Histomorphometric and immunohistochemical analysis of infectious agents, T-cell subpopulations and inflammatory adhesion molecules in placentas from HIV-seropositive pregnant women

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to compare histomorphometric changes and the results of immunohistochemical tests for VCAM, ICAM-1, CD4 and CD8 in normal placentas from HIV-seropositive pregnant women.</p> <p>Methods</p> <p>Samples of normal placentas were divided into 2 groups: healthy HIV-seronegative pregnant women (control group = C = 60) and HIV-seropositive women (experimental group = E = 57). Conventional histological sections were submitted to morphometric analysis and evaluated in terms of the immunohistochemical expression of ICAM-1, VCAM, CD4 and CD8.</p> <p>Results</p> <p>The villi in group E were smaller than those in group C. The median for the CD8+ T cell count was higher in group E than in group C (p = 0.03). Immunohistochemical expression of ICAM-1 was observed in 57% of the cases in group E, compared with 21% of those in group C (p = 0.001). There was no difference in VCAM expression or CD4+ cell counts between groups and no correlation between the data for antiretroviral therapy and morphometric or immunohistochemical data.</p> <p>Conclusions</p> <p>The morphometric data showed that placentas of HIV-seropositive pregnant women tend to have smaller villi than those of seronegative women. In addition, immunohistochemical testing for infectious agents helped to identify cases that were positive for microorganisms (6/112) that routine pathological examination had failed to detect. The anti-p24 antibody had a limited ability to detect HIV viral protein in this study (2/57). Correlation of immunohistochemical expression of CD8+ T cells and ICAM-1 with the presence of HIV in the placenta revealed that those expressions can act as biomarkers of inflammatory changes. There was no correlation between the data for antiretroviral therapy and morphometric or immunohistochemical data.</p

The chemopreventive polyphenol Curcumin prevents hematogenous breast cancer metastases in immunodeficient mice

Dissemination of metastatic cells probably occurs long before diagnosis of the primary tumor. Metastasis during early phases of carcinogenesis in high risk patients is therefore a potential prevention target. The plant polyphenol Curcumin has been proposed for dietary prevention of cancer. We therefore examined its effects on the human breast cancer cell line MDA-MB-231 in vitro and in a mouse metastasis model. Curcumin strongly induces apoptosis in MDA- MB- 231 cells in correlation with reduced activation of the survival pathway NF kappa B, as a consequence of diminished I kappa B and p65 phosphorylation. Curcumin also reduces the expression of major matrix metalloproteinases (MMPs) due to reduced NF kappa B activity and transcriptional downregulation of AP-1. NF kappa B/p65 silencing is sufficient to downregulate c-jun and MMP expression. Reduced NF kappa B/AP-1 activity and MMP expression lead to diminished invasion through a reconstituted basement membrane and to a significantly lower number of lung metastases in immunodeficient mice after intercardiac injection of 231 cells (p=0.0035). 68% of Curcumin treated but only 17% of untreated animals showed no or very few lung metastases, most likely as a consequence of down-regulation of NF kappa B/AP-1 dependent MMP expression and direct apoptotic effects on circulating tumor cells but not on established metastases. Dietary chemoprevention of metastases appears therefore feasible. Copyright (c) 2007 S. Karger AG, Basel

Imprint cytology of osteosarcoma of the jaw: a case report

Introduction. Osteosarcomas are highly malignant bone-forming neoplasms that account for about 20% of all sarcomas. In light of their aggressive behavior, early diagnosis is crucial for determining adequate treatment. Dental professionals may be the first to detect jaw osteosarcomas in their initial stages. The aim of this case report is to draw attention to the possibility of diagnosing this tumor based on clinical, radiographical and cytological characteristics before confirmation by histology. Case presentation. A 24-year-old Afro-Brazilian man presented with swelling and pain on the left side of the mandible in the region of the third molar (tooth 38). Radiography showed a poorly delimited intraosseous lesion with radiolucent and radiopaque areas. The cytological aspects were consistent with the diagnosis of osteosarcoma, which was confirmed by biopsy. Conclusion. Imprint cytology was found to be a reliable, rapid and easy complementary examination. An early diagnosis of osteosarcoma of the jaw is fundamental to the early determination of an adequate treatment. © 2009 Cabral et al; licensee BioMed Central Ltd

Familial breast cancer: characteristics and outcome of BRCA 1–2 positive and negative cases

BACKGROUND: The clinical and pathological characteristics and the clinical course of patients with breast cancer and BRCA 1–2 mutation are poorly known. METHODS: From 1997, patients with breast cancer and a family history of breast or ovarian cancer were offered BRCA testing. The clinical and pathological features of patients with known BRCA status were retrospectively assessed and comparisons were made between cancers arising in BRCA positive and BRCA wild type (WT) patients respectively. Type of treatment, pattern of relapse, event (local relapse, contralateral breast cancer, metastases) free and overall survival were also compared in the two groups. Out of the 210 patients tested, 125 had been treated and followed-up at our Institution and were evaluated in this study. RESULTS: BRCA positive patients tended to be more often premenopausal (79% vs 65%) and to have positive lymphnodes (63% vs 49%), poorly differentiated tumours (76% vs 40% – p = 0.002 at univariate analysis, not significant at multivariate analysis) and negative estrogen receptors (43% vs 29%). Treatment was not different in the two groups. In the 86 BRCA-WT patients, the first event was a local relapse in 3 (3%), metachronous contralateral breast cancer in 7 (8%) and distant metastases in 16 (19%). In the 39 BRCA positive patients, the corresponding figures were 3 (8%), 8 (21%) and 3 (8%). There was no difference in event free survival, with a median of 180 months in both groups of patients. At 20 years, projected survival was 85% for BRCA positive patients and 55% for BRCA-WT, but this difference was not statistically significant. CONCLUSION: Although BRCA positive patients have more frequently negative prognostic factors, their prognosis appears to be equal to or better than in patients with BRCA-WT

Kupffer Cells Hasten Resolution of Liver Immunopathology in Mouse Models of Viral Hepatitis

Kupffer cells (KCs) are widely considered important contributors to liver injury during viral hepatitis due to their pro-inflammatory activity. Herein we utilized hepatitis B virus (HBV)-replication competent transgenic mice and wild-type mice infected with a hepatotropic adenovirus to demonstrate that KCs do not directly induce hepatocellular injury nor do they affect the pathogenic potential of virus-specific CD8 T cells. Instead, KCs limit the severity of liver immunopathology. Mechanistically, our results are most compatible with the hypothesis that KCs contain liver immunopathology by removing apoptotic hepatocytes in a manner largely dependent on scavenger receptors. Apoptotic hepatocytes not readily removed by KCs become secondarily necrotic and release high-mobility group box 1 (HMGB-1) protein, promoting organ infiltration by inflammatory cells, particularly neutrophils. Overall, these results indicate that KCs resolve rather than worsen liver immunopathology

Transketolase-Like 1 Expression Is Modulated during Colorectal Cancer Progression and Metastasis Formation

Background Transketolase-like 1 (TKTL1) induces glucose degradation through anaerobic pathways, even in presence of oxygen, favoring the malignant aerobic glycolytic phenotype characteristic of tumor cells. As TKTL1 appears to be a valid biomarker for cancer prognosis, the aim of the current study was to correlate its expression with tumor stage, probability of tumor recurrence and survival, in a series of colorectal cancer patients. Methodolody/Principal Findings Tumor tissues from 63 patients diagnosed with colorectal cancer at different stages of progression were analyzed for TKTL1 by immunohistochemistry. Staining was quantified by computational image analysis, and correlations between enzyme expression, local growth, lymph-node involvement and metastasis were assessed. The highest values for TKTL1 expression were detected in the group of stage III tumors, which showed significant differences from the other groups (Kruskal-Wallis test, P = 0.000008). Deeper analyses of T, N and M classifications revealed a weak correlation between local tumor growth and enzyme expression (Mann-Whitney test, P = 0.029), a significant association of the enzyme expression with lymph-node involvement (Mann-Whitney test, P = 0.0014) and a significant decrease in TKTL1 expression associated with metastasis (Mann-Whitney test, P = 0.0004). Conclusions/Significance To our knowledge, few studies have explored the association between variations in TKTL1 expression in the primary tumor and metastasis formation. Here we report downregulation of enzyme expression when metastasis appears, and a correlation between enzyme expression and regional lymph-node involvement in colon cancer. This finding may improve our understanding of metastasis and lead to new and more efficient therapies against cancer

Environmental surveillance and in vitro activity of antimicrobial agents against Legionella pneumophila isolated from hospital water systems in Campania, South Italy: a 5-year study.

Abstract Background Legionellosis' treatment failures have been recently reported showing the possibility of resistance development to traditional therapy, especially in healthcare related disease cases. Environmental impact of antibiotic residues, especially in hospital waters, may act on the resistome of Legionella resulting in developing resistance mechanisms. Objectives In this study we investigate the antibiotic susceptibility of environmental Legionella pneumophila (Lpn) strains isolated from hospital water systems in Campania, a region located in Southwest Italy. Methods 5321 hospital water samples were investigated for the presence of Lpn. Among positive samples, antibiotic susceptibility was tested for a random subset of 125 Lpn strains (25 Lpn isolates from each of the following serogroups: 1, 3, 5, 6, 8). Susceptibility testing was performed, using the E-test on buffered charcoal yeast extract agar supplemented with α-ketoglutarate, for 10 antimicrobial drugs: azithromycin, cefotaxime, clarithromycin, doxycycline, erythromycin, rifampicin, tigecycline, ciprofloxacin, levofloxacin and moxifloxacin. Non parametric tests were used to determine and assess the significant differences in susceptibility to the different antimicrobics between the serogroups. Results Among the isolated strains, none showed resistance to the antibiotics tested. Rifampicin was the most active antibiotic against overall Legionella strains, followed by levofloxacin. Between the macrolides the clarithromycin was overall the most active drug, instead the azithromycin was the less active. Analyzing the different serogroups a significant difference was found between serogroup 1 and non-1 serogroup isolates for doxycycline and tigecycline. Conclusions Antibiotic susceptibility of environmental isolates of Legionella spp. might be useful for the early detection of resistance to antibiotics that directly impacts on mortality and length of hospital stay

Pregabalin, celecoxib, and their combination for treatment of chronic low-back pain

Background - The efficacy and safety of the association of celecoxib [a selective cyclooxygenase-2 (COX-2) inhibitor] and pregabalin (commonly used to control neuropathic pain), compared with monotherapy of each, were evaluated for the treatment of chronic low-back pain, a condition known to be due to neuropathic as well as nociceptive pain mechanisms. Materials and methods - In this prospective randomized trial, 36 patients received three consecutive 4-week treatment regimes, randomly assigned: celecoxib plus placebo, pregabalin plus placebo, and celecoxib plus pregabalin. All patients were assessed by using a visual analogue scale (VAS, 0\u2013100 mm) and the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain scale by an investigator blinded to the administered pharmacological treatment. Results - Celecoxib and pregabalin were effective in reducing low-back pain when patients were pooled according to LANSS score. The association of celecoxib and pregabalin was more effective than either monotherapy in a mixed population of patients with chronic low-back pain and when data were pooled according to LANSS score. Adverse effects of drug association and monotherapies were similar, with reduced drug consumption in the combined therapy. Conclusions - Combination of celecoxib and pregabalin is more effective than monotherapy for chronic low-back pain, with similar adverse effects

Structural basis of nucleosome assembly by the Abo1 AAA+ ATPase histone chaperone

The fundamental unit of chromatin, the nucleosome, is an intricate structure that requires histone chaperones for assembly. ATAD2 AAA+???ATPases are a family of histone chaperones that regulate nucleosome density and chromatin dynamics. Here, we demonstrate that the fission yeast ATAD2 homolog, Abo1, deposits histone H3???H4 onto DNA in an ATP-hydrolysis-dependent manner by in vitro reconstitution and single-tethered DNA curtain assays. We present cryo-EM structures of an ATAD2 family ATPase to atomic resolution in three different nucleotide states, revealing unique structural features required for histone loading on DNA, and directly visualize the transitions of Abo1 from an asymmetric spiral (ATP-state) to a symmetric ring (ADP- and apo-states) using high-speed atomic force microscopy (HS-AFM). Furthermore, we find that the acidic pore of ATP-Abo1 binds a peptide substrate which is suggestive of a histone tail. Based on these results, we propose a model whereby Abo1 facilitates H3???H4 loading by utilizing ATP