幽门螺杆菌cagⅡ对胃上皮细胞IL-8基因转录的影响及机制

目的探讨HpcagⅡ对胃上皮细胞IL-8基因转录的影响及信号传导机制。方法构建 cagⅡ基因位点缺失Hp突变株及带有IL-8报告基因的人胃癌细胞系L5F11,用液体闪烁计数仪测定荧光素酶(IL8转录)活性,用ELISA法测定IL8蛋白浓度。结果所有Hp突变株诱导荧光素酶活性与IL8蛋白浓度较亲代菌株26695均降低[(0．13±0．01)×cpm比(0．59±0．05)×(P<0．01);(0．73±0．13)ng／ml比(2．22±0．65)ng／ml,(P<0．05)]。PTK抑制剂herbimycinA不仅抑制Hp诱导的荧光素酶活性[(0．71±0．18)×cpm比(1．51±0．23)×cpm,(P<0．05)],而且抑制IL-8蛋白表达[(0．83±0．41)ng／ml比(3．22±0．59)ng／ml,(P<0．05)],但herbimycinA对TNFα诱导的荧光素酶活性及IL8蛋白表达均无影响(P均>0．05);PKA抑制剂H7抑制TNFα诱导的荧光素酶活性[(0．74±0．16)×cpm比(2．62±0．26)×cpm,(P<0．001)]及IL8蛋白表达[(1．45±0．38)ng／ml比(4．12±0．43)ng／ml,(P<0．01)],而对Hp诱导的荧光素酶活性无影响(P>0．05)。结论HpcagⅡ中的多基因能够调节胃上皮细胞IL-8基因转录,且这一作用主要经蛋白酪氨酸激酶途径。     

Peptide digest studies of polymorphic proteins of Plasmodium falciparum

Previous work has shown that when a large number of Plasmodium falciparum isolates are examined by two dimensional electrophoresis, over 100 different proteins can be detected, 15 of which show polymorphism in electrophoretic characters. Eight of these proteins have now been subjected to limited proteolysis. Two methods of digestion were used: enzymic, with Streptomyces griseus Pronase E and chemical, using N-chlorosuccinimide to break proteins at tryptophan residues. When different forms of each variable protein were analysed most were found to exhibit similar peptide profiles, a finding indicating that they were determined by alleles of genes at single loci. Two of the proteins, A and K, exhibited higher degrees of polymorphism than the other variable proteins. The possible reasons for this are discussed.     

Moving beyond randomized controlled trials in the evaluation of compulsory community treatment

Compulsory community treatment for people with severe mental illness remains controversial due to conflicting research evidence. Recently, there have been challenges to the conventional view that trial‐based evidence should take precedence. This paper adds to these challenges in three ways. First, it emphasizes the need for critiques of trials to engage with conceptual and not just technical issues. Second, it develops a critique of trials centred on both how we can have knowledge and what it is we can have knowledge of. Third, it uses this critique to develop a research strategy that capitalizes on the information in large‐scale datasets.     

Biomechanical efficacy of unipedicular versus bipedicular vertebroplasty for the management of osteoporotic compression fractures.

STUDY DESIGN: Cadaveric study on the biomechanics of osteoporotic vertebral bodies augmented and not augmented with polymethylmethacrylate cement. OBJECTIVES: To determine the strength and stiffness of osteoporotic vertebral bodies subjected to compression fractures and 1) not augmented, 2) augmented with unipedicular injection of cement, or 3) augmented with bipedicular injection of cement. SUMMARY OF BACKGROUND DATA: Percutaneous vertebroplasty is a relatively new method of managing osteoporotic compression fractures, but it lacks biomechanical confirmation. METHODS: Fresh vertebral bodies (L2-L5) were harvested from 10 osteoporotic spines (T scores range, -3.7 to -8.8) and compressed in a materials testing machine to determine intact strength and stiffness. They were then repaired using a transpedicular injection of cement (unipedicular or bipedicular), or they were unaugmented and recrushed. RESULTS: Results suggest that unipedicular and bipedicular cement injection restored vertebral body stiffness to intact values, whereas unaugmented vertebral bodies were significantly more compliant than either injected or intact vertebral bodies. Vertebral bodies injected with cement (both bipedicular and unipedicular) were significantly stronger than the intact vertebral bodies, whereas unaugmented vertebral bodies were significantly weaker. There was no significant difference in loss in vertebral body height between any of the augmentation groups. CONCLUSIONS: This study suggests that unipedicular and bipedicular injection of cement, as used during percutaneous vertebroplasty, increases acute strength and restores stiffness of vertebral bodies with compression fractures.     

Additional mechanisms of hiatal hernia recurrence and its prevention

Summary The conventional hiatal hernia repair is a tension repair. Large defects such as those associated with an intrathoracic stomach can have a high rate of recurrence resulting in esophageal symptoms and in some instances gastric strangulation. Numerous additive procedures are used to secure the stomach in the abdominal cavity including mesh buttressing, fundoplication, anterior abdominal wall gastropexy and fundus diaphragmatic suture fixation. The optimal repair is unknown primarily because crura closure failure is poorly understood. A literature review was used to determine the proven causes of hiatal hernia recurrence. Early postoperative vomiting, surgeon inexperience, short esophagus and no crus closure are documented causes. In a series of 19 hiatal hernia recurrence repairs from our institution, additional causes such as suture pull-out and trauma have been established as additional mechanisms of recurrence. Increased intra-abdominal pressure associated with motor vehicle accidents was the precipitating factor in 2/19 patients. Suggested methods for prevention of hiatal disruption and resultant hernia are proposed which include: a postoperative antiemetic regimen, restricted activity in the early postoperative period, an assessment technique for the short esophagus when utilizing a laparoscopic approach, crus closure calibration and inclusion of the diaphragmatic fascia when performing hiatal closure for large paraesophageal hernias and the short esophagus.     

Body mass index, migraine, migraine frequency and migraine features in women

We evaluated the association of body mass index (BMI) with migraine and migraine specifics in a cross-sectional study of 63 467 women aged ≥ 45 years, of whom 12 613 (19.9%) reported any history of migraine and 9195 had active migraine. Compared with women without migraine and a BMI < 23 kg/m², women with a BMI ≥ 35 kg/m² had adjusted odds ratios (ORs) (95% confidence intervals) of 1.03 (0.95, 1.12) for any history of migraine. Findings were similar for active migraineurs. Women with a BMI of ≥ 35 kg/m² had increased risk for low and high migraine frequency, with the highest estimate for women who reported daily migraine. Compared with women with the lowest associated risk (migraine frequency < 6 times/year; BMI between 27.0 and 29.9 kg/m²), women with a BMI ≥ 35 kg/m² had an OR of daily migraine of 3.11 (1.12, 8.67). Among the women with active migraine, a BMI ≥ 35 kg/m² was associated with increased risk of phonophobia and photophobia and decreased risk of a unilateral pain characteristic and migraine aura. Our data confirm previous findings that the association between BMI with migraine is limited to migraine frequency and specific migraine features.     

Gestational PFOA exposure of mice is associated with altered mammary gland development in dams and female offspring.

Perfluorooctanoic acid (PFOA), with diverse and widespread commercial and industrial applications, has been detected in human and wildlife sera. Previous mouse studies linked prenatal PFOA exposure to decreased neonatal body weights (BWs) and survival in a dose-dependent manner. To determine whether effects were linked to gestational time of exposure or to subsequent lactational changes, timed-pregnant CD-1 mice were orally dosed with 5 mg PFOA/kg on gestation days (GD) 1-17, 8-17, 12-17, or vehicle on GD 1-17. PFOA exposure had no effect on maternal weight gain or number of live pups born. Mean pup BWs on postnatal day (PND) 1 in all PFOA-exposed groups were significantly reduced and decrements persisted until weaning. Mammary glands from lactating dams and female pups on PND 10 and 20 were scored based on differentiation or developmental stages. A significant reduction in mammary differentiation among dams exposed GD 1-17 or 8-17 was evident on PND 10. On PND 20, delays in normal epithelial involution and alterations in milk protein gene expression were observed. All exposed female pups displayed stunted mammary epithelial branching and growth at PND 10 and 20. While control litters at PND 10 and 20 had average scores of 3.1 and 3.3, respectively, all treated litters had scores of 1.7 or less, with no progression of duct epithelial growth evident over time. BW was an insignificant covariate for these effects. These findings suggest that in addition to gestational exposure, abnormal lactational development of dams may play a role in early growth retardation of developmentally exposed offspring.     

Presence of the Metabolic Syndrome in Obese Adolescents Predicts Impaired Glucose Tolerance and Nonalcoholic Fatty Liver Disease

PURPOSE: To evaluate whether the presence of metabolic syndrome (MS) in obese adolescents is associated with other comorbidities of obesity METHODS: A total of 85 obese teens (70% female and 30% male) with fasting insulin >25 microU/ml and family history of type 2 diabetes mellitus and/or acanthosis nigricans were studied. Mean age was 15.8 +/- 1.7 years and body mass index (BMI) was 39.3 +/- 6.6 kg/m(2). Of the subjects, 54% were Hispanic and 35% black, 5% white, 5% American Indian, and 1% Asian. Laboratory analysis included fasting lipids, glucose, gamma-glutamyl transpeptidase (GGT), and oral glucose tolerance testing. Additional liver transaminase levels were determined and liver ultrasound (US) was performed to evaluate the presence and severity of fatty liver. RESULTS: All subjects met MS criteria for children for waist circumference, 49% for blood pressure, 54% for high-density lipoprotein, 54% for triglycerides, and 20% for impaired fasting glucose (IFG) or impaired glucose tolerance [IGT]). In all, 47 subjects had three or more MS criteria. BMI was no different between groups with and without MS. Subjects with three or more MS criteria were more likely to have IGT (p = .004), elevated alanine aminotransferase (p = .039), elevated GGT (p = .036), fatty liver on US (p < .001), and more severe fatty liver (p = .001). CONCLUSIONS: Abnormal glucose regulation and evidence of nonalcoholic fatty liver disease (NAFLD) were more common in subjects meeting three criteria for MS than in those meeting fewer criteria. The identification of MS provides value to the primary care provider. Those patients meeting criteria for MS should be evaluated for glucose intolerance and NAFLD.