2005年 · 第118卷第05期

Plasma lipids are controlled by genes and play an important role in the development of atherosclerosis. Dysplipidemia is an important risk factor for coronary artery disease (CAD). Coronary artery disease is the leading cause of mortality and morbidity in the developed world. More than 14 million Americans are afflicted with clinically significant CAD.1 To illustrate the impact of CAD in developed countries, the medical and societal costs of CAD in the United States alone are in excess of $90 billion annually.1 More than 600 000 Americans each year develop new cardiac events, more than 10% of which occur in Americans <50 years of age.1 Identifying genetic predisposition to early onset of CAD could help in understanding basic disease mechanism, guiding targeted preventive efforts, and planning appropriate therapeutic strategies。

Rheumatic fever is a complication following an episode of group A streptococcal pharyngitis. It is an acute immunologically mediated, multisystem inflammatory disorder. Acute rheumatic heart disease during the active phase of rheumatic fever sometimes progresses to chronic rheumatic heart disease. Despite its declining importance in industrialised countries rheumatic fever remains the leading cause of death from heart disease in children and young adults in less developed regions. Fifteen to twenty million new cases emerge every year in developing countries.1

Abstract：Background Genetic factors account for approximately 50% of the individual variation in plasma low-density lipoprotein cholesterol (LDL-C) concentrations in the general population. Several candidate genes have been proposed but their relative contributions to the variance in LDL-C are not known, except for apolipoprotein E (apoE). We report here an investigation of the relationship between LDL-C and cholesterol 7α-hydroxylase (CYP7), as well as apoE and low-density lipoprotein receptor (LDLR), three pivotal genes in LDL metabolism. Methods Our study population included more than 200 nuclear families with increased coronary heart disease (CHD) risk from the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study. Variance-component linkage methods, a measured genotype approach, and a variance-component linkage analysis conditional on a measured genotype association were used. Results The results showed significant linkage between a genetic determinant of plasma LDL-C concentrations and a polymorphism near CYP7 with its allelic variation accounting for 27% of the total LDL-C variation. There is significant association between plasma LDL-C concentrations and apoE genotypes. Conditional on the apoE association, the total LDL-C variation accounted by allelic variation of a polymorphism near CYP7 was increased significantly.Conclusion Our results suggest the apoE and CYP7 may be two important genes accounting for the genetic variation of plasma LDL-C concentrations in a population with cardiovascular diseases.

Abstract：Background Rheumatic heart disease (RHD) is the most important sequela of rheumatic fever (RF): evidence that streptococcal infection is aetiological is prominent, but sometimes contradictory. Acute HSV-1 infection in mouse leads to carditis and valvulitis whereas recurrent infection results in inflammatory granulomatous lesions that resemble Aschoff bodies. Cells containing HSV-1 inclusions or virus infected giant cells appear similar to Anitschkow cells or Aschoff cells respectively. We hypothesized that HSV-1 infection also may be involved in RHD. Methods Formalin-fixed, paraffin-embedded valvular tissue samples from 32 patients with RHD were investigated for evidence of HSV-1 infection. HSV-1 antigen was detected by immunohistochemistry, using HSV-1-specific monoclonal and polyclonal antibodies. HSV-1 glycoprotein D gene sequences were amplified by nPCR, using β-globin gene amplification in the same samples as internal control. Valvular tissue from 5 cases of sudden death and 3 cases died of neisseria meningitis without a history of valvular disease was used for comparison. HSV-1-infected lung tissue was used as positive control. Results HSV-1 antigens were detected in valvular tissues from 21 of 32 (65.6%) patients. Fifteen of these 21 (46.9% of cases), but no antigen-negative sample, were positive also for HSV DNA. Nucleotide sequence of PCR products was homologous to the targeted region of the HSV-1 glycoprotein D gene. HSV-1 antigen was present also in one case of sudden death but viral DNA was not found in any tissue sample from the comparison group. Results from reagent and positive controls were as anticipated.Conclusions This is the first study to show the presence of HSV-1 antigen and genomic DNA in valvular tissues from patients with RHD and provides evidence for an association of HSV-1 infection with some cases of rheumatic valvular disease。

Abstract：Background Carvedilol, an antagonist of α1- and β-adrenergic receptors, has shown efficacy in reducing all-cause death and arrhythmia death for ischemic heart disease and congestive heart failure in several large-scale trials. It has been found to prevent ventricular remodeling, and recently was reported to reverse down-regulation of Na+ channel in a chronic heart failure model. This study was conducted to investigate whether carvedilol could reverse the ion remodeling in a myocardial infarction model of rabbit.Methods After the procedure of coronary ligation, animals were randomized to placebo or carvedilol treatment (5 mg/kg). Action potentials, L-type calcium current (Ica L) and the effect of isoproterenol stimulation on Ica L were measured using whole-cell patch method. Evaluation of the expression of calcium channel subunits was carried out by RT-PCR and Western blot. Results The results indicate that mean peak Ica L densities (pA/pF) at +10 mV was reduced in postinfarction myocytes (5.33±0.45, n=25) compared to sham myocytes (6.52±0.21, n=20). Treatment of myocardial infarction rabbits with carvedilol could restore it partially (5.91±0.39, n=20, P<0.05). However, steady-state activation parameters were similar in three groups. With stimulation by isoproterenol (1 μmol/L) Ica L increased in all three groups, but the increase was smaller in postinfarction myocytes. mRNA levels of calcium channel subunit CaA1 gene was decreased but CaB2a, CaB2b and CaB3 mRNA levels did not change after MI. Corresponding change in CaA1 protein was also observed. Conclusions The results demonstrate that carvedilol restores Ica L density and reverse the downregulation of CaA1 postinfarction.

Abstract：Background Alendronate, a nitrogen-containing bisphosphonate is a specific inhibitor of bone resorption and now in the forefront of treatment of osteoporosis. In this study, we reported a significant increase in bone mineral density (BMD) of the spine and the hip in postmenopausal women taking alendronate at 10 mg/d for 1, 2 and 3 years. Methods Participants had received daily, oral, 10 mg dose of alendronate for one to three years and placed into one of three groups according to alendronate treatment duration: 41 women received alendronate for 1 year (group Ⅰ), 46 received alendronate for 2 years (group Ⅱ), and 30 received alendronate for 3 years (group Ⅲ). Measurements of bone density had been made by dual energy X-ray absorbtiometry once each year. Results The differences in L2-L4, L2, L4, femoral neck and trochanter BMD values before and after treatment for first group were significantly different. In second group, significant differences between initial and after treatment were found at the other sites except at the Ward's triangle. In the third group, only a significant increase in the L2-L4, L2, L3, L4, trochanter BMD values between before treatment and at the end of third year was found. Comparisons between groups were performed with Student's t test. ANOVA was used to test the age, menopause age, menopause duration and initial BMD values between the three groups. Calculated P values of less than 0.05 were considered statistically significant. Conclusions Alendronate had increased BMD significantly at the spine and hip in postmenopausal women over three years. Increases of BMD in third group were significant during the first and second years. However, continued therapy with alendronate had been required to maintain the gain in BMD over the third year。

Abstract：Background Recent studies have indicated that chronic stress may give rise to brain damage, which is related to the genesis of depression. The purpose of this study is to investigate the effects of extract of Ginkgo biloba (EGb) and venlafaxine on depression.Methods Rats were treated with chronic and comprehensive stress to create a depression model. Immunohistochemistry was used to detect the expression of brain-derived neurotrophic factor (BDNF) in the hippocampal CA3 neurons of rats treated with different drugs. Behavioral changes of these rats were also examined. Results The expression of BDNF in the hippocampal CA3 neurons of the depression model decreased with a reduction in exploring behavior and a significant increase in fecal production. The expression of neuron nitric-oxide synthase (nNOS) protein also increased in the rats compared to normal controls. The rats treated with EGb and venlafaxine showed an increase in expression of BDNF and exploring behavior compared to untreated rats, but a decrease in nNOS and fecal production.Conclusions Rats sustain damage to the brain after being subjected to chronic and comprehensive stress. Our research has indicated that combined EGb with venlafaxine enhances the protection of neurons and decreases damage to the brain, while relieving the side effects of synthetic antidepressants。

Abstract：Background A new brain region, the marginal division (MrD), was discovered at the caudal margin of the neostriatum. The MrD was shown to be involved in learning and memory in the rat. The aim of this study was to investigate the expression of the immediate-early genes c-fos and c-jun in the MrD of the striatum during learning and memory processes in the rat, immunocytochemical and Western blot methods were used to examine Y-maze trained rats.Methods The rats were divided into three groups, namely the training, pseudotraining, and control groups. After Y-maze training, the expression of the immediate-early genes c-fos and c-jun in the MrD of the rats was investigated using immunocytochemical and Western blot methods. Results After one hour of Y-maze training, the expression of c-jun and c-fos proteins was significantly enhanced in the MrD; the c-jun protein, in particular, was more intensely expressed in this region than in other parts of the striatum. The expression of these two proteins in the training group was significantly higher than in the pseudotraining and control groups. In addition, positive expression was also found in the hippocampus, cingulum cortex, thalamus, and in other areas. Western blot disclosed two immunoreactive bands for the anti-c-fos antibody (47 kD and 54 kD) and two immunoreactive bands for the anti-c-jun antibody (39 kD and 54 kD). Conclusions These results indicate that the immediate-early genes c-fos and c-jun participate in signal transduction during the learning and memory processes associated with Y-maze training in rats。

With the development of the technology of electrophysiological study and radiofrequency catheter ablation, electrophysiologists realized that the coronary sinus (CS) was involved in several types of arrhythmias due to its special anatomic and histological characteristics. In this article we review the anatomy, histology and electrophysiology of the CS and the relation between the CS and selected types of arrhythmias。

On the hypothesis that telomerase reverse transcriptase (TERT) of cardiac myocytes (CMs) is consistent with cell cycle distribution as well as tumour cells, we plan to investigate the expression of TERT in CMs and how TERT is in keeping with CMs cycle distribution after birth and under hypoxia, and roughly understand how hypoxia affects activity of TERT promoter。

The heart is an organ frequently affected in the acquired immunodeficiency syndrome.1 But there is little information as to whether the coronary artery calcification can identify asymptomatic individuals at high risk for having cardiac morphological and functional abnormalities and cardiac risk factors in human immunodeficiency virus (HIV)-infected persons. Accordingly, the purpose of this study was to determine whether coronary artery calcification was associated with cardiac morphological and functional abnormalities, atherogenic lipid and C-reactive protein (CRP) changes in a black adult population with HIV-1 infection。

The two major pathogeneses of type 2 diabetes mellitus (T2DM) are insulin resistance and insulin secretion deficiency. During recent years, researches on the molecular target sites of insulin resistance and the mechanism of the signal transduction has made great progress: especially, the study of insulin receptor substrate-2 (IRS-2). Human IRS-2 gene is located at 13q8.6. IRS-2G1057D is a replacement of G (glycine) by D (aspartic acid) at site 1057 of insulin receptor substrate-2, which is caused by simple nucleotide polymorphism. The role of this variant is still not clear. We detected IRS-2G1057D variant in Han population in Liaoning Province by measuring body mass index (BMI), waistline/hip ratio (WHR) and other parameters of insulin secretion, as well as insulin action to explore the relationship between IRS-2G1057D variant and T2DM。

Though diabetes is common worldwide, the proportion of cases diagnosed is not high. Nearly fifty percent of patients with diabetes mellitus (DM) in US are undiagnosed.1 The ratio might be higher in China. It has been suggested that diabetes may be present 4 to 7 years before diagnosis.2 Many of the complications appear to be present at the time of diagnosis of the diabetic status.1 Screening for diabetes in early stage of diabetes is thus a worthwhile exercise。

In 1990, nanobacterium was found and named by Kajander.1 With distinct mineralizing ability, nanobacteria are thought to play a role in extraskeletal calcifying diseases. It have been found in many human tissues, but whether they exist in the bile or gallbladder mucosa remains unclear. The present study was undertaken to investigate by ELISA, bacterial culturing, immunohistochemical staining and transmission electron microscopy (TEM), whether nanobacteria exist in serum, bile or gallbladder mucosa of healthy people and patients with cholecystolithiasis.

Patients with metastatic thyroid cancer (MTC) was routinely treated with a small dose of 131I before 1989. After that we have been switched to multiple courses of large dose 131I therapy. In this paper, the therapeutic result and its effect, in particular on bone marrow depression, pulmonary, parathyroid and salivary gland function as well as chromosome aberration1-3 were observed and reported.

With widespread performance of coronary artery stenting, the number of in-stent restenosis (ISR) has increased in recent years. How to treat ISR effectively has been a great challenge in the field of cardiology. Recently, some notable clinical trials have confirmed that sirolimus-eluting stents (SESs) (CYPHERTM, Cordis, J&J Inc, USA) reduce ISR rate dramatically. So far, there have been few reports on the efficacy of using SESs to treat ISR.1,2 So, we used SESs to treat 27 patients with ISR and followed up for at least six months.

Spinal dural arteriovenous fistula (SDAVF) is the most common type of spinal vascular malformation.1 Surgical excision of SDAVF is the most effective treatment1,2 and the most often used procedure has been wide laminectomy,2,3 which causes instability of the spinal column. Therefore, we report the clinical results of 72 cases with SDAVF treated in our department by hemilaminectomy, which preserved the stability of the spinal column。

Trigeminal nerve schwannomas, which are rare, slowly growing, benign tumors, account for 0.2% to 1.0% of all intracranial tumors and 0.8% to 8.0% of intracranial schwannomas.1-5 These tumors are treated surgically.1-4 The development of microsurgery and skull base surgery has made complete resection possible in most patients. Nevertheless, cranial nerve sequelae appear after complete resection of these tumors because they are located close to the cavernous sinus and usually adhere to the vital vascular and neural structures. As an alternative to microsurgical resection, Leksell gamma knife (LGK) radiosurgery has been performed for patients with intracranial schwannomas to minimize the treatment-related morbidity and achieve a long-term control of tumor growth.6,7 In this report, we describe our 6-year experience in the treatment of 38 patients with trigeminal schwannomas by LGK。