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Hiroshi Tsuji

Publications and source records attributed to Hiroshi Tsuji.

17 recordsLinked to original sources
PubMed2003

Differential non-target-derived repulsive signals play a critical role in shaping initial axonal growth of dorsal root ganglion neurons.

Initial trajectories of dorsal root ganglion (DRG) axons are shaped by chemorepulsive signals from surrounding tissues. Although we have previously shown that axonin-1/SC2 expression on DRG axons is required to mediate a notochord-derived chemorepulsive signal, Dev. Biol. 224, 112-121), other molecules involved in the non-target-derived repulsive signals are largely unknown. Using coculture assays composed of tissues derived from the chick embryo or mutant mice treated with function-blocking antibodies and phosphatidylinositol-specific phospholipase C, we report here that the chemorepellent semaphorin 3A (Sema3A) and its receptor neuropilin-1 are required for mediating the dermamyotome- and notochord-derived, but not the ventral spinal cord-derived, chemorepulsive signal for DRG axons. The dermamyotome-derived chemorepulsion is exclusively dependent on Sema3A/neuropilin-1, whereas other molecules are also involved in the notochord-derived chemorepulsion. Chemorepulsion from the ventral spinal cord does not depend on Sema3A/neuropilin-1 but requires axonin-1/SC2 to repel DRG axons. Thus, differential chemorepulsive signals help shape the initial trajectories of DRG axons and are critical for the proper wiring of the nervous system.

Animals↗
PubMed2003

Rat nerve regeneration through a silicone chamber implanted with negative carbon ions.

We investigated whether a tube with its inner surface implanted with negatively-charged carbon ions (C(-) ions) would enable axons to extend over a distance greater than 10 mm. The tube was found to support nerves regenerating across a 15-mm-long inter-stump gap. Silicone treated with C(-) ions showed increased hydrophilic properties and cellular affinity, and axon regeneration was promoted with this increased biocompatibility.

Animals↗
PubMed2003

Change in the protein level of mevalonate pyrophosphate decarboxylase in tissues of mouse by pravastatin.

We previously reported that treatment of rats with a diet containing 0.1% pravastatin and 5% cholestyramine markedly increased mevalonate pyrophosphate decarboxylase (MPD) activity in liver crude extracts compared with nontreated rats. In this study, we examined the change in the protein level of MPD in the tissues of mice administered pravastatin. When MPD content in the tissues of nontreated mice was analyzed by quantitative immunoblotting, a single protein band with an apparent molecular weight of 46 kDa was detected in all tissues and the specific protein content of MPD in liver and kidney was markedly higher than that in other tissues. When MPD content in the tissues of pravastatin-treated mice was analyzed by immunoblotting, MPD was markedly increased (9-fold) only in the liver compared with nontreated mice. Next, when MPD activity was measured in the liver between nontreated and pravastatin-treated mice, MPD activity as well as protein levels were markedly increased (11-fold) in the liver of pravastatin-treated mice compared with nontreated mice. These data suggest that a marked induction of MPD in the liver by pravastatin is responsible for the tissue-specific effect of pravastatin.

Animals↗
PubMed2003

Subcellular distribution of mouse mevalonate pyrophosphate decarboxylase.

Mevalonate pyrophosphate decarboxylase (MPD) is considered to be a cytosolic protein. Recently, other groups reported that MPD is mostly located in the peroxisomes. In this study, we examined whether the expression of MPD in mice depends on the proliferation of peroxisomes, and whether MPD is predominantly located in the peroxisomes or the cytosol of mice. No increase in the protein level of MPD was observed in the crude extract of the livers of mice administered with peroxisome proliferative drugs. The result suggests that the expression of MPD is independent of the proliferation of peroxisomes, and may be maintained via a specific regulatory mechanism, different from the regulation of the expression of peroxisome proliferator-activated receptor alpha. When the subcellular distribution of MPD in mouse melanoma (B16F10) cells was examined by cell fractionation, MPD was detected in the cytosol of B16F10 cells, but not in the peroxisomes. In permeabilized B16F10 cells treated with digitonin, which lack cytosolic enzymes, 80% and 20% of MPD, 75% and 25% of lactate dehydrogenase, or 2% and 98% of catalase, existed in the medium and in the cell, respectively. From these results, it indicated that MPD was predominantly located in the cytosol and did not exist in the peroxisomes of B16F10 cells.

Animals↗
PubMed2003

Peroxisome proliferative drugs do not induce an increase of rat mevalonate pyrophosphate decarboxylase.

To determine whether or not the expression of mevalonate pyrophosphate decarboxylase (MPD) depends on the proliferation of peroxisomes, we examined change in the protein level of MPD in the crude extract, the cytosol and the peroxisome-enriched fraction of the livers of rats administered peroxisome proliferative drugs. No increase of MPD was observed in any of these fractions. These data suggest that the expression of MPD is independent of the proliferation of peroxisomes and may be maintained via a specific regulatory mechanism different from that of the expression of peroxisome proliferator-activated receptor alpha.

Animals↗
PubMed2003

[Thyroid function in patients with Yusho].

To evaluate chronic effect of polychlorinated biphenyl (PCB) on thyroid functions, thyroid hormone levels were studied in 115 patients with Yusho in 2002. Serum level of thyroid stimulating hormone (TSH) was elevated in 13 cases (11.3%). All of them showed normal triiodothyronine (T3) and thyroxine (T4) levels, and regarded as latent hypothyroidism. There were no significant correlations between blood PCB concentrations and TSH levels, T3 levels or T4 levels. We conclude that abnormality of TSH levels in patients with Yusho is frequent, but it may not be associated with blood PCB concentration.

Adult↗
PubMed2003

Active elimination of causative PCDFs/DDs congeners of Yusho by one year intake of FBRA in Japanese people.

Thirty-five years have been passing since the outbreak of Kanemi rice oil poisoning, namely, Yusho in the western Japan. However, even now the patients with Yusho have been still suffering from several objective and subjective symptoms. In order to improve or, if possible, to cure the such symptoms, the most important therapeutic treatment is considered to actively excrete the most toxic causative PCDFs/DDs congeners, that is, 2,3,4,7,8-pentachlorodibenzofuran (PenCDF) and 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin (HxCDD) from the bodies of the patients and to reduce their body burdens. In rats, dietary fiber and chlorophyll have been shown to promote the fecal excretion of dioxins and to reduce their levels in rat liver. In this study, we examined whether such kinds of effect were also observed by FBRA, which was the health food and relatively rich with dietary fiber and chlorophyll in nine married Japanese couples. As a result, concentrations of PenCDF and HxCDD on the lipid weight basis in the blood of the FBRA-intake group in which they took 7.0 to 10.5 g of FBRA after each meal and three times a day for one year were more lowered than those in the blood of the non-intake group; Blood levels of PenCDF and HxCDD in the FBRA-intake group were decreased by 30.5 and 33.9%, respectively, and those decreases were 22.0 and 24.5% in the non-intake group. Their total body burdens just before and one year after the study were calculated on the assumptions that the body fat was also contaminated with these congeners at their blood levels on the lipid weight basis and the content of body fat was 20% of the body weight. Then, we computed the average amounts in excretion of PenCDF and HxCDD from the body in both the FBRA-intake and non-intake groups. Consequently, the amounts of excretion of PenCDF and HxCDD in the FBRA-intake group were 2.1 and 1.9 times, respectively, greater than those in the non-intake group. Therefore, FBRA seemed to promote the fecal excretion of PenCDF and HxCDD, the main causative PCDFs/DDs congeners of Yusho, from the human body. We also expect FBRA to reduce their body burdens of patients with Yusho and to improve some objective and subjective symptoms of Yusho patients.

Adult↗
PubMed2002

Efficacy and safety of carbon ion radiotherapy in bone and soft tissue sarcomas.

PURPOSE: To evaluate the tolerance for and effectiveness of carbon ion radiotherapy in patients with unresectable bone and soft tissue sarcomas. PATIENTS AND METHODS: We conducted a phase I/II dose escalation study of carbon ion radiotherapy. Fifty-seven patients with 64 sites of bone and soft tissue sarcomas not suited for resection received carbon ion radiotherapy. Tumors involved the spine or paraspinous soft tissues in 19 patients, pelvis in 32 patients, and extremities in six patients. The total dose ranged from 52.8 to 73.6 gray equivalent (GyE) and was administered in 16 fixed fractions over 4 weeks (3.3 to 4.6 GyE/fraction). The median tumor size was 559 cm(3) (range, 20 to 2,290 cm(3)). The minimum follow-up was 18 months. RESULTS: Seven of 17 patients treated with the highest total dose of 73.6 GyE experienced Radiation Therapy Oncology Group grade 3 acute skin reactions. Dose escalation was then halted at this level. No other severe acute reactions (grade > 3) were observed in this series. The overall local control rates were 88% and 73% at 1 year and 3 years of follow-up, respectively. The median survival time was 31 months (range, 2 to 60 months), and the 1- and 3-year overall survival rates were 82% and 46%, respectively. CONCLUSION: Carbon ion radiotherapy seems to be a safe and effective modality in the management of bone and soft tissue sarcomas not eligible for surgical resection, providing good local control and offering a survival advantage without unacceptable morbidity.

Adolescent↗
PubMed2002

Ile (476), a constituent of di-leucine-based motif of a major lysosomal membrane protein, LGP85/LIMP II, is important for its proper distribution in late endosomes and lysosomes.

Lysosomal membrane glycoprotein termed LGP85 or LIMP II extends a COOH-terminal cytoplasmic tail of R459GQGSMDEGTADERAPLIRT478, in which an L475 I476 sequence lies as a di-leucine-based motif for lysosomal targeting. In the present study, we explored the role of the I476 residue in the localization of LGP85 to the endocytic organelles using two substitution mutants called I476A and I476L in which alanine and leucine are replaced at I476, respectively, and I476R477T478-deleted LGP85 called Delta 476-478. Immunofluorescence analyses showed that I476A and I476L are largely colocalized in intracellular organelles with an endogenous late endosomal and lysosomal marker, LAMP-1, but there were some granules in which staining for the LGP85 mutants was prominent, while Delta 476-478 is detected in LAMP-1-positive and LAMP-1-negative intracellular organelles, and on the cell surface. The subcellular fractionation studies revealed that I476A, I476L, and Delta 476-478 are different from wild-type LGP85 in the distribution of early endosomes, late endosomes, and lysosomes. I476A and I476L are present more in late endosomes than in the densest lysosomes, whereas wild-type LGP85 is mainly lysosomal. Substitution of I476 for A and L differentially modified the ratios of late endosomal to lysosomal LGP85. A major portion of Delta 476-478 resided in the light buoyant density fraction containing plasma membrane and early endosomes. Taken together, these results indicate that the existence of the 476th amino acid residue is essential for localization of LGP85 to late endocytic compartments. The fact that isoleucine but not leucine is in the 476th position is especially of importance in the proper distribution of LGP85 in late endosomes and lysosomes.

Amino Acid Motifs↗
PubMed2002

A rare case of ulcerative colitis complicating Wilson's disease: possible association between the two diseases.

A case of ulcerative colitis complicated by Wilson's disease is described. In this case, ulcerative colitis occurred 12 years after the diagnosis of Wilson's disease, and the colitis was intractable to prednisolone and salazosulfapyridine. Because copper is one of the trace elements necessary for antioxidant defenses during inflammatory process, altered copper metabolism may have contributed to the intractability of the ulcerative colitis in this case.

Adult↗
PubMed2002

Purification and characterization of mouse mevalonate pyrophosphate decarboxylase.

Mevalonate pyrophosphate decarboxylase (MPD) in mouse liver was purified by affinity chromatography. The purified enzyme was a homodimer of 46-kDa subunits and had an isoelectric point of 5.0. Kinetic analysis revealed an apparent Km value of 10 microm for mevalonate pyrophosphate. The enzyme required ATP as a phosphate acceptor and Mg as a divalent cation, which could be substituted with Mn or Co. Its optimum pH was 4.0-7.0. A comparison with MPD from various other sources revealed the mouse MPD to have essentially the same properties as rat MPD, expect for the optimum pH range. An excess of rabbit anti-rat MPD antibody deleted approximately 80% of the MPD activity in the crude extract of mouse liver. These results suggested that the homodimer of 46-kDa subunits represents the major active form of MPD in mice.

Animals↗
PubMed2002

Comparison of subcellular distribution of mevalonate pyrophosphate decarboxylase between stroke-prone spontaneously hypertensive rat and Wistar Kyoto rat.

We previously reported that the lower activity of mevalonate pyrophosphate decarboxylase (MPD) was caused by the reduced amount of this enzyme in stroke-prone spontaneously hypertensive rat (SHRSP) by immunoblot analysis using 20,000 x g supernatant containing cytosol and microsomes. A recent study showed that at least three different subcellular compartments, including peroxisomes, are involved in cholesterol synthesis. In this study, we examined the subcellular distribution of 45- and 37-kDa MPD in the liver of SHRSP and compared normotensive Wistar Kyoto rat (WKY) and SHRSP. 45-kDa MPD was detected in the cytosol and peroxisomes of SHRSP, while 37-kDa MPD was detected in the cytosol of SHRSP, but not in the peroxisomes. The relative enrichment of 45-kDa MPD in peroxisomes was lower than that of LDH, suggesting the possibility that 45-kDa MPD of SHRSP did not exist in the peroxisomes. Also, 45-kDa MPD was decreased in the crude extract containing 1% Triton X-100, cytosol and peroxisomes of SHRSP, and 37-kDa MPD was decreased in the crude extract containing 1% Triton X-100 and cytosol of SHRSP, as compared with WKY. These data indicate that the cholesterol synthesis in the liver of SHRSP by the reduced amount of MPD is significantly reduced.

Animals↗
PubMed2002

MPO-ANCA-positive slowly progressive glomerulonephritis with focal tuft necrosis and crescents.

A 37-year-old woman had been found to have proteinuria in October 1996. About 8 months later, the first renal biopsy was performed, revealing focal segmental necrotizing and crescentic glomerulonephritis. At that time, serum creatinine was 1.0 mg/dl and urinary protein 3+. In October 1999, laboratory tests revealed positivity for MPO-ANCA and a serum creatinine level of 1.42 mg/dl, anemia and proteinuria of 2+. A second renal biopsy showed almost the same histological findings. Accordingly, a diagnosis of MPO-ANCA positive glomerulonephritis was made. This patient was thought to be a rare case of MPO-ANCA-positive slowly progressive glomerulonephritis presenting focal segmental tuft necrosis and crescents.

Adult↗
PubMed2002

Reasons for the delays in the definitive diagnosis of lung cancer for more than one year from the recognition of abnormal chest shadows.

OBJECTIVE: Primary lung cancer generally has a poor prognosis if not diagnosed at an early stage. But some lung cancers grow very slowly. In particular, adenocarcinoma is sometimes observed for years with no change of tumor size. In this study, we examined the reasons for the delays in reaching a definitive diagnosis of lung cancer. METHODS: We retrospectively reviewed primary lung cancer cases between January 1995 and December 1999 and examined those whose definitive diagnoses were delayed for more than a year. RESULTS: A total of 222 primary lung cancers were diagnosed. Of those, 19 patients (group A, 8.6%) were diagnosed after more than a year, and the other 203 (group B, 91.4%) were diagnosed within one year. The proportion of women in group A was significantly higher than that in group B (p<0.05). The mean age of group A was significantly younger than that of group B (p<0.05). The Brinkman Index of group A was significantly lower than that of group B (p<0.05). The histologic types were significantly different between the two groups (p<0.05). In group A, 18 patients (94.7%) had adenocarcinomas. Five primary reasons for the delays in group A were identified: 1) Four patients were tentatively diagnosed as inflammation or benign tumor on CT and were consequently not followed-up. 2) The chest CT shadows in 6 patients were suspected lung cancers but transbronchial lung biopsy findings did not show malignancy. 3) Four patients were tentatively diagnosed as inflammation or benign tumor on CT, but the tumors showed only very slow growth or no change at all. 4) The chest CT shadows of 2 patients were suspected lung cancer, but the patients refused to undergo video-assisted thoracic surgery (VATS) or closer examination. 5) Three patients did not consult medical facilities for a second examination. CONCLUSIONS: Many of the adenocarcinomas reviewed in our study grew slowly or remained unchanged for years. Doctors are mainly responsible for the delays in the definitive diagnosis and should aggressively perform VATS or closer examinations without hesitation.

Adenocarcinoma↗
PubMed2002

[A case of pyoderma gangrenosum involving the prostate gland after radiation therapy for prostate cancer].

A 76-year-old man complained of difficulty in urination and miction pain with abacterial pyuria after radiation therapy for prostate cancer. Transurethral resection of the prostate was performed and histopathologically widespread necrosis was observed in the prostate. Thereafter retention of urine and fever occurred and computed tomography scan revealed an abscess of the penile corpus. The abscess was drained, but the fever continued. He developed an abacterial lung abscess and abacterial necrotic ulcerating lesions on his back, his left leg and his lower abdomen. Macroscopic findings demonstrated typical features of pyoderma gangrenosum. Steroid treatment was initiated and the response to steroid therapy was dramatic. Finally urinary diversion using an ileal conduit was performed. We found few cases of pyoderma gangrenosum involving lesions other than those of the skin in the literature. This is the first report of pyoderma gangrenosum involving the prostate gland after radiation therapy for prostate cancer.

Aged↗