BACKGROUND: Gitelman's syndrome (GS) is an autosomal recessive disorder resulting from inactivating mutations in the thiazide-sensitive Na-Cl co-transporter (NCCT) gene. To date, almost 90 mutations have been identified. It is possible that there is a population-specific distribution of mutations. In this study, we analysed mutations in the NCCT gene of seven Japanese patients with GS. METHODS: Peripheral blood mononuclear cells were isolated from patients with GS, their family members and healthy control subjects. A mutation analysis of the NCCT gene was performed completely by direct automated sequencing of polymerase chain reaction-amplified DNA products. In patients with a deletion or splice site mutation, we undertook cDNA sequence analysis. RESULTS: We identified nine mutations. Five of them [c.185C>T (Thr60Met), c.1712C>T (Ala569Val), c.1930C>T (Arg642Cys), c.2552T>A (Leu849His) and c.1932delC] have been reported in Japanese patients, but not in GS patients from other ethnic groups. The remaining four mutations [c.7A>T (Met1Leu), c.1181_1186+20del26, c.1811_1812delAT and IVS16+1G>A] were novel. In cDNA derived from a patient with c.1181_1186+20del26, a deletion of exon 9 and a frameshift at the start of exon 10 were observed. In cDNA derived from patients with IVS16+1G>A, an additional 96 bp insertion between exons 16 and 17 was observed. Six out of seven patients were compound heterozygotes, and the remaining one carried a single heterozygous mutation. CONCLUSIONS: We found four novel mutations in the NCCT gene in seven Japanese patients with GS. Moreover, our study suggests that the distribution of mutations in the NCCT gene in Japanese GS patients potentially differs from that in other populations. 相似文献
Here we report the finding of enzymatic activity that specifically cleaves DNA containing 8-hydroxyguanine (oh8Gua) residues in various mammalian cells. To detect this activity, we used a synthetic double-stranded DNA containing a single oh8Gua at a defined position as the substrate, and analyzed the products of enzymatic digestion by polyacrylamide gel electrophoresis. Two cleavage sites near the oh8Gua residue were detected with partially purified fractions from cow brain and rat liver, and also with preparations from all mammalian tissues examined. These results suggest that enzymatic activity for the removal of oh8Gua from DNA is widely distributed in mammalian cells. 相似文献
Abstract The effectiveness of a 5% potassium nitrate dentifrice as a daily home treatment for dentinal hypersensitivity was evaluated in a double-blind study in 36 Japanese subjects who complained of cold and/or tactile hypersensitivity. The subjects were divided into 2 groups, with 18 being given a 5% potassium nitrate dentifrice (treated group) and the other 18 a vehicle paste (control group). Both groups were instructed to brush their teeth 2 × a day. The hypersensitivity levels of the affected teeth were assessed by 2 stimuli, one tactile and the other cold air, and by the perception of pain. The results of all 3 assessment methods indicated that the potassium nitrate dentifrice significantly decreased the level of hypersensitivity at weeks 4, 8, and 12. In the treated group, a rapid decrease of positive scores for both the cold air stimulus and the subjective symptoms appeared from week 2. Although a significant decrease of the assessment score was also observed in the control group, the reduction rate of the score was much greater in the treated group by ail 3 assessment methods at weeks 4, 8, and 12. Complete relief of subjective symptoms throughout the 12 weeks’examination was noted in 67% of the subjects in the treated group, but in only 6% in the control group. These results suggest the usefulness of a 5% potassium nitrate dentifrice in Japanese patients with dentinal hypersensitivity. 相似文献
The case of a 53-year-old man with hematospermia and massive postejaculation hematuria that caused urinary retention is described. This is the sixth case in the English and Japanese language literature. Cystourethroscopic examination revealed that a solitary raised tumor was present just distal to the vermontanum, and that bleeding was from its apex. Histologic examination of an excisional biopsy sample showed features compatible with hemangioma. 相似文献
Background: The effects of inhalational anesthetics on the microcirculation, including leukocyte dynamics, remain to be clarified. The authors investigated halothane and sevoflurane anesthesia to determine if these agents evoked leukocyte adhesion through endothelial cell-dependent mechanisms involving such adhesion molecules.
Methods: Rats were anesthetized with halothane or sevoflurane in 100% oxygen and the lungs were mechanically ventilated. Leukocyte behavior in mesenteric venules was recorded through intravital video microscopy under monitoring microvascular hemodynamics. To examine the mechanisms for leukocyte rolling and adhesion, these studies were repeated after animals were pretreated with a monoclonal antibody against P-selectin (MAb PB1.3) or against intracellular adhesion molecule-1 (ICAM-1; MAb 1A29): P-selectin required for rolling of circulating leukocytes and ICAM-1 for firm adhesive interactions with leukocyte integrins.
Results: Under baseline anesthetic conditions (1 minimum alveolar concentration [MAC]), venular wall shear rates, an index of the disperse force on marginating leukocytes, in the sevoflurane-treated rats were about two times higher than those with halothane. At 2 MAC, halothane caused a marked arteriolar constriction and decreasing shear rates concurrent with an increasing density of venular leukocyte adhesion. Sevoflurane at 2 MAC induced leukocyte rolling and adhesion, which were attenuated by PB1.3 and 1A29, without alterations in the wall shear rates. Halothane-induced leukocyte adhesion was not prevented by PB1.3 but it was by 1A29. 相似文献
The mechanism of the vasodilator effect of pinacidil was examined. Pinacidil (0.1–100 μM) inhibited the increases in cytosolic Ca2+ ([Ca2+]i) and muscle tension due to norepinephrine in rat aorta. In contrast, a Ca2+ channel blocker, verapamil, inhibited the norepinephrine-stimulated [Ca2+]i more strongly than the contraction. Higher concentrations of pinacidil (3–100 μM) inhibited the verapamil-insensitive portion of the contraction and [Ca2+]i. An inhibitor of ATP-sensitive K+ channels, glibenclamide, antagonized the inhibitory effect of low concentrations ( 10 pM) of pinacidol. Pinacidil did not change the contraction induced by Ca2+ in vascular smooth muscle permeabilized with Staphylococcus aureus -toxin. Norepinephrine (in the presence of GTP), 12-deoxyphorbol 13-isobutyrate (in the absence of GTP), and treatment with GTPγS potentiated the contraction of permeabilized smooth muscle induced by the addition of Ca2+. Pinacidil (100 μM) inhibited the potentiation due to GTPγS or noepinephrine but not to phorbol ester. These results suggest that pinacidil has dual effects on vascular smooth muscle contraction. At lower concentrations (>0.1 μM), it decreases [Ca2+]i, possibly by activating ATP-sensitive K+ channels. At higher concentrations (> 3 μM), it may additionally inhibit the receptor-mediated, GTP-binding protein-coupled phosphatidyl inositol turnover. 相似文献
A case of hepatic infarction with portal thrombosis is reported. A 63-year-old woman with liver cirrhosis and esophageal varices
was admitted for treatment of the esophagel varices. Endoscopic variceal ligation (EVL) and endoscopic injection sclerotherapy
(EIS) were performed. Two months later, she experienced right hypochondralgia and right flank pain. Serum transaminase levels
were suddenly elevated, and computed tomography scans of the liver showed multiple small nodular lesions. Her condition worsened,
and she died of hepatic failure. Autopsy revealed splenic and portal vein thrombosis, multiple hepatic infarction, and evidence
of chronic pancreatitis. We believe that liver cirrhosis and chronic pancreatitis were the main risk factors for the portal
thrombosis, and the treatment for esophageal varices appeared to have triggered the thrombosis. The hepatic infarction was
caused by the portal thrombosis. 相似文献
A 37-year-old man visited our hospital with the chief complaint of a painless mass in subcutaneous tissue of the pubis. We extirpated the localized cyst 2.5 x 4 cm in size. Histological diagnosis was cystic lymphangioma without malignant findings. We reviewed the literature on lymphangioma, a rare disease seldom seen in urological fields. 相似文献