肝炎病毒利用DC-SIGN逃逸机体免疫作用

DC-SIGN是DC表面识别多种病原微生物的受体.一方面,DC借助DC-SIGN对固有免疫及适应性免疫发挥免疫调节作用;另一方面,DC-SIGN又成为某些病原微生物如肝炎病毒借以逃逸机体免疫防御功能的靶分子.我们就DC-SIGN的结构及功能、与病毒的相互作用等方面进行阐述.     

A web-based simulation of a longitudinal clinic used in a 4-week ambulatory rotation: a cohort study

Background  

Residency training takes place primarily on inpatient wards. In the absence of a resident continuity clinic, internal medicine residents rely on block rotations to learn about continuity of care. Alternate methods to introduce continuity of care are needed.     

Difficulties in diagnosing tuberculosis of the cervix in a post menopausal woman: Case report and literature review

Tuberculosis (TB) of the cervix is a rare disease, especially in developed countries. We presented a patient with primary TB of the cervix with no concurrent immune deficiency or HIV infections. The case clinically mimicked carcinoma of the cervix. Difficulties in diagnosis have been discussed. Given the recent increase in migration patterns including travel from TB endemic areas, an abnormal-looking cervix should be regarded with a degree of suspicion for TB.     

Stress and quality of sleep among individuals diagnosed with diabetes

Several studies have suggested that stress and sleep may be related to diabetic disease progression. Cortisol is one physiological indicator of stress that has been well validated in previous research. The primary objectives of the present study were (1) to examine the experiences of stress among patients diagnosed with diabetes and (2) to evaluate the quality of sleep among these participants. Participants (mean age = 34.99 years) were 20 adolescents and adults with Diabetes Mellitus; 13 had Type 1 and 17 were female. Primary measures included actigraphy, the Pittsburgh Sleep Quality Index (PSQI), salivary cortisol and the Perceived Stress Scale (PSS). Participants reported a moderate amount of stress (mean PSS scores = 20.2), slept an average of 6.51 h and exhibited at least one clinical indicator of sleep disturbance. Objectively measured total sleep time was associated with awakening cortisol (r = 0.62, p = 0.004) and PSQI Global scores (r = ‐0.51, p = 0.021). Awakening cortisol and PSS scores were not associated with PSQI Global scores, but were related to specific self‐reported sleep disturbances. Given the interacting physiological pathways of stress and sleep, both of which were evident in this small sample, these variables warrant further study. Copyright © 2009 John Wiley & Sons, Ltd.     

Mammographic density and candidate gene variants: a twins and sisters study.

BACKGROUND: Mammographic density, the light/white radiographic appearance on a mammogram that represents connective and epithelial tissue, is a strong risk factor for breast cancer which seems to be highly heritable. Little is known about its genetic determinants. METHODS: We studied 457 women from 207 sisterhoods (104 monozygotic twins, 182 dizygotic twins, and 171 singletons). Percentage mammographic density (PMD) as well as dense area and nondense area were calculated using a computer-assisted method. We measured six single nucleotide polymorphisms from six candidate genes (COMT, HSD3B1, IGFBP3, HER2, XPD, and XRCC3). Associations between genotypes and mammographic measures were tested (a) cross-sectionally using a multivariate normal model fitted using FISHER that allowed separate correlations for monozygotic, dizygotic, and nontwin pairs and (b) within sister pairs using paired t tests. RESULTS: Cross-sectionally, each additional copy of the HSD3B1 Asn(367)Thr variant allele was associated with lower PMD (-3.47% per allele; SE = 1.65; P = 0.035). Within-pair regression estimates confirmed this association. There was no evidence for an association between the mammographic density measures and any of the other variants studied. CONCLUSION: We have replicated an association between a variant in the HSD3B1 gene and PMD, which suggests that HSD3B1 may be genetic determinant of mammographic density.     

Haptoglobin phenotype is an independent risk factor for cardiovascular disease in individuals with diabetes: The Strong Heart Study

OBJECTIVES: The goal of this study was to determine if the haptoglobin phenotype was predictive of cardiovascular disease (CVD) in diabetic mellitus (DM). BACKGROUND: Cardiovascular disease is the most frequent, severe, and costly complication of type 2 DM. There are clear geographic and ethnic differences in the risk of CVD among diabetic patients that cannot be fully explained by differences in conventional CVD risk factors. We have demonstrated that a functional allelic polymorphism in the haptoglobin gene acts as a major determinant of susceptibility for the development of diabetic microvascular complications. METHODS: We sought to determine if this paradigm concerning the haptoglobin gene could be extended to CVD in DM. We tested this hypothesis in a case-control sample from the Strong Heart study, a population-based longitudinal study of CVD in American Indians. Haptoglobin phenotype was determined by polyacrylamide gel electrophoresis in 206 CVD cases and 206 matched controls age 45 to 74 years. Median follow-up was six years. RESULTS: In multivariate analyses controlling for conventional CVD risk factors, haptoglobin phenotype was a highly statistically significant, independent predictor of CVD in DM. The odds ratio of having CVD in DM with the haptoglobin 2-2 phenotype was 5.0 times greater than in DM with the haptoglobin 1-1 phenotype (p = 0.002). An intermediate risk of CVD was associated with the haptoglobin 2-1 phenotype. CONCLUSIONS: This study suggests that determination of haptoglobin phenotype may contribute to the algorithm used in CVD risk stratification, and in evaluation of new therapies to prevent CVD in the diabetic patient.     

Nonconvulsive status epilepticus after subarachnoid hemorrhage

OBJECTIVE: Although in-hospital seizures have been reported for 3 to 24% of patients with aneurysmal subarachnoid hemorrhage (SAH), nonconvulsive status epilepticus (NCSE) has not been previously described. We sought to determine the frequency and clinical features of NCSE among comatose patients with SAH. METHODS: Between November 1997 and February 2000, we performed continuous electroencephalographic (cEEG) monitoring for at least 24 hours for all patients with aneurysmal SAH who were treated in our neurological intensive care unit and exhibited unexplained coma or neurological deterioration. NCSE was diagnosed when cEEG monitoring demonstrated continuous or repetitive electrographic seizures exceeding 1 hour in duration. Refractory NCSE was treated aggressively with intravenous anticonvulsant administration and continuous-infusion midazolam therapy. RESULTS: Of 233 patients with SAH who survived the first 48 hours of hospitalization, 101 were stuporous or comatose at some point during their hospitalization. Twenty-six of those patients underwent cEEG monitoring, and eight were diagnosed as having NCSE, an average of 18 days (range, 5-38 d) after SAH. All eight patients were receiving prophylactic anticonvulsant therapy. Four patients were persistently comatose and four demonstrated deterioration to stupor or coma; only one exhibited overt tonicoclonic activity. A worst Hunt and Hess grade of IV or V, older age, ventricular drainage, and cerebral edema on computed tomographic scans were identified as risk factors for NCSE (all P < 0.01). NCSE was successfully terminated for five patients (63%), but only one experienced clinical improvement, which was transient; all eight patients eventually died after a period of prolonged coma. CONCLUSION: cEEG monitoring detected NCSE for 8% of patients with SAH and otherwise unexplained coma or neurological deterioration. The seizures were highly refractory to therapy, and the prognosis for these patients was extremely poor. Routine postoperative cEEG monitoring of patients with SAH who are at high risk for NCSE, allowing earlier diagnosis and treatment, offers the best chance of improving the outcomes for patients with this disorder.     

Interleukin-10 fails to modulate low shear stress-induced neointimal hyperplasia.

INTRODUCTION: Overexpression of the anti-inflammatory cytokine interleukin-10 (IL-10) blocks atherosclerotic events in vivo, and IL-10 has been recently hailed as an "immunologic scalpel" for atherosclerosis. Alternatively, mice lacking IL-10 receiving atherogenic diets have increased occlusive lesions. It remains unclear whether such IL-10 modulation broadly applies to other forms of occlusive arterial remodeling. We hypothesized that lack of IL-10 would exacerbate, and exogenous or overexpression of IL-10 would abrogate low shear stress-induced neointimal hyperplasia (NIH). METHODS: Wild-type (WT) and IL-10-deficient (IL-10-/-) mice underwent unilateral common carotid artery (CCA) ligation. Low shear stress in the patent ligated artery results in remodeling and formation of neointima containing BrdU and SMC alpha-actin-positive cells. Additional groups of WT mice underwent CCA ligation and were treated daily with intraperitoneal saline or 1 microg of human IL-10. Chronic delivery gene therapy approaches were also utilized to define the role of IL-10 signaling. WT mice were treated adventitially with 1 x 10(10) adenovirus/green fluorescent protein (Ad/gfp) and an Ad/empty control to confirm the veracity of adventitial delivery. Then, Ad viral IL-10 (vIL-10), Ad/empty, and virus buffer alone were applied directly to the adventitia of the CAA immediately following ligation. In separate experiments, 1 x 10(10) Ad/empty or Ad/vIL-10 was injected intramuscularly. CCAs were perfusion fixed 28 days postligation, the time at which NIH is near maximum. RESULTS: IL-10-/- mice developed identical NIH areas compared to WT controls. Mice receiving IL-10 demonstrated NIH equivalent to saline controls. Mice receiving intramuscular or adventitial Ad/IL-10 developed high serum levels of IL-10 yet formed NIH areas similar to those of controls. Serum IL-10 levels were significantly higher (P = 0.04) with adventitial delivery. Mice treated adventitially with Ad/gfp showed reliable transfection of cells within the adventitia of CAA. No antibody to human IL-10 was found in the sera of intraperitoneal IL-10-treated mice, which failed to attenuate NIH. CONCLUSION: Under the conditions of this experiment, lack of IL-10 does not exacerbate low shear stress-induced NIH, nor does exogenous administration or overexpression of IL-10 attenuate it. Despite high serum levels of vIL-10 in mice treated with ad/vIL-10 adventitially, there appears to be no therapeutic effect despite the confirmed transfection of adventitial cells. Discrepancies between these findings and previous research may be related to IL-10 dosing, inflammation induced by the adenoviral vector, or disparities between the NIH models.