Dopamine transporter mutants, small molecules, and approaches to cocaine antagonist/dopamine transporter disinhibitor development.
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Animals↗
Biomedical subjects
Z Lin
Publications and source records attributed to Z Lin.
Mechanism of cardioprotective effect of orotic acid.
The pyrimidine base, orotic acid (OA), markedly improves the function of recently infarcted hearts subjected to global ischemia. The mechanism of cardiac action of OA is unclear, but it has been proposed that OA acts by correcting a relative deficiency of nucleotide precursors required for RNA synthesis in the stressed myocardium or by improving myocardial energy supply. The aim of this study was to investigate the mechanism of action of OA by (1) determining whether a high dose of OA can raise the concentration of pyrimidine metabolites in plasma, liver, and heart; (2) examining the effects of OA on adenine nucleotide (AN) concentrations in normal and infarcted hearts, before and after global ischemia; and (3) determining the effect of uridine, an important metabolite of OA, on myocardial energy metabolism. Three studies were performed: (1) The time course of changes in tissue and plasma concentrations of pyrimidine compounds was examined in unoperated rats after the administration of 100 mg/kg OA. (2) Rats were given OA (30 mg/kg/d) for 2 days after experimental infarction, and tissue and plasma pyrimidine concentrations were examined; the hearts were removed for perfusion in the isolated working rat heart model (37 degrees C), subjected to 30 minutes of global ischemia, and recovery of function was assessed. AN content was assessed in the noninfarcted myocardium before and after ischemia. Isolated hearts were subjected to 30 minutes of hypoxic perfusion and the effect of adding 17 microM uridine to the perfusate was examined. Study 1 showed that OA administration produced an increase in hepatic uridine and cytidine, followed by increased plasma uridine and cytidine (cytidine, +55%, P < 0.001; uridine, +124%, P = 0.011). Myocardial uracil nucleotides increased temporarily after 4 hours (+21%, P < 0.01). In infarcted hearts after 2 days of OA administration, there were no significant changes in myocardial uracil or cytosine nucleotides or total RNA. Infarction significantly reduced functional recovery after global ischemia (sham = 62%; infarct = 26% of preischemic level; P < 0.05). OA improved the recovery of preischemic function by 133% (P < 0.05) in infarcted, but not sham-operated, hearts. Preischemic ATP and total adenine nucleotides (TAN) were decreased in the surviving myocardium of infarcted hearts (ATP reduced from 21.7 +/- 0.8 to 14.7 +/- 0.7 mumol/g dry wt, P < 0.001; TAN decreased from 30.3 +/- 0.8 to 22.4 +/- 1.1 mumol/g dry wt, P < 0.001). OA treatment prevented these reductions. Study 3 showed that uridine improved myocardial ATP and TAN levels, and decreased purine loss in hypoxic hearts. The increased AN levels were accompanied by evidence of enhancement of anerobic glycolysis. We conclude: (1) That OA acts on the heart via the liver by increasing the availability of plasma uridine and cytidine. (2) Uridine is capable of increasing myocardial ATP production by stimulating anerobic glycolysis. (3) OA treatment improves tolerance to global ischemia in infarcted but not normal hearts by preventing depletion of AN in the surviving myocardium.
Adenine Nucleotides↗
Effect of octreotide on gastric and small bowel motility in patients with gastroparesis.
BACKGROUND: Octreotide has been shown to have effects on gastric and small bowel motility with implications for its role in treating patients with upper gastrointestinal dysmotility syndromes. Our aim was to investigate the effect of octreotide on antral and small bowel motility in patients with gastroparesis. METHODS: Upper gastrointestinal manometry was carried out continuously for a period of 30 h in 11 patients with gastroparesis. The spontaneous migrating motor complex (MMC) in the fasting state and octreotide-induced MMCs were characterized and compared with regard to site of origin, duration of phase III, amplitude of phase III and propagation velocity of the MMC along the gut. The 2-h postprandial motility index was compared after a control meal as well as after a 100 microg octreotide administration. RESULTS: In all 11 gastroparetic patients, octreotide induced a phase III-like activity front within minutes after administration and this primarily originated in the small bowel (86% of activity fronts compared with 32% of fronts originating in the small bowel prior to octreotide administration (P < 0.004)). Gastric initiation of these activity fronts dramatically decreased after octreotide administration, occurring in 68% of activity fronts prior to octreotide administration and 14% of occasions after octreotide injection (P < 0.05). The postprandial antral motility index was markedly reduced after octreotide administration (11.33 +/- 0.39 vs. 7.96 +/- 0.76, P < 0.0003) and octreotide re-established a motility pattern during the postprandial period that was similar to that normally seen in the interdigestive state. The octreotide-induced phase III activity fronts appeared at a higher frequency and had a higher propagative velocity compared to the spontaneous phase III fronts in the fasting state (9.27 +/- 0.82 vs. 5.56 +/- 0.81 cm/min, P < 0.05). CONCLUSIONS: We conclude that octreotide's marked inhibitory effect on antral contractility may serve to worsen clinical symptoms in patients with gastroparesis and therefore this agent should not be given in the periprandial period. Those gastroparetic patients with associated small bowel dysmotility and diarrhoea from bacterial overgrowth may benefit from the nocturnal administration of octreotide because of its stimulatory effect of phase III MMC activity as well as its known inhibitory effect on small bowel secretions.
Adult↗
Bacterial wall lipopolysaccharide as a cause of intussusception in mice.
BACKGROUND: There is evidence that intussusception is associated with bacterial infection. It was hypothesized that a component of the bacterial wall may induce the intussusception. This study was intended to determine whether lipopolysaccharide from Escherichia coli or Salmonella can initiate intussusception in mice. METHODS: Lipopolysaccharide was injected intraperitoneally in mice, and the animals were examined for the presence of intussusception from 2 to 192 hours after injection. Gastrointestinal transit was assessed by measuring the passage of charcoal in the small intestine. Transit index was defined as the ratio between the distance traveled by charcoal and the total length of the small intestine. RESULTS: Intussusceptions were found in as much as 25.9% of lipopolysaccharide-injected animals, whereas in control animals, the incidence was zero. The threshold for the lipopolysaccharide effect was at 4 mg/kg and incidence reached a plateau at 8 mg/kg to 16 mg/kg. The incidence of intussusception peaked 6 hours after injection of lipopolysaccharide and declined to zero after 15 hours. To test the possibility that lipopolysaccharide induces intussusception by altering motility, its effect on transit index was measured. A dose of 12 mg/kg lipopolysaccharide reduced the transit index from 56.2+/-1.4% to 37.7+/-2.1% (p < 0.05). No microscopic histologic changes were found in the bowels with intussusception. CONCLUSIONS: Intraperitoneal bacterial wall lipopolysaccharide causes intussusception in mice by disturbing gastrointestinal motility.
Animals↗
Investigation of serine hydroxymethyltransferase in methanogens.
The cofactor specificity of serine hydroxymethyltransferase (SHMT) activities was tested in extracts of several methanogens using tetrahydromethanopterin (H4MPt) from Methanobacterium thermoautotrophicum Marburg, tetrahydrosarcinapterin (H4SPt) from Methanosarcina barkeri, and tetrahydrofolate (H4folate) as the potential C1 carrier. In Methanosphaera stadtmanae and Methanococcus thermolithotrophicus, the activities were H4MPt dependent. In Methanospirillum hungatei GP1, Methanosaeta concilii, Methanolobus tindarius, and Methanosarcina barkeri Fusaro, the activities were strictly H4folate dependent. H4SPt was reactive with the SHMT of Methanosphaera stadtmanae but not with that of Methanosarcina barkeri. In both Methanosarcina barkeri and Methanospirillum hungatei, pyridoxal phosphate stimulated SHMT activity. The apparent K(m) values for H4folate and L-serine were 0.086 and 0.29 mM in Methanosarcina barkeri and 0.065 and 0.31 mM in Methanospirillum hungatei, respectively.
Archaeal Proteins↗
Role of nitric oxide synthase in release of endothelin from cultured human endometrial cells.
The aim of this study was to investigate the influence of the nitric oxide/nitric oxide synthase (NO/NOS) system on the release of endothelin-1 (ET-1) in human endometrial cells. Human endometrial stromal cells in secretory phase were incubated for 72 h in serum-free RPMI 1640 medium in the absence or presence of different concentrations of interleukin-1beta (IL-1beta) and NG-monomethyl-L-arginine (LNMMA), a specific competitive inhibitor of NOS. ET-1 released from the cultured cells into the medium was determined by specific RIA. In all the experiments at various times, IL-1beta significantly increased the release of ET-1. LNMMA significantly attenuated the release of ET-1 when the cells were cultured with both IL-1beta and LNMMA, but LNMMA alone had no effect on ET-1 release. These results suggest that the NO/NOS system in human endometrium is involved in the regulation of ET-1 release via IL-1beta secretion. It can also be inferred that NO and ET-1 control the functions of endometrium in close association with IL-1beta.
Adult↗
Teenage smoking, attempts to quit, and school performance.
OBJECTIVES: This study examined the relationship between school performance, smoking, and quitting attempts among teenagers. METHODS: A logistic regression model was used to predict the probability of being a current smoker or a former smoker. Data were derived from the 1990 California Youth Tobacco Survey. RESULTS: Students' school performance was a key factor in predicting smoking and quitting attempts when other sociodemographic and family income factors were controlled. CONCLUSIONS: Developing academic or remedial classes designed to improve students' school performance may lead to a reduction in smoking rates among teenagers while simultaneously providing a human capital investment in their futures.
Achievement↗
Genomic DNA extraction from small amounts of sera to be used for genotype analysis.
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DNA↗
Immunophenotype of myeloid cells in myelodysplastic syndromes and its clinical implications.
OBJECTIVE: To explore the immunophenotype of myeloid cells in myelodysplastic syndyomes (MDS) and its clinical implications. METHODS: A panel of monoclonal antibody was used to detect CD13+, CD33+, CD15+ and CD14+ antigens on the membrane surfaces of myeloid cells in the bone marrow from 51 MDS, 21 aplastic anemia (AA), 21 paroxysmal nocturnal hemoglobinuria (PNH) patients. 10 acute myeloblastic leukemia (AML) patients and 15 normal subjects by immunoenzymatic assay. The morphology and chromosome karyotype of bone marrow cells of MDS patients were also examined. RESULTS: CD14+, CD13+ and CD33+ cells in the bone marrow were more in MDS patients than in normal controls, AA patients and PNH patients. CD15+ cells in the bone marrow were less in MDS patients than in normal controls. CONCLUSIONS: The percentages of CD14+, CD13+ and CD33+ positive cells in the bone marrow of MDS patients were related to the percentage of myeloblasts, the chromosomal aberrations and the response to treatment. It indicated that there is immunophenotypic misexpression of myeloid cells in MDS patients. Immunophenotype analysis of myeloid cells might be useful for the diagnosis and treatment of MDS patients.
Adolescent↗
Alterations of oncogenes, tumor suppressor genes and growth factors in hepatocellular carcinoma: with relation to tumor size and invasiveness.
OBJECTIVE: To make a better understanding of the molecular mechanisms involved in recurrence and metastasis of the hepatocellular carcinoma (HCC), some invasion related oncogenes, and growth factors have been investigated. METHODS: The studies were separately carried out, the results of which were summarized in this article with relation to tumor size and invasiveness of HCC. RESULTS: The aberration rates of p53 and CDKN2 in HCC were 45.9% and 36.4% respectively, which were higher in invasive HCC compared with non-invasive HCC. H-ras expression was positive in 29.3% of HCC, which was associated with recurrence and extrahepatic metastasis of HCC. Intralesional injection of H-ras antisense gene markedly inhibited the tumor growth and metastasis of HCC in nude mice. The positive rates of transforming growth factor (TGF)-alpha, epidermal growth factor receptor (EGFR) and c-erbB-2 were 45.7%, 47.1% and 92.3% respectively. The expression of EGFR was closely related to TGF-alpha, which was related to HCC recurrence. But no obvious difference of TGF-alpha or c-erbB-2 expression was found between HCC with and without recurrence, or with and without extrahepatic metastasis. Expression of nm23/tissue inhibitor of metalloproteinase (TIMP)-2 was positively associated with the prognosis of HCC patients (Log-rank, P < 0.001). The alterative rates of above-mentioned genes and growth factors in small HCC were slightly lower than that in large ones, but no significant difference was shown except the p53 mutation. CONCLUSIONS: The p53/CDKN2 mutation, over-expression of H-ras/EGFR, were associated with the invasiveness and recurrence of HCC. H-ras antisense gene might be of potential implication in the control of HCC recurrence and metastasis. Expression of nm23/TIMP-2 was closely related to the prognosis of HCC patients. Biological characteristics remained critical points to the prognosis even in small HCC.
Animals↗
[One-stage vagina reconstruction using the pudendal-thigh skin flap].
OBJECTIVE: This is to introduce a method for vagina reconstruction using the pudendal-thigh skin flap. METHODS: The pudendal-thigh skin flap has been used for vagina reconstruction in 70 cases since 1989. RESULTS: All the operations were successful and the method has become a mature technique. CONCLUSION: The advantages of the method are 1. the reconstructed vagina has good sensation and stable in maintaining its dimensions; 2. the linear scars of the donor site are hidden and inconspicuous; 3. the appearance of the perineum looks well; 4. the procedure is simple and favors its application.
Adolescent↗
[Effects of blocking CD18-mediated leukocyte adhesion on the survival of the island flap].
OBJECTIVE: This study was to investigate the role of leukocyte and leukocyte adhesion in tissue injury from ischemia and reperfusion. METHODS: The experiment utilized the monoclonal antibody (mAb) directed to the leukocyte adhesion glycoprotein CD18 to block leukocyte adhesion and aggregation in an island flap model in rats. Tissue content of myeloperoxidase (MPO) and malondialdehyde (MDA) were detected after transient treatment with either saline or mAb directed to CD18. Flap survival was assessed 7 days afterwards. RESULTS: The content of both MPO and MDA was significantly increased with 8 h ischemia and 1 h reperfusion of the flap. The treatment with anti-CD18 mAb significantly decreased the levels of MPO and MDA and also significantly improved the survival of flaps compared with the saline-treated controls. CONCLUSION: CD18-mediated leukocyte adhesion plays an important role in tissue injury from ischemia and reperfusion. Blocking leukocyte adhesion can attenuate leukocyte-mediated injury, providing protective effects on island flaps.
Animals↗
[Surgical treatment of perplexing renal cell carcinoma].
OBJECTIVE: To summarize the experience of surgical treatment of perplexing renal cell carcinoma in order to increase survival rate. METHODS: From 1987 through 1996, 20 patients with perplexing renal cell carcinoma were surgically treated. There were 3 patients in stage I, 9 in stage II, and 8 in stage III. The operative proceduce was described and the follow-up results were analysed. RESULTS: Among 20 patients, 18 were evaluable. The 1-, 3-, 5-year survival rate was 100%, 91.7% and 75% for stage I-II; 87.5%, 62.5% and 37.5% for stage III, respectively. CONCLUSION: Radical nephrectomy is still effective for the patients with perplexing renal cell carcinoma.
Adolescent↗
[Relationships between intrahepatic metastasis of hepatocellular carcinoma and in situ microenvironment, and the abundance of nm23-H1 H-ras mRNA].
OBJECTIVE: To reveal intrahepatic metastasis of hepatocellular carcinoma (HCC) in relation to its micro-environment and nm23-H1 H-ras mRNA expression. METHODS: In HCC specimens from 25 patients, the level of nm23-H1 and H-ras mRNA was examined by quantitative reverse transcription-polymerase chain reaction(RT-PCR). Tumor microvessel density(MDV), an essential factor of microenvironment and proliferating cell nucleus antigen (PCNA), an index of tumor cell proliferation, were also studied by immunohistochemical methods using antibodies against endothelial protein factor VIII-related antigen(F8RA) and antibody PC-10. RESULTS: The MDV and PCNA index in the group with intrahepatic metastasis were remarkably higher than those in the group without it (P < 0.01), while nm23-H1 mRNA expression level was negatively correlated with PCNA index (P < 0.05). The level of H-ras mRNA expression did not correlate with intrahepatic metastasis. MDV was positively correlated with PCNA index (P < 0.01). CONCLUSION: Intrahepatic metastasis of HCC depends very much on its in situ microenvironment. The decline in nm23-H1 mRNA may implicate a preferential proliferation of nm23-negetive HCC cells with highly metastastic potential which adapt well to the microenvironment.
Carcinoma, Hepatocellular↗
[An investigation on the risk factors of elderly falls in the countryside old folks' homes].
A case-control study was conducted among 154 cases of falls aged over 60 years in 18 old folks' homes in the countryside, using 1:1 pair-matching to explore the risk factors for the elderly falls. Data were analysed through Linear Logistic Regression. Results showed that spouseless, poor physical condition, abnormal gait, sufferying chronic situations as hypertension and sequelae of cerebral apoplexy, taking anti-hypertension drugs, abnormalities in taking static dynamic balance and walking tests in the elderly were main risk factors of the elderly falls. The strategies of prevention of the elderly falls were also discussed in the paper.
Accidental Falls↗
[Effects of selective induceble nitric oxide synthase inhibitor on immunological hepatic injury in rat].
OBJECTIVE: To investigate the role and induced regulation of nitric oxide (NO) in rat immunological hepatic injury, and the effect of selective inhibitor on induceble nitric oxide synthase (iNOS). METHODS: The intracellular NOS gene expression in the immune damaged hepatocytes was determined by in situ PCR technique, and NO concentration and lactate dehydrogenase (LDH) activity in culture supernatant were measured. RESULTS: Administration of bacille calmette guerin (BCG, 15, 30, 50 mg/rat, i.v.) alone or BCG with the inflammatory cytokines mixture (CM), including IL-1 beta, IFN-gamma, TNF-alpha and lipopolysacchride (LPS) significantly increased NO production and LDH release in culture medium(P < 0.05). NO production was enhanced with hepatic injury degree in direct proportion, and with BCG dose in inverse proportion. Under immunological stimuli condition, hepatocytes NOS mRNA mainly expressed an induceble and soluble isoform (iNOS) in cytoplasm. Aminoguanidine (AG), a selective iNOS inhibitor, inhibited NO production and LDH release (83.4% and 36.0%, P < 0.05), but the transcription inhibitor actinomycin D enhanced LDH level in the medium (25.5%, P < 0.05). CONCLUSION: NO produced by immunological stimuli participates in rat hepatic injury mechanism.
Animals↗
[The clinical significance of biological characters on non-small cell lung cancer].
OBJECTIVE: To study the biological characters of 137 cases of surgically treated NSCLC and their correlation with stages, types and survival rates. METHOD: Electronmicroscopy, immunohistochemistry and FCM were employed in this prospective, randomized study. K-P curve, COX univariance and multivariance were used for statistic analysis. RESULTS: (1) Electronmicroscopy showed that 40% of squamous cancer and 40% of adenocarcinoma diagnosed microscopically were mixed type. (2) The positive rate of p53 expression increased in advanced stage of NSCLC, and the survival rate was lower in cases with positive p53 expression. (3) A higher survival rate was seen in cases with positive Hras expression. (4) Lower survival rates were seen in cases with abnormal DI and PI. (5) Miscellaneous: expression rates of c-erbB2 and PCNA were related to adenocarcinoma and mixed type electronmicroscopically confirmed respectively. CONCLUSION: From this study p53, Hras, DI, PI, c-erbB2 and PCNA were found related to stages, types and survival rates, respectively.
Adenocarcinoma↗
[The pre-experiment on space crystallization of pig heart mitochondrial F1-ATPase].
ATP synthase (H(+)-ATPase) plays a key role in oxidative phosphorylation. Its catalytic moiety F1-ATPase is under intense structural study because of different crystallographic results and diverse hypotheses of its catalytic mechanism. To obtain high quality crystals, F1-ATPase sample is going to be carried to outer space by recovable satellite for crystal growth under microgravity. And to make it suitable for space crystal growth, F1-ATPase was purified from pig heart and the conditions were optimized for its maintenance, transportation, and crystallization. By using hanging drop vapor diffusion method and sitting drop vapor diffusion method, the crystals were obtained within 5 d and with a size of 0.1 mm x 0.1 mm x 0.l mm on the 7th day. The reproducibility of these experiments is also good.
Animals↗