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991.
Hitoshi Yokoyama Miho Shimizu Takashi Wada Keiichi Yoshimoto Yasunori Iwata Kazuaki Shimizu Norihiko Sakai Kengo Furuichi Yukimasa Hisada Hiroshi Takakuwa Ken-Ichi Kobayashi 《Therapeutic apheresis》2002,6(2):167-173
A considerable permeability factor (or factors) derived from circulating T cells has a crucial role in proteinuria of nephrotic syndrome (NS). We attempted to remove pathogenic T cells through lymphocytapheresis (LCAP) in 6 patients with primary NS, 2 patients with minimal change nephrotic syndrome (MCNS), 2 patients with focal segmental glomerulosclerosis (FSGS), 1 patient with membranous nephropathy (MN), and 1 patient with MN and FSGS using Cellsorba (Asahi Medical Co., Osaka, Japan). LCAP was performed 2 times in 2 consecutive weeks and was followed with corticosteroid therapy with or without cyclosporine A in 5 patients. Two patients with MCNS, 1 with FSGS, and 1 with MN and FSGS showed a dramatic decrease of proteinuria (-30% and -94%) in their urine protein/creatinine ratio. Three out of 4 patients had a complete or partial remission (proteinuria <1g/day) within 8 weeks following immunosuppressive therapy. During the LCAP, T cells, especially activated T cells, decreased significantly in the response group. The other 2 patients, 1 with FSGS and 1 with MN, however, had no response to LCAP and following immunosuppressive therapy or low-density lipoprotein apheresis and suffered from end-stage renal failure or death by pneumonia. These results suggested that LCAP might have a beneficial effect on the treatment of NS, especially MCNS and in some patients with FSGS, despite varying responses to LCAP and concomitant immunosuppressive therapy. 相似文献
992.
Neurotrophic factor receptors in epiretinal membranes after human diabetic retinopathy 总被引:7,自引:0,他引:7
Harada T Harada C Mitamura Y Akazawa C Ohtsuka K Ohno S Takeuchi S Wada K 《Diabetes care》2002,25(6):1060-1065
OBJECTIVE: Formation of epiretinal membranes (ERMs) in the posterior fundus results in progressive deterioration of vision. ERMs have been associated with numerous clinical conditions, including proliferative diabetic retinopathy (PDR), but its pathogenic mechanisms are still unknown. This study was conducted to determine whether neurotrophic factor receptors (tyrosine kinase receptors trkA, trkB, and trkC; low-affinity neurotrophin [NT] receptor p75 [p75(NTR)]; glial cell line-derived neurotrophic factor receptor-alpha1 [GFR alpha 1] and GFR alpha 2; and Ret) are involved in the formation of ERMs after PDR. RESEARCH DESIGN AND METHODS: ERM samples were obtained by vitrectomy from 19 subjects with PDR aged 57 +/- 8 years with 17 +/- 8 years of diabetes and 15 subjects with idiopathic ERM. They were processed for RT-PCR analysis. In addition, 11 ERM samples from PDR patients aged 47 +/- 18 years with 13 +/- 4 years of diabetes were processed for immunohistochemical analysis. RESULTS: Expressions of trkA, trkB, trkC, p75(NTR), and Ret mRNAs were similar in both groups. In contrast, GFR alpha 2 expression levels were significantly higher (17 of 19 vs. 2 of 15 subjects in idiopathic ERM, P < 0.0001) in PDR subjects. Accordingly, immunohistochemical analysis revealed expression of GFR alpha 2 protein in all of the 11 ERMs derived from PDR patients, and that region was double-labeled with glial cell-specific markers. On the other hand, GFR alpha 1 expression was lower (8 of 19 vs. 12 of 15 subjects with idiopathic ERM, P = 0.0258) in PDR subjects. CONCLUSIONS: These results suggest a possibility that glial cell line-derived neurotrophic factor receptor (GDNF) subtypes are differently involved in the formation of ERMs. 相似文献
993.
Social adaptation of children with congenital fecal dysfunction: from the viewpoint of the mother-child relationship 总被引:1,自引:0,他引:1
Funakosi S Hayashi J Kamiyama T Ueno T Ishii T Wada M Hayashi Y Matsuoka H 《The Tohoku journal of experimental medicine》2005,206(2):117-124
Excretory dysfunction associated with congenital anal anomalies (a generic term that includes anal atresia and Hirschsprung's disease) is presumed to greatly affect the psychology of the affected children. In this study, we conducted a survey on the psychological status of children with excretory dysfunction, and investigated the relationship between the affected children and their families in addition to their social life. Four children with fecal dysfunction due to a congenital anal anomaly and their mothers were interviewed. The results of psychological tests in the children and mothers along with our findings in the interviews with the children and mothers, were included in the data analysis. We found that regardless of the degree of excretory dysfunction, the child's state of mind was influenced by whether the mother exhibited warmth or criticism towards her child and whether there was a support system for the mother and child. We suggest that psychiatric consultation is necessary for these children. 相似文献
994.
Miho Shimizu Kengo Furuichi Tadashi Toyama Tomoaki Funamoto Shinji Kitajima Akinori Hara Daisuke Ogawa Daisuke Koya Kenzo Ikeda Yoshitaka Koshino Yukie Kurokawa Hideharu Abe Kiyoshi Mori Masaaki Nakayama Yoshio Konishi Ken-ichi Samejima Masaru Matsui Hiroyuki Yamauchi Tomohito Gohda Kei Fukami Daisuke Nagata Hidenori Yamazaki Yukio Yuzawa Yoshiki Suzuki Shouichi Fujimoto Shoichi Maruyama Sawako Kato Takero Naito Kenichi Yoshimura Hitoshi Yokoyama Takashi Wada Research Group of Diabetic Nephropathy the Ministry of Health Labour Welfare of Japan Japan Agency for Medical Research Development 《Clinical and experimental nephrology》2018,22(2):377-387
Background
There is increased interest in surrogate endpoints for clinical trials of chronic kidney disease.Methods
In this nationwide observational study of 456 patients with type 2 diabetes and clinically suspected diabetic nephropathy followed for a median of 4.2 years, we evaluated the association between estimated glomerular filtration rate (eGFR) and albuminuria at baseline or during follow-up and risk of ESRD.Results
Low eGFR (<60 mL/min/1.73 m2) and macroalbuminuria at enrollment were independently associated with risk of ESRD. In patients with macroalbuminuria, both ≤?50% change and ?50 to ?30% change in eGFR over 1 and 2 years were predictive of ESRD. The higher cut point (≥50% decline in eGFR) was more strongly predictive but less common. Remission of macroalbuminuria to normo-/microalbuminuria at 1 and 2 years was associated with a lower incidence of ESRD than no remission; however, it was not a determinant for ESRD independently of initial eGFR and initial protein-to-creatinine ratio.Conclusion
These results suggest that a ≥30% decline in eGFR over 1 or 2 years adds prognostic information about risk for ESRD in patients with type 2 diabetes and macroalbuminuria, supporting the consideration of percentage decline in eGFR as a surrogate endpoint among macroalbuminuric cases in type 2 diabetes. On the other hand, our study suggests that additional analyses on the relationship between remission of macroalbuminuria and risk of ESRD are needed in type 2 diabetes.995.
Kengo Furuichi Miho Shimizu Yukio Yuzawa Akinori Hara Tadashi Toyama Hiroshi Kitamura Yoshiki Suzuki Hiroshi Sato Noriko Uesugi Yoshifumi Ubara Junichi Hohino Satoshi Hisano Yoshihiko Ueda Shinichi Nishi Hitoshi Yokoyama Tomoya Nishino Kentaro Kohagura Daisuke Ogawa Koki Mise Yugo Shibagaki Hirofumi Makino Seiichi Matsuo Takashi Wada Research Group of Diabetic Nephropathy Ministry of Health Labour Welfare of Japan and Japan Agency for Medical Research Development 《Clinical and experimental nephrology》2018,22(3):570-582
Background
The Japanese classification of diabetic nephropathy reflects the risks of mortality, cardiovascular events and kidney prognosis and is clinically useful. Furthermore, pathological findings of diabetic nephropathy are useful for predicting prognoses. In this study, we evaluated the characteristics of pathological findings in relation to the Japanese classification of diabetic nephropathy and their ability to predict prognosis.Methods
The clinical data of 600 biopsy-confirmed diabetic nephropathy patients were collected retrospectively from 13 centers across Japan. Composite kidney events, kidney death, cardiovascular events, all-cause mortality, and decreasing rate of estimated GFR (eGFR) were evaluated based on the Japanese classification of diabetic nephropathy.Results
The median observation period was 70.4 (IQR 20.9–101.0) months. Each stage had specific characteristic pathological findings. Diffuse lesions, interstitial fibrosis and/or tubular atrophy (IFTA), interstitial cell infiltration, arteriolar hyalinosis, and intimal thickening were detected in more than half the cases, even in Stage 1. An analysis of the impacts on outcomes in all data showed that hazard ratios of diffuse lesions, widening of the subendothelial space, exudative lesions, mesangiolysis, IFTA, and interstitial cell infiltration were 2.7, 2.8, 2.7, 2.6, 3.5, and 3.7, respectively. Median declining speed of eGFR in all cases was 5.61 mL/min/1.73 m2/year, and the median rate of declining kidney function within 2 years after kidney biopsy was 24.0%.Conclusions
This study indicated that pathological findings could categorize the high-risk group as well as the Japanese classification of diabetic nephropathy. Further study using biopsy specimens is required to clarify the pathogenesis of diabetic kidney disease.996.
Abe T Yoshida M Tomita H Kano T Sato M Wada Y Fuse N Yamada T Tamai M 《The Tohoku journal of experimental medicine》2000,191(1):7-20
Autologous iris pigment epithelial cell transplantation was performed on patients with exudative age-related macular degeneration (AMD). Autologous IPE cell culture was performed using autologous serum after iridectomy in 7 patients with AMD. The cell suspensions (2 approximately 20 x 10(4) cells) were transplanted into the submacular lesion of individuals after removal of neovascular membranes. Subsequent ophthalmological examinations, including best corrected visual acuity and fluorescein or indocyanine green angiography, were performed. In addition, 15 patients with AMD, who underwent removal of neovascular membrane without transplantation, were evaluated as non randomized controls. Varying degrees of atrophy or defects of choriocapillaris and retinal pigment epithelium were observed in all of the patients. No cystoid macular edema or fluorescein leakage was observed after treatment, but window defects were present. No patient had decreased visual acuity. One treated patient developed mild subretinal fibrosis and an other patient developed mild preretinal fibrosis, however no difference was significant when compared with the control. In conclusion, the treatment resulted in no significant improvement in macular function, as compared with the control; however, no rejection or deterioration in visual acuity occurred up to the 13 month follow up. 相似文献
997.
Loeser S Loser K Bijker MS Rangachari M van der Burg SH Wada T Beissert S Melief CJ Penninger JM 《The Journal of experimental medicine》2007,204(4):879-891
The concept of tumor surveillance implies that specific and nonspecific components of the immune system eliminate tumors in the early phase of malignancy. Understanding the biochemical mechanisms of tumor immunosurveillance is of paramount significance because it might allow one to specifically modulate spontaneous antitumor activity. We report that inactivation of the E3 ligase Casitas B cell lymphoma-b (Cbl-b) confers spontaneous in vivo rejection of tumor cells that express human papilloma virus antigens. Moreover, cbl-b(-/-) mice develop significantly fewer ultraviolet B (UVB)-induced skin malignancies and reject UVB-induced skin tumors. CD8(+) T cells were identified as key players in the spontaneous tumor rejection response. Loss of Cbl-b not only enhances antitumor reactivity of CD8(+) T cells but also occurs in the absence of CD4(+) T cells. Mechanistically, cbl-b(-/-) CD8(+) T cells are resistant to T regulatory cell-mediated suppression and exhibit enhanced activation and rapid tumor infiltration. Importantly, therapeutic transfer of naive cbl-b(-/-) CD8(+) T cells is sufficient to mediate rejection of established tumors. Even up to 1 yr after the first encounter with the tumor cells, cbl-b(-/-) mice carry an "anticancer memory." These data identify Cbl-b as a key signaling molecule that controls spontaneous antitumor activity of cytotoxic T cells in different cancer models. Inhibition of Cbl-b is a novel approach to stimulate long-lasting immunity against cancer. 相似文献
998.
Shin-ichiro Ohmura Taio Naniwa Shin-ya Tamechika Toshiaki Miyamoto Daisuke Shichi Nobukata Kazawa Shiho Iwagaitsu Shinji Maeda Jun-ichi Wada Akio Niimi 《Journal of infection and chemotherapy》2019,25(4):253-261
Objectives
To evaluate the effectiveness and safety of lower-dose sulfamethoxazole/trimethoprim therapy (SMX/TMP) for Pneumocystis jirovecii pneumonia (PCP) in patients with systemic rheumatic diseases.Methods
In this multicenter retrospective study, we compared effectiveness and safety of SMX/TMP for the treatment of PCP among patients divided into three groups according to the initial dosage of SMX/TMP: the low, ≤10 mg/kg/day; the intermediate, 10–15 mg/kg/day; and the high and conventional, 15–20 mg/kg/day for TMP dose.Results
Eighty-one patients, including 22, 30, and 29 patients in the low-, the intermediate- and the high-dose group could be analyzed and the 30-day survival rate were 100%, 93.3%, and 96.7%, respectively (P = 0.28). There were significant dose-dependent increasing trends of severe adverse drug reactions (ADRs) for SMX/TMP that were graded as ≥3 according to the Common Terminology Criteria for Adverse Events. When stratified by presence of severe hypoxemia defined by alveolar-arterial O2 gradient ≥45 mmHg, the 30-day survival and treatment modification rate were similar among the three groups, but frequency of severe ADRs were significantly decreased in the low-dose group. The low-dose group was independently and negatively associated with treatment modification within 14 days and severe ADRs.Conclusions
Lower dose SMX/TMP therapy with ≤10 mg/kg/day for TMP was as effective as higher dose therapy for the treatment of PCP and associated with lower rates of treatment modification and severe ADRs in patients with systemic rheumatic diseases. 相似文献999.
B. Inoue M. Hata Y. Ichiba H. Wada H. Misumi T. Mori 《Journal of inherited metabolic disease》1990,13(1):93-101
Summary A screening strategy has been used which uses the Paigen and Beutler methods for the determination of galactose and galactose-1-phosphate. A blood spot test for epimerase has also been developed. In the last 10 years, 265019 samples from newborns have been tested by these methods. Among the 154 screening positives, we have detected seven cases of epimerase-deficient galactosaemia (Type III), seven cases of Duarte/galactosaemia heterozygotes, 48 cases of other various types of heterozygotes, four cases of persistent hypergalactosaemia, three cases of hepatitis and one case of congenital atresia of the bile duct. These results indicate that our screening system has effectively detected the infants with galactose metabolic disorders. 相似文献
1000.
Experimentally induced immunity to chlamydial abortion of cattle 总被引:3,自引:0,他引:3
D G McKercher G L Crenshaw J H Theis E M Wada C M Mauris 《The Journal of infectious diseases》1973,128(2):231-234