More on: tissue factor in neutrophils.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to A Carbone.
Explore the source record for details and available documents.
BACKGROUND: The unusual occurrence of a metastatic Kaposi's sarcoma (KS) in a lymph node affected by Hodgkin lymphoma (HL) was originally reported when knowledge of the specific virological features of these tumours was lacking. AIM: To re-evaluate this case by assessing whether the simultaneous presence of the two tumours was linked with common aetiopathogenetic factors. METHODS: The presence of EBV was investigated by in situ hybridisation, whereas KS associated herpesvirus (KSHV)/human herpesvirus 8 (HHV-8) was detected by immunohistochemistry. Both viruses were analysed in the case reported, in 30 lymph nodes from patients with classic HL, and in 22 skin biopsies from patients with KS. RESULTS: Consistent with the findings in the HL and KS cases analysed, in the case showing features of both HL and KS in the same lymph node, EBV was detectable only in Reed-Sternberg (RS) cells, but not in KS spindle cells, whereas KSHV/HHV-8 was detectable only in KS spindle cells, and not in RS cells. CONCLUSION: It is probable that the development of KS and HL was related to two independent aetiological cofactors-KSHV/HHV-8 and EBV, respectively-and that the occurrence of the two malignancies in the same patient was merely fortuitous.
BACKGROUND: Kaposi sarcoma associated herpesvirus (KSHV)/human herpesvirus 8 (HHV-8) associated lymphomas, which often develop in human immunodeficiency virus (HIV) infected patients with advanced AIDS, present predominantly as primary effusion lymphoma (PEL) or, less frequently, as "solid" extracavitary based lymphomas, associated with serous effusions. These last lymphomas, also called "solid PEL", have been reported before the development of an effusion lymphoma and after resolution of PEL. Interestingly, KSHV/HHV-8 associated lymphomas that present as solid or extracavitary based lesions in HIV seropositive patients without serous effusions have been reported recently. METHODS/RESULTS: This paper provides evidence for the existence of a previously undescribed KSHV/HHV-8 associated lymphoma in HIV seronegative patients without serous effusions. These lymphomas exhibit a predilection for the lymph nodes and display anaplastic large cell morphology. These tumours were completely devoid of common cell type specific antigens, including epithelial and melanocytic cell markers. B and T cell associated antigens and other commonly used lymphoid markers were absent or weakly demonstrable in a fraction of the tumour cells. Conversely, immunohistochemical studies showed strong immunostaining with plasma cell reactive antibodies. CONCLUSIONS: Analysis of viral infection and immunohistological studies are of primary importance to define this lymph node based KSHV/HHV-8 associated lymphoma with anaplastic large cell morphology and plasmablastic immunophenotype occurring in HIV seronegative patients without serous effusions.
AIM: It has been previously suggested that t(14;18) translocation of bcl-2 to the immuno-globulin heavy chain (IgH) locus may contribute to pathogenesis of lymphoproliferative disorders related to hepatitis C virus (HCV) infection, including type II mixed cryoglobulinemia (MC). METHODS: In this study, the presence or absence of t(14;18) translocation was determined in tumor biopsy specimens and peripheral blood mononuclear cells (PBMCs) for 48 NHL patients with chronic HCV infection. RESULTS: In tumor biopsy specimens from 32 HCV-positive NHL patients, bcl-2/IgH translocation was detected in 1 of 13 patients with MC syndrome (7.7%) and 3 of 19 patients without MC syndrome (15.8%). In PBMCs from 23 HCV-positive NHL patients, this translocation was observed in 3 of 6 patients with MC syndrome (50%) and 4 of 17 patients without MC syndrome (23.5%). Interestingly, bcl-2/IgH translocation was found in 2 extranodal marginal zone B-cell lymphoma tissues from HCV-infected patients. CONCLUSIONS: However, additional studies are required to better clarify the relationship between this translocation and extranodal marginal zone B-cell lymphoma development. Although the frequency of bcl-2/IgH translocation in PBMCs from patients with chronic HCV infection is higher than that of other NHL patients, this increased translocation rate remains to be elucidated.
Pancreatic ductal carcinoma still is an aggressive disease with a fatal prognosis due to late diagnosis and resistance to pharmacological and surgical treatments. Molecular investigations of pancreatic cancer are complicated by the restricted accessibility of the organ for biopsies. However, recent studies have indicated that pancreatic cancer is a multi-stage process resulting from the accumulation of genetic changes in the somatic DNA of normal cells. These molecular alterations, including overexpression of receptor-ligand systems, oncogene activation and loss of tumour suppressor genes, leads to a profound disturbance in cell cycle regulation and continuous growth. The molecular findings are now integrated in a pancreatic tumour progression model, with genetically and morphological defined precursor lesions. However, it remains unclear whether the initial target cells of this cancer develop from ductal or acinar cells. This review will present recent emerging questions on the biology of pancreatic cancer with particular emphasis on the cell origin and tumour microenvironment.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
New and simple numerical criteria based on a codon adaptation index are applied to the complete genomic sequences of 80 Eubacteria and 16 Archaea, to infer weak and strong genome tendencies toward content bias, translational bias, and strand bias. These criteria can be applied to all microbial genomes, even those for which little biological information is known, and a codon bias signature, that is the collection of strong biases displayed by a genome, can be automatically derived. A codon bias space, where genomes are identified by their preferred codons, is proposed as a novel formal framework to interpret genomic relationships. Principal component analysis confirms that although GC content has a dominant effect on codon bias space, thermophilic and mesophilic species can be identified and separated by codon preferences. Two more examples concerning lifestyle are studied with linear discriminant analysis: suitable separating functions characterized by sets of preferred codons are provided to discriminate: translationally biased (hyper)thermophiles from mesophiles, and organisms with different respiratory characteristics, aerobic, anaerobic, facultative aerobic and facultative anaerobic. These results suggest that codon bias space might reflect the geometry of a prokaryotic "physiology space." Evolutionary perspectives are noted, numerical criteria and distances among organisms are validated on known cases, and various results and predictions are discussed both on methodological and biological grounds.
We analyze the stochastic function C(n)(i) identical with y(i)-y(n)(i), where y(i) is a long-range correlated time series of length N(max) and y(n)(i) identical with (1/n) Sigma(n-1)(k=0)y(i-k) is the moving average with window n. We argue that C(n)(i) generates a stationary sequence of self-affine clusters C with length l, lifetime tau, and area s. The length and the area are related to the lifetime by the relationships l approximately tau(psi(l)) and s approximately tau(psi(s)), where psi(l)=1 and psi(s)=1+H. We also find that l, tau, and s are power law distributed with exponents depending on H: P(l) approximately l(-alpha), P(tau) approximately tau(-beta), and P(s) approximately s(-gamma), with alpha=beta=2-H and gamma=2/(1+H). These predictions are tested by extensive simulations on series generated by the midpoint displacement algorithm of assigned Hurst exponent H (ranging from 0.05 to 0.95) of length up to N(max)=2(21) and n up to 2(13).
Several 1,3-thiazolidin-4-ones bearing a 2,6-dihalophenyl group at C-2 and a substituted pyrimidin-2-yl ring at the N-3 were synthesised and evaluated as anti-HIV agents. The results of the in vitro tests showed that some of them were highly effective inhibitors of human immunodeficiency virus type-1 (HIV-1) replication at 10-40 nM concentrations with minimal cytotoxicity. Structure-activity relationship studies revealed that the nature of the substituents at the 2 and 3 positions of the thiazolidinone nucleus had a significant impact on the in vitro anti-HIV activity of this class of potent antiretroviral agents. The compounds had significantly reduced activity against the characteristic NNRTI-resistant virus mutants (bearing the K103N and Y181C RT mutations), thereby acting as non-nucleoside HIV-1 reverse transcriptase (RT) inhibitors (NNRTIs).
BACKGROUND: Benign melanocytic skin lesions may be difficult to differentiate from melanoma both clinically and dermoscopically. One of the most confounding dermoscopic features, commonly seen in melanoma but in our experience also in melanocytic naevi, is represented by the so-called blue-white structures (BWS). OBJECTIVES: To evaluate diagnostic significance and histopathological correlates of BWS seen by dermoscopy in a series of clinically equivocal melanocytic skin lesions that were excised. METHODS: Patients were recruited from six specialized pigmented lesion clinics in Austria, Italy and Spain over a period of 9 months. All consecutive patients showing one or more melanocytic lesions with BWS, but not classified as melanoma dermoscopically, were included. Each lesion was photographed clinically and dermoscopically. All images were reviewed by one of us and the degree, type and location of BWS evaluated for each lesion. A panel of four experienced dermatopathologists independently reviewed all specimens for diagnosis and one of them evaluated presence and degree of melanosis and/or fibrosis. The main outcome measures were the percentage and histopathological correlates of lesions with different degree, type and location of BWS. RESULTS: All included lesions with BWS (n = 158) showed partial or focal regression histopathologically. One hundred and thirty-five (85.4%) lesions were diagnosed as melanocytic naevi (complete histopathological interobserver agreement), whereas 23 (14.6%) were defined as equivocal because at least one of four pathologists diagnosed the given lesion as melanoma. Only one lesion was diagnosed as melanoma by all four pathologists. The majority of naevi exhibited blue areas (84.4%) with a central distribution (57%) and involving < 50% of the lesion surface (89.6%). By contrast, 78.3% of equivocal lesions revealed a combination of white and blue areas with an irregular distribution (60.9%) and involving > 50% of the lesion surface (47.8%). CONCLUSIONS: Using degree and type of BWS, an algorithm was constructed that can be applied for the management of lesions exhibiting dermoscopic features of regression.
Explore the source record for details and available documents.
OBJECTIVES: To evaluate the clinical and video-urodynamic outcome in women with by stress urinary incontinence (SUI) treated with a bone-anchored pubovaginal sling. PATIENTS AND METHODS: The study included 70 women with SUI (as evaluated by a clinical examination, a voiding questionnaire, a short pad-test and video-urodynamics) who had a bone-anchor sling procedure, with or without cystocele repair, from January 1999 to December 2001; they were re-evaluated after a long-term follow-up (mean 30 months). RESULTS: The long-term outcome showed a success rate of > 95%; the clinical and video-urodynamic findings showed good functional and anatomical results, and an improvement in voiding performance in most patients. There was a low incidence of complications during and after surgery (2.8%). CONCLUSIONS: This approach gives, in highly selected patients, a high success rate and low incidence of complications. The technique is easy to learn and the costs to the financing bodies and public healthcare are low, making it a candidate for an alternative procedure to the standard techniques for SUI.
Dissection of the vertebral artery represents a significant potential cause of strokes among young and middle-aged people. We present a case of dissection of the vertebral artery observed at the forensic autopsy of a professional basketball player who was suddenly taken ill during a practice game and died seven days after the event. A medico-legal autopsy was performed in order to establish an essential causal relationship between arterial dissection and basketball activity. No preceding trauma possibly contributing to the dissection was discovered. The histology of the arterial wall did not show specific alterations in the adventitia, the muscular layer, or the intima. In addition, the toxicological examination excluded any effects of drugs of abuse. We describe macroscopic and microscopic findings in the autopsy, and discuss possible mechanisms of the arterial rupture as well as the autopsy procedure in similar cases.
UNLABELLED: We propose a simple algorithm to detect dominating synonymous codon usage bias in genomes. The algorithm is based on a precise mathematical formulation of the problem that lead us to use the Codon Adaptation Index (CAI) as a 'universal' measure of codon bias. This measure has been previously employed in the specific context of translational bias. With the set of coding sequences as a sole source of biological information, the algorithm provides a reference set of genes which is highly representative of the bias. This set can be used to compute the CAI of genes of prokaryotic and eukaryotic organisms, including those whose functional annotation is not yet available. An important application concerns the detection of a reference set characterizing translational bias which is known to correlate to expression levels; in this case, the algorithm becomes a key tool to predict gene expression levels, to guide regulatory circuit reconstruction, and to compare species. The algorithm detects also leading-lagging strands bias, GC-content bias, GC3 bias, and horizontal gene transfer. The approach is validated on 12 slow-growing and fast-growing bacteria, Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster. AVAILABILITY: http://www.ihes.fr/~materials.
The aim of this study was to examine the relationship between history of cancer in first-degree relatives and ovarian cancer risk. Between 1992 and 1999, we conducted a case-control study in Italy on 1031 women with epithelial ovarian cancer and 2411 women admitted to hospital for acute non-neoplastic conditions. Odds ratios (OR) were estimated using unconditional logistic regression, adjusted for age and several potential confounders. Overall, 27 cases and nine controls reported a family history of ovarian cancer (OR = 7.0; 95% confidence interval (CI) 3.1-16). The OR was 23 (95% CI 2.6-212) below age 50 years, based on 10 cases and one control only. The risk of ovarian cancer was also increased in women with a family history of cancer of the stomach (OR = 1.5; 95% CI 1.0-2.1), intestine (OR = 1.7; 95% CI 1.2-2.4), lung (OR = 1.3; 95% CI 1.0-1.8), breast (OR = 2.3; 95% CI 1.7-3.1), lymphomas (OR = 2.3; 95% CI 1.0-5.1) and all sites (OR = 1.6; 95% CI 1.4-1.9). Our results confirm the higher ovarian cancer risk in women with a family history of ovarian and breast cancer, and suggest a few associations with other sites.
Explore the source record for details and available documents.
OBJECTIVE: To characterize the therapeutic variables correlated to outcome in 370 patients with primary CNS lymphoma. METHODS: Planned treatment was radiotherapy (RT) in 98 patients, chemotherapy (CHT) in 32, RT followed by CHT in 36, and CHT followed by RT in 197 patients. High-dose methotrexate (HD-MTX; 1 to 8 g/m2) was used in 169 patients and intrathecal CHT in 109. RESULTS: One hundred sixteen patients are alive (median follow-up 24 months), with a 2-year overall survival of 37%. Patients treated with CHT followed by RT had improved survival with respect to patients treated with RT alone. Patients receiving HD-MTX-based primary CHT survived longer than those treated with other drugs. HD-MTX associated with other cytostatics, in particular HD-cytarabine, produced better results than HD-MTX alone. No correlation between MTX dose and survival was found. In patients receiving HD-MTX, consolidation RT or intrathecal CHT did not improve survival. Age, performance status, lactate dehydrogenase serum level, CSF protein level, site of disease, and use of HD-MTX were all predictors of survival. CONCLUSIONS: Combination CHT-RT is superior to RT alone. Patients treated with primary CHT containing HD-MTX exhibited improved survival. In these patients, the addition of HD-cytarabine was associated with a better survival, whereas intrathecal CHT was not correlated to outcome. RT may be unnecessary in patients achieving complete remission after receiving HD-MTX-based primary CHT.