Search PubMed⌕ Search

Biomedical subjects

T Noguchi

Publications and source records attributed to T Noguchi.

At least 253 records · Page 14Linked to original sources

Anti-proliferative capsular-like polysaccharide antigen from Actinobacillus actinomycetemcomitans induces apoptotic cell death in mouse osteoblastic MC3T3-E1 cells.

Actinobacillus actinomycetemcomitans (A. actinomycetemcomitans) has been implicated in the etiology of localized juvenile periodontitis (LJP), and produces a multiplicity of tissue-damaging products. Among those products, the capsular-like polysaccharide antigen (CPA) from A. actinomycetemcomitans is a potent mediator of bone resorption. In fact, this CPA (serotype b) is known to promote osteoclast-like cell formation via interleukin (IL)-1alpha production in mouse marrow cultures. Although osteoblasts complete bone formation, there are few reports focusing on the effect of CPA in bone-forming activity of osteoblasts in inflammatory disease sites. We hypothesized that CPA plays a mediating role in osteoblastic cells. Therefore, the purpose of this study was to examine the effect of CPA from A. actinomycetemcomitans on the mouse osteoblastic cell line MC3T3-E1 and human osteosarcoma SaOS-2 cells. A. actinomycetemcomitans serotype c resulted in a potent dose-dependent inhibition of cell proliferation of both cell lines. Characterization of the antiproliferative activity in the CPA demonstrated that it was not cytotoxic for MC3T3-E1. A 20-hour incubation with CPA-c resulted in a significant increase in apoptotic cell death in the cells, as evaluated by both cellular DNA fragmentation ELISA and FACS analysis. In contrast to the results obtained with a cytokine mixture (tumor necrosis factor-alpha, IL-1beta, and interferon-gamma), no inducible nitric oxide (NO) synthase gene expression or NO release could be detected in MC3T3-E1 after incubation with CPA-c. Further, both CPA-b and -c caused potent induction of apoptosis-related modifiers, e.g., Fas mRNA, whereas bcl-2 mRNA levels were unchanged. Therefore, this study has shown that CPA from A. actinomycetemcomitans contains a potent antiproliferative polysaccharide whose activity is associated with apoptotic cell death in MC3T3-E1, and that CPA per se is an inducer of apoptosis mediated by the Fas system but not by NO.

Aggregatibacter actinomycetemcomitans↗

The efficacy of a custom-fabricated nasal mask on gas exchange during nasal intermittent positive pressure ventilation.

Commercially available nasal masks have a large mask volume and give rise to considerable air leaks around the mask during nasal intermittent positive pressure ventilation (NIPPV) which may reduce alveolar ventilation (VA per breath). The effects of a custom-fabricated nasal mask (F-mask) versus a commercially available mask (C-mask) on arterial blood gas measurements, dead space including both physiological and apparatus dead space (VD), air leak and VA per breath were compared in patients with restrictive thoracic disease during short-term NIPPV sessions while using a volume cycled ventilator with equivalent settings for both masks. The mask volume of the C-mask was significantly larger than that of the F-mask (p<0.003). The arterial carbon dioxide tension (Pa,CO2) during NIPPV with either the F-mask (5.56+/-1.35 kPa) (mean+/-SD) or the C-mask (6.87+/-0.96 kPa) was significantly lower than during spontaneous breathing (7.75+/-0.81 kPa; p<0.003), but the Pa,CO2 decreased more during NIPPV with the F-mask than with the C-mask (p<0.003). The VD was significantly smaller (p<0.03), the air leak was significantly less (p<0.03), and the VA per breath was significantly larger (p<0.03) during NIPPV with the F-mask than with the C-mask. In conclusion, nasal intermittent positive pressure ventilation with the F-mask was more effective than nasal intermittent positive pressure ventilation with the commercially available mask due to its smaller dead space and less air leak. Further studies are needed to extend these results to all the commercially available-masks.

Blood Gas Analysis↗

Synthesis and biological activity of N-(aminoiminomethyl)-1H-indole carboxamide derivatives as Na+/H+ exchanger inhibitors.

A series of N-(aminoiminomethyl)-1H-indole carboxamide derivatives were synthesized and their inhibitory potencies against the Na+/H+ exchanger were measured. Variation of the carbonylguanidine group at the 2- to 7-position of the indole ring system showed that a substitution at the 2-position improved the Na+/H+ exchanger inhibitory activity the most in vitro. This led to the synthesis and evaluation of an extensive series of N-(aminoiminomethyl)-1H-indole-2-carboxamide derivatives. Derivatives having an alkyl or substituted alkyl group at the 1-position of the indole ring system showed higher levels of in vitro activities. N-(aminoiminomethyl)- 1-(2-phenylethyl)-1H-indole-2-carboxamide (49) had the strongest activity.

Animals↗

Dexamethasone stabilizes IGFBP-1 mRNA in primary cultures of rat hepatocytes.

We have shown that dexamethasone stimulates insulin-like growth factor binding protein-1 (IGFBP-1) production due to an increase in IGFBP-1 mRNA content in primary cultures of rat hepatocytes. In the present study, we investigated the effect of dexamethasone on the stabilization of IGFBP-1 mRNA in this system. We found that dexamethasone stabilized IGFBP-1 mRNA from the dot blot analysis with actinomycin D in the culture medium. It is suggested that the stabilization of IGFBP-1 mRNA is one of the mechanisms in which IGFBP-1 mRNA increases during dexamethasone treatment in primary cultures of rat hepatocytes.

Animals↗

Influence of calcium antagonists on long-term survival of patients treated with coronary angioplasty.

A meta-analysis reported that nifedipine increased mortality dose-dependently in patients with coronary artery disease. However, there have been few studies (specifically in Asians) on the long-term prognosis of patients treated with calcium antagonists after successful coronary angioplasty (PTCA). The subjects consisted of 583 consecutive patients (461 males, aged 59 +/- 10), who underwent successful elective PTCA between 1985 and 1990. First, they were divided into two groups; the calcium antagonist (+) group (n = 560) and the calcium antagonist (-) group (n = 23), and were evaluated in terms of total survival and cardiac events. Second, the calcium antagonist (+) group was further divided into 4 groups according to calcium antagonist type, i.e., short-acting nifedipine group (n = 156), long-acting nifedipine group (n = 203), diltiazem group (n = 184) and the other group (n = 17), and these groups were evaluated in the same way. The primary end-point was set as death from any cause. Secondary end-points were any cardiac events, including non-fatal acute myocardial infarction, coronary artery bypass surgery and repeat PTCA. The mean follow-up period was 4.5 +/- 1.8 years. A multivariate analysis was performed with the Cox proportional-hazard model. The Kaplan-Meier analysis showed that the calcium antagonist (-) group had significantly worse prognoses than the calcium antagonist (+) group (p < 0.05), and that there was no significant difference among the prognoses of the four calcium antagonists groups. The multivariate analysis revealed that the use of a calcium antagonist was one of the independent factors positively contributing to the prognosis. The use of any type of calcium antagonist did not increase mortality in patients who underwent successful elective PTCA, rather, it contributed to a favorable outcome.

Aged↗

[A clinical study on renal pelvic and ureteral tumor associated with bladder tumor with special reference to risk factors of subsequently recurrent bladder tumor].

PURPOSE: The purpose of this report is to analyze the clinical feature of renal pelvic and/or ureteral tumor (RUT) associated with bladder tumor (BT) with special reference to risk factors of subsequently recurrent BT. METHODS: Of the 49 patients with RUT who underwent surgery and were diagnosed pathologically as transitional cell carcinoma at the Department of Urology, Osaka National Hospital from April 1986 to October 1996, 20 patients (40.8%) had associated BTs. These patients were categorized to the following 4 groups, Group 1: 5 patients with BT preceding RUT, Group 2: 5 patients with concomitant BT, Group 3: 10 patients with subsequent BT following RUT operation and Group 4: 29 patients without any associated BT. The clinical course of these 4 groups were studied and compared with each other retrospectively. RESULTS: In group 1, the first BTs preceded RUTs by 19 to 81 months (mean 54.6 months). And during this relatively long period, the preceding BTs were treated by TUR for each recurrence, 1 to 9 times (mean 5.2 times). Two of 5 were bilateral RUT cases, which were observed only in this group. In group 2, the prognosis were relatively poor (5-year survival rate: 0%), because all RUTs of this group were high stage. And also the concomitant BTs were showing invasive feature during the observation period, despite they were superficial at first. Thus 3 of 5 underwent radical cystectomy. On the other hand, in group 3, the subsequent BTs, which developed at 2 to 26 month (mean 13.4 month) after RUT operation, were all superficial and resectable by TUR. The 5-year disease specific survival rate was 50% in group 1, 0% in group 2, 63.5% in group 3, 64.9% in group 4. Group 2 had the most poor prognosis. However there was no significant difference in prognosis among the 4 groups. Incidence of preoperative urine positive cytology was significantly higher in group 3, than in group 4 (87.5% vs. 44.8%). CONCLUSIONS: These results indicated that the RUTs with associated BTs have distinct clinical features depending on the sequence of association with the BTs. Especially the RUTs with concomitant BTs should be watched carefully as a high risk group with poor prognosis and possible development of invasive BTs. Positive urine cytology prior to RUT operation may reflect biological activity of tumor cell for dissemination in the lower urinary tract and we suggested preoperative urine cytology was possible predictor of subsequently recurrent BTs after RUT operation in this study.

Adult↗

[A case of crossed fused kidney with simple ureterocele].

A 32-year-old man consulted Osaka National hospital with chief complaints of dysuria and macrohematuria. DIP and CT revealed that the right kidney deviated to the lower pole of the left kidney and they fused together. The right ureter crossed over the supine. The calcified shadow existed in the lower end of the left ureter with cobra head image. He had no external anomalies. Under diagnosing crossed fused kidney (inverted L shaped) complicated the left ureterocele with a stone, transurethral incision of ureterocele (TUI) was performed. We made transverse incision and extracted stone, 7 mm in size (calcium oxalate 96% and calcium phosphate 4%). Three months later after the operation, IVP, CG and VCG revealed the down-sized ureterocele and no VUR. Crossed renal ectopia complicated many anomalies about 50%. Among them anomalies of the urinary tract was most frequent about 30%. But crossed renal ectopia with ureterocele wasn't reported so far in Japanese literature.

Adult↗

[Dynamic MRI of intraductal papilloma].

MRI findings were retrospectively investigated in five cases of papilloma of the breast. The tumors, which had a smooth margin, were 8-28 mm in size and round(3), oval(1), and irregular(1)in shape. All tumors were well enhanced with Gd-DTPA: four were enhanced homogeneously and one inhomogeneously. Dynamic study demonstrated two different time-intensity curves: 1) an early enhancement pattern and 2) a slower enhancement pattern. Three tumors showed the early enhancement pattern, which is well known to be characteristic of malignancy, while the other two showed the slower enhancement pattern. In the latter cases, the intensity could not be measured accurately because the tumors were too small to set the ROI exactly within them. In conclusion, three of five papillomas demonstrated the early enhancement pattern on dynamic study, which means that the time-intensity curve cannot distinguish papilloma from carcinoma. Therefore, morphological features should also be taken into consideration in making the diagnosis.

Adult↗

[A trial of new protocol of rush immunotherapy with standardized mite antigen].

The objective of the present study was (1) to establish a new protocol of rush immunotherapy (IT) using a purified mite antigen for the treatment of house-dust-mite-sensitive bronchial asthma. Ten adult asthmatics were enrolled in the initial trial which was based on a 7-day protocol using a house-dust antigen, to determine the optimal maintenance dose of mite antigen. No systemic side effects were observed when the antigen dose was lower than 50 AU. Consequently, the duration of rush IT was shortened to 5 days, and the maintenance dose was determined as 50 AU in the new protocol. To confirm its safety, another ten asthmatics were enrolled in a second trial. Rush IT using the new protocol was able to be performed without any systemic side effects in all patients except one who showed urticaria at 40 AU. These results suggest that the 5-day protocol of rush IT using the mite antigen is safe in patients with house-dust-mite-sensitive asthma.

Adolescent↗

[Evaluation of amrubicin with a 5 day administration schedule in a mouse model].

It was reported that amrubicin hydrochloride (9-aminoanthracycline SM-5887), showed a higher therapeutic activity than doxorubicin against human tumor xenografts implanted into nude mice with a single treatment schedule. In order to find a more effective treatment schedule, the efficacy, toxicity and pharmacokinetic properties with a 5 consecutive day treatment schedule were investigated. The total amount of the maximum tolerated dose and tumor growth inhibiting activity with a 5 day schedule was found to be higher than with a single administration. High levels of amrubicinol, the active metabolite of amrubicin, was detected in the tumor tissue. It was thus assumed that the improved efficacy with the 5-day schedule resulted from the high accumulation of amrubicinol. Bone marrow suppression at the MTD with the 5 day schedule was severer than with a single dose, but recovery was rapid, similar to that following a single dose. In conclusion, it was demonstrated that a 5 day treatment schedule was more effective than a single administration.

Animals↗

[Lung and bone marrow granulomas associated with human parvovirus B19 infection].

A 56-year-old man was admitted with flu-like symptoms, and his platelet count abruptly decreased. A chest X-ray film showed granular shadows, and lung and bone marrow specimens disclosed non-caseating epithelioid cell granulomas. The patient's serum IgM titer for human parvovirus (HPV) B19 was elevated. Our conclusion was that HPV B19 must be kept in mind as a possible pathogenic agent of granuloma formation.

Antibodies, Viral↗

Cardioprotection of SM-15681, an Na+/H+ exchange inhibitor in ischemic and hypoxic isolated perfused rat hearts.

We investigated the effects of SM-15681 (N-(aminoiminomethyl)-1-methyl-1H-indole-2-carboxamide monohydrochloride) on Na+/H+ exchange activity in the myocardium and in ischemic and hypoxic injury in isolated perfused rat hearts. These effects were compared with those of ethylisopropyl amiloride (EIPA). Na+/H+ exchange activity was studied with a NH4Cl prepulse technique under HCO3(-)-free conditions. SM-15681 (10(-8)-10(-7) M) inhibited pH recovery of acidosis in the rat myocardium in a concentration-dependent manner and the IC50 value of SM-15681 (80 nM) was similar to that of EIPA. In perfused rat hearts, SM-15681 (10(-6) M) and EIPA (10(-6) M) significantly improved cardiac functions and prevented enzyme release and abnormal elevation of tissue Ca2+ content during 20 min of reperfusion after 40 min of ischemia and 20 min of reoxygenation after 30 min of hypoxia. We conclude that an Na+/H+ exchange inhibitor, SM-15681, shows cardioprotective effects on ischemia/reperfusion and hypoxia/reoxygenation injury. Our results also support the hypothesis that Na+/H+ exchange contributes to the pathophysiology of cardiac ischemic reperfusion injury.

Amides↗

The Arabidopsis dwf7/ste1 mutant is defective in the delta7 sterol C-5 desaturation step leading to brassinosteroid biosynthesis.

Lesions in brassinosteroid (BR) biosynthetic genes result in characteristic dwarf phenotypes in plants. Understanding the regulation of BR biosynthesis demands continued isolation and characterization of mutants corresponding to the genes involved in BR biosynthesis. Here, we present analysis of a novel BR biosynthetic locus, dwarf7 (dwf7). Feeding studies with BR biosynthetic intermediates and analysis of endogenous levels of BR and sterol biosynthetic intermediates indicate that the defective step in dwf7-1 resides before the production of 24-methylenecholesterol in the sterol biosynthetic pathway. Furthermore, results from feeding studies with 13C-labeled mevalonic acid and compactin show that the defective step is specifically the Delta7 sterol C-5 desaturation, suggesting that dwf7 is an allele of the previously cloned STEROL1 (STE1) gene. Sequencing of the STE1 locus in two dwf7 mutants revealed premature stop codons in the first (dwf7-2) and the third (dwf7-1) exons. Thus, the reduction of BRs in dwf7 is due to a shortage of substrate sterols and is the direct cause of the dwarf phenotype in dwf7.

Alleles↗

Fourier transform infrared study of the cation radical of P680 in the photosystem II reaction center: evidence for charge delocalization on the chlorophyll dimer.

A Fourier transform infrared (FTIR) difference spectrum of the primary electron donor (P680) of photosystem II upon its photooxidation (P680+/P680) was obtained in the frequency region of 1000-3000 cm-1. The reaction center (RC) complex (D1-D2-Cytb559) was used for the measurements in the presence of ferricyanide as an exogenous electron acceptor. Control measurements of electronic absorption (300-1200 nm) showed that illumination of the RC complex at 150 K induced major oxidation of P680 concomitant with oxidation of a carotenoid and an accessory chlorophyll (Chl). Illumination at 250 K also specifically bleached one of the two beta-carotene molecules bound to the RC complex, and the sample thus treated exhibited little formation of a carotenoid cation on subsequent illumination at 150 K. The P680+/P680 FTIR difference spectrum (with minor contamination of Chl+/Chl) was measured at 150 K using this partially carotenoid-deficient RC complex. The spectrum showed a broad positive band centered at approximately 1940 cm-1, which could be ascribed to an infrared electronic transition of P680+ analogous to that previously observed in various bacterial P+. This finding indicates that a positive charge is delocalized over (or hopping between) the two Chl molecules in P680+. The low intensity of this electronic band compared with that of the bacterial band could have three possible explanations: weak resonance interaction between the constituent Chl molecules, an asymmetric structure of P680+, and the difference in Chl species. Bands in the C=O stretching region (1600-1750 cm-1) were interpreted in comparison with resonance Raman spectra of the RC complex. The negative peaks at 1704 and 1679 cm-1 were proposed as candidates for the keto C9=O bands of P680. The observation that neither of these bands agreed with the main keto C9=O band at 1669 cm-1 in the previous 3P680/P680 FTIR spectrum [Noguchi et al. (1993) Biochemistry 32, 7186-7195] led to the idea that the triplet state migrates to a Chl (designated as ChlT) different from P680 at low temperatures. Based on these results, structural models of Chl molecules including P680 and ChlT and their coupling in the cation, triplet, and Qy singlet states are discussed.

Carotenoids↗

Assembly of flammutoxin, a cytolytic protein from the edible mushroom Flammulina velutipes, into a pore-forming ring-shaped oligomer on the target cell.

Flammutoxin has been previously isolated as a cardiotoxic and cytolytic polypeptide of 22 or 32 kDa from the fruiting bodies of the edible mushroom Flammulina velutipes. In the present study, we purified flammutoxin as a single haemolytic protein of 31 kDa and studied the mode of its cytolytic action. (1) Flammutoxin caused efflux of potassium ions from human erythrocytes and swelling of the cells before haemolysis. (2) Flammutoxin did not lyse human erythrocytes in the presence of non-electrolytes with hydrodynamic diameters of >5.0 nm, although it caused leakage of potassium ions and swelling of the cells under the same conditions. (3) Experiments including solubilization of cell-bound toxin with 2% (w/v) SDS at 20 degrees C and subsequent Western immunoblots showed that flammutoxin formed a band corresponding to 180 kDa under the conditions where it lysed erythrocytes. (4) Electron microscopy of flammutoxin-treated human erythrocytes revealed the presence of a ring-shaped structure with outer and inner diameters of 10 and 5 nm, respectively, on the cells. (5) A ring-shaped toxin oligomer of the same dimensions was solubilized from the toxin-treated human erythrocytes with 2% (w/v) SDS at 20 degrees C and isolated by a sucrose-gradient ultracentrifugation. These data indicated that flammutoxin assembles into a ring-shaped oligomer possessing a hydrophilic pore of 4-5 nm on target cells.

Basidiomycota↗

The polyphosphate kinase gene of Pseudomonas aeruginosa.

We have cloned and sequenced a gene encoding polyphosphate kinase (PPK) from Pseudomonas aeruginosa PAO1. The gene immediately follows the hemB gene encoding porphobilinogen synthase responsible for heme synthesis. The predicted amino acid sequence of P. aeruginosa PPK is similar to those of PPKs previously characterized except that it possesses an extra stretch of 46 amino acids at its N-terminus, which has significant similarity to the Ras-related protein ARA5 of Arabidopsis thaliana. When P. aeruginosa PPK was overproduced in Escherichia coli, ATP-dependent polyphosphate-synthesizing activity was drastically enhanced, confirming that the protein is a PPK.

Amino Acid Sequence↗

Lysophosphatidic acid-induced association of SHP-2 with SHPS-1: roles of RHO, FAK, and a SRC family kinase.

SHPS-1 is an approximately 120 kDa glycosylated receptor like protein that contains three immunoglobulin-like domains in its extracellular region as well as four potential tyrosine phosphorylation and SRC homology 2 (SH2) domain binding sites in its cytoplasmic region. Lysophosphatidic acid (LPA) stimulated the rapid tyrosine phosphorylation of SHPS-1 and its subsequent association with SHP-2, a protein tyrosine phosphatase containing SH2 domains in Rat-1 fibroblasts. LAP-induced tyrosine phosphorylation of SHPS-1 was inhibited by Clostridium botulinum C3 exoenzyme (which inactivates RHO) but not by pertussis toxin. The protein kinase C activator phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA) also stimulated tyrosine phosphorylation of SHPS-1; however, down-regulation of protein kinase C by prolonged exposure of cells to TPA did not affect LAP-induced tyrosine phosphorylation of SHPS-1. LPA-induced tyrosine phosphorylation of SHPS-1 was markedly reduced in either focal adhesion kinase (FAK)-deficient mouse cells or CHO cells overexpressing the tyrosine kinase CSK. Overexpression of a catalytically inactivate SHP-2 markedly inhibited MAP kinase activation in response to low concentrations of LPA in CHO cells, whereas overexpression of a wild-type SHPS-1 did enhance this effect of LPA. Furthermore, MAP kinase activation in response to a low concentration of LPA was inhibited by botulinum C3 exoenzyme. These results indicate that LPA-induced tyrosine phosphorylation of SHPS-1 and its association with SHP-2 may be mediated by a RHO-dependent pathway that includes FAK and a SRC family kinase. Thus, in addition to its role in receptor tyrosine kinase-mediated MAP kinase activation, the formation of a complex between SHPS-1 and SHP-2 may, in part, play an important role in the activation of MAP kinase in response to low concentrations of LPA.

ADP Ribose Transferases↗