Isolation and genetic characterization of human KB cell lines resistant to multiple drugs

Human KB cell lines resistant to high levels of colchicine were isolated by several successive single-step selections. Most of these selection steps resulted in cross-resistance to vincristine, vinblastine, adriamycin, actinomycin D, and puromycin; however, at the highest levels of colchicine resistance, increased cross-resistance to other drugs was not observed. There was no major change in protein synthesis or alteration in protein phosphorylation or [^14C]glucosamine labeling patterns accompanying the development of multiple drug resistance as measured by analysis of metabolically labeled proteins on SDS gels. Cell-cell hybridization experiments showed that the colchicine-resistant and multiple drug-resistant phenotypes were incompletely dominant. In addition, colchicine resistance was found to segregate independently from resistance to other drugs in one somatic cell hybrid, suggesting that complex genetic loci are involved in the development of the multiple drug-resistant phenotype. These mutants should be useful for the study of the clinically important problem of multiple drug resistance in human cancer.     

Conservative treatment of benign prostatic hypertrophy--clinical effects of increased administration of Hachimijiogan and the relation between these effects and the "Sho" of Chinese medicine

Tsumura Hachimijiogan, 7.5 g a day, was administered to 30 patients with benign prostatic hypertrophy (BPH). Clinical effects were estimated based on subjective symptoms and objective findings obtained by uroflowmetry. Twenty patients (66.7%) showed improvement of subjective symptoms and 14 patients (46.7%) showed good response in uroflowmetry. An improvement of overall clinical efficacy was observed in 21 patients (70%). These results were better than those obtained with 5.0 g a day doses of Tsumura Hachimijiogan. No significant relation between the "Sho" in Chinese medicine and the clinical effects of Hachimijiogan was detected. No side effects or abnormal laboratory data were found in any of these 30 patients.     

Gut Microbiota Prevents Sugar Alcohol-Induced Diarrhea

While poorly-absorbed sugar alcohols such as sorbitol are widely used as sweeteners, they may induce diarrhea in some individuals. However, the factors which determine an individual’s susceptibility to sugar alcohol-induced diarrhea remain unknown. Here, we show that specific gut bacteria are involved in the suppression of sorbitol-induced diarrhea. Based on 16S rDNA analysis, the abundance of Enterobacteriaceae bacteria increased in response to sorbitol consumption. We found that Escherichia coli of the family Enterobacteriaceae degraded sorbitol and suppressed sorbitol-induced diarrhea. Finally, we showed that the metabolism of sorbitol by the E. coli sugar phosphotransferase system helped suppress sorbitol-induced diarrhea. Therefore, gut microbiota prevented sugar alcohol-induced diarrhea by degrading sorbitol in the gut. The identification of the gut bacteria which respond to and degrade sugar alcohols in the intestine has implications for microbiome science, processed food science, and public health.     

Correlation between mutated genes and forearm deformity in patients with multiple osteochondroma

BackgroundsExostosin-1 (EXT1) and exostosin-2 (EXT2) cause multiple osteochondromas (MO). In this study, we investigated the correlation between forearm deformity and mutant EXTs in Japanese families with MO.MethodsWe evaluated 112 patients in 71 families with MO. Genomic DNA was isolated from peripheral blood leucocytes. Of these, 28 patients were selected and underwent radiography for their forearms since they had gross forearm deformities. We measured the radial articular angle (RAA), ulna variance (UV), carpal slip (CS), and percentage of radial bowing (%RB) to compare between patients with mutant EXT1 or EXT2 and those with missense or other mutations using Student's t-test.ResultsTwenty-two (78.6%) and 6 (11.4%) out of 28 patients had mutations in EXT1 and EXT2, respectively. Nine (32.1%) and 19 (67.9%) of the 28 patients had missense and other mutations, respectively. The mean age of patients with EXT1 and EXT2 were 25.9 ± 20.3 and 33.5 ± 25.4 years, respectively and those with missense mutation and other mutations were 28.7 ± 27.0 and 24.6 ± 17.0 years, respectively. There were no significant differences in RAA, UV, and RB between patients harbouring mutant EXT1 or EXT2 (RAA, 40.1 ± 8.7 and 31.5 ± 13.9°; UV, ?2.7 ± 5.7 and ?3.1 ± 3.7 mm; %RB, 8.6 ± 1.5 and 8.3 ± 2.0%). CS was significantly greater in patients with mutant EXT1 than that in those with mutant EXT2 (EXT1, 44.1 ± 16.8%; EXT2, 18.6 ± 14.0%). There were no significant differences in RAA, UV, CS and %RB between patients with missense and other mutations.ConclusionsPatients with mutant EXT1 displayed greater CS than patients with mutant EXT2, indicating that patients with MO harbouring EXT1 mutations sustain more severe ulnar drift deformities than those with EXT2 mutations.     

A digest of the Evidence-Based Clinical Practice Guideline for Nephrotic Syndrome 2020

Clinical and Experimental Nephrology -     

VAMP2 is expressed in myogenic cells during rat development

Vesicle-associated membrane protein 2 (VAMP2) is a member of the SNARE family of proteins that regulate the intracellular vesicle fusion process. This study investigated the developmental expression of VAMP2 in the rat embryo. In the trunk, VAMP2 was primarily found in the heart on embryonic day (E) 10. On E12.5, VAMP2 expression was found in nerve fibers, somites, and heart. In somites, epithelial cells in the dorsomedial lip, and elongated myoblasts in myotome were positive for VAMP2. On E16.5, VAMP2 was expressed in the heart, nerve fibers, and skeletal muscles. In skeletal muscles, multinuclear myotubes were positive for VAMP2. In the head, where muscles are derived both from somitic and non-somitic origin, VAMP2 was found in myotubes of the extrinsic ocular muscles and masseter muscle on E16.5. These findings suggest the involvement of VAMP2 in the development of skeletal muscles of somitic and non-somitic origins.