3p21, 5q21, 9p21 and 17p13.1 allelic deletions are potential markers of individuals with a high risk of developing adenocarcinoma in Barrett's epithelium without dysplasia

BACKGROUND/AIMS: A common genetic abnormality detected in Barrett's adenocarcinoma is LOH (loss of heterozygosity) at the sites of known or putative tumor suppressor genes. Thus, some deletions have also been determined in peritumoral Barrett's epithelium. These findings suggest that a tissue field of somatic genetic alterations precede the histopathological phenotypic changes of carcinoma. We investigated 32 cases of Barrett's esophagus with no evidence of dysplasia for LOH at 5q21 (APC), 3p21, 9p21 (p16) and 17p13.1 (p53) chromosomal regions. METHODOLOGY: Two groups were randomly selected and compared: 16 cases of Barrett's epithelium adjacent to adenocarcinoma and 16 cases of Barrett's epithelium with no evidence of malignant transformation in a 5-10 years follow-up period. In three adenocarcinomas cases several previous endoscopic biopsies of Barrett's esophagus were available. RESULTS: We determined frequent allelic losses in adenocarcinomas at p53 (54%), p16 (50%), 3p21 (40%) and 5q21 (33%). Identical LOH was present in most cases in the Barrett's epithelium adjacent to adenocarcinoma. LOH at these loci was unusual in Barrett's epithelium with no evidence of malignant transformation. However, in cases where sequential endoscopic biopsies were performed in advance to the adenocarcinoma diagnosis LOH was already present in the Barrett's epithelium. CONCLUSIONS: We suggest that LOH at these loci may be present before the onset of the malignant growth and LOH studies may supplement the histopathological evaluation of Barrett's epithelium. LOH at 3p21, 5q21, 9p21 and 17p13 chromosomal regions in cells of Barrett's epithelium without dysplasia may have a role as a potential marker for individuals with a high risk of developing adenocarcinoma.     

MT1-MMP collagenolytic activity is regulated through association with tetraspanin CD151 in primary endothelial cells

MT1-MMP plays a key role in endothelial function, as underscored by the angiogenic defects found in MT1-MMP deficient mice. We have studied the molecular interactions that underlie the functional regulation of MT1-MMP. At lateral endothelial cell junctions, MT1-MMP colocalizes with tetraspanin CD151 (Tspan 24) and its associated partner alpha3beta1 integrin. Biochemical and FRET analyses show that MT1-MMP, through its hemopexin domain, associates tightly with CD151, thus forming alpha3beta1 integrin/CD151/MT1-MMP ternary complexes. siRNA knockdown of HUVEC CD151 expression enhanced MT1-MMP-mediated activation of MMP2, and the same activation was seen in ex vivo lung endothelial cells isolated from CD151-deficient mice. However, analysis of collagen degradation in these experimental models revealed a diminished MT1-MMP enzymatic activity in confined areas around the cell periphery. CD151 knockdown affected both MT1-MMP subcellular localization and its inclusion into detergent-resistant membrane domains, and prevented biochemical association of the metalloproteinase with the integrin alpha3beta1. These data provide evidence for a novel regulatory role of tetraspanin microdomains on the collagenolytic activity of MT1-MMP and indicate that CD151 is a key regulator of MT1-MMP in endothelial homeostasis.     

Congenital apical left ventricular aneurysm

Congenital ventricular aneurysm is an infrequently occurring disease entity that usually affects the left ventricle. Its etiopathology is unknown. Clinical presentation is variable, and the condition is potentially lethal in some cases. Various imaging techniques are useful in diagnosis and enable the condition to be differentiated from congenital left diverticulum. We present a patient with a calcified congenital ventricular aneurysm who presented with supraventricular and ventricular arrhythmias and who was treated by surgical resection.     

Cutaneous reactions due to diltiazem and cross reactivity with other calcium channel blockers

BackgroundThe spectrum of cutaneous eruptions in association with calcium channel blockers is extensive, varying from exanthemas to severe adverse events. Reactions due to diltiazem occur more frequently than with other calcium channel blockers. Patch testing has been used as confirmatory testing in patients with extensive cutaneous reactions. Cross-reactivity among these drugs have not been established.MaterialWe present 3 patients: 1) A 54-year-old man developed a generalized eythema-multiformelike reaction followed by erythrodermia and exfoliative dermatitis 6-7 days after starting on diltiazem. The drug was stopped and remission was obtained with emollients and systemic corticosteroids and antihistamines within 12 days. 2) A 80-year-old woman experienced a pruritic exanthematous eruption on her trunk which evolved to generalized erythrodermia and superficial desquamation. This reaction appeared 10 days after taking diltiazem, and gradually improved in 10-12 days after discontinuation of this drug.3) A 79-year-old man presented with erythema and pruritus initially on the back, and then affecting thorax, extremities and face. He had started treatment with diltiazem three days before. Diltiazem was stopped and steroid and antihistamine therapy was given. His skin condition improved, but 3 days later the patient received verapamil with worsening of previous situation. He recovered within 7 days.Methods and resultsTwo to six months after the reaction, we carried out epicutaneous tests with calcium channel blockers from different groups. Diltiazem proved positive (at 48 and 96 hours) in the three patients; nifedipine was also positive in patient 2, and verapamil in patient 3. Controlled administration of verapamil was well tolerated in patient 2 after the reaction, and the patient 1 has taken nifedipine without problems.Conclusions1) We report 3 cases of cutaneous reactions due to diltiazem. 2) Epicutaneous tests have been useful for diagnosis. 3) As one of patients had positive patch tests to diltiazem and nifedipine, and other one with diltiazem and verapamil, more studies are needed to demonstrate cross reactions among calcium channel blockers.     

Increasing heterosexual transmission of HIV‐1 subtype C in Inland Central Western Brazil

The molecular epidemiology of HIV‐1 in Brazil is complex and heterogeneous because several subtypes co‐circulate with some important regional differences. This study evaluated HIV‐1 subtypes amongst pregnant women living in the metropolitan area and in the interior cities from central western Brazil. From June 2008 to June 2010, 86.9% of confirmed cases of HIV‐1 infection amongst pregnant women (172 out of 198 cases) were recruited in Goiania/Goias state. The HIV‐1 pol gene was sequenced after nested‐PCR. HIV‐1 subtypes were assigned by REGA, phylogenetic, and bootscan analyses. The median age of participants was 26 years (15–41 years range); 58.7% of participants were diagnosed during prenatal care and 51.7% of participants came from >50 interior cities within Goias state. Amongst the 131 HIV‐1 pol sequences, 64.9% were subtype B, 13.0% were BF1 recombinant, 11.4% were subtype C, 7.6% were subtype F1, and 2.3% were BC recombinant. According to the HIV‐1 diagnosis date (1994–2010), a significant increase in subtype C and a decrease of BF1 mosaics were observed over time. All subtype C patients lived in interior cities where the highest prevalence of subtype C outside southern Brazil was observed (18.4%). Phylogenetic analysis revealed multiple independent introductions of the Brazilian subtype C clade from the southern/southeastern regions of Brazil. The HIV‐1 epidemic in women from central western Brazil infected by the heterosexual route is characterized by an unexpectedly high prevalence of subtype C viruses highly related to those circulating in southern/southeastern Brazil. These findings highlight the importance of molecular surveillance programs outside large metropolitan regions in Brazil. J. Med. Virol. 85:396–404, 2013. © 2012 Wiley Periodicals, Inc.     

Revisiting the pathogenic mechanism of the GJB1 5’ UTR c.-103C > T mutation causing CMTX1

neurogenetics - The second most common form of Charcot-Marie-Tooth neuropathy (CMT), X-linked CMT type X1 (CMTX1), is caused by coding and non-coding mutations in the gap junction beta 1 (GJB1)...     

Fungal Diversity and Use in Decomposition of Environmental Pollutants

This article presents a critical review of the actual state of fungal activities on environmental pollutants, fungal diversity, the use of fungi in the degradation of chemical pollutants, enzyme degrading systems and perspectives on the use of fungi in bioremediation and unexplored research. The ability of fungi to transform or metabolize chemical pollutants has received much attention due to environmental persistence and chemical toxicity. The fungal degradation of xenobiotics is looked upon as an effective method of removing these pollutants from the environment by a process which is currently known as bioremediation. This review summarizes information from fundamental works that have revealed that a wide variety of fungi are capable of degrading an equally wide range of toxical chemical. The capacity of non-ligninolytic and ligninolytic fungi in the bioremediation of polycyclic aromatic hydrocarbon (PAHs), benzene-toluene-ethylbenzene-xylene (BTEX), chlorophenols, polychlorinated biphenyl, munitions waste and pesticides have been discussed. Besides this, several extracellular enzymes are involved in the metabolism of xenobiotic compounds as well as other factors related to these processes.     

Cytomegalovirus prevention strategies in seropositive kidney transplant recipients: an insight into current clinical practice

There is notable heterogeneity in the implementation of cytomegalovirus (CMV) prevention practices among CMV‐seropositive (R+) kidney transplant (KT) recipients. In this prospective observational study, we included 387 CMV R+ KT recipients from 25 Spanish centers. Prevention strategies (antiviral prophylaxis or preemptive therapy) were applied according to institutional protocols at each site. The impact on the 12‐month incidence of CMV disease was assessed by Cox regression. Asymptomatic CMV infection, acute rejection, graft function, non‐CMV infection, graft loss, and all‐cause mortality were also analyzed (secondary outcomes). Models were adjusted for a propensity score (PS) analysis for receiving antiviral prophylaxis. Overall, 190 patients (49.1%) received preemptive therapy, 185 (47.8%) antiviral prophylaxis, and 12 (3.1%) no specific intervention. Twelve‐month cumulative incidences of CMV disease and asymptomatic infection were 3.6% and 39.3%, respectively. Patients on prophylaxis had lower incidence of CMV disease [PS‐adjusted HR (aHR): 0.10; 95% confidence interval (CI): 0.01–0.79] and asymptomatic infection (aHR: 0.46; 95% CI: 0.29–0.72) than those managed preemptively, with no significant differences according to the duration of prophylaxis. All cases of CMV disease in the prophylaxis group occurred after prophylaxis discontinuation. There were no differences in any of the secondary outcomes. In conclusion, antiviral prophylaxis was associated with a lower occurrence of CMV disease in CMV R+ KT recipients, although such benefit should be balanced with the risk of late‐onset disease.