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Biomedical subjects

J Mei

Publications and source records attributed to J Mei.

At least 37 records · Page 2Linked to original sources

Tumor necrosis factor-alpha and ceramides in insulin resistance.

The present studies tested the hypothesis that some effects of tumor necrosis factor-alpha (TNF-alpha) are mediated by activation of sphingomyelinases and the production of ceramides. Differentiated 3T3-L1 adipocytes were incubated with short-chain ceramide analogs, (C2- and C6-ceramides: N-acetyl- and N-hexanoyl-sphingosines, respectively), and this treatment increased 2-deoxyglucose uptake in the absence of insulin progressively from 2-24 h. This effect was inhibited by blocking the activations of mitogen-activated protein kinase, phosphatidylinositol 3-kinase (PI 3-kinase), and ribosomal S6 kinase which mediated an increase in GLUT1 concentrations. Long-term increases in PI 3-kinase activity associated with insulin receptor substrate-1 (IRS-1) increased the proportion of GLUT1 and GLUT4 in plasma membranes. These events explain the increases in noninsulin-dependent glucose uptake and incorporation of this glucose into the fatty acid and glycerol moieties of triacylglycerol. The mechanisms by which TNF-alpha and ceramides increase PI 3-kinase activity were investigated further by using rat2 fibroblasts. Incubation for 20 min with TNF-alpha, bacterial sphingomyelinase, or C2-ceramides increased PI 3-kinase activity by about fivefold, and this effect depended upon a stimulation of tyrosine kinase activity and an increase in Ras-GTP. This demonstrates the existence of a novel signaling pathway for TNF-alpha that could contribute to the effects of this cytokine in stimulating basal glucose uptake. By contrast, treating the 3T3-L1 adipocytes for 2-24 h with C2-ceramide diminished insulin-stimulated glucose uptake by decreasing the insulin-induced translocation of GLUT1 and GLUT4 to plasma membranes. This inhibition was observed when there was no increase in basal glucose uptake, and it occurred downstream of PI 3-kinase. Our work provides further mechanisms whereby TNF-alpha and ceramides produce insulin resistance and decrease the effectiveness of insulin in stimulating glucose disposal from the blood. Conversely, TNF-alpha and ceramides increase the ability of adipocytes to take up glucose and store triacylglycerol in the absence of insulin.

3T3 Cells↗

A comparison of correlates of cigarette smoking behavior between Jiangxi province, China and Japanese high school students.

We conducted surveys on cigarette smoking among junior and senior high school students in Jiangxi province, China and throughout Japan using the same anonymous, self-administered questionnaire in order to compare correlates of adolescent smoking between the two areas. Cross-sectional surveys were used to measure smoking behavior and correlates in two samples of 57,566 Japanese students and 11,836 Jiangxi students. The correlate on smoking with the highest relative risk was friend's smoking in both sexes in each area. The magnitude of the relative risk was bigger for Japanese students. The relative risk of the variable that a student doesn't think cigarette smoking harms his/her health was higher among Jiangxi students than among Japanese students. Mother's smoking and sister's smoking were significantly related to smoking experiment of Japanese students. In Japan, important measures are to support students getting coping techniques against peer pressure and to elevate concern toward adolescent smoking among family members and society. In Jiangxi, the anti-smoking education to teach students to correctly recognize the harm of smoking to their health is more important.

Adaptation, Psychological↗

[Effect of artemether on nucleoside uptake and nucleic acid content in Schistosoma japonicum].

AIM: To observe the effect of artemether (Art) on nucleoside uptake and nucleic acid content in Schistosoma japonicum. METHODS: RNA and DNA contents of both male and female worms harbored in mice treated intragastrically (i.g.) with Art 300 mg/kg for 24 h or 48 h were determined, respectively. After in vivo drug treatment, the schistosomes recovered were in vitro maintained in drug-free medium containing [3H]adenosine, [5-(3)H] uridine or [methyl-3H]thymidine at a final concentration of 37 MBq/L or 74 MBq/L for 2 h or 4 h, the tritiated nucleoside uptake and incorporation into nucleic acid of schistosomes were measured. RESULTS: The RNA and DNA contents of female worms recovered from the host 48 h after dosing were markedly decreased by 51.6% and 23.5%, respectively, while the RNA content of male worms showed 42.4% reduction. When the above-mentioned schistosomes were in vitro exposed to the tritiated nucleoside for 2 h or 4 h, apparent decrease in tritiated nucleoside uptake with reduction rates of 35.2%-50.1% was seen in female worms. The incorporation of [methyl-3H]thymidine into the female worm DNA 2 h after incubation was reduced by 71.4% while the incorporation of [3H]adenosine into the female worm RNA and DNA 4 h after incubation was reduced by 65.2% and 50.0%, respectively. CONCLUSION: Art exhibited an apparent effect on the nucleic acid metabolism in schistosomes, especially in female worms.

Animals↗

Tomographic evidence for localized lithospheric shear along the altyn tagh fault

Seismic tomography across the Altyn Tagh fault, at the north edge of the Tibetan Plateau, reveals a low P-wave velocity anomaly below the fault down to 140 kilometers. This anomaly probably reflects strike-slip shear in the lithosphere. Slip-partitioning may also induce a wedge of crust from the Tarim Basin to plunge into the mantle.

Journal Article↗

[The food habit and its affecting factors of preschool children in Guangzhou].

A survey of nutritional knowledge-attitude-practice was conducted among 1300 preschool children, their parents, 203 teachers and nurses in Kindergarten in 1997. Results showed that the food habit of preschool children was unsuitable. Most preschool children rejected eating animal liver, peanut product and animal blood, but often ate snacks. From statistic analysis among affecting factors, the mother's and teachers' nutritional knowledge and the food habit of parents had significant effect on food habit of preschool children. The family income did not significantly affect food habit of preschool children. Moreover, there was little nutrition education involved in the preschool children courses in 4 kindergartens. The result suggested that the nutrition education plan should be done.

Adult↗

Opposing effects of intracerebroventricularly injected norepinephrine on oxytocin and vasopressin neurons in the paraventricular nucleus of the rat.

Our previous study shows that intracerebroventricularly (i.c.v.) injected norepinephrine (NE) had different effects on the discharge of different firing patterns of magnocellular neurons in the paraventricular nucleus (PVN). In the present study we further classified antidromically identified magnocellular neurons into two groups: vasopressin (VP) and oxytocin (OT) secreting neurons, and found that of all 48 cases of magnocellular neurons, NE had mainly excitatory effects on 36 cases of putatively OT-secreting neurons, and inhibitory effects on 12 cases of VP-secreting neurons. The third ventricular injected NE had almost the same effect on two types of neurons as that of lateral ventricular injection, partly ruling out the possibility that the lateral ventricularly injected NE may have acted indirectly on the magnocellular neurons in PVN. The results show that different mechanisms may be involved in mediating the effect of i.c.v. injected NE on VP- and OT-secreting neurons in the PVN.

Animals↗

Methotrexate regulates ICAM-1 expression in recipients of rat cardiac allografts.

The means by which methotrexate (MTX) mediates immunosuppression at low doses remains to be elucidated. MTX has been shown to inhibit the adherence of neutrophils and fibroblasts to endothelial cells in vitro. The hypothesis that MTX treatment may affect cellular adherence by downregulating cell adhesion molecule expression formed the rationale for these studies. Previous studies of rat cardiac transplant recipients in our laboratory demonstrated that low-dose MTX treatment alone significantly inhibits the expression of the leucocyte beta 2 integrin subunit, CD18. These investigations have addressed whether low-dose MTX treatment might also affect the expression of the beta-integrin counter-receptor, ICAM-1, a cell adhesion molecule which may be induced on endothelial cells during an immune response. The degree to which low-dose cyclosporine A and low-dose MTX treatment alone, and in combination, impact cell adhesion molecule expression has been studied in Brown Norway (BN) to Lewis (Lew) rat accessory cervical heart allografts. According to both Northern blot and immunohistochemical analysis, ICAM-1 expression was upregulated in graft regional lymph nodes and in the spleen of untreated cardiac allograft recipients within 6 h post-transplantation. Despite induction of VCAM-1 expression, ICAM-1 expression remained low or undetectable in cardiac allograft tissue as measured both by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemical analysis. These data suggest that ICAM-1 may function in leucocyte trafficking through lymphoid organs, such as the lymph nodes and spleen, but not directly in graft leucocyte recruitment during BN to Lew rat cardiac allograft rejection. Despite prolonged allograft survival with cyclosporine A alone and combination cyclosporine A/MTX, these treatments did not result in diminished steady-state ICAM-1 mRNA levels in regional lymph nodes or spleen of cardiac allograft recipients. MTX treatment alone, however, substantially diminished ICAM-1 expression in allograft recipient lymphoid tissues. These studies demonstrate for the first time in vivo using a rat model of acute allograft rejection that MTX but not cyclosporine treatment downregulates cell adhesion molecule expression. Low-dose MTX treatment alone, however, is not sufficient to result in prolonged BN to Lew rat cardiac allograft survival. The means by which combination low-dose cyclosporine A and MTX treatment results in prolonged rat cardiac allograft survival over low-dose cyclosporine treatment alone remain(s) to be clarified.

Animals↗

Effects of cyclosporine A and methotrexate on CD18 expression in recipients of rat cardiac allografts.

Recent advances in the study of the molecular basis of inflammation suggest that cell-cell interactions mediated by specific adhesion molecules could be new targets for immunosuppression. Methotrexate (MTX)-treated cells in vitro have demonstrated decreased neutrophil-endothelial cell adhesion associated with increased release of adenosine from endothelial cells, while the direct role of cyclosporine A (CSA) in the regulation of cell adhesion molecule (CAM) expression is less well-defined. Since the adhesion of leucocytes to endothelial cells via CAMs is necessary for leucocyte extravasation and infiltration into graft tissue during allograft rejection, these studies have addressed the hypothesis that MTX treatment of cardiac transplant recipients may affect cellular adherence by downregulating cell adhesion molecule expression. Using a vascularized method of rat cardiac transplantation, our studies have previously demonstrated that low doses of the immunosuppressive agents CSA and MTX, when used in combination, significantly increase allograft survival. According to reverse transcriptase-polymerase chain reaction (RT-PCR) methodology to measure changes in steady-state CD18 mRNA levels, and immunohistochemistry to assess transplant CD18 protein levels in situ, both CD18 transcript and protein levels were significantly increased in untreated allografts when compared to isograft tissues on days 3 through to 7 post-transplant. Whereas, both low-dose CSA alone and low-dose MTX alone treatment resulted in similar levels of graft leucocyte infiltration, MTX-treated recipients demonstrated lower levels of CD18 expression when compared to low-dose CSA alone treatment. The results of immunohistochemical staining for T cells, where significantly fewer T cells were observed in rat cardiac allografts after low-dose MTX treatment alone compared to low-dose CSA treatment, were noteworthy. Results of these studies indicate that CD18 expression and infiltrating T cell numbers in Brown Norway (BN) to Lewis (Lew) rat cardiac allografts are significantly diminished with low-dose MTX treatment. The immunosuppressive effects of MTX, therefore, may be related to its ability to interfere with an early step during the cell-mediated immune response, namely the firm binding or 'adhesion' of leucocytes to the endothelium during transendothelial migration.

Animals↗

Cloning and characterization of a mouse sigma1 receptor.

A cDNA clone (S2-1a) isolated from a mouse brain cDNA library, using a guinea pig sigma1 cDNA as probe, has high homology to the predicted protein sequence of the guinea pig (88%) and human (90%) sigma1 receptors. Northern analysis revealed a major mRNA of approximately 1.8 kb in a wide range of mouse tissues, with highest levels in brain, liver, kidney, and thymus. Southern analysis and chromosomal mapping in the mouse suggested a single-copy gene in region A5-B2 of chromosome 4. Expression of the clone in MCF-7 and CHO cells led to a pronounced increase in (+)-[3H]pentazocine binding with a selectivity profile consistent with sigma1 receptors. In vitro translation yielded a protein of approximately 28 kDa, as did transfection of a probe containing the hemagglutinin (HA) epitope (S2-1a.HA) into CHO cells, as determined by western analysis using an antibody directed against HA. (+)-[3H]-Pentazocine binding to immunopurified HA-tagged receptor demonstrated conclusively that S2-1a.HA encodes a high-affinity (+)-[3H]pentazocine binding site with characteristics of a murine sigma1 receptor. An antisense oligodeoxynucleotide designed from S2-1a potentiated opioid analgesia in vivo.

Amino Acid Sequence↗

[Efficacy of beta-carotene on lipid peroxidation induced by N-nitrosodimethylamine in rats].

The effect of beta-carotene (beta-C) on lipid peroxidation induced by N-nitrosodimethylamine (NDMN) in rats was studied. Thirty clear conventional SD rats were randomly devided into 3 groups and were intragastricly given daily water (10 ml/kg). NDMN (1.75 mg/kg), and NDMN (1.75 mg/kg) plus beta-C (25 mg/kg) respectively. The results showed that: compared with group 1, the activities of SOD and GSH-Px in NDMN group were significantly decreased (P < 0.05), the values of MDA and ROOH increased (P < 0.05). The activities of SOD and GSH-Px in group 3 were significantly higher and the contents of ROOH and MDA were significantly lower than that of NDMN group (P < 0.05). These results suggested that free radicals and lipid peroxidation may be a carcinogenic path for NDMN and other nitrosamines. beta-C had ability to inhibit the lipid peroxidation induced by NDMN.

Animals↗

Effect of artemether on hexokinase, glucose phosphate isomerase and phosphofructokinase of Schistosoma japonicum harbored in mice.

AIM: To study the effect of artemether (Art) on hexokinase (HK), glucose phosphate isomerase (GPI) and phosphofructokinase (PFK) of Schistosoma japonicum. METHODS: Mice infected with schistosome cercariae for 4-5 wk were treated ig with Art 100 or 300 mg.kg-1 and killed 24 h or 48 h after medication for collection of schistosomes. The activities of HK, GPI and PFK of the worms were determined by measuring the formation of NADPH or consumption of NADH. RESULTS: Worms from the infected mice treated ig with Art at a single dose of 300 mg.kg-1 the inhibition rates of HK activity of female and male worms were 33.7% and 13.7%, respectively 24 h after administration. Similar results were seen in GPI activity, but 48 h after medication, the inhibition rate of GPI increased to 46.2% (female) and 32.9% (male), respectively. Worms from mice treated with Art 100 or 300 mg.kg-1, the inhibitory effect on PFK in female worms was found much higher than that of male worms the inhibition rates of PFK were 64.9%-71.0% in female worms and 16.3%-54.2% in male worms, respectively at 24 h and 48 h after treatment. CONCLUSION: The results suggest that in the glycolytic pathway of schistosome PFK might be one of the targets attacked by Art.

Animals↗

In vitro and in vivo effect of levopraziquantel, dextropraziquantel versus racemic praziquantel on different developmental stages of Schistosoma japonicum.

AIM: To compare the antischistosomal effect of racemic praziquantel (Pra) and its enantiomers, levopraziquantel (L-Pra) and dextropraziquantel (D-Pra), on different developmental stages of Schistosoma japonicum. METHODS: The in vitro effects of the drugs were determined in different stages of schistosomes maintained in RPMI 1640 supplemented with 20% calf serum. In vivo study mice infected with schistosome cercariae were treated intragastrically (ig) with Pra, L-Pra or D-Pra at different intervals after infection. The efficacy of the drugs was evaluated by residual mean worm number. RESULTS: Based on the degree of tegument damage induced by L-Pra, d28 and d35 schistosomes were most susceptible to L-Pra, while d14 schistosomules being least susceptible. At comparable concentrations of 0.1-1 g/ml, L-Pra was more active than Pra even when the concentration of L-Pra was reduced to one-half of the minimum effective concentration of Pra. At above-mentioned concentrations D-Pra exhibited no apparent in vitro effect on different stages of schistosomes. When infected mice were treated ig with L-Pra, Pra or D-Pra at a single dose of 300 mg/kg or 500 mg/kg, only the former two drugs showed apparent effect on d0, d21, d28 and d35 schistosomes and less or much less effect on d3, d7 and d14 schistosomules. D-Pra only exhibited a negligible effect on d35 adult schistosomes as compared with L-Pra and Pra. When mice infected with d35 adult schistosmes were treated ig with L-Pra 150 mg/kg, the efficacy was similar to that of mice treated with Pra 300 mg/kg. CONCLUSION: L-Pra is the principal active component against schistosomes in racemic Pra.

Animals↗

Enhanced kappa-opioid receptor-mediated analgesia by antisense targeting the sigma1 receptor.

In the current study, we used an antisense oligodeoxynucleotide targeting the recently cloned sigma1 receptor to assess its functions within the nervous system. Sigma1 antagonists potentiate the analgesic actions of opioids. Similarly, the antisense probe targeting the sigma1 receptor enhanced the analgesic activity of the kappa1-opioid receptor agonist U50,488H (trans-3,4-dichloro-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeacetamidel++ +) and the kappa3-opioid receptor agonist naloxone benzoylhydrazone. A mismatch control was inactive. These results confirm the role of sigma1 receptors in an anti-opioid analgesic system and illustrate the utility of antisense approaches towards the elucidation of sigma receptor functions.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Inhibition of insulin release by intraduodenally infused enterostatin-VPDPR in rats.

Enterostatin, an amino-terminal pentapeptide produced in the intestinal lumen after cleavage of pancreatic procolipase, has been shown to suppress fat intake in rats after intraduodenal infusion. In this study, female Sprague-Dawley rats fitted with a duodenal catheter were intestinally infused with enterostatin (Val-Pro-Asp-Pro-Arg, 11.3 and 22.6 nmol/kg/min) plus 20% Intralipid for 30 min. Plasma insulin levels were significantly reduced, whereas plasma glucose concentrations were not altered by enterostatin-VPDPR. The tripeptide Asp-Pro-Arg was also found to decrease the levels of plasma insulin. However, the pentapeptide with the sequence Val-Pro-Gly-Pro-Arg, des-Arg-enterostatin Val-Pro-Asp-Pro and the tripeptide Pro-Asp-Pro failed to cause the reduction of plasma insulin levels in rats following intestinal infusion of these peptides. Radiolabeled enterostatin ([3H]VPDPR) was identified in plasma by HPLC following intraduodenal infusion of the peptide, indicating that the appearance of an intact enterostatin-VPDPR in blood. It is concluded that intestinally administered enterostatin-VPDPR and its metabolites reduce plasma levels of insulin stimulated by Intralipid.

Animals↗

Effects of cyclosporine A and methotrexate on induction of tumour necrosis factor-alpha in rat cardiac allografts.

Experimental and clinical studies have yet to determine the extent to which methotrexate (MTX) or cyclosporine A (CSA) treatment alone affects the expression in vivo of tumour necrosis factor-alpha (TNF alpha), a cytokine produced primarily by macrophages and believed to be directly involved in the pathogenesis of cardiac allograft rejection. In light of previously published findings from this laboratory examining the effects of combination CSA/MTX treatment, these studies were designed to examine the individual effects of CSA and MTX upon TNF alpha gene expression post-transplant (post-tx) using an accessory cervical heart transplant model in the rat. These studies have focused on a highly sensitive method with which to detect changes in gene expression, reverse transcriptase-polymerase chain reaction (RT-PCR) methodology and enzyme-linked immunosorbent assay (ELISA) assessment of transplant TNF alpha protein levels. Both techniques consistently demonstrated biphasic TNF alpha expression in cardiac transplant tissue obtained from untreated allograft recipients during the first week post-tx in contrast to isograft recipients. Previously demonstrated in combination to prolong cardiac allograft survival, low-dose MTX and low-dose CSA were each evaluated alone in the course of these studies to determine their impact on TNF alpha gene expression. While TNF alpha levels were up-regulated during untreated allograft rejection, both TNF alpha RNA and protein were significantly diminished with low-dose combination CSA/MTX treatment, with CSA alone, but not significantly with MTX treatment alone. In conclusion, TNF alpha gene expression in untreated allografts is consistent with the hypothesis that TNF alpha may play a role in events leading to allograft rejection. Results of these studies indicate that TNF alpha levels are significantly regulated in vivo by CSA but not by MTX treatment. These studies further implicate a role for low-dose MTX in mediating statistically significant immunosuppressive effects in conjunction with low-dose CSA.

Animals↗

Dissociation of affinity and efficacy in KOR-3 chimeras.

KOR-3 chimeras were constructed in which the first coding exon of KOR-3 was exchanged for the corresponding first coding exon of either MOR-1 (MOR-1/KOR-3) or DOR-1 (DOR-1/KOR-3). All three clones were expressed in CHO cells and characterized with regards to their binding profiles for orphanin FQ/nociceptin (OFQ/N) and a variety of opioids as well as their functional activities in cyclase studies. 125I[Tyr14]OFQ/N labels both KOR-3 (KD 37 pM) and the MOR-1/KOR-3 chimera (KD 39 pM) equally well. Although its affinity for the DOR-1/KOR-3 chimera is quite good (KD 135 pM), it is slightly lower than the other two. Competition studies confirm the high affinity of OFQ/N for all three clones. However, several competitors clearly distinguish the chimeras from KOR-3. OFQ/N(1-11) competes KOR-3 (Ki 55 nM) over 6-fold more potently than either of the chimeras. (Ki values > 350 nM). Conversely, the modest affinity of naloxone benzoylhydrazone for KOR-3 (310 nM) is greatly increased in both the MOR-1/KOR-3 (Ki 69 nM) and DOR-1/KOR-3 (Ki 74 nM) chimeras. The remainder of the opioids tested have no appreciable affinity against any of the clones. Functionally, OFQ/N inhibits forskolin-stimulated cAMP accumulation in both the KOR-3 and the MOR-1/KOR-3 chimera by almost 40%, with IC50 values in the low nanomolar range. Little activity is seen against the DOR-1/KOR-3 chimera. Naloxone benzoylhydrazone inhibits cAMP accumulation in the KOR-3 and the DOR-1/KOR-3 chimera. Although naloxone benzoylhydrazone has higher affinity for the MOR-1/KOR-3 chimera in binding studies than KOR-3 itself, it is inactive in cyclase studies using the MOR-1/KOR-3 chimera, implying that the replacement of the first coding exon increases affinity while decreasing intrinsic activity.

Animals↗