2006年 · 第119卷第13期

Abstract：Backgroud Angiotensin Ⅱ (Ang Ⅱ), a principal effector of renin-angiotensin system (RAS) and increased in aging tissues, can stimulate JAK/STAT pathway via the G-protein-coupled Ang Ⅱ receptor type Ⅰ (AT1) and induce nuclear translocation of signal transducers and activators of transcription (STAT). To further explore the role of Ang Ⅱ in aging, we examined the effect of Ang Ⅱ on human replicative senescent diploid fibroblast WI-38cells.Methods Human senescent WI-38 cells were incubated with Ang Ⅱ, receptor antagonist PD123319, valsartan,STAT3 sense plasmid, and/or STAT3 antisense plasmids. Methods were applied including electrophoretic mobility shift assay (EMSA), Western blot, transfection, and laser scanning confocal microscopy.Results It was found that cultured human senescent WI-38 cells constitutively expressed tissue inhibitor of metalloproteinase-1 (TIMP-1), and Ang Ⅱ induced TIMP-1 protein expression in both time- and dose-dependent manners. Ang Ⅱ induced STAT-DNA binding activity also in both time- and dose-dependent manners. And supershift assay showed that the sis-inducing factor (SIF) band contained STAT3 proteins. STAT3 antisense oligonucleotides could inhibit both Ang Ⅱ-induced STAT3-DNA binding activity as well as TIMP- 1 expression.Conclusion Ang Ⅱ could up-regulate TIMP-1 expression through activating STAT3 signal pathway in human senescent cells, indicating that Ang Ⅱ-STAT3-TIMP-1 pathway may be involved in the mechanism of sclerosis in aging tissues。

Abstract：Background Advanced oxidation protein products (AOPPs) are new uremic toxins reported by Witko-Sarsat in 1996, which are associated with the pathogenesis of atherosclerosis. However, the mechanisms by which AOPPs enhance atherosclerosis have not been fully understood. Monocyte chemoattractant protein-1 (MCP-1) is a chemokine which stimulates migration of monocytes and plays a critical role in the development of atherosclerosis. In this study, we investigated the effect of AOPPs on MCP-1 expression in cultured vascular smooth muscle cells (VSMCs).Methods VSMCs were cultured and then co-incubated with AOPP (200 μ mol/L, 400 μ mol/L) for different times with or without pretreatment with specific p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580. RT-PCR and Western blott were used to detect MCP-1 mRNA and protein expression at different time points after AOPP stimulation in rat smooth muscle cells. Western blot was used to detect the expression of phosphorylated p38 MAPK.Results Treatment of VSMC with AOPPs resulted in a significant increase of the expression of MCP- 1 mRNA and protein in time- and dose-dependent manner, and could activated p38 MAPK. Pretreatment of VSMCs with SB203580 resulted in a dose-dependent inhibition of AOPPs-induced MCP-1 mRNA and protein expression.Conclusions AOPPs can stimulate MCP-1 expression via p38 MAPK in VSMCs. This suggests that AOPPs might contribute to the formation of atherosclerosis through this proinflammatory effect。

Abstract：Background Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive, allelic disorders. This study was conducted to look into the spectrum of DMD gene mutations in Hong Kong Chinese patients with Duchenne or Becket muscular dystrophy (DMD/BMD), and to study genotype-phenotype correlation.Methods A retrospective review of 67 patients.Results Twenty-three (34.3%) patients had exon deletions; whereas 5 (7.5%) patients had exon duplications.Twenty-three (34.3%) patients had small mutations, including 17-point mutations and 6 small insertions or deletions. No correlation was found between the type of mutation and the muscle phenotype or mental retardation.Significantly fewer maternal carriers were found in patients with exon deletions, and a positive family history was more common in those with small mutations. DMD phenotype was significantly less common in patients with exon deletions/duplications at the 5' hotspot, whereas all 4 small mutations associated with mental retardation were located in the 3' end of the gene.Conclusions The percentage of DMD exon deletions in local Chinese patients was significantly lower than the commonly quoted 60%. This indicated an ethnic or regional difference in predisposition to DMD exon deletions。

Abstract：Background Mutations in the hepatocyte nuclear factor-1A gene cause the type 3 form of maturity-onset diabetes of the young (MODY3). This study was undertaken to determine mutations and sequence variations of the HNF-1A gene in Chinese with familial early-onset and/or multiplex diabetes mellitus.Methods We screened all ten exons of the HNF- 1A gene, including exon/intron junctions, by direct sequencing in 272 unrelated Chinese, including 80 healthy controls and 192 probands of early-onset and/or multiplex diabetes pedigrees.Results In addition to one silent mutation of c.864 G ＞C [p. G288G] in exon4 at codon 288, which had been reported previously, a total of four novel mutations including two missense mutations (c.245C＞T [p.T82M] and c.390 G ＞ T [p. Q130H]) and one frameshift mutation P353fsdelACGGGCCTGGAGC and one silent mutation c.759 G ＞ T [p. G253G] were identified. Moreover, eleven substitutions were identified in 192 probands. Of these,three variants (-8 G＞A, -128 T＞G and IVS2+21 G＞A) were not observed in 80 healthy controls and one of them (-8 G＞A) was not reported previously and the two promoter variants co-segregated with diabetes. The genotype and allele frequencies of the other eight variants in the diabetic patients were not significantly different from those in the healthy controls. No significant relationships were observed between the eight variants of the HNF-1A gene and clinical variables (plasma glucose, insulin, C-peptide and fasting lipid profile).Conclusion The prevalence of structural mutations in the HNF-1A gene responsible for familial early-onset and/or multiplex diabetes appears to be rare among Chinese patients。

Abstract：Background Nitric oxide (NO) synthesized by endothelial nitric oxide synthase (eNOS) plays an important role in both the regulation of endothelial function and the control of blood pressure. Up to now, there has been conflicting data regarding the association between three clinically relevant polymorphisms (T-786C, intron4b/a and G894T) of the eNOS gene and essential hypertension.Methods To examine the contribution of the three eNOS gene polymorphisms to the development of hypertension in the northern Han Chinese, a case-control study including 503 hypertensive cases and 490 age-,gender-, and area-matched controls recruited from the International Collaborative Study of Cardiovascular Disease in Asia (InterASIA) was conducted. Genotyping was performed by polymerase chain reaction (PCR) or PCR-restriction fragment length polymorphism (RFLP).Results The T-786C and intron4b/a polymorphisms were observed in significant linkage disequilibrium (D'=0.87, P＜0.001). The minor allele frequencies of these three polymorphisms in healthy controls were much lower than those of Caucasians (9.3% vs 39.6%-42.0%, 8.9% vs 15.0%- 16.0% and 10.9% vs 34.5%-34.9%for -786C, intron4a and 894T, respectively). Genotype distributions and allele frequencies of the three polymorphisms did not differ between cases and controls (all P ＞ 0.05). In addition, none of the eight estimated haplotypes significantly increased or decreased the risk of hypertension before or after adjustment for several known risk factors.Conclusion The study results suggest that the three eNOS gene polymorphisms are unlikely to be major genetic susceptibility factors for essential hypertension in the northern Han Chinese population。

Abstract：Background In-stent restenosis (ISR) remains a challenge for interventional cardiologists. Some data suggest that drug-eluting stents (DES) represent a promising new option for the treatment of patients with ISR. Currently,2 DES platforms are available [sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) ], but the superiority of either approach for treating ISR has not been convincingly demonstrated. The aim of the present study was to retrospectively compare angiographic and clinical outcomes after treatment of ISR with SES or PES in a series of consecutive patients with ISR.Methods A total of 745 consecutive patients were treated with bare metal stents from April 12, 2004 to December 31, 2004 in our center. Of these, clinically driven target lesion revascularization (TLR) was performed in 54 ISR from 54 patients at 7 months. Of the 54 patients with ISR, 36 received SES and 18 received PES.Follow-up included angiography and assessment of clinical outcome, both performed 7 months after DES implantation.Results There were no significant differences in baseline clinical data (including medication usage and lesion characteristics) between the two groups. Except for overlapping of multiple stents, procedural parameters were also similar in both groups. Seven-month angiographic follow-up showed that the binary restenosis rate was higher in patients treated with PES than that in patients treated with SES (in-stent binary restenosis: 27.8% vs 5.6%, P＜0.023; In-segment binary restenosis: 44.4% vs 13.9%, P＜0.014). Major adverse cardiac events (MACE)occuring during hospitalization or during the follow-up period including thrombosis and TLR was similar in both groups (22.2% vs 8.3%, P＞0.05).Conclusions Results from this small sample size, retrospective, single-center study showed that SES might be superior to PES in treating ISR because of lower 7-month restenosis rates (both in-stent and in-segment binary restenosis) with no increased incidence of MACE。

Abstract：Objective To review recent developments in therapeutic DNA vaccines against tuberculosis.Data sources The data used in this review were obtained mainly from the studies of therapeutic DNA vaccines against tuberculosis reported from 2000 to 2006.Study selection Relevant articles about studies of therapeutic DNA vaccines against tuberculosis were selected.Data extraction Data were mainly extracted from the 32 articles listed in the reference section of this review.Results Some DNA vaccines which previously showed to induce protective immunity against infection by Mycobacterium tuberculosis in a prophylactic manner are also surprisingly effective when used therapeutically,including persistent Mycobacterium tuberculosis and multidrug-resistant tuberculosis which are refractory to immune system and antibacterial chemotherapy alone. When used in combination with antibacterial drugs,therapeutic DNA vaccines could effectively eliminate residual bacteria in infected animals and shorten the therapy course of conventional chemotherapy. Detailed studies demonstrated that therapeutic effects of DNA vaccines may at least partly be due to the restoration of the Th1/Th2 balance. Some problems have also emerged along with these exciting results.Conclusions Therapeutic DNA vaccine is a promising strategy against tuberculosis, however developing an ideal DNA vaccine for therapy of tuberculosis will require further development。

Transitional cell carcinoma (TCC) of bladder is the most common malignant tumor in uropoiesis system. Up to date, there is still lack of an ideal marker for the diagnosis of TCC except CT and MRI imaging and cystoscopy. Cystoscopy is an invasive examination, which increases the possibility of urinary tract infection. Urine cytology has low sensitivity (21%-40%) in diagnosis of bladder cancer, especially for those with medium or high differentiation. The specificity is often affected by factors such as specimen collection, urinary tract infection, etc. Detecting the expression of survivin mRNA in urine by real time-PCR is simple in specimen collection and is sensitive and relatively specific, which provides a simple and noninvasive diagnostic method for TCC. Moreover it allows comparing the gene expression levels at different stages and grades of TCC, which can help define malignancy degree of TCC。

CTNNB1 (or beta-catenin) is regarded as a central effecter in molecules of the wingless/Wnt signalling pathway. It is a key component of the cadherin mediated cell to cell adhesion system and forms a complex with the protein product of adenomatous polyposis coli (APC), glycogen synthase kinase 3β (GSK3β) and conductin.1 One mutation of APC is also responsible for activation of wingless/Wnt signalling pathway and accumulation of free beta-catenin in the cell. Beta-catenin upregulates oncogenes, such as cyclin D1 and c-myc.2 Beta-catenin expression in cytoplasm and nuclei was reported to increase in many cases of intestinal tumorigenesis.3,4 In addition, the hyperexpression of integrin linked kinase (ILK) in colonic polyposis has been demonstrated.5

Iodine deficiency disease (IDD) is common in China.An universal salt iodization (USI) program has been implemented by the Chinese government since 1996. As a result, the goiter rate in 8- to 10-year old children decreased from 20.4% in 1995 to 5.8% in 2002.1 But the adverse effects of iodine excess such as iodine-induced hyperthyroidism, iodine-induced goiters, iodine-induced hypothyroidism, etc. have become a great concern to healthcare professionals as well as the general population. The impact of USI on antithyroid drugs (ATDs) might become a potential challenge to address. With a special grant from the Department of Disease Control, the Health Ministry of China, we conducted a prospective study on the effects of USI on ATDs at the thyroid section of the Endocrinology Clinic of Peking Union Medical College Hospital (PUMCH), Beijing。

Hypertrophic obstructive cardiomyopathy (HOCM)is a genetic disorder characterized by severe asymmetric hypertrophy of the interventricular septum (IVS) in the absence of any other systemic or cardiac diseases。

The clinical findings frequently presented in trisomy 4q syndrome including mental retardation, developmental delay and multiple abnormalities such as microcephaly, acrocephaly, as well as malformed ears, high/broad/depressed nasal bridge, teeth and thumb anomalies. It has been proposed that trisomy 4q is caused by a familial balanced translocation or a de novo imbalance. We reported a new case of trisomy 4q with a karyotype of 46, XY, der(5)t(4;5)(q27;q35) and this karyotye was reported for the first time。

The clinical picture of actinomycosis was first described in 1878.1 Actinomvcosis agents are found in the natural flora of the oral cavity, upper gastrointestinal system and female genital systems.Actinomyces israelii is usually responsible for the infections and causes chronic suppurative and granulomatous infections.1 The most common disease form is cervicofascial infection。

Relapsing polychondritis (RP) is a recurrent disease involving cartilage mainly of the ear,nose, larynx, trachea, and bronchus.1 The typical manifestations of the disease in the ear and nose can be easily recognized, but the symptoms could be ignored or easily confused with those of other diseases when the cartilage of other sites is involved.Thus, it is necessary to develop a new technique for the diagnosis of this disease. Few cases of abnormal accumulation of radioactivity at cartilage shown by 99mTc methylene diphosphonate (MDP) bone scintigraphy are described in the literature. In this report, we present 4 patients of whom 3 had positive findings on 99mTc MDP bone scintigraphy with an assessment of 99mTc MDP bone scintigraphy in the diagnosis of RP。

There are a wide range of computed tomography (CT) findings in patients with pulmonary tuberculosis, including diffuse or localized nodules,reticular opacities, ground glass attenuation, air trapping, consolidation, cavitation, fibrosis, lymph nodes enlargement, and septal thickening.1-3However, CT findings of pulmonary tuberculosis that appeared as multiple cystic lesions were very rare.3,4Herein, the CT findings appeared as multiple cystic lesions in a patient with pulmonary tuberculosis are reported。