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51.
Okada H Takagi A Murate T Adachi T Yamamoto K Matsushita T Takamatsu J Sugita K Sugimoto M Yoshioka A Yamazaki T Saito H Kojima T 《British journal of haematology》2004,126(2):219-225
Eight distinct and potentially causative mutations were identified in eight unrelated Japanese patients with protein S (PS) deficiency, by direct DNA sequencing of the protein Salpha (PSalpha) gene-specific polymerase chain reaction products of all 15 exons and exon/intron boundaries. There were five missense mutations, including two novel mutations (Cys80Tyr and Arg314His), and three showed a major impact on the expected gene products: novel mutations of a 5-bp deletion (delCTCTG887:Cys206Stop) and a nonsense mutation (Glu208Stop), as well as a previously reported splice site (exon 10 +5 A-->G) mutation. One of the patients showed compound heterozygosity for delCTCTG887 and 732A-->G. Investigation for the cosegregation state of these two mutations with PS deficiency in the patient's family suggested that the delCTCTG887 mutation was responsible for the abnormal phenotype and that the 732A-->G (Lys155Glu) mutation did not appear to play a key role. However, we also identified the same 732A-->G (Lys155Glu) mutation in an unrelated patient with apparent PS deficiency with severe pulmonary embolism, and found that this mutation seemed to cosegregate with a PS-deficient state in her family members. These data implied that unknown factor(s) other than the 732A-->G mutation itself might influence phenotypic expression of PS status in different individuals. 相似文献
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Dietary iodine intake in Japan varies from as little as 0.1 mg/day to as much as 20 mg/day. The present study was undertaken to assess the frequency of iodine-induced reversible hypothyroidism in patients diagnosed as having primary hypothyroidism, and to clarify the clinical backgrounds responsible for the spontaneous recovery of thyroid functions. Thirty-three consecutive hypothyroid patients (25 women and eight men) with a median age of 52 years (range, 21-77 years) without a history of destructive thyroiditis within 1 year were asked to refrain from taking any iodine-containing drugs and foods such as seaweed products for 1-2 months. The median serum thyrotropin (TSH) level, which was initially 21.9 mU/L (range, 5.4-285 mU/L), was reduced to 5.3 mU/L (range, 0.9-52.3 mU/L) after iodine restriction. Twenty-one patients (63.6%) showed a decrease in serum TSH by >50% and to <10 mU/L. Eleven patients (33.3%) became euthyroid with TSH levels within the normal range (0.3-3.9 mU/L). The ratios of TSH after iodine restriction to TSH before iodine restriction (aTSH/bTSH) did not correlate significantly with titers of anti-thyroid peroxidase antibody and anti-thyroglobulin antibody or echogenicity on ultrasonography, but correlated inversely with (99m)Tc uptake (r = 0.600, p < 0.001). Serum non-hormonal iodine levels, although not correlated significantly with aTSH/bTSH values, were significantly higher in the 21 patients with reversible hypothyroidism than in the remaining 12 patients. TSH binding inhibitor immunoglobulin was negative in all except one weakly positive case. In conclusion, (1) primary hypothyroidism was recovered following iodine restriction in more than half of the patients, and (2) the reversibility of hypothyroidism was not significantly associated with Hashimoto's thyroiditis but with increased (99m)Tc uptake and elevated non-hormonal iodine levels. 相似文献
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OBJECTIVE: Controversy abounds on the issue of seasonal variation in new onset of Graves' disease, partly due to the difficulty of precisely dating the exact start of symptoms. To address the possible relationship between climatic changes and disease activity from a different perspective, we reviewed time of relapse during regular follow-up after successful drug treatment with thionamides. DESIGN: Retrospective analysis of a case series in a university clinic. PATIENTS AND MEASUREMENTS: We consecutively registered patients who experienced re-emergence of hyperthyroidism between 1992 and 2001 after successful antithyroid drug therapy. Excluded were subjects with superimposing painless thyroiditis, in postpartum, on immunomodulatory drugs, or off thionamides prematurely on their own volition. RESULTS: Fifty-two patients recurred 2 to 36 months after drug cessation. The frequency was higher in spring and summer (March to August) than in autumn and winter (September to February). With a new coated-tube radioreceptor assay, TSH binding inhibitor immunoglobulin activity was detected in sera from 87.5% of the reworsened patients. CONCLUSIONS: Graves' disease tends to relapse more frequently in spring and summer. Further clinical studies are warranted to clarify underlying mechanism (s) for this seasonal variation. 相似文献
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The neuropeptide Y (NPY)/Agouti-related protein (AgRP) neurons of the hypothalamic arcuate nucleus are thought to promote feeding. Here, we demonstrate that feeding state in vivo, through a leptin-dependent process, induces large and persistent changes in the electrophysiological activity of these neurons as measured extracellularly in vitro. Consistent with an orexigenic role, fasting induced a 4-fold increase in the basal action potential frequency of NPY/AgRP neurons. Leptin, when injected into fasted wild-type mice, induced a dose- and time-dependent decrease in spike frequency, which approached fed levels 2-3 h post treatment. In leptin-deficient (lep(ob)/lep(ob)) and leptin receptor-deficient (lepr(db)/lepr(db)) mice, NPY/AgRP spike frequency was not significantly increased by fasting, and even in mutant mice fed ad libitum, spike frequency was at least as high as in fasted wild-type mice. All recordings included GABA(A) and ionotropic glutamate receptor antagonists, suggesting that expression of this modulation is potentially intrinsic and not synaptically dependent. Recorded neurons were unambiguously identified using NPY-Sapphire transgenic mice. This is a remarkably straightforward example of a very robust in vitro electrophysiogical effect produced by a simple behavioral manipulation, food restriction. 相似文献
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We report on a carrier of human T-lymphotropic virus type 1 (HTLV-1) who developed mixed connective tissue disease (MCTD). This patient suddenly manifested clinical symptoms and interstitial pneumonia ascribable to MCTD following long-term infection with HTLV-1. After initiation of oral prednisolone all manifestations quickly improved in parallel with a decrease in inflammatory reactions. In this patient HTLV-1 infection might have played an important role in the pathogenesis of MCTD. Since HTLV-1 can cause adult T-cell leukemia and HTLV-1-associated myelopathy, and also collagen diseases including MCTD, careful observation is necessary even in a carrier, particularly when autoantibodies are detectable in serum. 相似文献
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Junya Yamamoto Daigo Nakazawa Saori Nishio Yasunobu Ishikawa Minoru Makita Yoshihiro Kusunoki So Nagai Yuichiro Fujieda Masahiko Takahata Kanji Yamada Tsuyoshi Yamamura Akihiko Yotsukura Masanobu Saito Masaru Shimazaki Tatsuya Atsumi 《Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy》2020,24(2):146-153
Adynamic bone disease in HD patients is characterized by skeletal resistance to parathyroid hormone (PTH) or suppression of PTH release, leading to a downregulated bone turnover and bone fracture. Hence, we examined the efficacy of weekly teriparatide for HD patients with low PTH indicating adynamic bone disease without a history of parathyroidectomy. Fifteen HD patients with low PTH were recruited in this prospective observational study. Of them, 10 received teriparatide for 12 months and five nontreated patients were enrolled as control. Primary outcomes were defined as the changes in bone mineral density and bone turnover markers. Bone mineral density at the lumbar spine increased by 3.7% and 2.5% at 6 and 12 months, respectively, and bone formation markers increased, while bone resorption markers did not change in the teriparatide group. At 12 months after teriparatide administration, endogenous PTH was secreted followed by the recovery of low bone turnover. 40% of patients in the teriparatide group dropped out due to adverse events and the most common adverse event was transient hypotension. This study suggests that weekly teriparatide for HD patients with low PTH in the absence of parathyroidectomy accelerates bone formation and bone turnover, leading to increased trabecular bone mass and secretion of endogenous PTH. 相似文献
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