cell line (DITNC), we showed that lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta) but not interferon-alpha (IFN-alpha) could individually induce secretory phospholipase A2 (sPLA2) mRNA and enzymatic activity. However, induction of inducible nitric oxide synthase (iNOS) mRNA and NO production by cytokines required the presence of IFN-gamma. Using a three-cytokine mixture (TNF-alpha, IL-1beta, and IFN-gamma) that could maximally induce both iNOS and sPLA2, the increase in these mRNA species reached a maximum by 4-8 h, followed by a decline up to 48 h. L-N6-(1-Iminoethyl)lysine acetate (L-NIL) inhibited cytokine-induced NO production with IC50 of 25 microM, but this compound did not affect iNOS mRNA. Furthermore, L-NIL exerted no effect on sPLA2 mRNA or sPLA2 activity. Pyrrolidine dithiocarbamate (PDTC), an inhibitor for NF-kappaB, was more effective in inhibiting iNOS mRNA and NO production than for sPLA2. Surprisingly, genistein inhibited both NO production and sPLA2 activity with IC50 of 72 microM and 88 microM, respectively. On the other hand, daidzein, a genistein analog lacking tyrosine kinase inhibitor activity, was not effective in inhibition of NO production at 250 microM. These results demonstrate distinct pathways for induction of iNOS and sPLA2 in DITNC cells by cytokines and shed new insight on transcriptional regulation for these two mRNA species.

Animals↗
PubMed1999

Dietary supplementation of grape polyphenols to rats ameliorates chronic ethanol-induced changes in hepatic morphology without altering changes in hepatic lipids.

Increase in oxidative stress after chronic ethanol consumption can result in hepatic injury. Because polyphenolic compounds can offer antioxidant protection to the cardiovascular system, this study was designed to investigate whether dietary supplementation of polyphenols from grapes may ameliorate hepatic injury resulting from chronic ethanol consumption. Male Sprague-Dawley rats were administered the following diets for 2 mo: 1) Lieber-DeCarli (L-D) diet with isocaloric amount of maltose instead of ethanol (Basal), 2) the L-D diet with 50g/L ethanol (EtOH); 3) L-D diet with 50 mg/L of grape polyphenols (GP) and 4) ethanol diet with GP (EtOH + GP). Rats given EtOH or EtOH + GP diets had significantly more hepatic triacylglycerols (P < 0.0001) and lipid peroxidation products (P < 0.01) compared with those given the Basal and GP diets. In addition, ethanol ingestion also decreased significantly (P < 0.01) the proportion of 16:0 and increased 18:0 and 18:1 in hepatic phospholipids, suggesting a perturbation of the de novo fatty acid biosynthesis pathways. However, GP supplementation alone and GP added to the ethanol diet did not alter the lipid changes mediated by ethanol except for the levels of 22:6(n-3) which were significantly (P < 0.05) higher in the EtOH + GP group than in the EtOH group. Despite a lack of gross lipid changes, histologic assessment showed significantly (P < 0.05) less hepatic damage in the GP + EtOH group compared with the EtOH group. These results clearly distinguished ethanol-mediated changes in hepatic morphology from the changes in hepatic lipids and further demonstrated the ability of GP to ameliorate hepatic damage resulting from chronic ethanol consumption.

Animals↗
PubMed1999

Decreased plasma membrane thiol concentration is associated with increased osmotic fragility of erythrocytes in zinc-deficient rats.

Zinc deficiency leads to pathological signs that are related to impaired function of plasma membrane proteins. The purpose of this study was to assess the effect of dietary zinc status on the sulfhydryl (SH) content of erythrocyte plasma membranes and erythrocyte function. Three experiments were performed. In the first, immature male rats were fed for 21 d either a low-zinc (<1.0 mg/kg) diet free choice (-ZnAL), an adequate-zinc (100 mg/kg) diet free choice (+ZnAL), or the adequate-zinc diet limited to the intake of -ZnAL pair-mates (+ZnPF). Tail blood was sampled to measure osmotic fragility and SH concentration of erythrocyte membrane proteins. The zinc-deficient rats were then repleted for 2 d and erythrocytes assayed for fragility and SH content. In the second experiment blood was sampled at 3-d intervals to determine the time course of change in fragility and SH concentration. In the third experiment the SH concentration of erythrocyte band 3 protein and the binding of zinc to isolated plasma membranes were measured. SH concentration decreased from approximately 75 nmol/mg protein to 68 nmol/mg protein during 21 d of depletion and returned to control level within 2 d of repletion. There was an inverse relationship between osmotic fragility and SH concentration of erythrocyte membrane proteins. Maximal decrease in SH occurred within 6 d of consuming the low-zinc diet. The SH content of band 3 protein isolated from deficient rats was also significantly lower than that of pair-fed controls (45 vs. 51 nmol/mg protein). The zinc-binding affinity of plasma membrane proteins tended to be decreased by zinc deficiency. In summary, low-zinc status lowers the plasma membrane SH concentration, and the decreased reducing potential is inversely related to osmotic fragility, and presumably, with impaired volume recovery of erythrocytes.

Animals↗
PubMed1999

Skeletal muscle uncoupling protein 3 expression is a determinant of energy expenditure in Pima Indians.

The recent discovery of uncoupling protein (UCP)-2 and UCP-3, and their high expression in skeletal muscle, has renewed interest in a possible role for these proteins in underlying the variability in energy expenditure and therefore metabolic efficiency. Using reverse transcription-polymerase chain reaction, levels of expression of UCP-2 and long and short forms of UCP-3 were measured in skeletal muscle of 19 nondiabetic, male Pima Indians covering a wide range of body weight. Twenty-four-hour energy expenditure was measured in a respiratory chamber in 16 of these individuals. BMI was negatively correlated with the expression levels of the long (r = -0.53, P = 0.025) and short (r = -0.46, P = 0.047) forms of UCP-3. BMI was not correlated with UCP-2 expression. Metabolic rate during sleep, adjusted for fat-free mass and fat mass, was positively correlated with the long form of UCP-3 (r = 0.69, P = 0.006). These results indicate that UCP-3 may be a determinant of energy expenditure and metabolic efficiency in Pima Indians.

Adult↗
PubMed1999

Chronic ethanol and iron administration on iron content, neuronal nitric oxide synthase, and superoxide dismutase in rat cerebellum.

Excessive chronic ethanol administration to animals has been shown to cause oxidative insults to many body organs, including the liver and brain. In many instances, iron supplementation to the diet may further aggravate ethanol-induced liver damage. However, whether increased dietary iron can enhance the damage in the brain is unknown. In this study, four groups of Sprague-Dawley rats were fed a Lieber-DeCarli liquid diet containing 5% (w/v) ethanol or isocaloric amount of maltase and/or 0.25% (w/v) carbonyl iron for 2 months. At the end of the feeding regimen, iron contents were determined in the plasma, liver, cerebral cortex, and cerebellum. Cerebellar superoxide dismutase (SOD) and nitric oxide synthase (NOS) activities were measured and mRNA levels of MnSOD, CuZnSOD, and nNOS in the cerebellar granule cell layer were quantitated by in situ hybridization. Ethanol treatment alone caused an increase in iron levels in plasma, no change in the liver and cerebral cortex, but a decrease in the cerebellum. Iron supplementation increased liver iron >4-fold but did not alter iron contents in the cerebellum and cortex. All of the mRNA species examined and SOD activity were not affected by either iron or ethanol administration. However, NOS activity in the cerebellum was significantly enhanced by ethanol, whereas iron supplementation had an opposite effect. Our results indicate that iron supplementation to animals consuming ethanol may have tissue-specific effects. Furthermore, ethanol-induced increase in NOS activity in the cerebellum may explain the sensitivity of cerebellar neurons to oxidative insult.

Animals↗
PubMed1999

Distinctions in the molecular determinants of charged and neutral dihydropyridine block of L-type calcium channels.

We investigated block of the alpha1Cb subunit of L-type calcium channels by dihydropyridines (DHPs) in which a permanently charged or neutral head group was linked to the active DHP moiety by a spacer chain containing ten methylene (-CH2) groups. We compared the sensitivity of channel modulation by the charged (DHPch) and neutral (DHPn) forms to specific alpha1Cb mutations in domains IIIS5, IIIS6, and IVS6, which had previously been shown to reduce channel modulation by the neutral DHP (+)-isradipine. The effects of these mutations were studied on channel block recorded from polarized (-80 mV) and depolarized (-40 mV) holding potentials (HPs). We found that channel block by DHPn was markedly reduced at both HPs by each mutation studied. In contrast, channel block by DHPch was only modestly reduced by mutations in IIIS6 and IVS6 for block from either -40 mV or -80 mV. Replacement of IIIS5 Thr1061 by Tyr, which abolished block by DHPn in an HP-independent manner, had little effect on channel block by DHPch recorded from -40 mV. However, this mutation markedly reduced DHPch block of currents recorded from a -80 mV HP. Inhibition of current by DHPch was not markedly use-dependent, in contrast with block by verapamil, another charged calcium channel blocker. These results suggest that the presence of a permanently charged head group restricts the access of the attached DHP moiety to a subset of interaction residues on the alpha1C subunit in a voltage-dependent manner. Furthermore, these restricted interactions confer distinct functional properties upon the charged DHP molecules.

Amino Acid Sequence↗
PubMed1999

[Identification of mutations in the human EXT1 and EXT2 genes].

OBJECTIVE: To investigate further the genetic basis of hereditary multiple exostoses (EXT) and provide useful information for gene diagnosis of the disease. METHODS: Polymerase chain reaction-single strand conformation polymorphism was used to examine the entire coding regions of EXT(1) gene on chromosome 8 and EXT(2) gene on chromosome 11 for mutation in thirty EXT families. Mutations were further identified by sequencing. RESULTS: Two frameshift mutations were identified in two unrelated EXT families. One was the deletion of one base(T) in exon 6 of the EXT(1) gene, and the other was the deletion of four bases (tgtt) in exon 2 of the EXT(2) gene. Both of the mutations resulted in a frameshift and premature termination of translation. CONCLUSION: EXT is a genetically heterogeneous bone disorder caused by the mutation of EXT tumor suppressor gene. These results could be directly applied in the genetic counseling and prenatal genetic diagnosis of EXT.

Chromosome Deletion↗
PubMed1999

[CAG trinucleotide mutation detection in patients with hereditary spinocerebellar ataxia].

OBJECTIVE: To assess the frequency of the SCA1, SCA2,SCA3/MJD, SCA6, SCA7 and DRPLA CAG trinucleotide repeat expansions(CAG)n among individuals diagnosed with hereditary spinocerebellar ataxia(SCA) from Chinese families. METHODS: The SCA1, SCA2, SCA3/MJD, SCA6, SCA7 and DRPLA(CAG)n mutations were detected by polymerase chain reaction (PCR), denaturing polyacrylamide gel electrophoresis and silver staining technique in 167 patients with autosomal dominant SCA from 85 Chinese families and 37 sporadic SCA patients. RESULTS: Among 85 families, four families(4.70%) had seven SCA1 patients with the CAG repeat expanded to 53 to 62 repeats, five (5.88%) had twelve SCA2 patients with the CAG repeat expanded to 43 to 47 repeats, and 41 (48.23%) had 83 SCA3/MJD patients with the CAG repeat expanded to 68 to 83 repeats. Analysis of the mutation in these families showed a strong negative correlation between the size of the expanded CAG repeat and the age of disease onset. None of the SCA patients were positive for SCA6, SCA7, or DRPLA. Nor was any of the sporadic SCA patients positive for the CAG repeat expansion in the SCA1, SCA2, SCA3/MJD, SCA6, SCA7, or DRPLA gene. CONCLUSION: The frequency of SCA3/MJD is substantially higher than that of SCA1 and SCA2 in the autosomal dominant SCA from Chinese families. Chinese SCA3/MJD patients are non-Portuguese. Clinical expressions of the various SCAs overlap one another and hence can make the phenotype-based diagnostic classification inaccurate in many instances. It is important for SCA clinical studies to make an SCA gene diagnosis and genotype analysis.

Adult↗
PubMed1999

[Comparative genomic hybridization analysis of primary gastric carcinomas].

OBJECTIVE: To investigate whether unknown genes are involved in the tumorigenesis of gastric cancer. METHODS: Fourty-three primary gastric carcinomas were analyzed by comparative genomic hybridization(CGH). RESULTS: A gain in chromosome 3p(8/43), 8q(8/43), 20[20(9/43), 20p(7/43), 20q(4/43)], 12q (16/43), and 13q(12/43) was observed while a loss of 19[19(15/43), 19p (13/43)], 17[17(8/43), 17p(10/43)], 16(10/43) and 1p(11/43) was discovered. CONCLUSION: There were characteristic changes in 3p, 8q, 20, 12q, 13q, 19, 17, 16, and 1p in gastric carcinoma, and some unknown genes located in the above regions might be of importance to gastric carcinoma pathogenesis.

Chromosome Aberrations↗
PubMed1999

Identification of mutation in a candidate gene for hereditary multiple exostoses type II.

OBJECTIVES: To identify possible mutations in our previously cloned candidate gene for hereditary multiple exostoses type II (EXT2) in affected members of EXT families so as to confirm that it is the disease-causing gene. METHODS: The mutation was detected first by single strand conformational polymorphism (SSCP) of all coding exons of the candidate gene and then by sequencing analysis. RESULTS: After analyzing 37 patients from 20 Chinese EXT families by SSCP and DNA sequencing analysis, one 2-bp insertion mutation was identified in this candidate gene in affected members of an EXT family. This mutation resulted in the frameshift and generated a truncated gene product consisting of 105 amino acids. CONCLUSIONS: The identification of the mutation in the candidate gene indicates that this novel gene is responsible for EXT2 (one of the disease-causing gene of EXT).

Amino Acid Sequence↗
PubMed1999

Effects of ultraviolet-irradiated urocanic acid on IL-10 secreted by T lymphocytes.

OBJECTIVE: To further investigate the effects of ultraviolet (UV)-irradiated urocanic acid (UCA) on T lymphocytes, the effects of cis-UCA on T lymphocyte IL-10 secretion was studied. METHODS: Four groups of normal lymphocytes were cultured in RPMI-1640 containing 15% fetal calf serum. Besides negative and phytohemagglutinin (PHA) positive control, the cis-UCA and trans-UCA groups were set. The number of lymphocytes was 1.5 x 10(6). PHA was 0.05 mg/ml in each group. Both cis-UCA and trans-UCA were detected by 1.00, 0.75, 0.50 and 0.20 mmol/L respective concentrations. IL-10 was detected by ELISA method after 48 hours' culture. IL-10 mRNA expression level was assayed by RT-PCR. RESULTS: The results indicated cis-UCA could reduce IL-10 secreted by T lymphocytes much more than trans-UCA (t = 2.91, P < 0.05) could. It was also found that the concentrations of cis-UCA were negatively correlated with IL-10 levels (r = -0.99, tr = 9.23, P < 0.01). The IL-10 mRNA expression of T lymphoctytes was inhibited by cis-UCA. CONCLUSION: Our investigations revealed that cis-UCA, a major UV receptor in the stratum comeum of epidermis, could inhibit T lymphoctes secreting IL-10 by suppressing IL-10 mRNA expression, finally affects the humoral immune response.

Adult↗
PubMed1999

[STK11 gene mutation in Chinese with PJS].

OBJECTIVES: To understand the mutation characteristic of STK11 gene in Chinese with Peutz-Jeghers syndrome and establish the gene diagnosis of PJS. METHODS: STK11 gene was analysed by PCR-SSCP and DNA sequencing in 8 Chinese pedigrees with PJS. RESULTS: Two novel point mutations of STK11 gene were detected in two pedigrees: one was nonsense in exon1, and another mutation occurred in splice spot in the donor site of intron 1. It was estimated that these mutations would lead to produce truncated protein. CONCLUSION: Point mutation in STK11 may be chief in Chinese with PJS and the frequency of mutation was fewer than that in previous reports. It suggested that there may be genetic heterogeneity in PJS.

Asian People↗
PubMed1999

Surgical treatment of hepatocellular carcinoma and related basic research with special reference to recurrence and metastasis.

OBJECTIVE: To summarize the progress of surgical treatment of hepatocellular carcinoma (HCC) and related basic research at the Liver Cancer Institute of Shanghai Medical University in the recent years, with special reference to recurrence and metastasis. METHODS: Published and unpublished update clinical and experimental data in the above-mentioned areas are summarized. RESULTS: Surgical resection has played an important role in improving prognosis of HCC, the 5-year survival were 63.4% for small HCC resection (n = 806), 39.6% for large HCC resection (n = 1061), 64.7% for cytoreduction (using hepatic artery cannulation and ligation) and sequential resection of initially unresectable HCC (n = 93), 56.0% for cytoreduction using transcatheter arterial chemoembolization (TACE) and followed by resection (n = 65), and 22.4% for hepatic resection with removal of tumor thrombi in portal vein (n = 103). Unfortunately, the 5-year recurrent rate after curative resection of HCC was up to 61.5%, which was mainly a result of intrahepatic "metastasis" and multicentric origin of HCC. Clinically, re-resection of subclinical recurrence yielded 56% of 5-year survival (n = 202); prevention of recurrence by transcatheter arterial chemoembolization (TACE) + Interferon, or LAK/IL-2 therapy have decreased 3-year recurrent rate from 33% to 11%-18%. In experimental aspect, metastatic human HCC model in nude mice (LCI-D20) and HCC cell line with metastatic potential (MHCC97) have been established; studies on HCC invasiveness in the molecular level revealed similar results that reported in other solid cancers, and small HCC showed slightly better biological characteristics as compared with large HCC; microvessel density (MVD) that reflecting angiogenesis adversely correlated with 5-year survival of small HCC; experimental interventions using antisense H-ras, bispecific antibody, BB94, as well as anti-angiogenic agents (TNP470, suramin, CAI, heparin, antisense VEGF, etc.) have been demonstrated to inhibit tumor growth and lung metastasis in nude mice model. CONCLUSIONS: Recurrence and metastasis are the major obstacle to further improve prognosis of HCC, studies should be conducted both in clinical and experimental aspects, "HCC invasiveness" will be the major target to be studied, particularly in the molecular level, and anti-angiogenesis will be one of the important approach.

Angiogenesis Inhibitors↗
PubMed1999

[Direct chromosome analysis and FISH study of primary gastric cancer].

OBJECTIVE: To investigate chromosome aberrations and their role in the genesis and progression of primary gastric cancer. METHODS: An improved, direct method of chromosome preparation from solid tumors was adopted for G-banding analysis followed by FISH on decolored G-banding chromosomes so that chromosome aberrations could be confirmed at DNA level. RESULTS: A total of 28 primary gastric cancer specimens were studied. Case 1 and case 2 had simple chromosome numerical changes: 49, XY, +2, +8, +9 and 47, XX, +8, +20, respectively. All but case 1 and 2 had complicated chromosome abnormalities. Structural changes of frequent occurrence involved del(7q) (21/26), del(3p)(14/26), del(1p)(11/26) and del(17p)(10/26). The chromosome abnormalities could be simple or complicated. In the former, numerical changes involving 1 to 3 chromosomes could be observed. Trisomies 8 and 9 appeared to be a cytogenetic subgroup of primary gastric cancer. In the latter, del(7q) was the most consistent structural aberration. The 7q32-qter was the commonly lost segment. CONCLUSION: Numerical and structural alterations of chromosomes are present in primary gastric cancer. Del(7q) is one of the structural changes characteristic of primary gastric cancer. In the 7q32-qter segment, a tumor suppressor gene probably exists and it may have close relation to the genesis and progression of gastric cancer.

Chromosome Aberrations↗