Four novel mutations in the thiazide-sensitive Na-Cl co-transporter gene in Japanese patients with Gitelman's syndrome.

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.     

Clinical studies on the occurrence and the pathogenesis of optociliary veins

We reviewed retrospectively 20 cases of optociliary vein over the past 5 years. Fifteen of the 20 cases (75%) were over 40 years of age. There was no sex differences (9 males and 11 females). Causative ocular diseases were: central retinal vein occlusion (14 cases, 70%); optic disc drusen (2 cases, 10%); and optic nerve sheath meningioma, high myopia, glaucoma, congenital anomaly (1 case each, total 20%). The number of patients with an optociliary vein was high in central retinal vein occlusion (14/190 cases, 7.4%). We concluded that occurrence of optociliary vein is not restricted to cases with optic nerve sheath meningioma and this shunt vessel may occur under other conditions in which central retinal venous return is seriously disturbed. The most common cause of optociliary vein is central retinal vein occlusion.     

Analysis of a decreased Na+ conductance by tumor necrosis factor in identified neurons of Aplysia kurodai.

The ionic mechanisms of the effect of extracellularly ejected recombinant human tumor necrosis factor-alpha (rhTNF-alpha) on the membrane of identified neurons R9 and R10 of Aplysia kurodai was investigated with conventional voltage-clamp, micropressure ejection, and ion substitution techniques. Micropressure-ejected rhTNF caused a marked hyperpolarization in the unclamped neuron. Clamping the same neuron at it resting potential level (-60 mV) and reejecting rhTNF-alpha with the same dose produced a slow outward current [Io (TNF)] associated with a decrease in input membrane conductance. Io (TNF) was decreased by depolarization and increased by hyperpolarization. The extrapolated reversal potential of Io (TNF) was approximately +10 mV. Ion substitution and pharmacological experiments suggest that Io (TNF) in identified neurons R9 and R10 of A. kurodai is due to a decreased Na+ conductance but not due to an activation of the Na(+)-K+ pump. Our results demonstrate that the immunomodulator TNF can act directly on the nervous system as well as on the immune system.     

MRI in subacute combined degeneration

We describe a patient with clear lesions in the spinal cord on MRI due to subacute combined degeneration. T2-weighted images clearly showed abnormal high signals in the posterior columns, which disappeared on recovery from the disease.     

Human parvovirus-induced transient anemia and leukopenia after delivery]

A 30-year-old female at 27 weeks' gestation, was hospitalized on September 24 1990 because of the premature rupture of the amniotic sac. She underwent Caesarean section on the same day with 700 ml blood loss, but no blood transfusion was required. For several days after the operation, her hemoglobin level remained 7.8 g/dl and did not increase significantly in spite of parenteral iron therapy. On the 9th postoperative day, chills and pyrexia developed with leukopenia. Bone-marrow aspiration revealed severe erythroblastopenia with giant proerythroblasts, suggesting recent HPV infection, which was confirmed by the presence of anti-HPV IgM and HPV antigen by ELISA. The hemoglobin level gradually decreased to 6.0 g/dl by the 21st day, then began to increase rapidly. The serum of acute-phase containing HPV antigens inhibited BFU-E and CFU-E but not CFU-GM. The serum of convalescent-phase inhibited neither erythroid colony growth nor myeloid colony growth. These results indicate that the inhibitory effect of HPV in colony assay is highly specific for erythropoiesis and that HPV play a role in transient cessation of erythropoiesis. The reason, however, for leukopenia in HPV infection remained unclear. This case shows that HPV infection may induce severe hematological disorders even in normal person under erythropoietic stress.     

The effect of continuous topical application of heparin on flap survival.

To evaluate the beneficial effects of heparin on flap survival area, an experimental study was carried out on dorsal flaps in rats. Topical applications of heparin, released from a silicone gel sheet onto the critical area (which generally necrosed without treatment), resulted in an increase in the flap survival area and rate as compared to controls (p < 0.01). When heparin was applied topically but solely to an area proximal to the critical area however, no increase in the survival area resulted.     

A prostacyclin analogue reduces free radical generation in heart-lung transplantation.

The mechanism by which prostacyclin acts to prevent in vivo reperfusion injury is still uncertain. This study was therefore undertaken to assess the effect of a stable prostacyclin analogue (OP 41483-alpha-CD [OP]) on oxygen-derived free radicals after heart-lung transplantation. OP was administered to the heart-lung graft through the pulmonary artery for 25 minutes encompassing the reperfusion process. Free radicals were directly measured by electron spin resonance spectroscopy. The radical intensities of pulmonary venous blood were significantly lower in the OP group than in the control group, suggesting that fewer free radicals were generated in the lungs of the OP group. The cardiac and respiratory function were better in the OP group than in the control group. The lung is the primary source of oxygen free radical attack, and the beneficial action of OP on free radical generation is almost exclusively restricted to the lung and does not apply to the heart. This result suggested that OP probably is effective in inhibiting free radical generation from the endothelium.     

Globus pallidus calcification in Down syndrome with progressive neurologic deficits.

We report a 10-year-old Down syndrome patient who developed dystonia, choreoathetosis, dysarthria, and dysphagia beginning with hemiparesis. Cranial computed tomography disclosed bilateral calcification in the globus pallidus which resembled a sign of premature aging. Conversely, the clinical course and magnetic resonance imaging findings resembled those of Hallervorden-Spatz syndrome.     

Serotonin reduction in the mouse neostriatum during hyperthermia-induced convulsions studied by immunohistochemistry

Summary Changes occurring in serotonin neurons during hyperthermia-induced convulsions were examined by means of a modified immunohistochemical method. All mice (8–12 weeks of age) exposed to the temperature of 50°C had convulsions, showing a generalized tonic and/or clonic pattern. Immediately after the convulsions, the animals were perfused transcardially with a fixative. A significant reduction in serotonin immunoreactivity was observed in the neostratum (caudate-putamen complex) of the mice which had hyperthermia-induced seizures, while the serotonin immunoreactivity remained unchanged in the neocortex and paleostriatum. These results suggest that serotonin may be an important mediator in the mechanism of hyperthermia-induced convulsions or that the susceptibility of serotonin neurons to a convulsive state is greatest in the neostriatum.Supported in part by Grant No. 86-05 from the National Center for Nervous, Mental and Muscular Disorders (NCNMMD) of the Ministry of Health and Welfare and Grant No. 62770677 from the Ministry of Education, Science and Culture, Japan