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T Sugimoto

Publications and source records attributed to T Sugimoto.

At least 91 records · Page 5Linked to original sources
PubMed2001

Histological changes in monoaminergic neurons of Long-Evans Cinnamon rats.

The Long-Evans Cinnamon rat, an animal model of Wilson's disease, is an inbred mutant strain with spontaneous hepatitis isolated from Long-Evans rats. The copper concentration in the brains of Long-Evans Cinnamon rats at 4 weeks of age was lower than that of controls, but higher than that of controls at 20 weeks of age. We investigated the tyrosine hydroxylase and 5-hydroxytryptamine immunoreactive fiber densities in the brains of Long-Evans Cinnamon rats aged 4, 10, and 20 weeks by immunohistochemistry, comparing them with Long-Evans Agouti rats used as controls. Tyrosine hydroxylase immunoreactive fiber densities in the cingulate cortex, hippocampus and cerebellum in Long-Evans Cinnamon rats were significantly lower than those of Long-Evans Agouti rats at 4 and 10 weeks of age. On the other hand, 5-hydroxytryptamine immunoreactive fiber densities in the cingulate cortex, caudate-putamen, hypothalamus, and hippocampus in Long-Evans Cinnamon rats were significantly higher than those of controls at 4, 10 and 20 weeks of age. In the cingulate cortex and caudate-putamen, 5-hydroxytryptamine immunoreactive fiber densities became gradually higher with age. The number of aberrant 5-hydroxytryptamine immunoreactive fibers in the cingulate cortex, caudate-putamen, hypothalamus and hippocampus in LEC rats was significantly higher than that of controls. The number of another type of aberrant 5-hydroxytryptamine immunoreactive fibers, which were detected only at 20 weeks of age in the caudate-putamen in LEC rats was significantly higher than that of controls. These results suggest that age-dependent changes in copper concentrations of Long-Evans Cinnamon rats were related to changes in monoaminergic neuron systems.

Animals↗
PubMed2001

Pharmacodynamic analysis of steroid 5alpha-reductase inhibitory actions of Z-350 in rat prostate.

The pharmacodynamics of (S)-4-[3-[4-[1-(4-methylphenyl)-3-[4-(2-methoxyphenyl)piperazine-1-yl]propoxy]benzoyl]indole-1-yl] butyric acid hydrochloride (Z-350), which has alpha(1)-adrenoceptor antagonistic and steroid 5alpha-reductase inhibitory effects, were investigated in rats. The disposition of Z-350 was a function of linear kinetics at doses from 1 to 30 mg/kg; the bioavailability was calculated to be 65.2%. The inhibition of 5alpha-reductase was dependent on the concentration of Z-350 in plasma and in the prostate. Analysis of the relationship between the concentration in the prostate and the inhibition seen after a single oral administration showed that the Hill constant was almost 1.0 and EC(50)(n(H)) was 47.4 ng/g of tissue; these parameters did not change after multiple administration. Z-350 inhibited 5alpha-reductase 1 h after oral administration at a dose of 3 mg/kg; maximum inhibition was observed after 2-4 h, and the inhibition (%) was maintained for 24 h after oral administration.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2001

Clinical and biologic characteristics for recurring neuroblastoma at mass screening cases in Japan.

BACKGROUND: It is said that most cases detected by neuroblastoma mass screening at 6 months of age tend to have a favorable clinical course after a surgical resection either with or without mild chemotherapy. However, a few cases have an unfavorable outcome. In the current study, the authors analyzed the clinical and biologic characteristics for recurring neuroblastoma in mass screening cases. METHODS: In 245 cases detected through mass screening in the Kyushu area in Japan, the clinical data and biologic features (N-myc status, DNA ploidy, Shimada histology, neuron-specific enolase (NSE), ferritin) were investigated, whereas, in particular, the data for recurring cases also were analyzed. RESULTS: Of 245 cases, 28 tumors had one or more biologically unfavorable prognostic factors, and 6 patients experienced recurrence. Three of the six patients with recurring disease underwent a complete resection of the primary tumor, whereas three cases had undergone an incomplete resection of the tumor. Regarding the initial chemotherapy, three cases received mild chemotherapy, two cases received no chemotherapy, and one case had high-dose multidrug chemotherapy. Regarding biologic prognostic factors, four of six cases with recurring disease had one or more unfavorable factors, whereas two cases had no unfavorable factors. Regarding the outcome after recurrence, four cases are CR, one case has a stable residual tumor, and one case died of disease with N-myc amplification. CONCLUSIONS: Most neuroblastomas detected by mass screening at 6 months of age have biologically favorable factors. However, approximately 10% of the cases had one or more unfavorable factors and thus might have a higher risk of recurrence than the patients with no unfavorable factors. Conversely, some cases with recurring disease had no unfavorable factors; however, the reason for this is still unclear. A long-term follow-up for mass screening cases is important, and it also might be necessary to research the established biologic factors and identify other new prognostic factors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

VRL-1 immunoreactivity in the rat cranial autonomic ganglia.

Immunohistochemistry for VRL-1, a newly cloned capsaicin-receptor homologue, was performed on the rat cranial autonomic ganglia. The immunoreactivity (ir) was detected in the majority of neurones in the pterygopalatine (66%) and submandibular ganglia (68%). In the tongue and carotid body, parasympathetic neurones contained VRL-I ir. In the superior cervical ganglion, only 2% of postganglionic sympathetic neurones showed the immunoreactivity. VRL-1-ir nerve endings could not be detected in their peripheral tissues. These findings may suggest that VRL-1 has functions within neuronal cell bodies of the cranial autonomic ganglia.

Animals↗
PubMed2001

Three-year follow-up of patients with right bundle branch block and ST segment elevation in the right precordial leads: Japanese Registry of Brugada Syndrome. Idiopathic Ventricular Fibrillation Investigators.

OBJECTIVES: We sought to determine the prevalence of right bundle branch block (RBBB) and ST segment elevation in the working Japanese population, as well as the event rate during a three-year prospective follow-up period. BACKGROUND: A poor prognosis of RBBB and ST segment elevation has been reported in Europe and South America, even in asymptomatic patients; however, a large population of asymptomatic patients with sporadic RBBB and ST segment elevation has not been studied. METHODS: Ten thousand 12-lead electrocardiograms (ECGs) were obtained during annual check-ups of working adults in the Tokyo area. This three-year prospective follow-up study consisted of 105 patients, including 20 with ventricular fibrillation, 18 with syncope and 67 who were asymptomatic. They were registered from 46 institutions in Japan. RESULTS: The prevalence of ECG abnormalities in working adults was 0.16%. A coved-type ST segment elevation was related to a history of cardiac events, and 18% of registered patients had PR prolongation and 9.5% had left-axis deviation. The cumulative cardiac event-free rate was 67.6% in the symptomatic group and 93.4% in the asymptomatic group (p = 0.0004) after three years. CONCLUSIONS: The recurrence rate of cardiac events in symptomatic patients was similar to that reported previously, but it was very low in sporadic asymptomatic patients. The ECG findings may help us to select patients for further examination and more accurate evaluation of their prognoses.

Adult↗
PubMed2001

Positional dissociation between the genetic mutation responsible for pseudohypoparathyroidism type Ib and the associated methylation defect at exon A/B: evidence for a long-range regulatory element within the imprinted GNAS1 locus.

Pseudohypoparathyroidism type Ib (PHP-Ib) is a paternally imprinted disorder which maps to a region on chromosome 20q13.3 that comprises GNAS1 at its telomeric boundary. Exon A/B of this gene was recently shown to display a loss of methylation in several PHP-Ib patients. In nine unrelated PHP-Ib kindreds, in whom haplotype analysis and mode of inheritance provided no evidence against linkage to this chromosomal region, we confirmed lack of exon A/B methylation for affected individuals, while unaffected carriers showed no epigenetic abnormality at this locus. However, affected individuals in one kindred (Y2) displayed additional methylation defects involving exons NESP55, AS and XL, and unaffected carriers in this family showed an abnormal methylation at exon NESP55, but not at other exons. Taken together, current evidence thus suggests that distinct mutations within or close to GNAS1 can lead to PHP-Ib and the associated epigenetic changes. To further delineate the telomeric boundary of the PHP-Ib locus, the previously reported kindred F, in which patient F-V/51 is recombinant within GNAS1, was investigated with several new markers and direct nucleotide sequence analysis. These studies revealed that F-V/51 remains recombinant at a single nucleotide polymorphism (SNP) located 1.2 kb upstream of XL. No heterozygous mutation was identified between exon XL and an SNP approximately 8 kb upstream of NESP55, where this affected individual becomes linked, suggesting that the genetic defect responsible for parathyroid hormone resistance in kindred F, and probably other PHP-Ib patients, is located >or=56 kb centromeric of the abnormally methylated exon A/B. A region upstream of the known coding exons of GNAS1 is therefore predicted to exert, presumably through imprinting of exon A/B, long-range effects on G(s)alpha expression.

Chromosome Mapping↗
PubMed2001

Androgen regulation of CYP4B1 responsible for mutagenic activation of bladder carcinogens in the rat bladder: detection of CYP4B1 mRNA by competitive reverse transcription-polymerase chain reaction.

Significant sex differences exist among cases of bladder cancer in humans as well as in experimental animals such as rats. Aromatic amines such as benzidine and 2-naphthylamine are known to induce bladder cancer. These carcinogenic amines are activated to genotoxic substances by cytochrome P 450 CYP4B1, which is present in bladder mucosa. In this study, regulation of CYP4B1 was investigated to elucidate sex difference in bladder carcinogenesis. Competitive reverse transcription-polymerase chain reaction was used to investigate the expression of rat CYP4B1 mRNA occurring in small amounts of tissue such as bladder tissue. Expression of CYP4B1 in the bladder of male rats increased with development but not in that of female rats. Moreover, mature male rats exhibited higher expression of CYP4B1 in the bladder than did mature female rats. Castration of male rats decreased CYP4B1 levels and treatment with testosterone led to a partial recovery of CYP4B1 levels. These results indicate that CYP4B1 levels in the rat bladder are partly regulated by androgens. Furthermore, the present findings suggest that the sex difference observed in bladder carcinogenesis was due to sex-different expression of CYP4B1 in bladder tissue.

Age Factors↗
PubMed2001

Effect of L-carnitine treatment for valproate-induced hepatotoxicity.

The authors analyzed the association of L-carnitine treatment with hepatic survival in 92 patients with severe, symptomatic, valproate-induced hepatotoxicity. Forty-eight percent of the 42 patients treated with L-carnitine survived, but only 10% of the 50 patients treated solely with aggressive supportive care survived (p < 0.001). Early intervention with IV rather than enteral L-carnitine was associated with the greatest hepatic survival. Specifically, all 10 patients who were diagnosed in <5 days and treated with IV L-carnitine survived. Most patients had features of chronic illness and most children appeared to be malnourished.

Adolescent↗
PubMed2001

Developmental dependency of Merkel endings on trks in the palate.

Immunohistochemistry for protein gene product 9.5 was performed on Merkel cells in the palate of wildtype and knockout mice for trkA, trkB or trkC. In wildtype mice, numerous Merkel cells were observed at the top of anterior four rugae. In the posterior four rugae, Merkel cells were fewer and mostly located at the base of rugae. In knockout mice for trkA, trkB and trkC, Merkel cells at the top of rugae mostly disappeared although those at the base of rugae remained unchanged. Therefore, the number of Merkel cells in anterior four rugae decreased. In posterior four rugae, however, the number of Merkel cells in the mutant mice was similar to that for wildtype mice. Immunohistochemistry for S100 also demonstrated that the loss of genes for trkA, trkB and trkC caused the absence of the immunoreactive innervation of Merkel cells. The normal development of Merkel endings at the top of palatal rugae is probably dependent on trkA, trkB and trkC.

Animals↗
PubMed2001

Inhibitory effect of theophylline on recombinant GABA(A) receptor.

Convulsions due to systemic toxicity are a major and frequently fatal side effect of theophylline. The cause of theophylline-induced convulsions is not clear, but antagonism of the inhibitory nervous system may be implicated, so we examined the effects of theophylline on GABA-induced currents using recombinant GABA(A) receptor (GABA(A)-R). Theophylline dose-dependently inhibited GABA-induced currents: the IC50 value was 1841+/-63 microM and Hill coefficient 1.09+/-0.03. The inhibitory action of theophylline on GABA-induced currents was competitive and voltage dependent. The inhibition of GABA-induced currents by theophylline may be a primary mechanism underlying theophylline-induced convulsions.

Animals↗
PubMed2001

Overexpression of connective tissue growth factor/hypertrophic chondrocyte-specific gene product 24 decreases bone density in adult mice and induces dwarfism.

Connective tissue growth factor/hypertrophic chondrocyte-specific gene product 24 (CTGF/Hcs24) is a multifunctional growth factor for fibroblasts, chondrocytes, and vascular endothelial cells. In the present study, we established transgenic (Tg) mice that overproduce CTGF/Hcs24 under the control of mouse type XI collagen promoter. Tg mice could develop and their embryonic and neonatal growth occurred normally. But they showed dwarfism within a few months of birth. X-ray analysis revealed that their bone density was decreased compared with normal mice. The femurs in the hindlimbs in particular showed an apparent low density. These results indicated that overexpression of CTGF/Hcs24 affects certain steps of endochondral ossification. In addition, the testes were much smaller than normal and fertility was affected in Tg mice, indicating that CTGF/Hcs24 may also regulate the embryonic development of the testis.

Animals↗
PubMed2001

Testosterone inhibits osteoclast formation stimulated by parathyroid hormone through androgen receptor.

Androgens play an important role in the regulation of bone metabolism in animals and humans. The present study was performed to investigate whether androgens would affect osteoclast formation stimulated by parathyroid hormone (PTH) in mouse bone cell cultures and its mechanism. Testosterone as well as alpha-dihydrotestosterone (DHT) concentration-dependently inhibited osteoclast formation induced by PTH-(1-34). 10(-8) M ICI 182780, an estrogen receptor inhibitor, did not affect PTH-induced osteoclast formation antagonized by 10(-8) M testosterone, although it completely antagonized the effects of 10(-8) M 17beta-estradiol. Moreover, 3 microM 4-androsten-4-ol-3,17-dione, an aromatase inhibitor, did not affect PTH-induced osteoclast formation antagonized by testosterone. Hydroxyflutamide, an androgen receptor antagonist, concentration-dependently antagonized the inhibitory effects of testosterone as well as DHT on PTH-stimulated osteoclast formation. In conclusion, the present study first demonstrated that testosterone inhibited osteoclast formation stimulated by PTH through the androgen receptor, but not through the production of intrinsic estrogen in mouse bone cell cultures.

Androgen Antagonists↗
PubMed2001

VR1-immunoreactive primary sensory neurons in the rat trigeminal ganglion.

Immunohistochemistry for VR1, a nociceptive transducer for vanilloid compounds, protons and heat (>43 degrees C), was performed on the rat trigeminal ganglion (TG). The immunoreactivity (IR) was detected in 20% of TG cells and these neurons were mostly small- to medium-sized (mean+/-S.D. 427+/-189 microm(2)). Twenty-six percent of the TG neurons retrogradely labeled from the facial skin exhibited VR1-IR, while the IR was detected in only 8% of those labeled from the tooth pulp. Co-expression of VR1 was common among the calcitonin gene-related peptide-immunoreactive cutaneous neurons (63%) but not among the similar tooth pulp neurons (20%). The present study indicates that primary nociceptive neurons which respond to vanilloid compounds, protons and heat are abundant in the facial skin but not in the tooth pulp.

Animals↗
PubMed2001

Peripheral neuroglial death induced by cisplatin administration in newborn rats.

To determine the target of cytotoxicity of cisplatin (CDDP), we injected newborn rats with 2 mg/kg CDDP and examined the trigeminal ganglion for possible cell death. A nick translation method for DNA fragmentation revealed CDDP-induced glial cell death. DNA fragmentation was detected in both Schwann cells and satellite cells. Satellite cell death was observed as early as 0.5 day after injection, most frequent at 1-3 days and subsided thereafter. The incidence of neuronal death was very low and comparable to that observed in vehicle control rats. CDDP has selective toxicity to peripheral glial cells, though the damage did not culminate in cell death in adults. The glial toxicity may contribute to clinical symptoms of CDDP neuropathy.

Animals↗
PubMed2001

Signaling pathway of ciliary neurotrophic factor in neuroblastoma cell lines.

BACKGROUND: Ciliary neurotrophic factor (CNTF) is a member of the interleukin-6 (IL-6) cytokine family and affects the survival and differentiation of several classes of neurons. For signal transduction, CNTF requires a receptor complex, composed of the IL-6 signal transducing molecule gp130, leukemia inhibitory factor receptor (LIFR)-beta, and CNTFR-alpha. There are two major independent pathways (Jak-STAT and Ras-MAPK) in cell signaling, and some recent reports show interaction between these pathways. The signal of the IL-6 family is mainly transduced to the Jak-STAT pathway through gp130. However, it has not been examined in neuroblastoma in detail. PROCEDURE AND RESULTS: Here we examine the signaling pathway of CNTF in 11 neuroblastoma cell lines. Northern blot analysis revealed that 3 of the 11 cell lines expressed c-fos mRNA after CNTF stimulation. Cell lysates were immunoprecipitated with agarose-conjugated antiphosphotyrosine antibody and blotted with anti-gp130, anti-Jak1, or anti-STAT3 antibody. Tyrosine phosphorylation of gp130, Jak1, and STAT3 was observed after CNTF stimulation in these three cell lines. Furthermore, tyrosine phosphorylation of ERK1 (one of the MAPKs) was also observed in all of them. CONCLUSIONS: These results demonstrate that CNTF signaling is conserved in some of the neuroblastoma cell lines and suggest that not only a Jak-STAT pathway but a MAPK pathway is activated by CNTF through gp130 in neuroblastoma cell lines.

Antigens, CD↗
PubMed2001

Clinical characteristics of acute pulmonary thromboembolism in Japan: results of a multicenter registry in the Japanese Society of Pulmonary Embolism Research.

BACKGROUND: Although the incidence of acute pulmonary thromboembolism (APTE) has been increasing in Japan, patient characteristics, management strategies, and outcome have not yet been assessed in large series. HYPOTHESIS: The present study was designed to investigate the current status of APTE in Japan. METHODS: Of a total of 533 registry patients with pulmonary thromboembolism, 309 with APTE were analyzed with respect to clinical symptoms and signs, predisposing factors, diagnostic procedures, estimation of deep venous thrombosis, treatment, and clinical course. RESULTS: Main risk factors were recent major surgery, cancer, prolonged immobilization, and obesity; only a few patients had coagulopathy and 36% were in cardiogenic shock at presentation. The majority of registry patients underwent lung scans or pulmonary angiography; 30% were diagnosed only by lung scanning. Venous ultrasonography was used in only 34 patients, while 188 patients underwent at least one diagnostic procedure for deep venous thrombosis. Thrombolysis was more frequently performed in patients with cardiogenic shock, and only a few patients received thromboembolectomy. In-hospital mortality rate was 14%. In patients with cardiogenic shock, the mortality rate was reduced by thrombolysis. The predictors of in-hospital mortality were male gender, cardiogenic shock, cancer, and prolonged immobilization. CONCLUSIONS: The patients in this registry had almost the same findings as those in Western patients, except for some points that had the possibility of demonstrating a difference between Westerners and Japanese in the development of APTE. These results can prove especially helpful in planning prospective, randomized trials that will clarify the impact of widely used treatment modalities on the outcome of patients with APTE.

Age Distribution↗
PubMed2001

Prevalence of deep venous thrombosis in the lower limbs and the pelvis and pulmonary embolism in patients with positive antiphospholipid antibodies.

BACKGROUND: Antiphospholipid antibodies (AA) are immunoglobulins that cross-react with phospholipid on cell membrane, and are therefore associated with a hypercoagulable state manifested by arterial/venous thromboses. We aimed to determine the prevalence of deep venous thrombosis in the lower limbs and the pelvic region (DVT) and pulmonary embolism (PE) in patients with positive AA. METHODS: Sixty-six patients (48 female, 18 male) with positive lupus anticoagulant (LA) and/or positive anticardiolipin antibody (aCL) underwent radionuclide (RN) venography with 370 MBq of 99mTc-MAA. Pulmonary perfusion scintigraphy was performed in 58 patients. Fifteen patients had positive LA and positive aCL (LA+/aCL+), 33 patients had positive LA only (LA+/ aCL-) and 18 patients had positive aCL only (LA-/aCL+). 43 patients were diagnosed with primary antiphospholipid syndrome (APS) and 19 were diagnosed with APS associated with SLE. RESULTS: DVT was detected in 21 of 66 patients (32%). Patients with LA+/aCL+ showed higher prevalence of DVT (53%) as compared to LA+/aCL- (27%) and LA-/aCL+ (22%). PE was found in 13 of 58 patients (22%). The prevalence of PE was higher in patients with positive aCL (33% in LA+/aCL+; 36% in LA-/aCL+) than in patients with negative aCL (10%). CONCLUSION: Because of the high prevalence of DVT and PE in patients with AA, RN scintigraphy must be recommended in screening for these clinical troubles. These results indicate that the prevalence of DVT and PE may vary in subgroups of AA.

Adolescent↗