Correlation between depression, anxiety, and polymorphonuclear cells' resilience in ulcerative colitis: the mediating role of heat shock protein 70.

BACKGROUND: To investigate whether anxiety and depression levels are associated with Heat Shock Protein 70 (HSP70) induction in the colon of patients with ulcerative colitis (UC). METHODS: The design was cross-sectional. Clinical activity was assessed by the Rachmilewitz Index (CAI). Three psychometric questionnaires were used: Zung Depression Rating Scale (ZDRS), Spielberg State-Trait Anxiety Inventory (STAI), Hospital Anxiety and Depression Scale (HADS). Colon biopsies were obtained from each affected anatomical site. Severity of inflammation was assessed by eosin/hematoxylin. Constitutive (HSP70c) and inducible (HSP70i) HSP70 expression were immunohistochemically studied. RESULTS: 29 UC patients were enrolled (69% men). Mean age was 46.5 years (SD: 19.5). Inflammation severity was moderate in 17 patients, severe in 6, and mild in 6. The mean number of years since diagnosis was 7.9 (SD: 6.5). The mean CAI was 6.4 (SD: 3.1). In active UC, there was downregulation of HSP70c in inflamed epithelium, without significant HSP70 induction. In 22/29 cases of active cryptitis, polymorphonuclear cells (PMN) clearly expressed HSP70i, with weak, focal positivity in the other 7 cases. Except for the hospital anxiety scale, scores in all psychometric tools were higher in patients with strong HSP70i immunoreactivity in the PMN. Logistic regression showed a strong positive relationship between HSP70i immunoreactivity in the PMN cells and scores in the trait anxiety, ZDRS, and hospital depression scales, (Odds ratios 1.3, 1.3, and 1.5; P = 0.018, 0.023, and 0.038; Wald test, 5.6, 5.2, and 4.3 respectively) and a weaker but significant positive correlation with the CAI (Odds ratio 1.654; P = 0.049; Wald test 3.858). CONCLUSION: HSP70 is induced in PMN cells of UC patients and its induction correlates with depression and anxiety levels.

Imaging and Cytopathological Criteria Indicating Malignancy in Mucin-Producing Pancreatic Neoplasms: A Series of 68 Histopathologically Confirmed Cases.

OBJECTIVES: This study aims to evaluate the performance of clinical, imaging, and cytopathological criteria in the identification of high-grade dysplasia/carcinoma (HGD/Ca) in pancreatic mucin-producing cystic neoplasms. METHODS: Sixty-eight consecutive, histopathologically confirmed mucin-producing cystic neoplasms, evaluated by endoscopic ultrasound-guided fine-needle aspiration, were enrolled; specifically, 39 branch duct intraductal papillary mucinous neoplasms (BD-IPMNs), 21 main duct IPMNs, and 8 mucinous cystic neoplasms. The associations between HGD/Ca in histopathology and findings of endoscopic ultrasound and cytology, demographic, lifestyle, and clinical parameters were evaluated, separately in IPMNs and mucinous cystic neoplasms. RESULTS: Age 65 years or more was associated with HGD/Ca in IPMNs. In BD-IPMNs, cyst diameter 3 cm or greater (sensitivity, 68.8%; specificity, 65.2%), a mural nodule (sensitivity, 56.3%; specificity, 78.3%), main pancreatic duct diameter 5 to 9 mm (sensitivity, 50.0%; specificity, 87.0%), and suspicious cytology (sensitivity, 81.3%; specificity, 100%) signaled the presence of HGD/Ca. Similarly, in main duct IPMNs, suspicious cytology predicted HGD/Ca with high sensitivity (88.9%) and excellent specificity (100%). Regarding cytopathological criteria, in BD-IPMNs, HGD/Ca was associated with a high nuclear/cytoplasmic ratio, background necrosis, presence of papillary structures, hypochromatic nuclei, hyperchromatic nuclei, and major nuclear membrane irregularities (thickening and/or indentations). CONCLUSIONS: Clinical, imaging, and cytopathological criteria are useful in the identification of HGD/Ca in IPMNs.

Is there any potential link among caspase-8, p-p38 MAPK and bcl-2 in clear cell renal cell carcinomas? A comparative immunohistochemical analysis with clinical connotations.

BACKGROUND: Clear cell renal cell carcinomas (ccRCCs) constitute the most common renal carcinomas, characterized by a relatively aggressive clinical course. Thus, scientific research is targeting towards the identification of immunohistochemical and molecular markers that could be useful regarding diagnosis, appropriate therapy and prediction of prognosis. In the present study we assessed and correlated the expression of caspase-8, phosphorylated p38 mitogen-activated protein kinase (p-p38) and bcl-2 protein with histopathological features and clinical outcome of 27 patients with ccRCCs. METHOD: Immunohistochemistry in formalin-fixed and paraffin-embedded tissue sections was performed. The associations among various features were assessed utilizing statistical analysis. RESULTS: We found that increased expression of cytoplasmic caspase-8 and bcl-2 protein was strongly associated with low Fuhrman's grade of carcinomas (p = 0.019 and p = 0.041, respectively). On the other hand, increased p-p38 expression was significantly related to high Fuhrman's grade (p = 0.006). Moreover, high bcl-2 expression was correlated with low pathological stage of ccRCCs (p = 0.026). Increased expression of cytoplasmic caspase-8 as well as low-grade tumors (grade 1 and 2) implied a greater probability of patients' survival, in univariate statistical analysis (p = 0.037 and p = 0.019, respectively). Neither p-p38 nor bcl-2 expression was significantly linked to patients' survival. There were not emerged statistically significant associations among caspase-8, p-p38 kinase and bcl-2 protein. CONCLUSION: For the first time the prognostic impact of caspase-8 and p-p38 was studied in a series of ccRCCs, using immunohistochemistry in formalin-fixed and paraffin-embedded tissue sections. The suggestive relationship of caspase-8 with patients' clinical outcome, as well as the role of p-p38 within different grade categories, mandates further studies in larger cohorts of RCCs.

Statin treatment, carotid atherosclerotic plaque macrophage infiltration and circulating inflammatory markers.

BACKGROUND: Statin treatment is considered as first line therapy in patients with atherosclerotic disease. We evaluated the effect of pre-treatment with statins on carotid plaque infiltration by macrophages and on the circulating levels of proinflammatory cytokines in patients who underwent carotid endarterectomy. PATIENTS AND METHODS: One hundred fourteen patients were enrolled; 89 men and 25 women (mean age 67+/-8 years; range 42-83 years). Fifty three patients (46%) were on statin treatment at least 3 months before endarterectomy and 61 (54%) had never received statin treatment. The serum levels of high sensitivity C reactive protein (hsCRP), serum amyloid A (SAA), tumor necrosis factor alpha (TNFalpha), interleukin (IL)-1beta and IL-6 were evaluated preoperatively. The intensity of macrophage infiltration was evaluated by immunochemistry, using the monoclonal antibody CD 68. The area of the plaque covered by macrophages was measured as a proportion of the whole plaque area, using a custom designed image tool analysis. RESULTS: Patients on statins had lower serum total cholesterol levels (172+/-50 vs 194+/-35 mg/dl, p= 0.014), lower low density cholesterol levels (103+/-44 vs 123+/-31 mg/dl, p= 0.010) and lower serum hsCRP levels (1.8 [1.1-3.4] vs 3.4 [1.3-4.9] mg/l, p= 0.03), while SAA, TNFalpha, IL-6 and IL-1beta levels did not differ between the 2 groups. The infiltration of atherosclerotic plaque by macrophages was similar in statin treated patients and in controls (0.55+/-0.15% vs 0.49+/-0.19%, p= 0.21). CONCLUSION: Patients on statins have similar macrophage accumulation in their carotid atherosclerotic plaques compared with patients not on statins. Inflammatory markers were also similar in both groups except for hsCRP which was significantly lower in those taking statins.

Human immunodeficiency virus type 1 (HIV-1) accessory protein Vpr induces transcription of the HIV-1 and glucocorticoid-responsive promoters by binding directly to p300/CBP coactivators.

The accessory Vpr protein of human immunodeficiency virus type 1 (HIV-1) is a promiscuous activator of viral and cellular promoters. We report that Vpr enhances expression of the glucocorticoid receptor-induced mouse mammary tumor virus (MMTV) promoter and of the Tat-induced HIV-1 long terminal repeat promoter by directly binding to p300/CBP coactivators. In contrast, Vpr does not bind to p/CAF or to members of the p160 family of nuclear receptor coactivators, such as steroid receptor coactivator 1a and glucocorticoid receptor (GR)-interacting protein 1. Vpr forms a stable complex with p300 and also interacts with the ligand-bound glucocorticoid receptor in vivo. Mutation analysis showed that the C-terminal part of Vpr binds to the C-terminal portion of p300/CBP within amino acids 2045 to 2191. The same p300 region interacts with the p160 coactivators and with the adenovirus E1A protein. Accordingly, E1A competed for binding to p300 in vitro. Coexpression of E1A or of small fragments of p300 containing the Vpr binding site resulted in inhibition of Vpr's transcriptional effects. The C-terminal part of p300 containing the transactivating region is required for Vpr transactivation, whereas the histone acetyltransferase enzymatic region is dispensable. Vpr mutants that bind p300 but not the GR did not activate expression of the MMTV promoter and had dominant-negative effects. These results indicate that Vpr activates transcription by acting as an adapter linking transcription components and coactivators.