Immune predictors of cancer progression

The immune system has multiple, complex, and sometimes opposing roles during cancer progression. While immune-compromised individuals have a higher incidence of cancers, inflammation is also associated with increased risk of disease progression. It is becoming apparent that simple measures of immune responses in the blood are of limited use in cancer. Instead, the importance of the exact identity and functional characteristics of tumor-infiltrating immune cells is increasingly recognized. This realization has led to recent studies that have revealed a critical role for chemokine expression in the tumor microenvironment and suggested a therapeutic potential of manipulating intratumoral expression of chemokines to alter the local immune milieu.     

Interstitial myofibroblasts: predictors of progression in membranous nephropathy.

AIMS: To determine the role of interstitial myofibroblasts in the progression of membranous nephropathy; and to assess the predictive value of quantifying myofibroblasts in determining long term renal outcome. METHODS: All cases of membranous nephropathy, diagnosed by renal biopsy at University Hospital of South Manchester between 1984 and 1987, were studied retrospectively. The biopsy specimens (n = 26) were reviewed and analysed morphometrically to measure interstitial volume as a proportion of the total volume of renal cortex, and numbers of interstitial myofibroblasts (cells positive for alpha-smooth muscle actin within the interstitium). Clinical data, with a follow up of seven to eight years, was available for 24 patients, and renal outcome was correlated with pathological changes in the initial diagnostic biopsy specimen. RESULTS: The number of myofibroblasts and interstitial volume were inversely correlated with creatinine clearance at the initial biopsy, and at the end of follow up. Percentage sclerosed glomeruli or stage of glomerular disease, assessed by electron microscopy, did not correlate with renal function at initial biopsy or during follow up. The number of myofibroblasts, but not interstitial volume, correlated with severity of proteinuria at initial biopsy. Of 15 biopsy specimens showing no or mild interstitial fibrosis, four showed a notable increase in the number of interstitial myofibroblasts. All of these patients developed chronic renal failure, compared with three of 11 patients whose specimens showed no or a mild increase in myofibroblast numbers. CONCLUSIONS: Interstitial myofibroblasts play a role in the development of interstitial fibrosis and progressive renal failure in membranous nephropathy. Increased numbers of myofibroblasts in biopsy specimens showing only mild fibrosis may predict subsequent chronic renal failure.     

The health-related quality of life of people with peripheral arterial disease in the community: the Edinburgh Artery Study.

BACKGROUND: Previous studies investigating the health-related quality of life of those with peripheral arterial disease have focused on patients recruited from hospital clinics. The health-related quality of life of people with peripheral arterial disease in the general population is unknown. AIMS: We aimed to determine the health-related quality of life of people with intermittent claudication and asymptomatic peripheral arterial disease in the general population and to compare it with those with angina and those with no peripheral arterial disease or angina.Design of study: Analysis of cross-sectional data from the 12-year follow-up of a population-based cohort. SETTING: Edinburgh, Scotland. METHOD: Data from the Edinburgh Artery Study cohort's 12-year follow-up was analysed. Participants' peripheral arterial disease status was measured using the World Health Organisation intermittent claudication questionnaire and the ankle brachial pressure index. Self-assessed health-related quality of life data was collected using the SF-36 generic questionnaire. Health-related quality of life scores were calculated and their associations with peripheral arterial disease status groups were tested. RESULTS: Subjects with intermittent claudication had significantly worse median health-related quality of life scores than patients without claudication in all domains except social functioning and mental health. Patients with claudication had a significantly lower physical component summary score than those without claudication (P 相似文献   

Personality predictors of bulimic behavior and attitudes in males.

This study was an investigation of personality factors associated with bulimic behaviors and attitudes in males. Various measures that have been noted as predictors of female bulimia were tested on 96 college students. Chronic dietary restraint and interoceptive awareness were the strongest predictors of more maladaptive eating patterns. The results suggest that maladaptive eating patterns in males and females may share a common set of features.     

Personality and background predictors of a young wife's desired family size

A questionnaire that included 19 personality, socioeconomic, and general background variables was administered to 160 childless Caucasian, Protestant wives of college students to dicover variables that offered promise as predictors of desired family size. Of the sample, 66% wanted two children, and 14% wanted three children. Four variables-feelings of alienation, father's social class level, level of overt anxiety, and childhood family size-had a combined multiple correlation of 0.39 with desired family size in a stepwise regression analysis and accounted for almost 15% of the desired family size variance. Results suggest that although desired family size remains difficult to predict, personality factors may be as significant as socioeconomic factors in its prediction.     

Personality and symptom sensitivity predictors of alprazolam withdrawal in panic disorder

BACKGROUND: Discontinuation of benzodiazepine (BZ) treatment results in a well-characterized withdrawal syndrome in 40-50% of anxious patients. While numerous studies have established the role of BZ dose, treatment duration, half-life, potency, rate of withdrawal and severity of underling anxiety disorder in predicting severity of withdrawal symptoms, fewer studies have examined the role of psychological and personality factors. METHOD: In 123 panic disorder patients undergoing gradual tapered discontinuation of alprazolam in conjunction with pre-treatment with carbamazepine or placebo, the relationship between measures of 'symptom sensitivity' and 'harm avoidance', and severity of withdrawal symptoms measured as peak severity of symptoms, time before taper needed to be slowed due to symptoms, and ability to complete taper, was examined. RESULTS: After controlling for the less substantial effects of dose, treatment duration, pre-taper anxiety and panic attack frequency, measures of symptom sensitivity and harm avoidance accounted for an additional 3-6% of withdrawal variance. CONCLUSIONS: These results show an effect of symptom sensitivity and harm avoidance on BZ withdrawal symptoms, comparable to prior findings linking dependent personality characteristics to withdrawal severity. Failure to show the expected effect on ability to complete taper may be due to either the more symptomatic nature of the patients in this study.     

Contribution of neovascularization and intraplaque haemorrhage to atherosclerotic plaque progression and instability

Atherosclerosis is a continuous pathological process that starts early in life and progresses frequently to unstable plaques. Plaque rupture leads to deleterious consequences such as acute coronary syndrome, stroke and atherothrombosis. The vulnerable lesion has several structural and functional hallmarks that distinguish it from the stable plaque. The unstable plaque has large necrotic core (over 40% plaque volume) composed of cholesterol crystals, cholesterol esters, oxidized lipids, fibrin, erythrocytes and their remnants (haeme, iron, haemoglobin), and dying macrophages. The fibrous cap is thin, depleted of smooth muscle cells and collagen, and is infiltrated with proinflammatory cells. In unstable lesion, formation of neomicrovessels is increased. These neovessels have weak integrity and leak thereby leading to recurrent haemorrhages. Haemorrhages deliver erythrocytes to the necrotic core where they degrade promoting inflammation and oxidative stress. Inflammatory cells mostly presented by monocytes/macrophages, neutrophils and mast cells extravagate from bleeding neovessels and infiltrate adventitia where they support chronic inflammation. Plaque destabilization is an evolutionary process that could start at early atherosclerotic stages and whose progression is influenced by many factors including neovascularization, intraplaque haemorrhages, formation of cholesterol crystals, inflammation, oxidative stress and intraplaque protease activity.     

Proteomic analysis of differential protein expression in human atherosclerotic plaque progression

In this study, differential protein expression was assessed during human atherosclerotic plaque progression. A multifaceted approach was used in which differential protein expression was studied by two-dimensional (2D) gel electrophoresis and validated in individual patients using western blotting and immunohistochemistry. 2D profiles of whole-mount advanced stable lesions were compared to those of plaques containing a thrombus. Mass spectrometry analysis identified vinexin-beta and alpha1-antitrypsin (AAT) in the same spot that was differentially expressed in plaques with a thrombus. Immunohistochemistry and western blotting showed limited expression of both vinexin-beta and AAT in early lesions, whereas high expression of both proteins was found in advanced lesions. Differential expression of vinexin-beta in lesions with a thrombus compared to stable plaques could not be confirmed, indicating the importance of validation of proteomic analysis. For AAT, western blotting of 2D gels revealed expression of six isoforms in advanced plaques, one of which was confirmed to be solely expressed in thrombus-containing plaques. In conclusion, vinexin-beta is expressed in advanced human atherosclerotic plaques, but differential expression of this protein in lesions with a thrombus versus stable plaques could not be confirmed. However, this analysis revealed expression of six isoforms of AAT in advanced plaques, one of which was uniquely expressed in thrombus-containing plaques.     

Elimination of Ox-LDL through the liver inhibits advanced atherosclerotic plaque progression

Aim: In the late stage of atherosclerosis, the endothelial barrier of plaque is destroyed. The rapid deposition of oxidized lipids in the circulation leads to migration of numerous smooth muscle cells and macrophages, as well as foaming necrosis. The plaque progresses rapidly, and vulnerable plaques can easily induce adverse cardiovascular events. Here, we take the principle of gene editing to transfer the liver to express the LOX-1 receptor which is more sensitive to Ox-LDL by using AAV8 containing a liver-specific promoter. In this way, we want to explore whether the progress of advanced atherosclerosis and the stability of advanced plaque can be improved when the liver continues to clear Ox-LDL from the circulation.Methods and Results: In order to explore the effect of the physiological and continuous elimination of Ox-LDL through the liver on advanced atherosclerosis, we chose ApoE^-/- mice in high-fat diet for 20 weeks. After 16 weeks of high-fat diet, the baseline group was sacrificed and the specimens were collected. The virus group and the control group were injected with the same amount of virus dilution and normal saline through the tail vein, and continued to feed until 20 weeks of high-fat diet, and then sacrificed to collect specimens. The results showed that LOX-1 was ectopically and functionally expressed in the liver as an Ox-LDL receptor, reducing the content of it in circulation. Compared with the control group, the degree of plaque progression in the virus group was significantly reduced, similar to the baseline group, the plaque necrosis core decreased, and the collagen fiber content increased. In addition, there are more contractile smooth muscle cells in the plaques of the virus group instead of synthetic ones, and the content of macrophages was also reduced. These data suggested that the virus group mice have greatly increased advanced plaque stability compared with the control group mice.Conclusions: Due to the destruction of endothelial barrier in advanced plaques, rapid deposition of Ox-LDL can result in fast plaque progression, increased necrotic cores, and decreased stability. Our research shows that the use of AAV8 through gene editing allows the liver to express LOX-1 receptors that are more sensitive to Ox-LDL, so that it can continue to bind Ox-LDL in the circulation and exploit the liver''s strong lipid metabolism ability to physiologically clear Ox-LDL, which can inhibit the rapid progress of advanced plaque and increase the stability of plaque.     

Community social and place predictors of sense of community: A multilevel and longitudinal analysis

Sense of community (SOC) is empirically “unpacked” as a multilevel construct with place and social elements. SOC has been studied primarily at the individual level despite researchers acknowledging its effects at the community level. Little attention has been given to the roles of place and place attitudes in SOC. We argue that place and social are inextricably bound, and studying the impact of the social alone on community‐oriented constructs like SOC constrains our ability to adequately understand such multilevel, multifaceted phenomena. The present, cross‐sectional and longitudinal analyses demonstrate that SOC is intimately related to social capital (neighboring, citizen participation, collective efficacy, informal social control), communitarianism, place attachment, community confidence, and community satisfaction. Implications for community and environmental psychology theory are discussed. © 2007 Wiley Periodicals, Inc. J Comm Psychol 35: 563–581, 2007.     

Grade I Reye's syndrome--outcome and predictors of progression to deeper coma grades

We studied 83 biopsy-proved cases of Grade I Reye's syndrome to determine the outcome, possible clinical or laboratory predictors of progression to deeper coma grades, and hepatic ultrastructural findings. Seventy-eight patients had no change in coma grade during hospitalization, whereas five (6 per cent) had progression to deeper coma grades. All the patients survived without sequelae except one who sustained severe brain damage. The mean (+/- S.E.) level of serum ammonia on admission was significantly higher (P = 0.005) in patients whose disease progressed to deeper neurologic grades (291 +/- 42 micrograms per deciliter) than in those whose disease did not so progress (53 +/- 5 micrograms per deciliter), and the corrected prothrombin time was significantly more prolonged (P = 0.005) in patients with progressing coma (3.9 +/- 0.5 seconds) than in those whose coma grade did not change (1.6 +/- 0.2 seconds). The combination of a prothrombin time 3 seconds or longer than that of the control and a serum level of ammonia on admission of 100 micrograms per deciliter or more correctly predicted progression in 71.5 per cent of the cases (sensitivity, 100 per cent; specificity, 97.6 per cent). Our findings suggest that the prognosis is excellent for survival without sequelae in Grade I Reye's syndrome (98.8 per cent) when management includes hospital surveillance and intravenous glucose and electrolyte infusion.     

Depressive symptoms, social isolation, and progression of coronary artery atherosclerosis: the Stockholm Female Coronary Angiography Study

BACKGROUND: Although both depressive symptoms and social isolation in relation to coronary heart disease have been studied previously, few have examined their joint effects on coronary atherosclerosis progression in women. METHOD: Among the women enrolled in the Stockholm Female Coronary Angiography Study, Sweden, between 1991 and 1994, 102 were evaluated for coronary atherosclerosis progression using a computer-assisted standardized assessment, repeated quantitative coronary angiographic documentation, of the mean luminal diameter change over 3 years in 10 predefined coronary segments. Depressive symptoms and social isolation were assessed by standard questionnaires. RESULTS: Multivariable controlled mixed model ANOVAs revealed that women who were both depressed and socially isolated had the greatest disease progression: their absolute mean luminal diameter decreased by 0.18 mm [95% confidence interval (CI) = 0.11-0.24] and their percent narrowing was 5.5% (95% CI = 3.6-7.4), whereas in women who lacked both psychological risk factors, the mean luminal diameter decrease was 0.04 mm and their percent narrowing was 0.9%. These associations were independent of the baseline luminal diameter and standard risk factors, including age, smoking history, hypertension, and high-density lipoproteins. CONCLUSIONS: In women with coronary disease, depressive symptoms and social isolation in combination accelerated disease progression, suggesting a direct psychosocial effect on the atherosclerotic process. These findings provide an additional opportunity for therapeutic and preventive efforts against progression of coronary disease in women.     

青少年现实人格、理想人格与客观人格的比较研究

目的:考察青少年现实人格与理想人格和家长他评的客观人格之间的差异.方法:采用中国青少年人格量表(QZPS-Q)对509名中学生及其家长进行了调查.结果:青少年自评的现实人格与家长他评的客观人格在才干、善良、处世态度、情绪性和行事风格等5个大维度上存在显著差异;青少年的现实人格与理想人格除了在行事风格维度外.在外向性、才干、善良、人际关系、处世态度和情绪性等6个维度上都存在显著差异,19个小因子中有17个小因子存在显著差异.结论:青少年认为自己的人格发展现状与其理想状态之间存在一定的差异.