ABSTRACT
The claudin family shows organ- and tissue-specific expression of individual members. Deficiency or aberrant expression of distinct claudins has been reported to be associated with severe pathophysiological consequences. Claudin domain-containing 1 (CLDND1), also known as claudin-25, shows homology to this family of proteins. Furthermore, serum CLDND1-derived peptide antibody levels are elevated in patients with cerebral infarction, as compared with healthy controls. We previously reported that, in the adult murine brain, CLDND1 is abundantly expressed in the cerebellum in common sites of intracerebral hemorrhage, and CLDND1 levels are transiently decreased after hemorrhagic insult. However, regulation of CLDND1 expression levels in cerebrovascular disease is poorly studied, and most regulatory microRNAs remain to be defined. We assessed its expression level, according to the presence of early signs of cerebrovascular disease, in the brain of stroke-prone spontaneously hypertensive rats (SHRSPs) and investigated the microRNA regulation of Cldnd1 mRNA. We investigated the post-transcriptional regulation of Cldnd1 by examining the subcellular distribution of its mRNA and evaluating its translational regulation by microRNA in human brain endothelial cells (HBECs) and in the brain of SHRSPs. Using bioinformatics, we identified a conserved microRNA-124 (miR-124)-binding site in the 3'-untranslated region of Cldnd1 and demonstrated that miR-124 regulates the translation of Cldnd1 mRNA reporters in a sequence-specific manner in luciferase assays. HBECs transfected with an miR-124 mimic showed decreased levels of CLDND1 mRNA in reverse transcription quantitative PCR. miR-124 levels were markedly lower in SHRSP than in Wister Kyoto rat brains, whereas Cldnd1 mRNA and protein levels were significantly higher. In SHRSP brains, Cldnd1 mRNA levels increased with a decrease in miR-124. Therefore, by interacting with Cldnd1 mRNA, miR-124 influences CLDNL1 levels in the brain, thus playing a role in the development of cerebrovascular disease in SHRSPs.
Subject(s)
Claudins/genetics , Gene Expression Regulation , Hypertension/genetics , MicroRNAs/genetics , Stroke/genetics , Animals , Cell Line , Cerebellum/metabolism , HEK293 Cells , Humans , Male , RNA, Messenger/genetics , Rats , Rats, Inbred SHRABSTRACT
Medical treatment of pulmonary Mycobacterium avium complex (MAC) disease does not always provide curative effects and is frequently hampered by recurrence. This suggests the presence of a reservoir for MAC in the environment surrounding patients. We previously reported the recovery of MAC isolates from the residential bathrooms of outpatients. In the present study, to ascertain the colonizing sites and the possibility of an MAC reservoir in the bathrooms of patients, we tested the recovery and the genetic diversity of MAC isolates from 6 sites of specimens, including 2 additional sampling sites, inside the showerhead and the bathtub inlet, in the residential bathrooms of patients with pulmonary MAC disease. MAC isolates were recovered from 15 out of the 29 bathrooms (52%), including specimens from 14 bathtub inlets and 3 showerheads. Nearly half of these bathrooms (7/15) contained MAC strains that were identical or similar to their respective clinical isolates Additionally, in 5 out of 15 bathrooms, polyclonal colonization was revealed by pulsed-field gel electrophoresis. The results imply that colonization of MAC organisms in the bathrooms of MAC patients occurs predominantly in the bathtub inlets, and there is thus a risk of infection and/or reinfection for patients via use of the bathtub and other sites in the bathroom.
Subject(s)
Baths , Equipment Contamination , Hospitals , Mycobacterium avium Complex/isolation & purification , Patients' Rooms , Biofilms , Chi-Square Distribution , Electrophoresis, Gel, Pulsed-Field , Housekeeping, Hospital , Humans , Japan , Mycobacterium avium Complex/genetics , Mycobacterium avium Complex/growth & development , Mycobacterium avium-intracellulare Infection/microbiology , Sanitary Engineering , Statistics, Nonparametric , Water MicrobiologyABSTRACT
A 75-year-old man with a large pituitary adenoma presented with general muscular weakness, including difficulty in rising in the morning and forceless defecation and urination, and muscular pain, numbness and atrophy in the shoulder, neck and thigh. Testosterone replacement and subsequent resection of the pituitary tumor resulted in resolution of the symptoms. The value of pituitary imaging tests for men with hypogonadotropic hypogonadism is discussed.