Increased DNA-incorporated thiopurine metabolite as a possible mechanism for leukocytopenia through cell apoptosis in inflammatory bowel disease patients with NUDT15 mutation

Journal of Gastroenterology - Polymorphisms in the nucleotide diphosphate-linked moiety X-type motif 15 (NUDT15) gene are associated with thiopurine-induced leukopenia in patients with inflammatory...     

Case Report: Determination of Primary Foci of Metastatic Tumors by p53 Mutational Analysis in Intraesophageal Multiple Carcinomas

It is well known that squamous carcinomasfrequently develop multifocally, either synchronously ormetachronously, in the upper aerodigestive tract (1).Such phenomena were first reported by Slaughter et al in 1953, and they were named fieldcancerization (2). Using recent molecular biologytechniques, these multiple carcinomas have been revealedto arise from independent origins (3). Esophagealcarcinomas have been reported to frequently metastasize tothe lymph nodes even at the early stage of tumorextension (4). Furthermore, simultaneous multifocalcancer development is not rare in the esophagus (5). In cases of intraesophageal multiple carcinomaswith lymph node metastases, the primary focus of themetastatic tumors cannot be identified by conventionalhistologic examination. Here we report a case of intraesophageal multiple carcinomas in whichthe attributed foci of lymph nodal metastases could beclearly identified by analyzing the p53 gene mutationalstatus used as a clonal marker.     

Alteration of the Intestinal Environment by Lubiprostone Is Associated with Amelioration of Adenine-Induced CKD

The accumulation of uremic toxins is involved in the progression of CKD. Various uremic toxins are derived from gut microbiota, and an imbalance of gut microbiota or dysbiosis is related to renal failure. However, the pathophysiologic mechanisms underlying the relationship between the gut microbiota and renal failure are still obscure. Using an adenine-induced renal failure mouse model, we evaluated the effects of the ClC-2 chloride channel activator lubiprostone (commonly used for the treatment of constipation) on CKD. Oral administration of lubiprostone (500 µg/kg per day) changed the fecal and intestinal properties in mice with renal failure. Additionally, lubiprostone treatment reduced the elevated BUN and protected against tubulointerstitial damage, renal fibrosis, and inflammation. Gut microbiome analysis of 16S rRNA genes in the renal failure mice showed that lubiprostone treatment altered their microbial composition, especially the recovery of the levels of the Lactobacillaceae family and Prevotella genus, which were significantly reduced in the renal failure mice. Furthermore, capillary electrophoresis–mass spectrometry-based metabolome analysis showed that lubiprostone treatment decreased the plasma level of uremic toxins, such as indoxyl sulfate and hippurate, which are derived from gut microbiota, and a more recently discovered uremic toxin, trans-aconitate. These results suggest that lubiprostone ameliorates the progression of CKD and the accumulation of uremic toxins by improving the gut microbiota and intestinal environment.     

Association of a single-nucleotide polymorphism in the promoter region of leukemia inhibitory factor receptor gene with low bone mineral density in adult women

Background:   Osteoporosis is believed to result from the interaction among multiple environmental and genetic determinants that regulate bone-mineral density (BMD).
Methods:   To investigate a potentially predisposing genetic factor in the onset of osteoporosis, we looked for a possible association between BMD in adult Japanese women and known polymorphisms in the leukemia inhibitory factor receptor gene (LIFR).
Results:   An association analysis of chromosomes from 384 volunteer subjects revealed significant correlation between the −603T > C variant of LIFR and radial BMD ( r  = 0.11, P  = 0.032) in this test population. Comparisons of mean values of adjusted radial BMD among separate genotypic groups implied an allelic dosage effect, because homozygous carriers of T alleles of that SNP had the highest adjusted BMDs (0.403 ± 0.054 g/cm²); women homozygous for the C-allele had the lowest (0.373 ± 0.042 g/cm²), and heterozygous individuals had intermediate scores (0.394 ± 0.056 g/cm²).
Conclusion:   This polymorphism in LIFR may be an important determinant of predisposition to postmenopausal osteoporosis.