Association of <Emphasis Type="Italic">SLC22A4/5</Emphasis> Polymorphisms with Steroid Responsiveness of Inflammatory Bowel Disease in Japan

Purpose We investigated the association between steroid responsiveness and single nucleotide polymorphisms of SLC22A4/A5 located within inflammatory bowel disease 5 locus. Our goal is personalized steroid therapy adjusted to match individual variations in drug responsiveness in each inflammatory bowel disease patient. Methods Unrelated Japanese cohorts of 94 patients with Crohn’s, 94 patients with ulcerative colitis, and 257 healthy control subjects were consecutively enrolled in this study. Genotyping and haplotype analysis focusing on steroid responsiveness was performed by using 15 single nucleotide polymorphisms. Results The G allele of −368T > G in SLC22A5, in which strong linkage disequilibrium was observed and the limited diversity of three haplotypes was estimated, was significantly associated with steroid resistance in Japanese patients with Crohn’s disease (P = 0.016). Haplotype analysis between −446C > T and −368T > G in the SLC22A5 promoter region showed that the CG allele appeared to be a risk haplotype for steroid resistance (CG: odds ratio, 4.13; 95 percent confidence interval, 1.41–12.1; P = 0.016). Conclusions This extensive linkage disequilibrium may form a general risk haplotype for steroid resistance in Crohn’s disease in Japanese. Further analyses of the pharmacogenomics of steroid responsiveness are warranted to achieve the goal of individualized steroid therapy against inflammatory bowel disease. Supported by a grant-in-aid from the Ministry of Health, Labour and Welfare (K.I.), Japan. Address of correspondence: Yoshiaki Arimura, M.D., First Department of Internal Medicine, Sapporo Medical University, S-1, W-16, Chuo-ku, Sapporo, 060-8543, Japan. E-mail: arimura@sapmed.ac.jp     

Gastric Mucosal Injury Induced by Local Ischemia-Reperfusion in Rats (Role of Endogenous Endothelin-1 and Free Radical)

We investigated the role of an endogenousvasoconstrictor peptide endothelin-1 (ET-1) and freeradicals in local gastric ischemia-reperfusion injury inrats. Local gastric ischemia was induced by clamping the left gastric artery for 15 min andreperfusion was done for 10-30 min in the presence of150 mM exogenous HCl intragastrically. Local gastricischemia and reperfusion resulted in significantmacroscopic and microscopic gastric mucosal damage togetherwith elevation of gastric tissue ET-1 concentration.Gastric tissue ET-1 was found to increase after 15 minof ischemia alone and also with 30 min of reperfusion. A novel nonpeptide endothelin receptorantagonist, bosentan, or a combination of radicalscavengers (superoxide dismutase, catalase, anddeferoxamine) both attenuated gastric mucosal injury.However, the greater protection observed with bosentan thanwith radical scavengers might reflect a preferentialrole of endothelin-1 in this type of injury.     

Perinatal anoxia degrades auditory system function in rats

Little is known about the neural bases of the reduced auditory and cortical processing speeds that have been recorded in language-impaired, autistic, schizophrenic, and other disabled human populations. Although there is strong evidence for genetic contributions to etiologies, epigenetic factors such as perinatal anoxia (PA) have been argued to be contributors, or causal, in a significant proportion of cases. In this article, we explored the consequences of PA on this elementary aspect of auditory behavior and on auditory system function in rats that were briefly perinatally anoxic. PA rats had increased acoustic thresholds and reduced processing efficiencies recorded in an auditory behavioral task. These rats had modestly increased interpeak intervals in their auditory brainstem responses, and substantially longer latencies in poststimulus time histogram responses recorded in the primary auditory cortex. The latter were associated with degraded primary auditory cortex receptive fields and a disrupted tonotopy. These processing deficits are consistent with the parallel behavioral and physiological deficits recorded in children and adults with a history of language-learning impairment and autism.     

Clinical and neuroendocrinological characteristics of delayed orthostatic hypotension in Parkinson’s disease

Clinical Autonomic Research - Delayed orthostatic hypotension (DOH), a fall in blood pressure after a 3-min cutoff, is clinically meaningful. The aim of this study was to elucidate the clinical and...     

The Maze-Making and Solving Technique for Coil Embolization of Large and Giant Aneurysms

BACKGROUND AND PURPOSE:Despite major progress in treating aneurysms by coil embolization, the complete occlusion of aneurysms of >10 mm in diameter (large/giant aneurysms) remains challenging. We present a novel endovascular treatment method for large and giant cerebral aneurysms called the “maze-making and solving” technique and compare the short-term follow-up results of this technique with those of conventional coil embolization.MATERIALS AND METHODS:Eight patients (65 ± 11.5 years of age, 7 women) with large/giant unruptured nonthrombosed cerebral aneurysm (mean largest aneurysm dimension, 19 ± 4.4 mm) were treated by the maze-making and solving technique, a combination of the double-catheter technique and various assisted techniques. The coil-packing attenuation, postoperative courses, and recurrence rate of this maze group were compared with 30 previous cases (conventional group, 65.4 ± 13.0 years of age; 22 women; mean largest aneurysm dimension, 13.4 ± 3.8 mm).RESULTS:Four maze group cases were Raymond class 1; and 4 were class 2 as indicated by immediate postsurgical angiography. No perioperative deaths or major strokes occurred. Mean packing attenuation of the maze group was significantly higher than that of the conventional group (37.4 ± 5.9% versus 26.2 ± 5.6%). Follow-up angiography performed at 11.3 ± 5.4 months revealed no recurrence in the maze group compared with 39.2% in the conventional group.CONCLUSIONS:The maze-making and solving technique achieves high coil-packing attenuation for efficient embolization of large and giant cerebral aneurysms with a low risk of recurrence.

Substantial progress in the endovascular treatment of cerebral aneurysms, such as balloon- and stent-assisted coil embolization, has resulted in the widespread use of these techniques with relatively high efficacy and safety. However, large and giant aneurysms remain difficult to treat by using assist techniques and bioactive coils,^1,2 possibly because the requisite coil-packing attenuation is often not achieved. We recently developed a “maze-making and solving” technique to occlude these large/giant aneurysms by achieving high packing attenuation. Here, we present the technical details of this procedure and compare the clinical outcomes and recurrence rates between large/giant aneurysm cases treated by the maze technique and matched cases treated by conventional coil embolization.     

Juxtaposition of the T-cell receptor alpha-chain locus (14q11) and a region (14q32) of potential importance in leukemogenesis by a 14;14 translocation in a patient with T-cell chronic lymphocytic leukemia and ataxia-telangiectasia.

We describe a t(14;14)(q11;q32) translocation in a patient with T-cell chronic lymphocytic leukemia and ataxia-telangiectasia (AT). By using a battery of joining (J)-segment probes from the T-cell receptor (TCR) alpha-chain locus TCRA, three distinct J alpha rearrangements were observed. One rearrangement reflected a normal TCRA variable (V) region V alpha-to-J alpha recombination. The second rearrangement was caused by the translocation even itself, which joined a DNA segment from 14q32 centromeric to the immunoglobulin heavy chain locus (IGH) and a J alpha gene located approximately 75 kilobases (kb) 5' of the TCRA constant region gene (C alpha). A third rearrangement involved a 17-kb internal deletion 3' to the translocation, a rearrangement within the J alpha locus that has been observed once before in a patient with AT. Analysis of these three rearrangements underscores the increase in aberrant locus-specific recombination in lymphocytes from patients with AT. Furthermore, these studies support the view that a growth-effecting gene is present in the 14q32 region that participates in the leukemogenic process.