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Biomedical subjects

T Noguchi

Publications and source records attributed to T Noguchi.

At least 127 records · Page 7Linked to original sources

Retinoid nutritional status differently affects the expression of Japanese quail retinoic acid receptor-beta isoform transcripts in a tissue-specific manner.

We investigated the effects of vitamin A (VA) nutritional status on the levels of expression of retinoic acid (RA) receptor-beta (RARbeta) gene in the various tissues of Japanese quail. VA deficiency caused a significant decrease in the mRNA levels of brain, liver, heart, lung and kidney RARbeta2/beta4, whereas no change was observed in the level of testis RARbeta2 transcript. In contrast, reduction in the RARbeta1 transcript caused by VA depletion was observed only in the lung, remaining unchanged in the other tissues. The administration of RA to the VA-deficient quail rapidly induced the expression of RARbeta2/beta4 mRNAs in all the tissues examined, but RA increased the expression of RARbeta1 transcript in the liver, heart, lung and kidney at a lower magnitude. RA could not change the expression of the brain RARbeta1 transcript, while it induced the expression of the testis RARbeta1 mRNA in a temporal way. These results clearly indicate that VA nutritional status differently regulates the expression of RARbeta1 and RARbeta2/beta4 transcripts in a tissue-specific manner.

Analysis of Variance↗

Effect of repeated local minocycline administration on periodontal healing following guided tissue regeneration.

BACKGROUND: Infection after a periodontal surgical site has been prepared for guided tissue regeneration (GTR) is one of the common complications that can compromise healing. The purpose of this study was to assess the effect of repeated local antimicrobial therapy following GTR for improving clinical attachment gains, and to histologically evaluate the various cell populations and bacterial contamination of the retrieved expanded polytetrafluoroethylene membrane (ePTFE). METHODS: Forty periodontal intrabony defects in 40 patients were treated by a flap procedure that included the use of ePTFE membranes to allow GTR. Patients were randomly assigned to 2 treatment groups: 20 patients were treated with the ePTFE alone (control group), and the other 20 were treated with the ePTFE combined with the administration of a weekly repeated local application of minocycline ointment for 8 weeks after membrane placement (test group). The membranes were retrieved 6 weeks after the initial surgery and sectioned serially in a coronal-apical plane. The sections were then divided into 9 fields and examined by light microscopy for the presence of inflammatory cells and oral bacteria. Clinical measurements were taken at the time of baseline examination and at a 6-month follow-up examination after removal of the ePTFE. RESULTS: At the 6-month follow-up examination, control and test groups showed significant improvement; i.e., reduction in the probing depth and increased clinical attachment gain compared with the values at the baseline examination. However, the mean clinical attachment gain of the test group (3.0+/-0.3 mm) was significantly (P = 0.03) greater than that of the control group (2.0+/-0.5 mm). Histologically, the total number of the cells of both groups was similar. In both groups, mononuclear cells were dominant and fibroblasts, neutrophils, and plasma cells were rarely encountered. There was a tendency for the number of macrophages to be somewhat higher in the control group. The total number of bacteria in the test group was significantly less than that in the control group. The number of bacteria in both control and test groups decreased toward the apical portion. CONCLUSIONS: In the present study, clinical attachment gain of intrabony defects following GTR was favorable with repeated local administration of minocycline ointment. However, a complete microbial eradication was not achieved.

Administration, Topical↗

MSH2 and MLH1 immunodetection and the prognosis of colon cancer.

MSH2 and MLH1 are proteins involved in DNA reparation. They are mutated in some forms of colon cancer, i.e. hereditary non-polyposis carcinomas and a subset of sporadic carcinomas. We have studied the expression of MSH2 and MLH1 in a retrospective series of 225 colorectal carcinomas by immunohistochemistry. The results were compared to molecular tests of microsatellite instability using amplification by PCR of BAT-25 and BAT-26 repeated sequences and to histoclinical data. Positivity of both proteins was never associated with MSI phenotype. MSH2 and/or MLH1 negative tumors were frequently tumors of the proximal colon; in this subpopulation or proximal tumors, MSH2 and/or MLH1 negativity was associated with a longer disease-free survival.

Adaptor Proteins, Signal Transducing↗

[The sensitivity and clinical implications of periodical bladder biopsy following transurethral resection of superficial bladder transitional cell carcinoma].

The role of the periodical bladder biopsy after transurethral resection (TUR-Bt) of superficial bladder cancer (sBT) was evaluated. Sixty-four patients (85 TURs) with sBT who underwent TUR-Bt between 1993 and 1998 were divided into 14 (22 TURs) who had carcinoma in situ (CIS) at the first TUR (group A), and 50 (64 TURs) who had papillary tumors without concomitant CIS (group B). Post-TUR intravesical instillation was performed with bacillus Calmette-Guerin for the majority of group A, and mitomycin C for the majority of group B. The first biopsy was performed at 3 months postoperatively, and the second biopsy was done at 8 to 12 months postoperatively. The mean observation time was 4 years and 6 months. Residual cancer was detected in 7 out of 34 biopsies (20.6%) in group A, and 19 out of 94 (20.2%) in group B. Every residual lesion in group A was CIS with negative cytology. In group B, with exclusion of 11 recurrent papillary tumors, the detection rate was only 8/83 (9.6%). In both groups, even in the cases with no sign of disease in biopsies, the recurrence immediately after the termination of the biopsy protocol was common. The progression of the cancer was more frequent in group A (4 patients), than in group B (2 patients) (p < 0.01, log-rank test), and no case in group B showed local progression. The periodical biopsy may have a certain, but limited advantage over conventional examinations. A less invasive and more sensitive method in awaited.

Biopsy↗

Chelonodon patoca, a highly toxic marine puffer in Japan.

Toxicity of a Japanese marine puffer Chelonodon patoca ("okinawafugu") was examined by mouse assay from 1996 to 1999. Frequency of the toxic specimens was found to be 100% with high toxicity scores. Among the tissues tested, toxicity in the skin ranged from 60 to 6,700 MU/g, in the ovary from 25 to 670 MU/g, in the testis from 45 to 550 MU/g, in the muscle from 2 to 390 MU/g, and in the liver from 5 to 380 MU/g. The liver, which is known as one of the most toxic organs in Japanese marine puffer in general, showed lower toxicity in the present study. Thus, the anatomical distribution of toxicity was unique in C. patoca, in comparison with that of other Japanese puffers. C. patoca toxin was characterized as tetrodotoxin (TTX), 4-epiTTX and anhydroTTX by HPLC.

Animals↗

Toxicity and toxin profiles of the newt, Cynops pyrrhogaster from western Japan.

A total of 382 specimens of a Japanese newt, Cynops pyrrhogaster, were collected from western Japan during 1996 to 1999, and assayed for their individual, geographical, sexual, seasonal variations, and anatomical distribution of toxicity by mouse. Most of the specimens tested showed toxicity scores ranging from 5 to 370 MU/g, where no seasonal, but large individual, sexual, and regional variations of toxicity were clearly recognized. Among the parts, skin and muscle showed higher toxicity scores (56 MU/g) than liver, stomach, intestine and gonad, whose toxicity ranged from less than 2 to 33 MU/g. The C. pyrrhogaster toxin was purified by several steps of column chromatography and was shown to consist of tetrodotoxin (TTX) and 6-epiTTX as main components, and 4-epiTTX, 4,9-anhydro-6-epiTTX, and 4,9-anhydroTTX as minor ones by means of HPLC and 1H-NMR analyses.

Animals↗

[Allogeneic bone marrow transplantation for refractory multiple myeloma: presence of a graft-versus-myeloma effect].

We investigated the graft-versus-myeloma effect (GVM) after allogeneic bone marrow transplantation (allo-BMT). Three patients with refractory multiple myeloma (MM) underwent related allo-BMT. Two of the patients showed disappearance of serum M protein 4 and 5 months after transplantation, respectively. One of them has remained in complete remission for more than 22 months after allo-BMT, with accompanying chronic GVHD. Two patients with relapse and disease progression after allo-BMT underwent donor lymphocyte infusion (DLI). Although one patient did not respond to DLI, the other developed acute GVHD after 4 weeks and achieved a 75% reduction in serum M protein. DLI did not produce severe acute GVHD or myelosuppression. These findings suggest the presence of a GVM effect. DLI may be an effective therapy for patients with MM who have relapsed after allo-BMT. Furthermore, non-myeloablative stem cell transplantation (mini-transplantation) for refractory MM should be investigated further as a potentially curative option.

Adult↗

[Reconstruction of the cervical esophagus by interposition of the transverse colon].

Currently, the first choice viscus for reconstruction after total pharyngolaryngoesophagectomy is a jejunal interposition. This requires at least one end-to-side anastomosis in the pharyngo-jejunal anastomosis, esophago-jejunal anastomosis, or both due to the small diameter of the jejunum and round shape of the mesenterium. Furthermore, the jejunal graft experiences a spasm when the patient swallows. For such reasons the jejunal free graft is not suitable for swallowing. On the other hand, the transverse colon graft is more appropriate for reconstruction for the following reasons: it has a straight shape; end-to-end anastomosis is possible to both the pharynx and esophagus; and there are postoperative complications due to simple anastomosis of the remaining colon after graft removal. Blood vessel anastomoses, performed using microsurgery techniques, are followed by esophageal reconstructive anastomoses. Fifteen patients successfully underwent this type of reconstruction in our institution.

Aged↗

Analgesic effects of flecainide on postherpetic neuralgia.

Sodium channel blockers have been reported to be effective in relieving neuropathic pain. However, although intravenous lidocaine has proved to be effective, in some patients oral mexiletine fails to produce adequate pain relief. In this study, we investigated the analgesic effect of flecainide, a long-lasting antitachyarrhythmic drug, on postherpetic neuralgia. Twenty patients with postherpetic neuralgia received an intravenous infusion of flecainide and 15 (75%) of those who achieved pain relief subsequently received oral flecainide. The patients were assessed using a 100 mm visual analog scale 1 month after treatment. Significant improvement compared with the pretreatment reading was found. This study suggests that the action of flecainide in blocking the sodium channel is potent and long-lasting and that, like the intravenous formulation, the oral formulation has a stable analgesic effect on postherpetic neuralgia.

Aged↗

[Anesthetic management of a patient with Cockayne's syndrome].

Cockayne's syndrome is a disease of childhood characterized by mental retardation and premature aging. An 11-year-old girl with Cockayne's syndrome underwent general anesthesia for acute appendicitis. Although we had expected the difficulty of intubation because of her small jaw with limited movement, we could visualize her vocal cord, and intubate easily. High peak airway pressure was needed to ventilate her lung after intubation suggesting decreased lung compliance for this syndrome. We have to consider anesthetic problems resulting not only from pediatric but also from geriatric anesthesia for the management of this syndrome.

Acute Disease↗

Reduced production of lactate during hypoxia and reoxygenation in astrocytes isolated from stroke-prone spontaneously hypertensive rats.

Lactate production and expressions of monocarboxylate transporter 1 (MCT1) and lactate dehydrogenase (LDH) mRNA after hypoxia and reoxygenation (H/R) were examined by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) using astrocytes in culture isolated from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar Kyoto rats (WKY). The basal production of lactate in SHRSP was the same as that observed in WKY. In contrast the lactate levels in SHRSP at 1 and 6 h of reoxygenation after hypoxia were significantly lower than those observed in WKY. In addition LDH and MCT1 mRNA expressions in SHRSP were significantly less strong compared with those in WKY during H/R. These findings indicate that decreased production and slow transport of lactate in SHRSP astrocytes are involved in neuronal energy depletion and possibly encourage neuronal damage, although hereditary weakness of cortical neurons is also related to cell death during H/R.

Animals↗

Inorganic polyphosphate kinase and adenylate kinase participate in the polyphosphate:AMP phosphotransferase activity of Escherichia coli.

Polyphosphate kinase (PPK), responsible for the processive synthesis of inorganic polyphosphate (polyP) from ATP in Escherichia coli, can transfer in reverse the terminal phosphate residue of polyP to ADP to yield ATP. PolyP also serves as a donor in a polyP:AMP phosphotransferase (PAP) activity observed in extracts of Acinetobacter johnsonii and Myxococcus xanthus. We have found that overexpression of the gene encoding PPK results in a large enhancement of PAP activity in E. coli. The PAP activity requires both PPK and adenylate kinase in equimolar amounts. PPK and adenylate kinase form a complex in the presence of polyphosphate. We discuss a phosphotransfer mechanism that involves both enzymes and enables polyP to be a phospho-donor to AMP.

Adenylate Kinase↗

SHPS-1 regulates integrin-mediated cytoskeletal reorganization and cell motility.

The transmembrane glycoprotein SHPS-1 binds the protein tyrosine phosphatase SHP-2 and serves as its substrate. Although SHPS-1 has been implicated in growth factor- and cell adhesion-induced signaling, its biological role has remained unknown. Fibroblasts homozygous for expression of an SHPS-1 mutant lacking most of the cytoplasmic region of this protein exhibited increased formation of actin stress fibers and focal adhesions. They spread more quickly on fibronectin than did wild-type cells, but they were defective in subsequent polarized extension and migration. The extent of adhesion-induced activation of Rho, but not that of Rac, was also markedly reduced in the mutant cells. Activation of the Ras-extracellular signal-regulated kinase signaling pathway and of c-Jun N-terminal kinases by growth factors was either unaffected or enhanced in the mutant fibroblasts. These results demonstrate that SHPS-1 plays crucial roles in integrin-mediated cytoskeletal reorganization, cell motility and the regulation of Rho, and that it also negatively modulates growth factor-induced activation of mitogen-activated protein kinases.

Animals↗

Homeobox gene Hex is essential for onset of mouse embryonic liver development and differentiation of the monocyte lineage.

Disruption of the mouse Hex gene resulted in embryonic lethality around embryonic age (E) 10.5, due to no substantial liver formation. Expression of albumin was detectable in heterozygous (Hex(+/-)) but not in homozygous (Hex(-/-)) [corrected] embryos at E8.5. Instead of liver bud formation at E9.5, a liver-like capsule structure was observed in Hex(-/-) [corrected] embryos. In Hex(-/-) [corrected] mutant liver, we found no hepatocytes but no signs of apoptotic cell death in the area. Expression of transcription factors involved in hepatocyte differentiation, hepatocyte nuclear factor (Hnf)3beta, Hnf6, Hnf4alpha and Hnf1alpha, were restricted to the capsule and internal matrix-like structure in the mutant liver and expression of a subset of these factors were reduced. Hematopoiesis of monocytes was impaired in mutant embryos while erythroid lineage was unaffected. These results indicate that Hex plays an essential role in progenitor cells which commit to the hepatic endoderm and in the hematopoietic differentiation of the monocyte lineage.

Albumins↗

Structure of an active water molecule in the water-oxidizing complex of photosystem II as studied by FTIR spectroscopy.

The vibrations of a water molecule in the water-oxidizing complex (WOC) of photosystem II were detected for the first time using Fourier transform infrared (FTIR) spectroscopy. In a flash-induced FTIR difference spectrum upon the S(1)-to-S(2) transition, a pair of positive and negative bands was observed at 3618 and 3585 cm(-1), respectively, and both bands exhibited downshifts by 12 cm(-1) upon replacement of H(2)(16)O by H(2)(18)O. Upon D(2)O substitution, the bands largely shifted down to 2681 and 2652 cm(-1). These observations indicate that the bands at 3618 and 3585 cm(-1) arise from the O-H stretching vibrations of a water molecule, probably substrate water, coupled to the Mn cluster in the S(2) and S(1) states, respectively. The band frequencies indicate that the O-H group forms a weak H-bond and this H-bonding becomes weaker upon S(2) formation. Intramolecular coupling with the other O-H vibration of this water molecule was studied by a decoupling experiment using a H(2)O/D(2)O (1:1) mixture. The downshifts by decoupling were estimated to be 4 and 12 cm(-1) for the 3618 (S(2)) and 3585 cm(-1) (S(1)) bands, both of which were much smaller than 52 cm(-1) of water in vapor, indicating that the observed water has a considerably asymmetric structure; i.e., one of the O-H groups is weakly and the other is strongly H-bonded. The smaller coupling in the S(2) than the S(1) state means that this H-bonding asymmetry becomes more prominent upon S(2) formation. Such a structural change may facilitate the proton release reaction that takes place in the later step by lowering the potential barrier. The present study showed that FTIR detection of the O-H vibrations is a useful and promising method to directly monitor the chemical reactions of substrate water and clarify the molecular mechanism of photosynthetic water oxidation.

Cyanobacteria↗

Arginine 56 mutation in the beta subunit of nitrile hydratase: importance of hydrogen bonding to the non-heme iron center.

Arginine 56 in the beta subunit (betaArg56) of the iron-containing nitrile hydratase (NHase), one of the strongly conserved residues within the NHase family, is known to form hydrogen bonds to the sulfinyl (-SO2H) and sulfenyl (-SOH) groups of the post-translationally modified cysteine residues in the catalytic center. BetaArg56 was substituted by tyrosine, glutamate or lysine, respectively, and the respective mutant enzymes generated by reconstitution were characterized. The betaR56K mutant complex exhibited about 1% of the enzymatic activity of native NHase, while the others were totally inactive. The kinetic analysis of the betaR56K mutant complex exhibited a drastic decrease in turnover number and decreases in kinetic constants for substrate and inhibitors as compared to the native NHase. Changes in UV-visible absorption and light-induced Fourier transform infrared difference spectra suggest that betaArg56 is involved in the positioning of the -SO2H and -SOH groups of the modified Cys residues in the catalytic center so as to fine tune the electronic state of the iron center suitable for catalysis. Thus, betaArg56 is essential for catalysis.

Arginine↗

Sp family members and nuclear factor-Y cooperatively stimulate transcription from the rat pyruvate kinase M gene distal promoter region via their direct interactions.

The three distal transcriptional regulatory elements of the rat pyruvate kinase M gene, referred to as boxes A, B, and C, are located around -270 base pairs upstream from the transcriptional initiation site. Electrophoretic mobility shift assays with specific competitors and antibodies show that both box A and box B bind to Sp1 and Sp3 and that box C binds nuclear factor-Y (NF-Y). Luciferase reporter assays revealed that although box A and box B alone have no independent effect on luciferase activities, box C alone stimulates transcription. However, the inclusion of all three elements lead to maximal activity because of a synergistic effect, mainly between box B and box C, suggesting that functional synergism between Sp1/Sp3 and NF-Y is critical for the pyruvate kinase M (PKM) gene distal promoter activity. In fact, co-transfection of a dominant negative mutant of NF-YA (NF-YA29) resulted in a decrease in reporter activity in a box C-dependent manner. In addition, the overexpression of Sp1 or Sp3 and NF-Y in Drosophila SL2 cells synergistically stimulated PKM gene distal promoter activity. Using a mammalian two-hybrid system in HeLa cells, it was shown that both Sp1 and Sp3 interacted with NF-YA but not NF-YB and NF-YC. Moreover, glutathione S-transferase pull-down assays revealed that only in vitro translated (35)S-labeled NF-YA interacted with both Sp1 and Sp3 in vitro. A subunit interaction domain of NF-YA, which forms a heterotrimer with NF-YB and NF-YC, is not required for these interactions with Sp1 or Sp3. Thus, we conclude that Sp1, Sp3, and NF-Y stimulate the transcription of the PKM gene via their interactions.

Animals↗