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Biomedical subjects

Z Ren

Publications and source records attributed to Z Ren.

At least 37 records · Page 2Linked to original sources

Effects of potassium channel opener KRN4884 on human conduit arteries used as coronary bypass grafts.

AIMS: The effects of a new potassium channel opener KRN4884 on human arteries have not been studied. This study was designed to investigate the effects of KRN4884 on the human internal mammary artery (IMA) in order to provide information on possible clinical applications of KRN4884 for preventing and relieving vasospasm of arterial grafts in coronary artery bypass grafting. METHODS: IMA segments (n = 140) taken from patients undergoing coronary surgery were studied in the organ chamber. Concentration-relaxation curves for KRN4884 were established in the IMA precontracted with noradrenaline (NA), 5-hydroxytryptamine (5-HT), angiotensin II (ANG II), and endothelin-1 (ET-1). The effect of glibenclamide (GBC) on the KRN4884-induced relaxation was also examined in NA or 5-HT-precontracted IMA. Concentration-contraction curves for the four vasoconstrictors were constructed without/with pretreatment of KNR4884 (1 or 30 microM) for 15 min. RESULTS: KRN4884 induced less relaxation (P < 0.05) in the precontraction induced by ET-1 (72.9 +/- 5.5%) than by ANG II (94.2 +/- 3.2%) or NA (93.7 +/- 4.1%) with lower EC50 (P < 0.05) for ANG II (-8.54 +/- 0.54 log M) than that for NA (-6.14 +/- 0.15 log M) or ET-1 (-6.69 +/- 0.34 log M). The relaxation in the IMA pretreated with GBC was less than that in control (P < 0.05). KRN4884-pretreatment significantly reduced the contraction (P < 0.05) induced by NA (151.3 +/- 18.4% vs 82.7 +/- 8. 7%), 5-HT (82.7 +/- 12.2% vs 30.1 +/- 7.3%), and ANG II (24.3 +/- 6. 3% vs 5.4 +/- 1.6%), but did not significantly reduce the contraction induced by ET-1 (P > 0.05). CONCLUSION: KRN4884 has marked vasorelaxant effects on the human IMA contracted by a variety of vasoconstrictors and the effect is vasoconstrictor-selective.

Aged↗

Circulating T-cell response to Helicobacter pylori infection in chronic gastritis.

BACKGROUND: Helicobacter pylori elicits a specific humoral and cellular immune response. There is increasing evidence that the type of T-cell response contributes to clinical outcome in H. pylori infection. MATERIALS AND METHODS: The host response to H. pylori infection in 34 subjects with chronic gastritis was examined in terms of T-cell proliferation and cytokine production in whole-blood cultures stimulated or unstimulated with H. pylori acid-glycine extract antigens (AGE). RESULTS: The proliferative response in whole-blood cultures was similar for both H. pylori-positive and -negative subjects stimulated with H. pylori AGE. While an increase in interferon-gamma (IFN-gamma) production was observed from both H. pylori-positive and -negative subjects with gastritis, significantly higher levels of IFN-gamma were detected in the former when stimulated with H. pylori AGE. In contrast, interleukin 4 (IL-4) was undetectable regardless of antigen stimulation. However, if an in situ IL-4 antibody capture assay was used, antigen-independent production of IL-4 was detected, but there was no difference between H. pylori-positive and -negative subjects with gastritis. After eradication of H. pylori, antigen-induced production of IL-4 was increased, with no decrease in the levels of secretion of IFN-gamma. IL-4 production was dependent on CD4+ T cells, as addition of anti-CD4 but not anti-CD8 mouse monoclonal antibody or matched IgG isotype to the whole-blood culture inhibited the production of IL-4. CONCLUSION: The results suggest that a shift toward a balanced Th1-Th2 response due to an increase in antigen-induced IL-4 production from CD4+ T cells follows eradication. We suggest that the downregulation of mucosal inflammation consequent on reduction in antigen levels or removal of downregulation after eradication of H. pylori contributes to this shift in cytokine balance.

Adult↗

Non-urease producing Helicobacter pylori in chronic gastritis.

BACKGROUND: Helicobacter pylori infection is the commonest cause of gastritis. Different patterns of immune response to H. pylori infection and characteristics of bacteria are considered to contribute to clinical outcomes. AIM: To determine characteristics of the host H. pylori relationship in subjects with non-ulcer dyspepsia and a histological diagnosis of gastritis. METHODS: Thirty-five subjects with chronic gastritis undergoing endoscopy (mean age 53 years, range 24-82, 14 male and 21 female) were studied, none of whom was on nonsteroidal anti-inflammatory drugs or antibiotics. H. pylori infection was determined by rapid urease test (CLOtest), culture, antibody and RT-PCR for Ure C, Cag A and 26 kDa gene and histology. Cytokine production of mucosal IL-6 and IL-8 were measured by ELISA. RESULTS: Fifteen subjects were positive by CLOtest and/or bacterial culture. In these subjects histology showed numerous helical forms of H. pylori (Group I). Nine subjects were negative by CLOtest, bacterial culture, and mRNA for urease C fragment, but positive by PCR for the 26 kDa protein encoding gene. Histology in these subjects showed the presence of either coccoid forms (four), or scant helical forms (two), or mixed coccoid/helical forms (three) (Group II). Eleven subjects were negative by all methods of detection (Group III). IgG and IgA antibody levels in serum (p<0.05) and gastric tissue culture supernatant (p<0.001) were significantly higher in Group I than those in Group II or III. There were significant differences in the IgG serum and IgA supernatant antibody levels (p<0.01 and p<0.05) when Group II was compared to Group III. Supernatant IL-6 levels were significantly higher in Group I (p<0.01) than those from Groups II and III. IL-8 levels were higher in Group I (p<0.01) and Group II (p<0.05) when compared to Group III. CONCLUSIONS: 'H. pylori-negative' gastritis can be associated with a non-urease producing form of H. pylori, with a reduction in both local and systemic antibody levels and mucosal pro-inflammatory cytokines.

Adult↗

Specific structural motifs determine TRAP220 interactions with nuclear hormone receptors.

The TRAP coactivator complex is a large, multisubunit complex of nuclear proteins which associates with nuclear hormone receptors (NRs) in the presence of cognate ligand and stimulates NR-mediated transcription. A single subunit, TRAP220, is thought to target the entire complex to a liganded receptor through a domain containing two of the signature LXXLL motifs shown previously in other types of coactivator proteins to be essential for mediating NR binding. In this work, we demonstrate that each of the two LXXLL-containing regions, termed receptor binding domains 1 and 2 (RBD-1 and RBD-2), is differentially preferred by specific NRs. The retinoid X receptor (RXR) displays a weak yet specific activation function 2 (AF2)-dependent preference for RBD-1, while the thyroid hormone receptor (TR), vitamin D(3) receptor (VDR), and peroxisome proliferator-activated receptor all exhibit a strong AF2-dependent preference for RBD-2. Using site-directed mutagenesis, we show that preference for RBD-2 is due to the presence of basic-polar residues on the amino-terminal end of the core LXXLL motif. Furthermore, we show that the presence and proper spacing of both RBD-1 and RBD-2 are required for an optimal association of TRAP220 with RXR-TR or RXR-VDR heterodimers bound to DNA and for TRAP220 coactivator function. On the basis of these results, we suggest that a single molecule of TRAP220 can interact with both subunits of a DNA-bound NR heterodimer.

Amino Acid Motifs↗

Norepinephrine transporter expression and function in noradrenergic cell differentiation.

The classical view of norepinephrine transporter (NET) function is the re-uptake of released norepinephrine (NE) by mature sympathetic neurons and noradrenergic neurons of the locus ceruleus (LC; [1-3]). In this report we review previous data and present new results that show that NET is expressed in the young embryo in a wide range of neuronal and non-neuronal tissues and that NET has additional functions during embryonic development. Sympathetic neurons are derived from neural crest stem cells. Fibroblast growth factor-2 (FGF-2), neurotrophin-3 (NT-3) and transforming growth factor-beta1 (TGF-beta1) regulate NET expression in cultured quail neural crest cells by causing an increase in NET mRNA levels. They also promote NET function in both neural crest cells and presumptive noradrenergic cells of the LC. The growth factors are synthesized by the neural crest cells and therefore are likely to have autocrine function. In a subsequent stage of development, NE transport regulates differentiation of noradrenergic neurons in the peripheral nervous system and the LC by promoting expression of tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH). Conversely, uptake inhibitors, such as the tricyclic antidepressant, desipramine, and the drug of abuse, cocaine, inhibit noradrenergic differentiation in both tissues. Taken together, our data indicate that NET is expressed early in embryonic development, NE transport is involved in regulating expression of the noradrenergic phenotype in the peripheral and central nervous systems, and norepinephrine uptake inhibitors can disturb noradrenergic cell differentiation in the sympathetic ganglion (SG) and LC.

Animals↗

[Appraisal of postoperative transcatheter arterial chemoembolization (TACE) for prevention and treatment of hepatocellular carcinoma recurrence].

OBJECTIVE: To evaluate the effect of postoperative TACE for prevention and treatment of hepatocellular carcinoma (HCC) recurrence after radical resection. METHODS: From Jan. 1995 through March 1998, 109 HCC patients after radical resection were followed up with serum AFP, liver US and CT, chest X-ray film, hepatic artery angiography, etc. They were divided into 2 groups. Patients in group A (n = 68) with no residual tumor were given prophylactic TACE treatment, 1-2 times at the second and fifth month after operation. Patients in group B (n = 41) with residual tumor left were treated with regular TACE, once every 2 months. The 2 groups of patients were followed up for 6-45 months after operation. RESULTS: In group A, the real curative resection rate was 62.4%. Tumor recurrence was found in 10 of the 68 patients, with a total recurrence rate of 14.7% within 3 years after radical resection. The 1-, 2-, and 3-year cumulative recurrence rate was 7.4%, 13.2% and 14.7%, respectively. The 1-, 2-, and 3-year survival rate was 100%, 93.4% and 85.7%, respectively, while that in group B was 78.1%, 57.7% and 57.7%, respectively. The differences between the 2 groups of patients were statistically significant. The predictive pathological factors hampering completeness of tumor resection were: tumor size > 5 cm, more than 2 tumor nodules, the presence of satellite nodules, tumor with partial or without encapsulation and tumor thrombus in portal vein. Hepatic artery angiography with LP-CT and maintenance of high serum AFP level were the most sensitive methods for detecting residual tumor after operation. CONCLUSION: Post-operative TACE is very useful for prevention and treatment of HCC recurrence. It helps improve survival of surgically treated HCC patients.

Adolescent↗

[Molecular diagnosis in a Korean family with thalassemia intermedia due to co-inheritance of triplicated alpha-globin genes (alphaalpha/alphaalphaalpha(anti 3.7)) and beta-thalassemia trait (IVS-II-1 G-->A)].

OBJECTIVE: To analyze the molecular abnormalities of beta-thalassemia intermedia in a Korean family with thalassemia intermedia. METHODS: Polymerase chain reaction (PCR), Southern blot hybridization and double strand DNA cycle sequencing were used to analyse alpha, beta and gamma globin gene organization. RESULTS: In the Korean family the interaction between a triplicated alpha-globin locus and a heterozygous beta-thalassemia gave rise to a clinical phenotype of thalassemia. The molecular defect was a heterozygosity for a single beta-thalassemia mutation (beta IVS-II-1 G-->A) and a triplicated alpha-globin gene (alphaalpha/alphaalphaalpha(anti 3.7)). CONCLUSION: Beta-thalassemia heterozygotes conjuncted with alpha-globin gene triplication was the major cause of the beta-thalassemia intermedia in this Korean family.

Adult↗

[The study of facial neurapraxia].

OBJECTIVE: To study the clinical characteristics and mechanism of facial neurapraxia. METHOD: Patients were tested with nerve excitability method and judged the degree of facial paralysis. Animal mode of neurapraxia was made and threshold of evoked electromyographic potential was tested. The fibers of facial nerve were observed under transmission electromicroscope. RESULT: Average restoration time of evoked electromyographic potential was 52.5 min. The lamellar separation of myelin sheath of facial nerve was found under electromicroscope. Patients with facial neurapraxia was judged as denervation negative and residual function of facial muscles was above 65%. CONCLUSION: Facial neurapraxia is mild reversible facial paralysis and relevant to the lamellar separation.

Animals↗

[Basement membrane in squamous cell carcinomas of the larynx: an immunohistochemical study].

OBJECTIVE: The study was to assess the distribution of basement membrane(BM) in laryngeal squamous cell carcinomas(LSCC). Correlation of BM and clinical parameters (TNM stage, histological grading, invasion mode, lymph node metastasis) was also examined. METHODS: The expression of BM around tumor cell was determined in 40 cases of LSCC by using monoclonal antibody against human type IV collagen. An intact continuous BM was found in 17 cases (42.5%), while partial or widespread loss of the BM was detected in the other 23 cases (57.5%). RESULTS: In cases with poor histological differentiation, the defect of BM was more severe than that in cases with high or middle histological differentiation (P < 0.05). Moreover, diffuse invasion carcinomas revealed lower type IV collagen expression comparing with cases with better tumor-host border (P < 0.05). There was a higher risk of regional lymph node metastasis among cases with poor BM expression (P < 0.01), but there was no association of clinical stage with BM defect (P > 0.05). CONCLUSION: These observations indicated that testing the distribution of BM seems to be useful to evaluate the histological grading of malignancy of laryngeal carcinoma and be helpful to prognosticate the frequency of regional lymph node metastasis.

Aged↗

[Surgical treatment of primary intracerebral neoplasms only presenting with epilepsy].

OBJECTIVE: To analyse the histopathology and the factors influencing the outcome of surgical treatment of primary intracerebral neoplasms only presenting with epilepsy. METHODS: 55 patients with primary intracerebral tumors presenting with epilepsy without other neurologic signs were retrospectively reviewed. RESULTS: 54(98.2%) cases were histologically diagnosed as gliomas among which 42(76.4%) were low-grade and 12(21.8%) high-grade. The incidence of complications for tumor removals was 32.7%. Of the 41 patients who had postoperative follow-up more than 6 months after operation, 20(48.8%) were seizure-free, 3 were rare, 4 were improved, and 14 (34.1%) had no appreciable reduction in seizure frequency. The position of the tumors was significantly correlated with the incidence of postoperative complications and the postoperative seizure control (P < 0.05). The incidence of postoperative complications for frontal and parietal tumors was higher than that for temporal tumors, while the temporal tumors had better postoperative seizure control than the frontal and the parietal ones. CONCLUSIONS: Most of the primary intracerebral tumors only presenting with epilepsy were low-grade gliomas. The position of tumors was an important factor influencing the extent of surgical removal and the postoperative seizure control.

Adolescent↗

[Ganciclovir induces apoptosis of rat C6 glioma cell transduced with HSV-tk gene].

OBJECTIVE: To observe whether apoptosis could be induced by ganciclovir (GCV) in the herpes simplex virus-thymidine kinase gene-ganciclovir system (HSV-tk-GCV system) gene therapy for glioma. METHODS: Transduced C6/tk glioma cell as treated group, wild C6 cell as control group, were studied with morphology, gel-electrophoresis of DNA fragment analysis, fluoroscopy, and flow cytometric study before or after exposed to GCV, and apoptosis of transduced C6/tk glioma cell was ascertained. RESULTS: When C6/tk cell was treated with GCV at 5 micrograms/ml for 72 hours, cell apoptosis occurred. Typical apoptotic morphological features included cell shrinkage, condensation, and margination of nuclear chromatin were showed by light and electron microscopy, condensed nuclear chromatin and the fragment of nuclei were demonstrated by fluoroscopy, DNA ladder was showed by DNA fragment analysis, apoptotic peak was identified by flow cytometric study. The apoptotic cells accounted for 23% of the cell population. Apoptosis was not observed in control group treated by GCV. CONCLUSIONS: The apoptosis of transduced C6/tk glioma was induced by GCV, which fit in with the basis of HSV-tk-GCV gene therapy for glioma.

Animals↗

Effect of multiple mutations in the hemoglobin- and hemoglobin-haptoglobin-binding proteins, HgpA, HgpB, and HgpC, of Haemophilus influenzae type b.

Haemophilus influenzae requires heme for growth and can utilize hemoglobin and hemoglobin-haptoglobin as heme sources. We previously identified two hemoglobin- and hemoglobin-haptoglobin-binding proteins, HgpA and HgpB, in H. influenzae HI689. Insertional mutation of hgpA and hgpB, either singly or together, did not abrogate the ability to utilize or bind either hemoglobin or the hemoglobin-haptoglobin complex. A hemoglobin affinity purification method was used to isolate a protein of approximately 120 kDa from the hgpA hgpB double mutant. We have cloned and sequenced the gene encoding this third hemoglobin/hemoglobin-haptoglobin binding protein and designate it hgpC. Insertional mutation of hgpC did not affect the ability of the strain to utilize either hemoglobin or hemoglobin-haptoglobin. An hgpA hgpB hgpC triple mutant constructed by insertional mutagenesis showed a reduced ability to use the hemoglobin-haptoglobin complex but was unaltered in the ability to use hemoglobin. A second class of mutants was constructed in which the entire structural gene of each of the three proteins was deleted. The hgpA hgpB hgpC complete-deletion triple mutant was unable to utilize the hemoglobin-haptoglobin complex and showed a reduced ability to use hemoglobin. We have identified three hemoglobin/hemoglobin-haptoglobin-binding proteins in Haemophilus influenzae. Any one of the three proteins is sufficient to support growth with hemoglobin-haptoglobin as the heme source, and expression of at least one of the three is essential for hemoglobin-haptoglobin utilization. Although the three proteins play a role in hemoglobin utilization, an additional hemoglobin acquisition mechanism(s) exists.

Amino Acid Sequence↗

Role of CCAA nucleotide repeats in regulation of hemoglobin and hemoglobin-haptoglobin binding protein genes of Haemophilus influenzae.

Haemophilus influenzae utilizes hemoglobin and hemoglobin-haptoglobin as heme sources. The H. influenzae hemoglobin- and hemoglobin-haptoglobin binding protein genes, hgpA, hgpB, and hgpC, contain lengths of tetrameric CCAA repeats. Using an hgpA-lacZ translational gene fusion, we demonstrate phase-variable expression of lacZ associated with alteration in the length of the CCAA repeat region.

Bacterial Outer Membrane Proteins↗

Coccoid forms of Helicobacter pylori can be viable.

Controversy exists as to whether the coccoid form of Helicobacter pylori can exist in a viable form. Conversion of helical to coccoid morphology occurs in culture over several days. In this study, the morphology was correlated with parameters of genetic integrity in the reference NCTC 11637 strain over 21 days of culture. The capacity to regrow colonies of helical form was demonstrated from a culture where the coccoid form constituted up to 95% and negligible urease activity could be detected. Urease enzyme activity and its mRNA decreased between day 0 and 10 while 26 kD mRNA and 16S rRNA were expressed unchanged for up to 14 and 21 days of culture, respectively. Expression of mRNA for the Cag A gene behaved in a similar fashion to that of urease. No evidence of DNA fragmentation was detected. These data suggest that a viable form of non-urease producing H. pylori exists after short to intermediate culture and that some if not all of these viable bacteria have coccoid morphology.

Antigens, Bacterial↗

Reversal of aberrant splicing of beta-thalassemia allele by antisense RNA in vitro and in vivo.

OBJECTIVE: To investigate the reversal of aberrant splicing of beta-thalassemia allele (IVS-2-654 C-->T, beta 654) by antisense RNA in vitro and in vivo. METHODS: The vector expressing antisense RNA which targeted against the aberrant splice sites of beta 654 pre-mRNA was constructed in pcDNA3, and then used to repair the defective splicing of the mutant pre-mRNA in an in vitro transcription and splicing system, as well as in HeLa beta 654 cells and cultured beta 654 erythroid cells by lipid-mediated DNA-transfection method. The effect of the antisense RNA was identified by RT-PCR mediated mRNA quantitative assay as well as globin chain microbiosynthesis. RESULTS: The antisense RNA decreased the aberrant splicing product and restored the correct splicing pattern in vitro and in vivo efficiently. In the in vitro transcription and splicing system, the level of normally spliced mRNA [beta/(beta + beta*)] increased from 0.25 to 0.60. In cultured HeLa beta 654 cells, the level of beta/(beta + beta*) increased from 0.07 to 0.43 on the 15th day after transfection. In cultured beta 654 erythroid cells, the level of mRNA [beta/(beta + beta*)] increased from 0.19 to 0.58 on the 8th day after transfection in beta 654/beta 654 erythroid cells, from 0.02 to 0.38 in beta 654/beta 41-42 erythroid cells, and from 0.45 to 0.83 in beta 654/beta A erythroid cells, respectively. Correspondingly, the ratios of globin chain (beta/alpha) biosynthesis increased from 0.16 to 0.52 on the 8th day after transfection in beta 654/beta 654 erythroid cells, 0.05 to 0.36 in beta 654/beta 41-42 erythroid cells, and 0.42 to 0.81 in beta 654/beta A erythroid cells, respectively. The splicing pattern did not show significant changes as compared to the untreated, as well as to the control antisense fragment. CONCLUSIONS: Antisense RNA transcribed from the expression vector described here could efficiently suppress the aberrant splicing pattern of beta 654 mutant mRNA and restore the correct splicing pathway in vitro and in vivo, leading to the improvement of globin chain biosynthesis in thalassemic cells. Our antisense strategy provides an alternative approach to the gene therapy of beta-thalassemia.

Adolescent↗

The diagnostic criteria for classic parasystole.

OBJECTIVE: To establish a diagnostic criteria of parasystole with high sensitivity and high specificity. METHODS: After excluded from nonparasystole and each variant parasystoles, based on the electrocardiographic data obtained from 61 patients with classic parasystole, we selected the quantitative indices which could reflect the features of ectopic focus with complete entrance block as the diagnostic criteria for parasystole. RESULTS: The common features of the electrocardiograms of this group were: 1) Take the earliest recorded eight interectopic intervals in which at least four intervals containing sinus beats or other beats having activated to the area within the ectopic focus. When in case of deficiency, it will fill up a vacancy in order. The ratios of the shortest coupling interval to the shortest ectopic cycle length (ECL) were all less than 80%; 2) The coefficients of variation of the eight ECLs were all less than 6%; 3) The maximal differences of coupling intervals were all equal to or more than 0.11 second. CONCLUSION: Three quantitative indices as necessary conditions have been used as diagnostic criteria for parasystole with high sensitivity and high specificity.

Electrocardiography↗

[Experimental study of interleukin-4 gene therapy for glioma].

OBJECTIVE: To study IL-4 gene therapy for glioma. METHODS: Using recombinant retrovirus vector, mIL-4 was transfected into psi 2 packaging cells and rat C6 glioma cells, respectively by lipofectamine. The IL-4 secretting cell clones psi 2 IL-4 and C6IL-4 were studied in vitro and in vivo. RESULTS: Apart from a decrease in cloning efficiency, no difference was observed between the transfected and the wild type glioma cells in proliferation and cell cycle in vitro. Tumorigenicity of subcutaneously and intracranially inoculated C6IL-4 was reduced. Tumor growth could be suppressed by perineoplastic inoculation of psi 2 IL-4 cells. CONCLUSION: IL-4 gene-modified C6 glioma has decreased tumorigenicity. Local production of IL-4 by psi 2 IL-4 cells can lead to regression of established glioma.

Animals↗

[Hepatic arterial infusion of 32P-radionuclide microspheres for radiation therapy of hepatocellular carcinoma].

OBJECTIVE: To investigate the efficacy of internal radiation of (32)P-glass microspheres ((32)P-GMS) in unresected hepatocellular carcinoma (HCC) via subcutaneous arterial port. METHODS: Hepatic arterial (99)technetium-macroaggregate albumin ((99)Tc-MAA) scanning via subcutaneous arterial port was undertaken to measure lung/liver shunting ratio and tumor/liver ratio. Hepatic arterial infusion of (32)P-GMS was performed in 17 cases of HCC with a dose from 1.11 to 1.30 GBq. Twenty cases of HCC undergoing hepatic arterial chemoembolization (HACE) in the same period served as controls group. RESULTS: There was no treatment-related death in the 17 cases. In 7 of the 17 cases, AFP level and/or tumor size decreased by 50% after treatment, with a response rate of 64.7%. The median survival time was 5.5 months, and the 3-, 6-, 9-, 12-month survival rates were 94.1%, 44.1%, 31.0%, 24.4%, respectively. The therapeutic efficacy was better than that of HACE. The survival time was significantly longer in patients with T/N ratio >or= 2 than in those with T/N < 2 (P < 0.05). CONCLUSIONS: Hepatic arterial infusion of (32)P-GMS is an alternative treatment for unresected HCC.

Adult↗