Blunted gamma delta T-lymphocyte response in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterised by an excessive inflammatory response to inhaled particles, mostly tobacco smoking. Although inflammation is present in all smokers, only a percentage of them develop COPD. T-lymphocytes are important effector and regulatory cells that participate actively in the inflammatory response of COPD. They comprise the T-cell receptor (TCR)-alpha beta (CD4+ and CD8+) and TCR-gamma delta T-lymphocytes. The latter represent a small percentage of the total T-cell population, but play a key role in tissue repair and mucosal homeostasis. To investigate TCR-alpha beta (CD4+ and CD8+) and TCR-gamma delta T-lymphocytes in COPD, the present authors determined, by flow cytometry, the distribution of both subpopulations in peripheral blood and bronchoalveolar lavage (BAL) samples obtained from patients with COPD, smokers with normal lung function and never-smokers. The present study found that: 1) the distribution of CD4+ and CD8+ lymphocytes in blood and BAL was similar in all three groups; 2) compared with nonsmokers, gamma delta T-lymphocytes were significantly increased in smokers with preserved lung function; and 3) this response was blunted in patients with COPD. These results highlight a novel, potentially relevant, pathogenic mechanism in chronic obstructive pulmonary disease.     

Epidermoid carcinoma of the urethra and glans penis: two independent tumors?

A 64 years-old man is treated in our hospital presenting a big tumor in glans penis. During the surgical act, another neoplasm is detected in the urethra. The microscopic study showed a concomintant epidermoid carcinoma of glans penis and urethra with non-affected tissue between both tumors.     

Prevention and Treatment of Postoperative Crohn’s Disease Recurrence: An Update for a New Decade

Poorly controlled Crohn’s disease (CD) often requires surgery for such complications as strictures, fistulas, and abscesses. The goal of postoperative treatment is to suppress or prevent inflammation and maintain mucosal healing. Probiotics, antibiotics, 5-aminosalicylates, immunomodulators, and antibodies to tumor necrosis factor are all used to prevent postoperative recurrence. In this article, recent studies are reviewed. Azathioprine/6-mercaptopurine are moderately effective at preventing and treating postoperative CD, whereas infliximab/adalimumab are highly effective and probiotics and 5-aminosalicylates minimally effective. We base the choice of postoperative medical therapy on the patient’s risk profile for postoperative recurrence. Whatever postoperative therapy is used, the mucosa should be assessed within 12 months to determine if the approach is effective. If active inflammation is found, then treatment should be intensified. By treating CD aggressively after a first surgery, future surgeries can be delayed or averted.     

Neolithic patrilineal signals indicate that the Armenian plateau was repopulated by agriculturalists

Armenia, situated between the Black and Caspian Seas, lies at the junction of Turkey, Iran, Georgia, Azerbaijan and former Mesopotamia. This geographic position made it a potential contact zone between Eastern and Western civilizations. In this investigation, we assess Y-chromosomal diversity in four geographically distinct populations that represent the extent of historical Armenia. We find a striking prominence of haplogroups previously implicated with the Agricultural Revolution in the Near East, including the J2a-M410-, R1b1b1(*)-L23-, G2a-P15- and J1-M267-derived lineages. Given that the Last Glacial Maximum event in the Armenian plateau occured a few millennia before the Neolithic era, we envision a scenario in which its repopulation was achieved mainly by the arrival of farmers from the Fertile Crescent temporally coincident with the initial inception of farming in Greece. However, we detect very restricted genetic affinities with Europe that suggest any later cultural diffusions from Armenia to Europe were not associated with substantial amounts of paternal gene flow, despite the presence of closely related Indo-European languages in both Armenia and Southeast Europe.     

Amino acid position 11 of HLA-DRβ1 is a major determinant of chromosome 6p association with ulcerative colitis

The major histocompatibility complex (MHC) on chromosome 6p is an established risk locus for ulcerative colitis (UC) and Crohn's disease (CD). We aimed to better define MHC association signals in UC and CD by combining data from dense single-nucleotide polymorphism (SNP) genotyping and from imputation of classical human leukocyte antigen (HLA) types, their constituent SNPs and corresponding amino acids in 562 UC, 611 CD and 1428 control subjects. Univariate and multivariate association analyses were performed, controlling for ancestry. In univariate analyses, absence of the rs9269955 C allele was strongly associated with risk for UC (P = 2.67 × 10(-13)). rs9269955 is a SNP in the codon for amino acid position 11 of HLA-DRβ1, located in the P6 pocket of the HLA-DR antigen binding cleft. This amino acid position was also the most significantly UC-associated amino acid in omnibus tests (P = 2.68 × 10(-13)). Multivariate modeling identified rs9269955-C and 13 other variants in best predicting UC vs control status. In contrast, there was only suggestive association evidence between the MHC and CD. Taken together, these data demonstrate that variation at HLA-DRβ1, amino acid 11 in the P6 pocket of the HLA-DR complex antigen binding cleft is a major determinant of chromosome 6p association with UC.     

Y-Chromosome distribution within the geo-linguistic landscape of northwestern Russia

Populations of northeastern Europe and the Uralic mountain range are found in close geographic proximity, but they have been subject to different demographic histories. The current study attempts to better understand the genetic paternal relationships of ethnic groups residing in these regions. We have performed high-resolution haplotyping of 236 Y-chromosomes from populations in northwestern Russia and the Uralic mountains, and compared them to relevant previously published data. Haplotype variation and age estimation analyses using 15 Y-STR loci were conducted for samples within the N1b, N1c1 and R1a1 single-nucleotide polymorphism backgrounds. Our results suggest that although most genetic relationships throughout Eurasia are dependent on geographic proximity, members of the Uralic and Slavic linguistic families and subfamilies, yield significant correlations at both levels of comparison making it difficult to denote either linguistics or geographic proximity as the basis for their genetic substrata. Expansion times for haplogroup R1a1 date approximately to 18 000 YBP, and age estimates along with Network topology of populations found at opposite poles of its range (Eastern Europe and South Asia) indicate that two separate haplotypic foci exist within this haplogroup. Data based on haplogroup N1b challenge earlier findings and suggest that the mutation may have occurred in the Uralic range rather than in Siberia and much earlier than has been proposed (12.9±4.1 instead of 5.2±2.7 kya). In addition, age and variance estimates for haplogroup N1c1 suggest that populations from the western Urals may have been genetically influenced by a dispersal from northeastern Europe (eg, eastern Slavs) rather than the converse.