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Severe myoclonic epilepsy (SMEI) or Dravet syndrome is caused by mutations of the SCN1A gene that encodes voltage-gated sodium channel alpha-1 subunit. Recently, we generated and characterized a knock-in (KI) mice with an SCN1A nonsense mutation that appeared in three independent SMEI patients. The SCN1A-KI mice well reproduced the SMEI disease phenotypes. Both homozygous and heterozygous knock-in mice developed epileptic seizures within the first postnatal month. In heterozygous knock-in mice, trains of evoked action potentials in inhibitory neurons exhibited pronounced spike amplitude decrement late in the burst but not in pyramidal neurons. We further showed that in wild-type mice the Nav1.1 protein is expressed dominantly in axons and moderately in somata of parbalbumin (PV) – positive inhibitory interneurons. Our immunohistochemical observations of the Nav1.1 are clearly distinct to the previous studies, and our findings has corrected the view of the Nav1.1 protein distribution. The data indicate that Nav1.1 plays critical roles in the spike output from PV interneurons and further, that the specifically altered function of these inhibitory circuits may contribute to epileptic seizures in the mice. These information should contribute to the understanding of molecular pathomechanism of SMEI and to develop its effective therapies. 相似文献
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Kazuo Yamakawa Masashi Takanashi Masao Watanabe Noriyuki Nakamura Tomonori Kobayashi Masato Hasegawa Yoshikuni Mizuno Shigeki Tanaka Hideo Mori 《Neuropathology》2006,26(6):586-591
We report on a male patient with Pick disease who had shown severe white matter atrophy and dilatation of the lateral ventricle in the frontal lobe from an early stage. Upon admission to our hospital 2 years after disease onset, the patient showed apathy, and MRI revealed severe atrophy of the cortex and white matter of the frontal lobe. He died at age 74, 11 years after disease onset. Autopsy revealed severe atrophy of the frontal and temporal lobes, severe loss of white matter in the frontal lobe, dilatation of the lateral ventricles, and cortical thinning. Histopathological examination showed severe loss of myelinated fibers in the frontal white matter and severe neuronal loss with gliosis in the frontal and temporal cortices. Many Pick bodies were seen. Our patient had a rare case of Pick disease predominantly affecting the frontal lobe with severe involvement of the white matter from an early stage. This case suggests that myelinated fibers in the white matter as well as cerebral neurons are primarily affected in Pick disease. 相似文献
5.
To elucidate the mechanisms of the intracellular signal transduction elicited with bradykinin in NG108-15 neuroblastoma x glioma hybrid cells, we examined the activation of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) by bradykinin stimulation. When the extract of NG108-15 cells was immunoprecipitated with the affinity-purified antibody to brain CaM kinase II, a 50-kDa protein in the immunoprecipitate mainly became autophosphorylated in a Ca2+/calmodulin-dependent manner. The results suggest that the 50-kDa protein is the subunit of CaM kinase II in NG108-15 cells. The Ca2+/calmodulin-independent activity (autonomous activity) of the enzyme increased twice within 10 s by stimulation with 1 microM bradykinin in the cells. The increase in the autonomous activity of the enzyme had two phases: the transient early-peak phase and the long late-plateau phase. The former was abolished by the pretreatment of the cells with 10 mM caffeine or 20 microM BAPTA-AM, and the latter was abolished by the removal of the extracellular Ca2+ with 1 mM EGTA or by the pretreatment with 1 microM nifedipine. Stimulation of 32P-labeled NG108-15 cells with 1 microM bradykinin increased the autophosphorylation of CaM kinase II and this increase was abolished by pretreatment with caffeine or BAPTA-AM. These results suggest that CaM kinase II is activated via the inositol phospholipid signaling pathway induced with bradykinin in NG108-15 cells. 相似文献
6.
M Kurihara S Shimauchi K Ohyama T Yamakawa H Watanabe S Hirakawa S Ohkuma 《Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan》1990,110(10):783-787
One mol perchloric acid-soluble fraction (PASF) obtained from ascitic fluid of a patient (blood group B) with metastatic omentum tumor from ovarian cancer was a glycoprotein fraction containing 35.4% carbohydrate and exhibited A, B and Thomsen-Friedenreich (T) activities. This fraction was separated into three fractions, Frs. 1-3, by a gel filtration with Bio-Gel A-1.5 m column. Among these fractions, Fr. 1 which was obtained in a 5.5% yield to PASF, was a glycoprotein fraction with a high molecular weight, 23.3% carbohydrate and A, B and T activities. Other minor fraction, Fr. 2, and the major fraction, Fr. 3, contained 43.2% and 43.9% carbohydrate, but did not show A, B and T activities, respectively. 相似文献
7.
K Shibata Y Yamakawa T Torii T Mizuno A Masaoka 《Nihon Kyōbu Shikkan Gakkai zasshi》1991,29(3):372-375
A 53-year-old man was admitted to Nagoya City University Hospital with complaining of bloody sputum and an abnormal shadow on chest X-ray film. The chest X-ray film showed a giant bulla in the right upper and middle lung fields and a mass shadow inside the bulla. In addition he had the swelling of bilateral inguinal lymph nodes. He was suspected to having bleeding from the lung bulla, and received a right upper lobectomy. The resected specimen showed a lobular tumor in the parenchyma of lung and an oval lymphoma nodule moving around inside of lung bulla. Histologically, both the lung tumor and inguinal lymph-nodes were non-Hodgkin's malignant lymphoma, diffuse and plasmacytoid large cell type. 相似文献
8.
Kazutoshi Hamada Akihito Tomonaga Masafumi Gotoh Hideyuki Yamakawa Hiroaki Fukuda 《Journal of orthopaedic research》1997,15(1):24-32
To determine the healing potential and healing process of torn supraspinatus tendons, in situ hybridization was used to localize cells containing α1 type-I procollagen mRNA. Biopsy specimens of torn supraspinatus tendons from 19 patients with complete-thickness tears and 13 patients with incomplete-thickness tears were obtained during surgery. Four macroscopically normal supraspinatus tendons were obtained to serve as normal controls. Specimens were fixed in 10% buffered formalin and embedded in paraffin. A 22-mer oligonucleotide probe was labeled with digoxigenin and used as an in situ marker. The labeled cells were mainly composed of tenocytes and undifferentiated mesenchymal cells. In complete-thickness tears, the labeled cells at the proximal tendon stumps in the specimens that were obtained less than 4 months after trauma were significantly more abundant than in the specimens obtained 4 months or more after trauma. However, the number of labeled cells was maintained at the torn portion even in long-standing incomplete-thickness tears. The labeled cells at the margins of concomitant intratendinous extensions of the tears were detected even in the long-standing tears. The intratendinous extensions exhibited more labeled cell than were bursal-side or joint-side layers of the tendon substance in the incomplete-thickness tears (p < 0.05). The torn supraspinatus tendon may possess an intrinsic healing capability in the intermediate and late phases of tendon healing. Incomplete-thickness tears and concomitant intratendinous extensions can continue to rupture after the initial injury. 相似文献
9.
T Morimoto K Komaki K Oshimo T Yamakawa N Mitsuyama T Tanaka Y Monden 《The Japanese journal of surgery》1987,17(5):377-381
In Tokushima prefecture, mass screening for breast cancer has been conducted using physical examination alone since 1970. Breast cancer was detected in 116 of 111,571 screened women up until 1984. The detection rate was 0.08 per cent in total examinees, 0.13 per cent in initial examinees, and 0.04 per cent in subsequent examinees. The patients with breast cancer were divided into three groups, i.e., 62 cases detected at initial screening, 28 cases detected at subsequent screenings, and 26 interval cancer cases. 510 patients with breast cancer in the outpatient clinic were serving as controls. The stage classification and nodal involvement were significantly different between the mass screening group and the control group, but not significantly different among the three groups. The interval cases were detected at an early stage. The survival rates were not significantly different between the three groups and the control group. Efforts should be doubled to educate women about the proper method of breast self-examination in order to promote the early detection of breast cancer. 相似文献
10.
Seventeen cases of pure red cell aplasia (PRCA) with thymoma were studied clinically, histologically, and immunologically. Two cases were associated with myasthenia gravis (MG), and three with hypogammaglobulinemia. Coombs test and antinucleus antibody test were positive in five cases. All thymomas were spindle cell types, and the adjacent thymuses had no germinal center, but showed epithelial clusters frequently. All patients, except one whose tumor was unresectable, had thymo-thymomectomy. The operation was effective in six cases (37.5%), and the effects were not different between two operative procedures (simple and extended thymectomy). Myasthenic symptoms in two patients remitted after the operation, but effects on hypogammaglobulinemia were conincident with those on PRCA. 相似文献