Implantation of a biventricular pacing system via a persistent left-sided superior vena cava

Cardiac resynchronization therapy by multisite biventricular pacing presents an additive therapeutic option in the treatment of severe heart failure. Biventricular pacemaker implantation is challenging in patients with persistent left superior vena cava. We describe in this case report the implantation of a biventricular pacemaker using a left-sided approach in a patient with persistent left superior vena cava.     

Interleukin-10 promoter polymorphisms in rheumatoid arthritis and Felty's syndrome

OBJECTIVE: To examine whether promoter polymorphisms associated with variation in interleukin-10 (IL-10) production are relevant to the development of rheumatoid arthritis (RA) or Felty's syndrome (FS). METHODS: DNA was obtained from 44 FS patients, 117 RA patients and 295 controls. The promoter region between -533 and - 1120 was amplified by polymerase chain reaction, and polymorphisms detected by restriction enzyme digest or sequence-specific oligonucleotide probing. RESULTS: We found no significant difference in allele or haplotype frequencies between the groups. CONCLUSION: There is no association between FS or RA and these recently identified IL-10 promoter polymorphisms. Other genetic or environmental factors could explain the alterations in IL-10 levels seen in these conditions.      

Hepatitis C virus entry and neutralization

The processes of hepatitis C virus (HCV) entry and antibody-mediated neutralization are intimately linked. The high frequency of neutralizing antibodies (nAbs) that inhibit E2-CD81 interaction(s) suggests that this is a major target for the humoral immune response. The observation that HCV can transmit to naive cells by means of CD81-dependent and -independent routes in vitro awaits further investigation to assess the significance in vivo but may offer new strategies for HCV to escape nAbs. The identification of claudins in the entry process highlights the importance of cell polarity in defining routes of HCV entry and release, with recent experiments suggesting a polarized route of viral entry into cells in vitro. In this review, the authors summarize the current understanding of the mechanism(s) defining HCV entry and the role of nAbs in controlling HCV replication.     

Interleukin 10 promoter region polymorphisms and susceptibility to advanced alcoholic liver disease

BACKGROUND: The factors determining why less than 10% of heavy drinkers develop advanced alcoholic liver disease (ALD) remain elusive, although genetic factors may be important. Interleukin 10 (IL-10) is an important cytokine with anti-inflammatory, anti-immune, and antifibrotic functions. Several polymorphisms have been identified in the IL-10 promoter and recent evidence suggests that some of these may have functional effects on IL-10 secretion. AIMS: To test the hypothesis that IL-10 promoter region polymorphisms are associated with susceptibility to ALD. METHODS: The allele frequencies for the two single base pair substitutions at positions -627 (C-->A) and -1117 (A-->G) in the IL-10 promoter were determined in 287 heavy drinkers with biopsy proved advanced ALD, 107 heavy drinkers with no evidence of liver disease or steatosis only on biopsy, and 227 local healthy volunteers. RESULTS: At position -627, 50% of patients with advanced ALD had a least one A allele compared with 33% of controls (p<0.0001) and 34% of drinkers with no or mild disease (p=0.017). At position -1117, the slight excess of the A allele in drinkers with advanced disease was because of linkage disequilibrium between the A alleles at the two sites. CONCLUSIONS: Among heavy drinkers, possession of the A allele at position -627 in the IL-10 promoter is associated with an increased risk of advanced liver disease. This is consistent with recent functional data that the -627*A allele is associated with low IL-10 expression which will favour inflammatory, immune mediated, and profibrotic mechanisms of alcohol related liver injury.     

Duodenal acidification and intra-arterial injection of CCK8 increase gallbladder motility in the rainbow trout, Oncorhynchus mykiss.

A sensitive method for in vivo measurement of intra-gallbladder pressure in free swimming rainbow trout (Oncorhynchus mykiss) is described. The method gives information on changes in gallbladder pressure after either instillation of liquids into the duodenum or infusion/injection of agents into the circulatory system. Blood samples can also be taken. Duodenal acidification is a potent initiating factor for gallbladder motility in the rainbow trout. Intra-arterially injected sulfated octapeptide of cholecystokinin is also a potent excitatory agent for activating the gallbladder. Acidification of the upper intestine causes release of cholecystokinin, which affects gallbladder motility in trout as in mammals.     

Ultra‐deep T cell receptor sequencing reveals the complexity and intratumour heterogeneity of T cell clones in renal cell carcinomas

The recognition of cancer cells by T cells can impact upon prognosis and be exploited for immunotherapeutic approaches. This recognition depends on the specific interaction between antigens displayed on the surface of cancer cells and the T cell receptor (TCR), which is generated by somatic rearrangements of TCR α‐ and β‐chains (TCRb). Our aim was to assess whether ultra‐deep sequencing of the rearranged TCRb in DNA extracted from unfractionated clear cell renal cell carcinoma (ccRCC) samples can provide insights into the clonality and heterogeneity of intratumoural T cells in ccRCCs, a tumour type that can display extensive genetic intratumour heterogeneity (ITH). For this purpose, DNA was extracted from two to four tumour regions from each of four primary ccRCCs and was analysed by ultra‐deep TCR sequencing. In parallel, tumour infiltration by CD4, CD8 and Foxp3 regulatory T cells was evaluated by immunohistochemistry and correlated with TCR‐sequencing data. A polyclonal T cell repertoire with 367–16 289 (median 2394) unique TCRb sequences was identified per tumour region. The frequencies of the 100 most abundant T cell clones/tumour were poorly correlated between most regions (Pearson correlation coefficient, –0.218 to 0.465). 3–93% of these T cell clones were not detectable across all regions. Thus, the clonal composition of T cell populations can be heterogeneous across different regions of the same ccRCC. T cell ITH was higher in tumours pretreated with an mTOR inhibitor, which could suggest that therapy can influence adaptive tumour immunity. These data show that ultra‐deep TCR‐sequencing technology can be applied directly to DNA extracted from unfractionated tumour samples, allowing novel insights into the clonality of T cell populations in cancers. These were polyclonal and displayed ITH in ccRCC. TCRb sequencing may shed light on mechanisms of cancer immunity and the efficacy of immunotherapy approaches. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Menarche,pregnancy, birth spacing and menopause among the Agta women foragers of Cagayan Province,Luzon, the Philippines

The reproductive histories of 74 post-menarcheal Agta Negrito women, tropical foragers of Cagayan province, north-eastern Luzon, the Philippines are described and analysed in comparison with data collected by Howell on Dobe! Kung hunter-gatherers. Among the Agta, mean age at menarche is 17, mean age at first live birth is 20·14 years, mean completed parity is 6·53 and mean age at menopause is 44. Average height is 141·24cm and average weight 36·72 kg. No time trends were detected in age at menarche and age at first live birth among the Agta. Average spacing between live births where an infant survives until the birth of the next sibling was 2·85 years. Compared to the Dobe !Kung, Agta women have later menarche, but shorter birth spacing and a longer active childbearing span.     

Interaction of Blood Manganese Concentrations with GSTT1 in Relation to Autism Spectrum Disorder in Jamaican Children

Journal of Autism and Developmental Disorders - Using data from 266 age- and sex-matched pairs of Jamaican children with autism spectrum disorder (ASD) and typically developing (TD) controls...