Polymorphic Alu Insertions and their Associations with MHC Class I Alleles and Haplotypes in the Northeastern Thais

Polymorphic Alu insertions (POALINs) are known to contribute to the strong polymorphic nature of the Major Histocompatibility Complex (MHC). Previous population studies on MHC POALINs were limited to only Australian Caucasians and Japanese. Here, we report on the individual insertion frequency of the five POALINs within the MHC class I region, their HLA‐A and ‐B associations, and the three and four locus alpha block POALIN haplotype frequencies in the Northeastern (NE) Thai population. Of the five POALINs, the lowest frequency was 0.018 for AluyHF and the highest frequency was 0.292 for AluyHJ and AluyHG. The strongest positive associations between the POALINs and HLA class I alleles was between AluyMICB and HLA‐B*57, AluyHJ and HLA‐A*24 and HLA‐A*01, and AluyHG and HLA‐A*02, supporting previous findings in Caucasians and Japanese. Single POALIN haplotypes were found more frequently than multiple POALIN haplotypes. However, of the seven different POALIN haplotypes within the MHC alpha block, there were only two significant differences between the NE Thais, Caucasians and Japanese. This study confirms that the MHC POALINs are in linkage disequilibrium with HLA‐A and –B alleles and that there are significant frequency differences for some of the POALINs when compared between NE Thai, Caucasians and Japanese.     

Identification of two mutations in a compound heterozygous child with dihydrolipoamide dehydrogenase deficiency

An infant girl with elevated blood lactate, pyruvate, and plasma branched-chain amino acids was diagnosed with dihydrolipoamide dehydrogenase (E3; dihydrolipoamide: NAD+ oxidoreductase, EC 1.8.1.4) deficiency. Activities of the pyruvate dehydrogenase complex and E3 from patient were 26 and 2% of controls in blood lymphocytes, and 11 and 14% in cultured skin fibroblasts, respectively. Western blot analysis demonstrated that the amount of E3 protein in fibroblasts from the patient and her father was about half of controls, while Northern blot analysis showed normal amounts of E3 RNA. DNA sequencing of cloned full-length E3 cDNAs from the patient revealed two mutations in separate alleles. One is a single base insertion of an extra adenine in the last codon of the leader peptide sequence (TAC-->TAAC) leading to a nonsense mutation which results in the premature termination of the precursor E3 polypeptide (Y35X). The other is a missense mutation due to substitution of guanine for adenine, causing an Arg-->Gly substitution at amino acid 460 of the mature protein (R460G) which triggers the loss of E3 activity probably by structural change in the E3 dimer. DNA sequencing of E3 cDNAs from the parents demonstrated that the nonsense mutation was inherited from the father and the missense mutation was inherited from the mother.      

Correlation of leukocyte interleukin-1 production with the stimulation of prostaglandin and tissue factor synthesis by human umbilical vein endothelial cells

Human leukocyte suspensions (neutrophils 80–85%, monocyte 15–20%) were incubated alone or with cultured human umbilical vein endothelial cells. Leukocytes were either directly added to the endothelial cell cultures or separated from them by a 0.4 micron insert filter. Supernatants or cell lysates were obtained at 0.5, 1, 2, and 4 hours of incubation. Supernatants were assayed for the prostacyclin (PGI₂) metabolite 6-keto prostaglandin F₁ and prostaglandin E₂ (PGE₂) by radioimmunoassay and for interleukin-1 (IL-1) by the thymocyte co-mitogen assay. Cell lysates were analyzed for cell-associated procoagulant activity (PCA). Co-incubation of endothelial cells with leukocytes stimulated the synthesis of PGI₂, PGE₂, and PCA. These biochemical changes correlated partially with the release of IL-1 beta. The results suggest that IL-1 released in monocyte/neutrophil co-cultures can produce prothrombotic (increased PCA expression) and inflammatory changes (increased synthesis of vasodilatory and permeability enhancing PGI₂ and PGE₂) in endothelial cells. Neutrophils may represent a source of the released IL-1 and/or may act to stimulate monocyte release of this cytokine and thus play an important role in vascular pathology by a mechanism unrelated to their more direct cytotoxic activity.     

Serotypic and genotypic characterization of human serotype 10 rotaviruses from asymptomatic neonates.

Human rotaviruses were isolated from asymptomatic neonates at various hospitals and clinics in the city of Bangalore, India, and were found to be subgroup I specific and possess long RNA patterns (M. Sukumaran, K. Gowda, P. P. Maiya, T. P. Srinivas, M. S. Kumar, S. Aijaz, R. R. Reddy, L. Padilla, H. B. Greenberg, and C. D. Rao, Arch. Virol. 126:239-251, 1992). Three of these strains were adapted to tissue culture and found by serotype analysis and neutralization assays to be of serotype 10, a serotype commonly found in cattle but infrequently found in humans and not previously identified in neonates. By RNA-RNA hybridization, a high level of relatedness to a serotype 10 bovine rotavirus strain and a low-to-medium level of relatedness to a human rotavirus strain were observed. Since this human isolate shares a genogroup with bovine rotavirus, it is likely that it originated by interspecies transmission. A human rotavirus strain isolated from asymptomatic neonates and similar to bovine rotavirus might represent a good vaccine candidate.     

32P-Postlabelling analysis of aromatic DNA adducts in human oral mucosal cells

Exfoliated mucosal cells were collected from the oral cavityof three groups at high risk for oral cancer: Indian betel nutchewers, Filipino inverted smokers (burning end of cigar inmouth) and Indian Khaini tobacco chewers. DNA was extractedfrom these samples, as well as from samples of exfoliated cellsof Canadian non-smoking controls. DNA was analyzed for the presenceof aromatic DNA adducts using ³²P-postlabel-ling analysis. Fivechromatographically distinct adducts were found in samples fromboth the high risk groups and the nonsmoking controls. Individualadducts were detectable in 30–95% of samples, dependingon the adduct and population group. Estimated levels of specificadducts ranged from non-detectable (prevalence relative to normalnucleotides < 1 x 10^-9) to occasionally > 1x 10^-7. Noadducts were found in high risk groups which did not also appearin control subjects.     

Development of a Programme Theory for Early Intervention Vocational Rehabilitation: A Realist Literature Review

Journal of Occupational Rehabilitation - Purpose Little is currently known about how early intervention vocational rehabilitation (EIVR) works for people with newly acquired neurological conditions...     

Mesenteric neovascularization during spring-mediated intestinal lengthening

BackgroundShort gut syndrome, a condition characterized by inadequate absorption of nutrients owing to decreased bowel length, has minimal avenues for treatment. We have proposed spring-mediated distraction enterogenesis to lengthen bowel in porcine jejunum as a treatment for short gut. We aim to evaluate the extent of mesenteric neovascularization in segments of lengthened bowel via spring-mediated enterogenesis.MethodsFemale juvenile Yucatan pigs underwent laparotomy and insertion of gelatin-encapsulated compressed nitinol springs, held in place with plication sutures, into the jejunum. At surgery and sacrifice, macroscopic mesenteric blood vessels were counted between the plication sites. Histologic samples of the mesentery were obtained to evaluate microscopic vasculature.ResultsA statistically significant increase in macroscopic mesenteric blood vessels was seen after intestinal lengthening (before: 1.9 ± 0.7 vessels, after: 4.7 ± 1.2 vessels, p = 0.001). A statistical significance is also seen in the density of arterioles (control: 3.0 ± 3.0 vessels/mm, spring: 7.0 ± 9.0 vessels/mm, p = 0.01) and venules (control: 4.0 ± 3.0 vessels/mm, spring: 8.0 ± 8.0 vessels/mm, p = 0.003).ConclusionIntestinal segments lengthened by intraluminal springs demonstrated total greater number of macroscopic vessels and microscopic blood vessels per length of mesentery as compared to control. This suggests local changes within the mesentery to recruit blood supply to growing intestine.Level of evidenceN/AType of studyTreatment study.