Biomedical subjects

D Tian

Publications and source records attributed to D Tian.

At least 37 records · Page 2Linked to original sources

PubMed2000

Aplastic anemia is associated with HLA-DRB1*1501 in northern Han Chinese.

It has been reported that aplastic anemia (AA) is more common in HLA-DR2-positive individuals than in the general population. We investigated the frequency of some HLA loci of 102 Northern Han Chinese patients with AA and 105 healthy control subjects. Polymerase chain reaction and sequence specific oligonucleotide probe hybridization were used to determine HLA-DR- and HLA-DR2-related DRB1 alleles. The frequency of DR2 is increased in AA patients; the relative risk (RR) was 2.86, and the difference was significant (chi 2 = 11.1, P = .004). The RR of HLA-DRB1*1501 was 3.07, and the difference was significant (chi 2 = 9.42, P = .008). The above results suggest that HLA-DR2 is significantly associated with AA in Northern Han Chinese. HLA-DRB1*1501 is the main subtype of HLA-DR2, and may be the susceptibility gene of AA.

Alleles↗

PubMed2000

[Arthroscopically assisted anterior cruciate ligament reconstruction using patellar tendon autograft fixed with interference screw].

OBJECTIVES: To evaluate the optimal position of bony tunnel, the firmness of tendon graft fixation and the effectiveness of postoperative function recovery in an arthroscopic approach for the minimally invasive reconstruction of anterior cruciate ligament (ACL). METHODS: In a single arthroscopic approach, the ACL was reconstructed by the bone-tendon-bone compound patellar tendon autograft with the fixation of an interference screw. RESULTS: ACL reconstruction was performed in 49 patients, of whom 20 were followed up for over one year (average 1 year and 5 months). Among the 20 patients, 13 were rated as excellent, 5 good, and 2 fair. The excellent and good rate went up to 90%. Reconstructed ACLs were reevaluated arthroscopically in 9 patients, in whom, 6 had good remodeling of ACLs. CONCLUSIONS: Our results indicated that this method has the advantages of less injury, optimal positioning of bone tunnel, firm graft fixation, and early rehabilitation. Compound bone-tendon-bone autograft allows firm fixation and biologic healing with good shape and tension remodeling.

Adolescent↗

PubMed2000

[Early arthroscopic reconstruction in treatment of acute complete rupture of anterior cruciate ligament].

OBJECTIVE: To early reconstruct acute and complete rupture of anterior cruciate ligament (ACL) and treat combined injuries for the recovery of knee joint stability. METHODS: Ten cases of acute complete rupture of anterior cruciate ligament and medial collateral ligament were treated arthroscopically by anterior cruciate ligament reconstruction using patellar tendon autograft fixed with interference screw from February 1998 to March 1999. RESULTS: Follow-up ranged from 5 months to 1 year and 3 months (average 10 months). Clinical results showed that the stability of knee joint was satisfactory in the early stage. CONCLUSIONS: Acute the ACL rupture can be reconstructed arthroscopically in the early stage and the injuries were moderate, combined injuries could be treated at the same time, and the stability of knee joint could recover in the early stage after operation.

Adolescent↗

PubMed1999

Design and synthesis of novel alpha(1)(a) adrenoceptor-selective antagonists. 1. Structure-activity relationship in dihydropyrimidinones.

Dihydropyrimidinones such as compound 12 exhibited high binding affinity and subtype selectivity for the cloned human alpha(1a) receptor. Systematic modifications of 12 led to identification of highly potent and subtype-selective compounds such as (+)-30 and (+)-103, with high binding affinity (K(i) = 0.2 nM) for alpha(1a) receptor and greater than 1500-fold selectivity over alpha(1b) and alpha(1d) adrenoceptors. The compounds were found to be functional antagonists in human, rat, and dog prostate tissues. Compound (+)-103 exhibited excellent selectively to inhibit intraurethral pressure (IUP) as compared to lowering diastolic blood pressure (DBP) in mongrel dogs (K(b)(DBP)/K(b)(IUP) = 40) suggesting uroselectivity for alpha(1a)-selective compounds.

Adrenergic alpha-1 Receptor Antagonists↗

PubMed1999

Design and synthesis of novel alpha(1)(a) adrenoceptor-selective antagonists. 2. Approaches to eliminate opioid agonist metabolites via modification of linker and 4-methoxycarbonyl-4-phenylpiperidine moiety.

We have previously described compound 1a as a high-affinity subtype selective alpha(1a) antagonist. In vitro and in vivo evaluation of compound 1a showed its major metabolite to be a mu-opioid agonist, 4-methoxycarbonyl-4-phenylpiperidine (3). Several dihydropyrimidinone analogues were synthesized with the goal of either minimizing the formation of 3 by modification of the linker or finding alternative piperidine moieties which when cleaved as a consequence of metabolism would not give rise to mu-opioid activity. Modification of the linker gave several compounds with good alpha(1a) binding affinity (K(i) = < 1 nM) and selectivity (>300-fold over alpha(1b) and alpha(1d)). In vitro analysis in the microsomal assay revealed these modifications did not significantly affect N-dealkylation and the formation of the piperidine 3. The second approach, however, yielded several piperidine replacements for 3, which did not show significant mu-opioid activity. Several of these compounds maintained good affinity at the alpha(1a) adrenoceptor and selectivity over alpha(1b) and alpha(1d). For example, the piperidine fragments of (+)-73 and (+)-83, viz. 4-cyano-4-phenylpiperidine and 4-methyl-4-phenylpiperidine, were essentially inactive at the mu-opioid receptor (IC(50) > 30 microM vs 3 microM for 3). Compounds (+)-73 and (+)-83 were subjected to detailed in vitro and in vivo characterization. Both these compounds, in addition to their excellent selectivity (>880-fold) over alpha(1b) and alpha(1d), also showed good selectivity over several other recombinant human G-protein coupled receptors. Compounds (+)-73 and (+)-83 showed good functional potency in isolated human prostate tissues, with K(b)s comparable to their in vitro alpha(1a) binding data. In addition, compound (+)-73 also exhibited good uroselectivity (DBP K(b)/IUP K(b) > 20-fold) in the in vivo experiments in dogs, similar to 1a.

Adrenergic alpha-1 Receptor Antagonists↗

PubMed1999

Design and synthesis of novel alpha(1)(a) adrenoceptor-selective antagonists. 3. Approaches to eliminate opioid agonist metabolites by using substituted phenylpiperazine side chains.

Dihydropyrimidinones, such as 1, represent a novel class of alpha(1a) adrenoceptor antagonists with potential for the treatment of benign prostatic hyperplasia (BPH) (see part 1 of this series). Analysis of the metabolites of 1 revealed that 4-methoxycarbonyl-4-phenylpiperidine is formed as the major metabolite and is an agonist at the mu-opioid receptor. To circumvent any potential liability resulting from the metabolite, we decided to identify alternate templates devoid of agonist activity at the mu-opioid receptor to replace the 4-methoxycarbonyl-4-phenylpiperidine moiety. The present study describes the synthesis and SAR of dihydropyrimidinones linked to substituted 4-phenylpiperazine containing side chains. Compound (+)-38 was identified as a lead compound with a binding and functional profile comparable to that of 1. The putative metabolite 2-carboxamidophenylpiperazine has negligible affinity for the mu-opioid receptor.

Adrenergic alpha-Antagonists↗

PubMed1999

Design and synthesis of novel alpha(1)(a) adrenoceptor-selective antagonists. 4. Structure-activity relationship in the dihydropyrimidine series.

We have previously disclosed dihydropyridines such as 1a,b as selective alpha(1a) antagonists as a potential treatment for benign prostatic hyperplasia (BPH). The propensity of dihydropyridines toward an oxidation led us to find suitable replacements of the core unit. The accompanying papers describe the structure-activity relationship (SAR) of dihydropyrimidinones 2a,b as selective alpha(1a) antagonists. We report herein the SAR of dihydropyrimidines such as 4 and highlight the similarities and differences between the dihydropyrimidine and dihydropyrimidinone series of compounds.

Administration, Oral↗

PubMed1999

[Study on endothlin and its gene expression in splanchnic vessels in cirrhotic rats].

OBJECTIVE: To investigate the role of endothelin(ET) in the pathogenesis of portal hypertension, ET-1 level and its gene expression in splanchnic vessels from cirrhotic rats were observed. METHODS: ET levels of both plasma and vascular tissues were determined by radioimmunoassay. ET mRNA in vascular tissues was probed with RT-PCR technique expressed as optical density(OD) value from image analysis. RESULTS: ET peptide and mRNA in PV and SMA vessels were all significantly higher in cirrhotic rats than those in normal rats, while in cirrhotic rats, ET and its gene expression of PV was dramatically higher than that of SMA(P < 0.05). In addition, the positive correlation was observed in difference between PV and SMA in ET concentration with portal pressure(r = 0.737, P < 0.01). CONCLUSION: ET may be involved in the mechanisms of the formation of portal hypertension mainly due to constructing portal vein, increasing portal flow resistance.

Animals↗

PubMed1999

[Acute rupture of anterior cruciate ligament: diagnosis and treatment by early arthroscopy].

OBJECTIVE: To early diagnose and treat acute rupture of anterior cruciate ligament (ACL). METHODS: 23 patients with acute rupture of ACL were examined and treated by early arthroscopy. RESULTS: The preoperative diagnosis of ACL rupture was similar to that of in 18 patients. Three patients were confirmed by early arthroscopy and 2 patients were found to have ACL rupture, 16 patients were combined with meniscus injuries and 6 patients with cartilaginous injuries. Patholanatomical type of ACL were rupture of parenchymal part (21 patients) and avulsion rupture of attachment point (2 patients). In 6 patients ACL was reconstructed under arthroscope. CONCLUSIONS: Early arthroscopy in the treatment of acute ACL rupture has advantages of minor injury, correct diagnosis, visible location of injury or combined injury and timely treatment. Early arthroscopy for acute ACL rupture is an important measure for diagnosis, treatment, and stabilization of the knee joint.

Acute Disease↗

PubMed1998

Multifocal accumulation of p53 protein in esophageal carcinoma: evidence for field cancerization.

A systematic characterization of the cancerization field of esophageal carcinoma based on p53 protein accumulation has not been reported previously. The present report presents such a study based on 50 specimens of esophageal squamous-cell carcinoma from northern China. To gain insight into the etiology of this disease among the 50 subjects, DNA was analyzed for a polymorphism of the aldehyde dehydrogenase-2 (ALDH2) gene, which has been associated with increased risk for esophageal cancer among alcohol-consuming patients in Japan. However, the frequency of this polymorphism among our subjects, 30% (15/50), was within published control frequencies for this allele, suggesting that this allele may not play a role in the etiology of esophageal cancer in this northern Chinese population. Immuno-histochemical staining showed that 66% of the tumors were p53+. Of 420 pieces near or adjacent to p53+ tumors, p53+ cells were present among 64% of basal-cell hyperplasia (BCH), 70% of dysplasia (DYS) and 88% of carcinoma in situ (CIS). Of 216 pieces near or adjacent to p53- tumors, p53+ frequencies were 25% of BCH, 25% of DYS and 0% of CIS. The proportion of BCH cells that were p53+ decreased at increasing distance from the tumor (p = 0.006). The sporadic distribution of p53+ cells and the distribution and frequency of p53+ precursor lesions support the view that accumulation of p53 protein is multifocal and occurs in precursor lesions in early stages of esophageal carcinogenesis.

Adult↗

PubMed1998

Protein kinase A stimulates binding of multiple proteins to a U-rich domain in the 3'-untranslated region of lactate dehydrogenase A mRNA that is required for the regulation of mRNA stability.

We have explored the molecular basis of the cAMP-induced stabilization of lactate dehydrogenase A (LDH-A) mRNA and identified four cytoplasmic proteins of 96, 67, 52, and 50 kDa that specifically bind to a 30-nucleotide uridine-rich sequence in the LDH 3'-untranslated region with a predicted stem-loop structure. Mutational analysis revealed that specific protein binding is dependent upon an intact primary nucleotide sequence in the loop as well as integrity of the adjoining double-stranded stem structure, thus indicating a high degree of primary and secondary structure specificity. The critical stem-loop region is located between nucleotides 1473 and 1502 relative to the mRNA cap site and contains a previously identified cAMP-stabilizing region (CSR) required for LDH-A mRNA stability regulation by the protein kinase A pathway. The 3'-untranslated region binding activity of the proteins is up-regulated after protein kinase A activation, whereas protein dephosphorylation is associated with a loss of binding activity. These results imply a cause and effect relationship between LDH-A mRNA stabilization and CSR-phosphoprotein binding activity. We propose that the U-rich CSR is a recognition signal for CSR-binding proteins and for an mRNA processing pathway that specifically stabilizes LDH mRNA in response to activation of the protein kinase A signal transduction pathway.

3' Untranslated Regions↗

PubMed1998

Protein kinase A-regulated instability site in the 3'-untranslated region of lactate dehydrogenase-A subunit mRNA.

Expression of the lactate dehydrogenase A subunit (LDH-A) gene can be controlled by transcriptional as well as posttranscriptional mechanisms. In rat C6 glioma cells, LDH-A mRNA is stabilized by activation and synergistic interaction of protein kinases A and C. In the present study, we aimed to identify the sequence domain which determines and regulates mRNA stability/instability by protein kinase A and focused our attention on the 3'-untranslated region (3'-UTR) of LDH-A mRNA. We have constructed various chimeric globin/lactate dehydrogenase (ldh) genes linked to the c-fos promoter and stably transfected them into rat C6 glioma cells. After their transfection, we determined the half-life of transcribed chimeric globin/ldh mRNAs. The results showed that at least three sequence domains within the LDH-A 3'-UTR consisting of nucleotides 1286-1351, 1453-1471, and 1471-1502 are responsible for the relatively rapid rate of LDH-A mRNA turnover in the cytoplasm. Whereas chimeric globin/ldh mRNAs containing the base sequences 1286-1351 and 1453-1471 were not stabilized by (Sp)-cAMPS, an activator of protein kinase A, instability caused by the 1471-1502 domain was significantly reversed. Additional deletion and mutational analyses demonstrated that the 3'-UTR fragment consisting of the 22 bases 1478-1499 is a critical determinant for the (Sp)-cAMPS-mediated LDH-A mRNA stabilizing activity. Because of its functional characteristics, we named the 22-base region "cAMP-stabilizing region."

Animals↗

PubMed1998

Extrahepatic and intrahepatic replication and expression of hepatitis C virus.

In order to determine the replication sites of hepatitis C virus, the in situ hybridization and immunohistochemical technique using digoxin-labeled 531 bp plus-strand and minus-strand HCVRNA probes were employed to detect HCVRNA in the liver tissues, bone marrow mononuclear cells and peripheral blood mononuclear cells (PBMCs) from the patients with chronic hepatitis C, and in HCV transfected COS cells. The results showed that both plus-strand and minus-strand HCVRNA were detected in 80% of liver tissues (4/5). Plus-strand HCVRNA could be detected in 90% of PBMCs and bone marrow mononuclear cells (18/20), minus-strand HCVRNA in 25% of PBMCs. In HCV transfected COS cells, plus-strand HCVRNA distributed evenly in 20% cellular nuclei and cytoplasms. No minus-strand HCVRNA was detected in the bone marrow mononuclear cells and HCV transfected COS cells. The positive signal appeared in more cells when the liver tissues, PBMCs and marrow mononuclear cells were hybridized by plus-strand probes than when hybridized by minus-strand probes. Our results suggested that the hepatocytic cytoplasms and PBMC cytoplasms were the replication sites of HCV, but the marrow mononuclear cells were not the replication sites of HCV although they were infected by HCV. HCV infection might be accounted for the pathogenesis of chronic hepatitis and relapse of hepatitis C after liver transplantation.

Animals↗

PubMed1998

[Study on relationship between ovulation inducing effect of drug-acupuncture and endometrial contents of estradiol receptor and progesterone receptor].

OBJECTIVE: To study the effect of Chinese herbal medicine for replenishing Kidney combined with acupuncture in treating anovulation and infertility, and the relationship between its ovulation inducing effect and endometrial contents of estradiol receptor (ER) and progesterone receptor (PR). METHODS: Twenty-nine cases were treated with replenishing Kidney drugs combined with acupuncture for 1-3 months. Patients' ER and PR were measured by immunohistochemical method. And patients were classified according to PR content into PR positive group and mild PR positive group. RESULTS: Fifteen cases of PR positive group, completed treatment for 45 cycles, among them, 40 cycles showed ovulation, the ovulation rate being 88.89%. Ten in 14 cases, who complicated with infertility, became pregnant, the pregnant rate being 71.43%. While in 11 cases of PR mild positive group, 9 complicated with infertility, completed treatment for 33 cycle, 10 cycles showed ovulation (30.30%), and pregnant rate 22.22% (2/9). The difference between the two groups was significant (P < 0.01). CONCLUSION: The replenishing Kidney drugs combined with acupuncture treatment could result a good effect in treating infertility due to anovulation, especially on those with high endometrial PR content.

Acupuncture Therapy↗

PubMed1998

[Image and quantity analysis of prostaglandin in rats' blood plasma and Na(+)-K(+)-ATPase in their cerebellum during the prevention of motion sickness by cinnarizine].

To study the mechanism of cinnarizine in preventing motion sickness, TXB2, 6-Keto-PGF1 alpha in rats' blood plasma and Na(+)-K(+)-ATPase activity in the endothelial cells of their cerebellar capillary were measured and analysed by a radioactive immunity analyser and a computer image system. The results showed that TXB2 and 6-Keto-PGF1 alpha in rats' blood plasma in the cinnarizine preventing group (CPG) decreased remarkably, compared with those in the motion sickness group(MSG) (p < 0.05). The activity of Na(+)-K(+)-ATPase in the endothelial cells of rats' cerebellar capillary in CPG was higher than that in MSG (p < 0.01). The authors suggest that the lower concentration of TXB2 and 6-Keto-PGF1 alpha in rats' blood plasma in CPG is closely related to cinnarizine which prevents Ca2+ from entering into the platelets and into the endothelial cells of blood vessels. The higher activity of Na(+)-K(+)-ATPase in the cerebellum may be caused by cinnarizene which dilates the blood vessels in the brain, increases the blood flow therein, and hinders Ca2+ from getting into the cerebellum cells. These change are believed to be the important mechanism of how cinnarizine prevents motion sickness.

Animals↗

PubMed1997

[The role of nitric oxide in the pathogenesis of asthma].

OBJECTIVE: To investigate the role of nitric oxide (NO) in the pathogenesis of asthma, we observed the influence of L-NG-arginine-methylester (L-NAME), the inhibitor of nitric oxide synthase (NOS), on the contraction of isolated guinea pig tracheal smooth muscles and observed the changes of NOS in the guinea pig asthma model lung tissues using histochemical detection. METHODS: Male Hartley guinea pig isolated tracheal ring were incubated with L-NAME 2.0 mmol/L for 30 min and histamine was given to make a concentration response curve. The sections of guinea pig asthma model lung tissues were stained with NADPH diaphorase. RESULTS: The histamine concentration response curve was significantly shifted upward in the L-NAME incubated group, the maximal response increased by 170% compared with that of control group. The numbers of alveolar macrophages were significantly increased and NADPH diaphorase staining was positive in asthma model group, in contrast, the alveolar macrophages were hardly seen and there was almost no positive staining of NOS in the control group. CONCLUSIONS: The inhibition of NO synthesis of guinea pig respiratory tract with L-NAME results in a marked increase in airway contraction in vitro after histamine provocation. This result indicate that NO has relaxant effect on tracheal smooth muscles and may decrease airway responsiveness to histamine. The increased alveolar macrophages and positive stained NOS in the lung tissues of asthma model indicate that NO, which is synthesized by the NOS in alveolar macrophages, may play an important role in asthma pathogenesis.

Animals↗

PubMed1997

[Reconstruction of anterior cruciate ligament using bone-patellar tendon-prepatellar periosteum free graft with impacting bone technique].

In order to make full and effective use of patellar tendon (middle one-third) during reconstruction of anterior cruciate ligament, we designed bone-patellar tendon-tendon of quadriceps femoris free graft with impacting bone technique and 38 cases were treated by this method. Follow-up for 2 years and 7 months showed that the clinical results were good. The exellent and good rate was 89.7%. Clinical results indicated that the fixation of this reconstructive method was firm and grafts in the joint cavity were patellar tendon tissue. The anterior medial rotatory instability of the knee joint could be corrected with the same graft that have enough length. The experience of acute rupture of anterior cruciate ligament and the rupture of anterior cruciate ligament combined with injury of meniscus were reported.

Adolescent↗

PubMed1997

[Influence of human bone morphogenetic protein (hBMP) on the articular cartilage pieces cultured in vitro].

To understand the influence of hBMP on the articular cartilage, we investigated the expression of osteocalcin (BGP) and hBMP, and calcium deposit in cartilage matrix induced by hBMP. Under the inducing of hBMP, chondrocytes in cartilage pieces begun to express BGP and hBMP. The hBMP promoted calcium deposition in the cartilage matrix, hBMP made some chondrocytes further differentiat into osteoblast-like cells. We consider that these osteoblast-like cells might be other source of osteoblasts in endochondral osteogenesis.

Bone Morphogenetic Proteins↗