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Yoshihito Yokoyama,Tadao Takano,Kenji Nakahara,Tadahiro Shoji,Hirokazu Sato,Hidekazu Yamada,Nobuo Yaegashi,Kunihiro Okamura,Hirohisa Kurachi,Toru Sugiyama,Toshinobu Tanaka,Akira Sato,Toru Tase,Hideki Mizunuma The purpose of this study was to evaluate the effectiveness and safety of concurrent chemoradiotherapy using weekly nedaplatin for the treatment of locally advanced squamous cell carcinoma of the uterine cervix. Nedaplatin at 30 mg/m(2) was administered weekly 6 times with a concurrent external bea... ( view more )m and intracavity radiotherapy. External beam radiation was delivered with a fraction dose of 2 Gy per day for 5 days a week during a 5-week period and intracavitary brachytherapy, of which the fraction size is 6 Gy to point A, was given once a week for a total of 4 times using a remote after-loading system. Forty-five patients were enrolled in this trial between April 2003 and December 2006. Of the 45 patients, 40 (88.9%) completed the scheduled treatment and were evaluated for efficacy and safety. Of these, 4 were stage Ib2, 12 were stage IIb, 18 were stage IIIb and 6 were stage IVa. The age distribution ranged from 27 to 79 years with a median age of 58. The 40 patients achieved an objective response, 36 (90%) a complete response and 4 (10%) a partial response. At a median follow-up of 29 months (range, 8-52), the 3-year progression-free and overall survival were 58.7% (95% confidence interval, 42-75%) and 78.0% (95% confidence interval, 56-90.0%), respectively. Acute toxicities were transient and rendered non-lethal. Of the 45 patients enrolled for the trial, only 3 (6.7%) had grade 4 leukopenia and neutropenia, respectively. Grade 3 diarrhea and nausea/ vomiting were observed in 2 (4.4%) and 1 (2.2%), respectively. These results indicate that weekly nedaplatin of 30 mg/m(2) with concurrent radiotherapy is an effective and well-tolerated regimen for advanced squamous cell carcinoma of the uterine cervix. ( view less ) Morio Matsumoto,Kazuhiro Chiba,Yoshiaki Toyama,Katsushi Takeshita,Atsushi Seichi,Kozo Nakamura,Jun Arimizu,Shunsuke Fujibayashi,Shigeru Hirabayashi,Toru Hirano,Motoki Iwasaki,Kouji Kaneoka,Yoshiharu Kawaguchi,Kosei Ijiri,Takeshi Maeda,Yukihiro Matsuyama,Yasuo Mikami,Hideki Murakami,Hideki Nagashima,Kensei Nagata,Shinnosuke Nakahara,Yutaka Nohara,Shiro Oka,Keizo Sakamoto,Yasuo Saruhashi,Yutaka Sasao,Katsuji Shimizu,Toshihiko Taguchi,Makoto Takahashi,Yasuhisa Tanaka,Toshikazu Tani,Yasuaki Tokuhashi,Kenzo Uchida,Kengo Yamamoto,Masashi Yamazaki,Toru Yokoyama,Munehito Yoshida,Yuji Nishiwaki STUDY DESIGN: Retrospective multi-institutional study OBJECTIVE: To describe the surgical outcomes in patients with ossification of the posterior longitudinal ligament in the thoracic spine (T-OPLL) and to clarify factors related to the surgical outcomes. SUMMARY OF BACKGROUND DATA: Detailed analys... ( view more )es of surgical outcomes of T-OPLL have been difficult because of the rarity of this disease. METHODS: The subjects were 154 patients with T-OPLL who were surgically treated at 34 institutions between 1998 and 2002. The surgical procedures were laminectomy in 36, laminoplasty in 51, anterior decompression via anterior approach in 25 and via posterior approach in 29, combined anterior and posterior fusion in 8, and sternum splitting approach in 5 patients. Instrumentation was conducted in 52 patients. Assessments were made on (1) The Japanese Orthopedic Association (JOA) scores (full score, 11 points), its recovery rates, (2) factors related to surgical results, and (3) complications and their consequences. RESULTS: (1) The mean JOA score before surgery was 4.6 +/- 2.0 and, 7.1 +/- 2.5 after surgery. The mean recovery rate was 36.8% +/- 47.4%. (2) The recovery rate was 50% or higher in 72 patients (46.8%). Factors significantly related to this were location of the maximum ossification (T1-T4) (odds ratio, 2.43-4.17) and the use of instrumentation (odds ratio, 3.37). (3) The frequent complications were deterioration of myelopathy immediately after surgery in 18 (11.7%) and dural injury in 34 (22.1%) patients. CONCLUSION: The factors significantly associated with favorable surgical results were maximum ossification located at the upper thoracic spine and use of instrumentation. T-OPLL at the nonkyphotic upper thoracic spine can be treated by laminoplasty that is relatively a safe surgical procedure for neural elements. The use of instrumentation allows correction of kyphosis or prevention of progression of kyphosis, thereby, enhancing and maintaining decompression effect, and its use should be considered with posterior decompression. ( view less ) Raijiro Katsuno,Toru Hasegawa,Toru Iwashina,Daisuke Sakai,Yoshihiro Mikawa,Joji Mochida STUDY DESIGN: A study of age-related effects on nitric oxide (NO) and cytokine production in cocultured rat nucleus pulposus (NP) cells and macrophages. OBJECTIVE: To evaluate the effects of age on NO and cytokine production in an in vitro model of cocultured NP cells and macrophages. SUMMARY OF BA... ( view more )CKGROUND DATA: It is well known that the clinical characteristics of lumbar disc herniation differ with age. The relationship between age-related differences in clinical features and immuno-chemical factors, such as NO and inflammatory cytokines, has not been established. METHODS: Male Sprague Dawley rats (n = 45), including 15 animals from 3 groups (3-, 12-, and 32-weeks old), were used. NP cells and exudated peritoneal macrophages were cocultured in serum-free media. NO levels were measured at 2-, 24-, 48-, and 72 hours using the Griess method. After 7 days of culture, the production of cytokines, including tissue inhibitor metalloproteinase-1, interferon-gamma (IFN-gamma), and interleukin-10 (IL-10) were evaluated. RESULTS: NO levels of coculture increased with age. In the coculture groups, tissue inhibitor metalloproteinase-1 and IFN-gamma level of 3 weeks old were statistically higher than 12 and 32 weeks old. IL-10 level of 3 weeks old was statistically lower than 12 and 32 weeks old. CONCLUSION: NO levels of cocultures increased with age that suggests inflammatory reactions increase with age. This study showed an age-related cytokine imbalance, as represented by levels of IFN-gamma and IL-10. Stress and aging are thought to affect the extracellular matrix and change the immunologic response. Younger rat NP cells had higher cell-mediated immunity activity, while the older rat had higher humoral immunity activity. These results demonstrate that age affects the immunologic response attributable to NP cells. Further studies are needed to elucidate the mechanism of this newly observed occurrence and to apply these findings clinically. ( view less ) Mami Kouchi,Kazuo Okimoto,Izumi Matsumoto,Yoshiko Michimae,Toru Yamada,Tadashi Inoue,Toru Kimura,Takaki Seki,Masashi Yasuba,Okio Hino Fibromatosis-type fibromas were found to develop at abdominal surgical sites in 4 heterozygous Nihon rats, a model for the human Birt-Hogg-Dubé syndrome. In all 4 rats, solitary and firm nodules were located within the lateral abdominal musculature involving the full thickness of the abdominal wall... ( view more ) at the sites of laparotomy. Histologically, the nodules consisted of well-differentiated fibroblastic spindle-shaped cells. These cells were surrounded by large amounts of collagen fibers, and appeared to infiltrate within the abdominal musculature. A portion of the spindle-shaped cells showed features of myofibroblasts. These characteristics are consistent with desmoid tumors in human. Although the etiology of desmoid tumors in human remains unclear, they are known to occur in association with hormonal factors, surgical trauma, and familial adenomatous polyposis. In animals, they have been reported in dogs, cats, horses, and genetically modified mouse models for human familial adenomatous polyposis. The development of the tumors in the Nihon rats was apparently associated with surgical incisions. Genetic factor should be involved in the occurrence of the tumor, since it was found only in the Nihon rats among many rats. Our present data suggest that Bhd gene mutation is not likely to be a candidate. ( view less ) Yasukazu Nakahata,Mayumi Yoshida,Atsuko Takano,Haruhiko Soma,Takuro Yamamoto,Akio Yasuda,Toru Nakatsu,Toru Takumi BACKGROUND: The circadian expression of the mammalian clock genes is based on transcriptional feedback loops. Two basic helix-loop-helix (bHLH) PAS (for Period-Arnt-Sim) domain-containing transcriptional activators, CLOCK and BMAL1, are known to regulate gene expression by interacting with a promot... ( view more )er element termed the E-box (CACGTG). The non-canonical E-boxes or E-box-like sequences have also been reported to be necessary for circadian oscillation. RESULTS: We report a new cis-element required for cell-autonomous circadian transcription of clock genes. This new element consists of a canonical E-box or a non-canonical E-box and an E-box-like sequence in tandem with the latter with a short interval, 6 base pairs, between them. We demonstrate that both E-box or E-box-like sequences are needed to generate cell-autonomous oscillation. We also verify that the spacing nucleotides with constant length between these 2 E-elements are crucial for robust oscillation. Furthermore, by in silico analysis we conclude that several clock and clock-controlled genes possess a direct repeat of the E-box-like elements in their promoter region. CONCLUSION: We propose a novel possible mechanism regulated by double E-box-like elements, not to a single E-box, for circadian transcriptional oscillation. The direct repeat of the E-box-like elements identified in this study is the minimal required element for the generation of cell-autonomous transcriptional oscillation of clock and clock-controlled genes. ( view less ) Jun Kubota,Takashi Ono,Megumi Araki,Suguru Torii,Toru Okuwaki,Toru Fukubayashi This study was designed to determine the regional differences of magnetic resonance (MR) measurements in the hamstrings [biceps femoris muscle long head (BFl) and short head (BFs), semimembranosus muscle (SM), and semitendinosus muscle (ST)] following eccentric knee-flexion exercise. Twelve male vo... ( view more )lunteers performed eccentric knee-flexion exercise. Maximum isometric torque, plasma creatine kinase (CK) activity, muscle soreness, and MR images of the hamstrings were measured before and immediately following exercise, and on the first, second, third and seventh days following the exercise. Cross-sectional areas (CSAs) and transverse relaxation times (T2s) of the hamstrings were measured from the T2-weightened MR imaging sequences of 30% (proximal), 50% (middle), and 70% (distal) areas of the thigh length. The CSA of the ST at proximal and middle regions had significantly increased on the third day, but no significant changes were found for the BFl or SM. Immediately following exercise, T2 values had increased significantly in the BFs, BFl, and ST. On the third day, T2 values of only ST increased significantly at proximal, middle and distal regions. Significant differences of T2 values between proximal and distal regions in the ST were found for the second, third and seventh days following the exercise. These results suggest that because of the anatomical characteristics of the muscles, the degrees of response following the exercise differed among the muscles and the regions of ST muscle. ( view less ) Yusuke Hattori,Yuichi Komachi,Toru Asakura,Toru Shimosegawa,Gen-Ichi Kanai,Hideo Tashiro,Hidetoshi SatoA small endoscope system equipped with a micro Raman probe is developed for in vivo Raman measurements in living rats. The measurements are done under anesthesia and artificial respiration to minimize the impact on the rats. Raman spectra of living rat esophagus and stomach are successfully measure... ( view more )d. Our results suggest that the Raman spectra reflect subsurface tissue structure that cannot be distinguished in the endoscope image. After the experiments, rats recover without any aftereffects. It is verified that the Raman measurement using the present system is safe and noninvasive for rats. ( view less ) Yoshikazu Ito,Kazuma Ohyashiki,Isao Yoshida,Makoto Takeuchi,Yasutaka Aoyama,Atsuko Mugitani,Yasuhiro Matsuura,Hisashi Wakita,Mitsuhiro Matsuda,Erina Sakamoto,Toru Kiguchi,Akio Urabe,Kazuo Tamura,Akihisa Kanamaru,Toru Masaoka We performed a randomized, controlled study comparing the prophylactic effects of capsule forms of fluconazole (n = 110) and itraconazole (n = 108) in patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) during and after chemotherapy. There were 4 cases with possible system... ( view more )ic fungal infection in the itraconazole group, and there were 8 possible and 3 probable cases in the fluconazole group. Adverse events did not significantly differ in the 2 groups. In patients with MDS or in the remission-induction phase of chemotherapy, the numbers of cases with probable or possible infections were lower in the itraconazole group than in the fluconazole group, whereas no difference was seen in patients with AML or in the consolidation phase of therapy. In patients with neutrophil counts of >0.1 x 10(9)/L lasting for more than 4 weeks, the frequency of infection in the fluconazole group (5 of 9 patients) was significantly higher than in the itraconazole group (0 of 7 patients; P = .03). Our results suggest that both drugs were well tolerated in patients with AML or MDS who received chemotherapy and that the efficacy of itraconazole for prophylaxis against systemic fungal disease is not inferior to that of fluconazole. ( view less ) Iwao Kaneko,Shinji Tanaka,Shiro Oka,Toru Kawamura,Toru Hiyama,Masanori Ito,Masaharu Yoshihara,Fumio Shimamoto,Kazuaki Chayama PURPOSE: Lymph node metastasis is an important factor that influences curability after endoscopic treatment of submucosal colorectal cancer. This study was designed to determine the usefulness of identification of lymphatic vessels by immunohistochemistry in predicting lymph node metastasis of subm... ( view more )ucosal colorectal cancer. METHODS: Lymphatic involvement was assessed by hematoxylin and eosin staining and podoplanin immunostaining on samples resected from 268 patients with submucosal colorectal cancer. Lymphatic vessel density was estimated by two investigators by average count of three fields (x200) in the area of greatest number of podoplanin-positive capillaries at the site of deepest submucosal penetration. Relations with other clinicopathologic parameters also were investigated. RESULTS: Lesions with high lymphatic vessel density (> or =9 vessels per field) showed a significantly greater incidence of lymph node metastasis than did those with low lymphatic vessel density (<9 vessels per field; 23.3 vs. 8.4 percent). By multivariate analysis, lymphatic vessel density was determined to be an independent risk factor for lymph node metastasis of submucosal colorectal cancer (P = 0.0044). Lymphatic vessel density also correlated with tumor budding and the degree of inflammation at the invasive front. CONCLUSIONS: Identification of lymphatic vessels by podoplanin immunostaining provides objective and accurate evaluation of lymphatic involvement. Lymphatic vessel density at the site of deepest penetration is a useful predictor of lymph node metastasis of submucosal colorectal cancer. ( view less ) Kazumasa Isobe,Shigeru Minowada,Ichiro Tatsuno,Kazumi Suzukawa,Sumiko Nissato,Toru Nanmoku,Hisato Hara,Toru Yashiro,Yasushi Kawakami,Kazuhiro Takekoshi The SDHA, SDHB, SDHC, and SDHD genes code for subunits of succinate dehydrogenase (SDH), which forms part of the mitochondrial respiratory chain. Germline mutations in the genes encoding SDHB and SDHD have been reported in familial paragangliomas/pheochromocytomas and in apparently sporadic pheochr... ( view more )omocytomas. SDHB and SDHD mutations are widely distributed along the genes with no apparent hot spots. SDHB mutations are often detected in malignant and extra-adrenal pheochromocytomas. SDHD mutations are also detected frequently in head and neck paragangliomas. We sequenced the entire coding regions of the SDHB and SDHD genes in 17 pheochromocytomas. We identified novel heterozygous G to A point mutations at the first base of intron 3 of the SDHB gene in a malignant extra-adrenal abdominal pheochromocytoma patient, and at the first base of codon 111 of the SDHD gene in an adrenal pheochromocytoma patient. Further, we confirmed the SDHD mutation by DHPLC. The prevalence of SDHB and SDHD mutations in pheochromocytomas we examined was 12% (2/17). Thus, we identified two novel SDH mutations in Japanese pheochromocytomas. Further studies will investigate the oncogenic potential of these mutations. ( view less ) Kyoichiro Tsuchiya,Takanobu Yoshimoto,Yuki Hirono,Toru Tateno,Toru Sugiyama,Yukio Hirata Both monocyte chemoattractant protein-1 (MCP-1), a member of chemokine family, and angiotensinogen, a precursor of angiotensin (ANG) II, are produced by adipose tissue and increased in obese state. MCP-1 has been shown to decrease insulin-stimulated glucose uptake and several adipogenic genes expre... ( view more )ssion in adipocytes in vitro, suggesting its pathophysiological significance in obesity. However, the pathophysiological interaction between MCP-1 and ANG II in adipose tissue remains unknown. The present study was undertaken to investigate the potential mechanisms by which ANG II affects MCP-1 gene expression in rat primary cultured preadipocytes and adipose tissue in vivo. ANG II significantly increased steady-state MCP-1 mRNA levels in a time- and dose-dependent manner. The ANG II-induced MCP-1 mRNA and protein expression was completely abolished by ANG II type 1 (AT1)-receptor antagonist (valsartan). An antioxidant/NF-kappaB inhibitor (pyrrolidine dithiocarbamate) and an inhibitor of 1kappaB-alpha phosphorylation (Bay 11-7085) also blocked ANG II-induced MCP-1 mRNA expression. ANG II induced translocation of NF-kappaB p65 subunit from cytoplasm to nucleus by immunocytochemical study. Luciferase assay using reporter constructs containing MCP-1 promoter region revealed that two NF-kappaB binding sites in its enhancer region were essential for the ANG II-induced promoter activities. Furthermore, basal mRNA and protein of MCP-1 during preadipocyte differentiation were significantly greater in preadipocytes than in differentiated adipocytes, whose effect was more pronounced in the presence of ANG II. Exogenous administration of ANG II to rats led to increased MCP-1 expression in epididymal, subcutaneous, and mesenteric adipose tissue. In conclusion, our present study demonstrates that ANG II increases MCP-1 gene expression via ANG II type 1 receptor-mediated and NF-kappaB-dependent pathway in rat preadipocytes as well as adipose MCP-1 expression in vivo. Thus the augmented MCP-1 expression by ANG II in preadipocytes may provide a new link between obesity and cardiovascular disease. ( view less ) Anoja Ariyasinghe,Sufi Reza M Morshed,M Kaiissar Mannoor,Hanaa Y Bakir,Hiroki Kawamura,Chikako Miyaji,Toru Nagura,Toshihiko Kawamura,Hisami Watanabe,Hiroho Sekikawa,Toru Abo Mice were fed ad libitum with a normal diet (25% protein) or low-protein diets (0-12.5% protein) for a wk and then infected with a nonlethal or lethal strain of Plasmodium yoelii, that is, blood stage infection. The same diet was continued until recovery. Mice fed with a normal diet showed severe p... ( view more )arasitemia during nonlethal infection, but survived the infection. They died within 2 wk in the case of lethal infection. However, all mice fed with low-protein diets survived without apparent parasitemia (there were small peaks of parasitemia) in cases of both nonlethal and lethal strains. These surviving mice were found to have acquired potent innate immunity, showing the expansion of NK1.1 -TCRint cells and the production of autoantibodies during malarial infection. Severe combined immunodeficiency (scid) mice, which lack TCRint cells as well as TCRhigh cells, did not survive after malarial infection of lethal strain of P. yoelii, even when low-protein diets were given. These results suggest that low-protein diets enhanced innate immunity and inversely decreased conventional immunity, and that these immunological deviations rendered mice resistant against malaria. The present outcome also reminds us of our experience in the field study of malaria, in which some inhabitants eventually avoided contracting malaria even after apparent malarial infection. ( view less ) Masahiro Yoneda,Toru Naito,Nao Suzuki,Toru Yoshikane,Takao Hirofuji We report a case of oral malodor associated with internal resorption. A 39-year-old male attended our hospital complaining of oral malodor. Utilizing organoleptic measurement, the halimeter test and gas chromatography, it was diagnosed as a strong halitosis caused by oral origin. The pocket probing... ( view more ) depth of tooth 21 was 10 mm, and X-ray examination revealed a vertical bone loss around this tooth. The patient had received periodontal treatment at two dental offices previously, but the periodontal conditions and oral malodor persisted. We performed an initial periodontal preparation, however a deep pocket remained. We therefore performed a surgical inspection including flap reflection, and found that the tooth had a large perforating defect in the distal surface. The extracted tooth had multiple perforating defects covered with granulation tissues on all root surfaces including the root apex. Taking into consideration the anamnesis and X-ray examination of the extracted tooth, internal absorption was considered to have been the cause of the multiple perforating defects. After extraction of the causative tooth, oral malodor dramatically decreased. To our knowledge, this is the first report of an oral malodor associated with internal resorption. ( view less ) Akira Tamura,Kazuhiro Shinozaki,Toru Watanabe,Toru Nakaishi,Kimiaki Nagase,Jun-ichi Kadota BACKGROUND: The aim of the present study was to clarify the effect of preinfarction angina pectoris (PIA) on myocardial blush grade (MBG), a simple marker of myocardial tissue-level reperfusion, in acute myocardial infarction (AMI). METHODS AND RESULTS: One hundred forty-two patients with first ant... ( view more )erior wall AMI who were admitted within 6 h after onset of symptoms were examined. PIA was defined as typical chest pain within 48 h before onset of symptoms. MBG was evaluated by coronary angiography after reperfusion. Patients with MBG 2 or 3 (n=103) had a higher frequency of PIA and a lower frequency of diabetes mellitus than those with MBG 0 or 1 (n=39) (57% vs 28%, p=0.004, and 23% vs 44%, p=0.03, respectively). The former had a lower peak creatine kinase level and a greater left ventricular ejection fraction at predischarge than the latter (3,652+/-2,440 vs 5,507+/-3,058 IU/L, p=0.0002, and 57+/-12% vs 45+/-11%, p<0.0001, respectively). Multivariate logistic regression analysis showed that PIA (p=0.004) and diabetes mellitus (p=0.03) were independently associated with MBG 2 or 3 after reperfusion. CONCLUSIONS: PIA has beneficial effects on myocardial tissue-level reperfusion evaluated by MBG in first anterior wall AMI. ( view less ) Kazuaki Yonemoto,Toru Eguro,Toru Maeda,Hisayoshi Tanaka OBJECTIVES: The purpose of this study was to investigate the DIAGNOdent values applicable as a guide for removal of outer layer of carious dentin with Er:YAG laser. METHODS: Carious dentin of human extracted molars was removed by bur with Caries Detector (Group 1: red stained dentin was left, Group... ( view more ) 2: light pink stained dentin was left) and by Er:YAG laser with DIAGNOdent value as a guide (30>Group 3>21, 20>Group 4>11, 10>Group 5). The cavity floor dentin after removing carious dentin was examined using microradiograms, EPMA and SEM. RESULTS: The cavity floor dentin of group 1,3 showed the decreases in the degree of X-ray absorption. In group 2,4 and 5, decrease of Ca, P were not observed. The decrease of Mg was observed on the more superficial part of the cavity floor for group 3 than for group 4. CONCLUSIONS: When carious dentin was removed using Er:YAG laser, the carious dentin outer layer was ideally removed with DIAGNOdent values: 11-20. DIAGNOdent values: 11-20, could indicate the completion of outer layer removal of carious dentin with Er:YAG laser, but there are some problems that must be addressed before the clinical application. ( view less ) Toru Nishiwaki,Toru Yamaguchi,Chen Zhao,Hitoshi Amano,Kurt D Hankenson,Paul Bornstein,Yoshiaki Toyama,Koichi Matsuo Fra1 transgenic (Tg) mice develop osteosclerosis and exhibit altered expression of bone matrix proteins. We found that expression of Thbs1 and Thbs2 was reduced in Fra1 Tg osteoblasts. Fra1 Tg and non-osteosclerotic Thbs1-/-Thbs2-/- mice share an edge-to-edge bite. Therefore, reduced expression of ... ( view more )thrombospondins may contribute to craniofacial dysmorphism independently of osteosclerosis. INTRODUCTION: Tg mice overexpressing Fra1, a component of the transcription factor activator protein-1 (AP-1), show progressive osteosclerosis caused by cell autonomous abnormalities in osteoblasts. The expression of several bone matrix proteins, including matrix gla protein, is dysregulated in Fra1 Tg osteoblasts. MATERIALS AND METHODS: In osteoblastogenic cultures, altered bone matrix production by Fra1 overexpression was monitored using Alizarin red staining, quantitative RT-PCR, and Western blotting. Responsiveness to ovariectomy was examined by bone histomorphometry. Craniofacial parameters were measured on radiographs and using CT. RESULTS: Thrombospondin-1 (Thbs1) and thrombospondin-2 (Thbs2) were reduced in Fra1 Tg osteoblasts differentiated in vitro and in bones from Fra1 Tg mice. Despite alterations in bone matrix proteins, ovariectomy induces high turnover bone loss in Fra1 Tg mice as in wildtype mice. Fra1 Tg mice, as well as Thbs1-/- Thbs2-/- mice, which do not show osteosclerosis, exhibit an edge-to-edge bite phenotype associated with craniofacial dysmorphism. CONCLUSIONS: These data suggest that reduced expression of thrombospondins in Fra1 Tg mice underlies craniofacial dysmorphism, independent of osteosclerosis. ( view less ) Yoshikazu Tsuji,Takashi Fujita,Toru Kimura,Atsushi Hirano,Katsuro Hatsuse,Toru Furukawa,Kuniaki Tanaka,Tsuneo Kinukawa,Yoshikatsu Nojiri,Kikuo Okamura,Yoshinari Ono,Shinichi Ohshima PURPOSE: We report a technique and outcome of endoscopic trigonoplasty II (ET II), anti-reflux surgery via a transvesicostomy transurethral approach and discuss its usefulness. MATERIALS AND METHODS: Fifteen female patients, aged 5 to 64, with 23 refluxing ureters (grade I : 5, II : 2, III : 14, IV... ( view more ) : 2) underwent the ET II. The principle of this surgery is tightening the muscular backing and elongating the intramural ureter. The operation consists of three steps: 1) two 5 mm locking trocars are placed into the bladder, 2) irrigating with 3% D-sorbitol solution, the bladder wall is incised upward along each side of the ureter using a resectoscope, to make a 2 to 3 cm U-shaped bladder flap including the ureter, 3) under a pneumobladder, the incised wall is sutured to make a muscular bed with a needle-holder via the urethra and forceps via the abdominal trocar. The U-shaped flap is fixed with two distal anchor sutures and four additional mucosal sutures. Urethral catheter is indwelled and the operation is finished. In recent four cases, we closed the tracts endoscopically. RESULTS: The average operative time was 144 minutes per ureter. In one patient with unilateral reflux, we switched to open surgery because of bleeding. Of 22 refluxing ureters, the reflux disappeared in 18 ureters (82%) and improved grade III to I in 1 ureter (5%) after 3 months and disappeared in 19 ureters (86%) after 12 months postoperatively. Ureteral injury was occurred in 3 patients during the transurethral incision of the bladder. Though we repaired it by placing a double-J stent in the 2 patients, reflux recurred in 12 months postoperatively in one of them. In the other patient cystoscopy revealed a vesicoureteral fistula in the injured portion. She subsequently underwent successful open Politano-Leadbetter ureteroneocystostomy. The average duration of indwelling catheter was shortened from 4.3 to 3.0 days by closing the tracts endoscopically. CONCLUSIONS: The overall cessation rate of the ET II was inferior to those of open anti-reflux surgeries or laparoscopic extravesical ureteral reimplantation. We do not recommend ET II for vesicoureteral reflux. ( view less ) Akira Tamura,Toru Watanabe,Kimiaki Nagase,Toru Nakaishi,Nobuko Aso,Yoshiyuki Kawano,Yusei Abe,Hirofumi Zaizen,Shoji Yano,Jun-ichi KadotaThe present study examined whether onset of symptomatic subacute stent thrombosis (SAT) varies in a circadian manner after bare metal coronary stent implantation. Among 2,305 patients who underwent bare metal coronary stent implantation, 21 (0.9%) developed symptomatic SAT. Results of the present s... ( view more )tudy indicate that onset of symptomatic SAT is more frequent between 6:00 A.M. and 12:00 P.M. than at any other measured 6-hour period during the day. ( view less ) Hanaa Y Bakir,Chikako Tomiyama-Miyaji,Hisami Watanabe,Toru Nagura,Toshihiko Kawamura,Hiroho Sekikawa,Toru Abo DBA/2 (H-2(d)) mice are known to be more resistant than C57BL/6 (B6, H-2(b)) mice to the non-lethal 17XNL strain of Plasmodium yoelii. This is a very strange phenomenon because the functions of conventional T cells, especially CD8(+) T cells, are known to be somewhat lower in DBA/2 mice than in oth... ( view more )er strains of mice. We examined herein how immune responses differed between DBA/2 mice and B6 mice during malarial infection. DBA/2 mice and (DBA/2 x B6)F(1) (BDF(1), H-2(b/d)) mice were found to have milder parasitaemia and to recover more quickly from malarial infection than B6 mice. These DBA/2 and BDF(1) mice were also found to experience a marked expansion of interleukin (IL)-2Rbeta(+) CD3(int) cells and gammadelta T cells in the liver, especially in the recovery phase. The expansion of unconventional T cells (i.e. B220(+) T cells) was also marked in DBA/2 and BDF(1) mice. The majority of B220(+) T cells were gammadelta T cells and these T cells were double-negative CD4(-) CD8(-). More importantly, the production of immunoglobulin M (IgM)-type anti-DNA autoantibody was also higher in DBA/2 and BDF(1) mice than in B6 mice. In conjunction with data on cytokine production, these results indicate that primitive T and B cells, namely autoreactive extrathymic T cells and autoantibody-producing B cells, may be much more activated in DBA/2 mice and therefore resistant to the non-lethal 17XNL strain of P. yoelii. ( view less ) Toru Hyodo,Takayasu Taira,Toru Takemura,Sumiko Yamamoto,Mayumi Tsuchida,Kazunari Yoshida,Toyoaki Uchida,Tadasu Sakai,Hideo Hidai,Shiro Baba We administered 2.5 g of Shakuyaku-kanzo-to granule to 61 patients who had muscle cramp during hemodialysis (HD) sessions and examined its immediate effects. We selected 10 patients who wanted to take the drug at home, out of cases, for whom the drug was effective on the study described above and h... ( view more )ad them take the drug in the same way at the beginning of muscle cramp at home examined the effects. In the study during HD sessions, muscle cramp and its associated pain disappeared in 5.3 +/- 3.9 min on average in 54 out of 61 cases. In the study of patients who took the drug at home, muscle cramp disappeared within 10 min in all cases. Shakuyaku-kanzo-to is thought to be very useful for muscle cramp during HD sessions of hemodialized patients because it has immediate effects by its oral administration on the occasion of cramp. With regard to the muscle cramp, which appears at home after HD sessions, the patients can cope with it by taking the drug by themselves. This is an epoch-making therapy, for it was impossible to cope with muscle cramp except in hospitals because the therapy of muscle cramp was limited to intravenous infusion of hypertonic solutions of dextrose, mannitol, and saline during HD sessions. ( view less ) Norihide Tachi,Toru Itani,Hidemaro Takeyama,Toru Yoshikawa,Koji Suzuki,Ariel B Castro The POSITIVE (Participation-oriented safety improvement by trade union initiative) programme was introduced into the Philippines in 1995. The monitoring of activities was carried out in 2004 among core trainers who had been trained before. The results of the questionnaire survey showed that the cor... ( view more )e trainers evaluated their activities satisfactory in general, and particularly the training activities were considered excellent. Also, the union workers who had been trained by the POSITIVE programme implemented improvements at the rate of around 5 examples a year on average. It was of note that the installation ratio (the number of installations/that of plans) was higher in small- and medium-sized enterprises than in larger companies, although the numbers of plans and installations of improvements were greater in large enterprises. Together with the previous findings, the present results suggest that the POSITIVE-style participatory training program is effective and efficient for workers to take actions for the OSH in not only larger enterprises but also small enterprises. ( view less ) Takayuki Hida,Eiki Takahashi,Kodo Shikata,Tomoko Hirohashi,Toru Sawai,Takashi Seiki,Hirokazu Tanaka,Takatoshi Kawai,Osamu Ito,Toru Arai,Akira Yokoi,Tetsuya Hirakawa,Hiroo Ogura,Takeshi Nagasu,Norimasa Miyamoto,Junro Kuromitsu Bolus-administered intracerebroventricular (ICV) relaxin-3 has been reported to increase feeding. In this study, to examine the role of relaxin-3 signaling in energy homeostasis, we studied the effects of chronically administered ICV relaxin-3 on body weight gain and locomotor activity in rats. Two... ( view more ) groups of animals received vehicle or relaxin-3 at 600 pmol/head/day, delivered with Alzet osmotic minipumps. In animals receiving relaxin-3, food consumption and weight gain were statistically significantly higher than those in the vehicle group during the 14-day infusion. During the light phase on days 2 and 7 and the dark phase on days 3 and 8, there was no difference in locomotor activity between the two groups. Plasma concentrations of leptin and insulin in rats chronically injected with relaxin-3 were significantly higher than in the vehicle-injected controls. These results indicate that relaxin-3 up-regulates food intake, leading to an increase of body weight and that relaxin-3 antagonists might be candidate antiobesity agents. ( view less ) Shuji Shimohara,Toru Murakami,Mari Morikawa,Junko Matsuo,Shin-Ichi Nagayama,Tsuyoshi Shuto,Mary Ann Suico,Tsukasa Okiyoneda,Isao Yamatsu,Toru Mizushima,Tatsuya Shimasaki,Hirofumi Kai Hyperthermia is used to treat various malignancies, including esophageal, stomach and rectal cancer. Since hyperthermia alone has produced limited results, much attention has been focused on combining hyperthermia with chemotherapy and on searching for substances able to sensitize tumor cells to hy... ( view more )perthermia-induced damage. Here, we show that vitamins K1 and K2 (VK1, VK2) inhibited the expression of heat-shock protein 72 (Hsp72) but did not affect the constitutive expression of Hsc70 or calnexin in vitro and in vivo. VK1 and VK2 sensitized A549 cells to heat-shock induced cell death, while the compounds alone had no effect on cell viability. The suppression of Hsp72 was apparently at the protein level because the mRNA expression of Hsp72 was unchanged. Moreover, the chaperone activity of Hsp72 was compromised after heat-shock when cells were pre-treated with VK2. The effect of VK2 on Hsp72 suppression, however, was also observed in normal mouse tissue after the mice were subjected to whole-body hyperthermia. To eliminate this side effect, local hyperthermia was performed on tumors in mice. The pre-treatment with VK2 potentiated the effect of local hyperthermia on tumor growth suppression. The findings here that VK1 and VK2 inhibit heat-shock-induced Hsp72 suggest their possible use as an adjuvant for hyperthermia in cancer therapy. ( view less ) Toru Sugiyama,Takanobu Yoshimoto,Yuki Hirono,Noriko Suzuki,Maya Sakurada,Kyoichiro Tsuchiya,Isao Minami,Fumiko Iwashima,Haruna Sakai,Toru Tateno,Ryuji Sato,Yukio Hirata Aldosterone is currently recognized as one of the important risk hormones for cardiovascular disease. However, the cellular mechanism by which aldosterone affects the process of cardiovascular injury has not been well understood. In the present study, we investigated whether aldosterone induces pro... ( view more )-inflammatory genes expression in rat aortic endothelial cells. Aldosterone significantly increased steady-state osteopontin mRNA and protein levels, but not those of adhesion molecules or chemokine. The stimulatory effect of aldosterone on osteopontin expression was time-dependent (3-24h) and dose-dependent (10(-10)-10(-6)M), and abolished by a mineralocorticoid receptor (MR) antagonist spironolactone, but not by a glucocorticoid receptor antagonist RU486. The aldosterone-induced osteopontin mRNA expression was completely blocked by a transcription inhibitor, actinomycin D, and a protein synthesis inhibitor, cycloheximide. Thus, the present study demonstrated for the first time that aldosterone directly acts on endothelial cells to induce osteopontin gene expression via MR-mediated genomic action, which may be responsible for the initiation of inflammation and fibrosis in cardiovascular tissue induced by aldosterone. ( view less ) Toru Hyodo,Haruki Wakai,Toru Takemura,Takayasu Taira,Hideo Hidai,Mayumi Tsuchida,Tetsuo Fujita,Kazunari Yoshida,Shiro Baba,Tadasu Sakai The aim of this study was to examine the therapeutic effect of hypocalcemic stimulation caused by sevelamer hydrochloride (SH) administration on adynamic bone disease (ABD). The subjects were 28 maintenance hemodialysis (HD) patients who had remained in ABD state in spite of no administration of vi... ( view more )tamin D(3) since HD induction (15 males and 13 females;12 diabetic patients and 16 non-diabetic patients). The mean age was 61.8+/-9.5 years and the mean HD duration was 5.5+/-3.9 years. The calcium concentration in the dialysate was 3.0 mEq/L. We made the final daily dose of SH after two months the same as the first daily dose of calcium carbonate (CC) in the following manner. At first we administered only CC at breakfast and lunch and SH at supper. And for the next two weeks we administered CC at breakfast and SH at lunch and supper. And for the final two weeks we administered only SH. After that we increased the dose of SH as much as possible. We evaluated the therapeutic effect of the above treatment on ABD using intact-osteocalcin (iOC) [Teijin. Tokyo] as a marker before and 6, 12 months after the beginning of the replacement. If iOC Ievel of 30 to 70 ng/mL showed normal tumover bone (NTB), 5 cases (17.9%) changed into NTB in 6 months. 9 cases (32.1%) changed into NTB in 12 months and one case (3.6%) changed into ostitis fibrosa in 12 months. It is thought that SH is effective for the treatment of ABD but we have to be careful for ostitis fibrosa. ( view less )
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