Biomedical subjects

M Kato

Publications and source records attributed to M Kato.

At least 289 records · Page 16Linked to original sources

PubMed2000

cDNA Cloning and mRNA analysis of PGC-1 in epitrochlearis muscle in swimming-exercised rats.

Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1), a cold-inducible coactivator of nuclear receptors, stimulates mitochondrial biogenesis and respiration in muscle cells. In the present study, we first cloned a rat PGC-1 gene from a brown adipose tissue cDNA library which encodes a predicted 796-amino-acid protein and exhibits respectively 98% and 95% identity with the mouse and human homologues. Next, we examined the effect of swimming exercise training on the level of expression of the PGC-1 gene in rat epitrochlearis (Epi) muscle. PGC-1 mRNA level in Epi muscle in rats that swam 2 h a day for 3 and 7 days increased dramatically by 154% and 163%, respectively, compared to the non-exercised control group. PGC-1 mRNA up-regulation was not observed in an immersion group treated at 35 degrees C during the training program but without swimming exercise. These results demonstrate that expression of the PGC-1 gene in Epi muscle is induced not only by cold exposure but also by prolonged low-intensity physical exercise.

Animals↗

PubMed2000

Value of reverse transcription polymerase chain reaction assay in pathological stage T3N0 prostate cancer.

BACKGROUND: We tested the ability of the nested reverse transcription polymerase chain reaction (RT-PCR) assay to detect signs of biochemical recurrence of prostate cancer in the lymph nodes and peripheral blood of patients with pT3N0 prostate cancer. METHODS: Using lymph nodes and pre- and postoperative peripheral blood dissected from 30 patients with pT3N0 prostate cancer treated by radical prostatectomy, we used RT-PCR for prostate-specific membrane antigen (PSM) and serum prostate-specific antigen (PSA) to determine the presence of prostate cancer. Results of the nested RT-PCR assay were compared with pathological stages and biochemical recurrence. RESULTS: Two of 13 patients with capsular penetration (15%), 6 of 10 patients with invasion of seminal vesicles (60%), and 3 of 7 patients with a positive surgical margin (43%) were RT-PCR-positive for PSM and/or PSA in the lymph nodes. Results of preoperative RT-PCRs of peripheral blood for PSM and for PSA significantly differed between positive and negative results of RT-PCR in lymph nodes (P < 0.001 and P < 0.001, respectively). Results of postoperative RT-PCRs of peripheral blood for PSM and for PSA also significantly different between positive and negative results of RT-PCR in lymph nodes (P = 0.011 and P = 0.001, respectively). Nine of 11 patients with positive nested RT-PCR for PSM and/or PSA in the lymph nodes (82%) experienced biochemical recurrence. Significant difference in Kaplan-Meier recurrence-free actuarial curves was noted between patients who nested positive and negative on RT-PCR in the lymph nodes, pre- and postoperative peripheral blood, biopsy and prostatectomy Gleason score, and preoperative PSA values. In multivariate analysis, biopsy and prostatectomy Gleason score (P = 0.026, P = 0.020, respectively), pre- and postoperative RT-PCR for PSM in peripheral blood (P = 0.030 and P = 0.040, respectively), and RT-PCR for PSM in lymph nodes (P = 0.035) were independent prognostic factors. CONCLUSIONS: Nested RT-PCR assay of the lymph nodes or peripheral blood significantly predicted biochemical recurrence after surgery. It may help identify patients at risk for recurrence and progression of prostate cancer.

Aged↗

PubMed2000

The low prevalence of high levels of expressed emotion in Bali.

The present study contrasts the expressed emotion (EE) status in family members of schizophrenic patients between Bali (Indonesia) and Tokyo (Japan), the former being a non-industrialized society and the latter an industrialized society in Asia. The EE ratings of each key relative for 62 consecutively hospitalized schizophrenic patients at the Bangli State Mental Hospital (Bali) and 33 consecutively admitted schizophrenics at Komagino Hospital (Tokyo) were obtained using the Five Minute Speech Sample (FMSS) method. A significantly lower prevalence of high EE (12.9%) was observed in Bali compared with Tokyo (36.4%) (P<0.01). This result may explain the better social adjustment of schizophrenics in Bali. In addition, in Bali, to clarify the EE effect in this non-industrialized society, we examined the relationship between each key relative's EE and the patient's psychotic symptoms at admission, as assessed by the Brief Psychiatric Rating Scale (BPRS) and the Scales for the Assessment of Negative Symptoms (SANS). Moreover, the association between each family member's EE and a patient's rate of re-admission over the 1-year period following discharge was evaluated. The EE value was significantly related to the anxious-depression factor score in the BPRS, but not to either of the other factor scores in the BPRS or SANS subscales. Furthermore, EE status was not a reliable predictor of patient re-admission over the 1-year period following discharge in Bali.

Adolescent↗

PubMed2000

Frame-shift mutations in NAD(P)H flavin oxidoreductase encoding gene (frxA) from metronidazole resistant Helicobacter pylori ATCC43504 and its involvement in metronidazole resistance.

Metronidazole is a critical ingredient for combination therapies of Helicobacter pylori infection, the major cause of peptic ulcer and gastric cancer. It has been recently reported that metronidazole resistance from H. pylori ATCC43504 is caused by the insertion of a mini-IS605 sequence and deletion of sequences in an oxygen insensitive NAD(P)H nitroreductase encoding gene (rdxA). We also found that an additional gene (frxA) encoding NAD(P)H flavin oxidoreductase in the same strain was truncated by frame-shift mutations. To assess whether the frxA truncation is also involved in metronidazole resistance, metronidazole sensitive H. pylori strains ATCC43629 and SS1 were transformed by the truncated frxA gene cloned from strain ATCC43504. All transformed cells grew on agar plates containing 16 microg ml(-1) of metronidazole. The involvement of the frxA gene in metronidazole resistance was also confirmed by insertion inactivation of frxA and/or rdxA genes from strain ATCC43629 and one metronidazole sensitive clinical isolate H. pylori 2600. In addition, the frxA gene cloned from the H. pylori 2600 showed metronidazole nitroreductase activity in Escherichia coli and rendered ordinary metronidazole resistant E. coli to metronidazole sensitive cell. These results indicate that the frxA gene may also be involved in metronidazole resistance among clinical H. pylori isolates.

Amino Acid Sequence↗

PubMed2000

Loss of fragile histidine triad gene expression is associated with progression of esophageal squamous cell carcinoma, but not with the patient's prognosis and smoking history.

BACKGROUND: Recently, fragile histidine triad (FHIT) gene abnormality has been thought to be associated with several malignancies and smoking history. The authors previously discovered that methylation of the 5' CpG island of the FHIT gene was closely associated with transcriptional inactivation in esophageal squamous cell carcinoma (SCC); however, the clinical impact of the FHIT gene in esophageal carcinoma is still unknown. METHODS: In this article, the authors evaluated the clinical impact of the FHIT gene in 149 esophageal squamous cell carcinoma (SCC) patients retrospectively using immunohistochemical analysis. They also examined the correlation between FHIT protein expression and smoking history. RESULTS: Among 149 curative resection (R0) cases of esophageal SCC, normal FHIT protein expression was noted in only 33 cases (22.1%), whereas reduced FHIT protein expression was noted in 67 cases and there was no FHIT expression in 50 cases. When a tumor invaded the muscle layer, FHIT protein expression was markedly reduced. The cases with reduction or loss of FHIT protein expression tended to have poor prognoses (P = 0.069). However, Cox multivariate analysis revealed that FHIT protein reduction had no relation to prognosis. FHIT protein expression had no relation to smoking history. CONCLUSIONS: FHIT protein expression was associated with progression of esophageal SCC, however, it may not be associated with the patient's prognosis and smoking history.

Aged↗

PubMed2000

A Theoretical Light-Curve Model for the 1985 Outburst of RS Ophiuchi.

A theoretical light-curve model of the 1985 outburst of RS Ophiuchi based on a thermonuclear runaway model is presented. The system consists of a very massive white dwarf (WD) with an accretion disk and a red giant. The early phase of the V light curve is well reproduced only by the bloated WD photosphere of the thermonuclear runaway model on a 1.35+/-0.01 M middle dot in circle WD, while the later phase is dominated both by the irradiated accretion disk and by the irradiated red giant underfilling the inner critical Roche lobe. The UV light curve is also well reproduced by the same model with a distance of 0.6 kpc to RS Oph. The envelope mass at the optical peak is estimated to be 2x10-6 M( middle dot in circle), indicating a rather high mass accretion rate of 1.2x10-7 M( middle dot in circle) yr(-1) between the 1967 and 1985 outbursts. About 90% of the envelope mass is blown off in the outburst wind, while the residual 10% (2x10-7 M( middle dot in circle)) has been left and added to the helium layer of the WD. The net increasing rate of the WD mass is 1.2x10-8 M( middle dot in circle) yr(-1). Thus, RS Oph is certainly a strong candidate for a Type Ia supernova progenitor.

Journal Article↗

PubMed2000

Novel antiarthritic agents with 1,2-isothiazolidine-1,1-dioxide (gamma-sultam) skeleton: cytokine suppressive dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase.

Various 1,2-isothiazolidine-1,1-dioxide (gamma-sultam) derivatives containing an antioxidant moiety, 2,6-di-tert-butylphenol substituent, were prepared. Some compounds, which have a lower alkyl group at the 2-position of the gamma-sultam skeleton, showed potent inhibitory effects on both cyclooxygenase (COX)-2 and 5-lipoxygenase (5-LO), as well as production of interleukin (IL)-1 in in vitro assays. They also proved to be effective in several animal arthritic models without any ulcerogenic activities. Among these compounds, (E)-(5)-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2-ethyl-1, 2-isothiazolidine-1,1-dioxide (S-2474) was selected as an antiarthritic drug candidate and is now under clinical trials. The structure-activity relationships (SAR) examined and some pharmacological evaluations are described.

Animals↗

PubMed2000

A Model for the Quiescent Phase of the Recurrent Nova U Scorpii.

A theoretical light curve is constructed for the quiescent phase of the recurrent nova U Scorpii in order to resolve the existing distance discrepancy between the outbursts (d approximately 6 kpc) and the quiescences (d approximately 14 kpc). Our U Sco model consists of a very massive white dwarf (WD), an accretion disk (ACDK) with a flaring-up rim, and a lobe-filling, slightly evolved, main-sequence star (MS). The model properly includes an accretion luminosity of the WD, a viscous luminosity of the ACDK, and a reflection effect of the MS and the ACDK irradiated by the WD photosphere. The B light curve is well reproduced by a model of 1.37 M middle dot in circle WD + 1.5 M middle dot in circle MS (0.8-2.0 M middle dot in circle MS is acceptable) with an ACDK having a flaring-up rim and the inclination angle of the orbit i approximately 80&j0;. The calculated color is rather blue (B-V approximately 0.0) for a suggested mass accretion rate of 2.5x10-7 M middle dot in circle yr-1, thus indicating a large color excess of E(B-V) approximately 0.56 with the observational color of B-V=0.56 in quiescence. Such a large color excess corresponds to an absorption of AV approximately 1.8 and AB approximately 2.3, which reduces the distance to 6-8 kpc. This is in good agreement with the distance estimation of 4-6 kpc for the latest outburst. Such a large intrinsic absorption is very consistent with the recently detected period change of U Sco, which is indicating a mass outflow of approximately 3x10-7 M middle dot in circle yr-1 through the outer Lagrangian points in quiescence.

Journal Article↗

PubMed2000

Pseudogap formation in the intermetallic compounds (Fe1-xVx)3Al

Optical conductivity data of the intermetallic compounds (Fe1-xVx)3Al ( 0</=x</=0.33) reveal that their density of states around the Fermi energy ( E(F)) is strongly reduced as x is increased. In particular, Fe2VAl ( x = 0.33) has a deep, well-developed pseudogap of 0.1-0.2 eV at E(F) and a small density ( approximately 5x10(20) cm(-3)) of carriers, which is highly unusual for intermetallic compounds. It is shown that the pseudogap results from the band structure of Fe2VAl, rather than from temperature-dependent correlation effects. Based on the present results, we propose a simple model that consistently explains both the semiconductorlike transport and the metallic photoemission results previously observed for Fe2VAl.

Journal Article↗

PubMed2000

Increased lipid peroxidation in the brains of aceruloplasminemia patients.

Aceruloplasminemia is characterized by excessive neurovisceral accumulation of iron due to mutations in the ceruloplasmin gene. We report that the levels of malonaldehyde (MDA) and 4-hydroxynonenals (4-HNE) were elevated both in the frontal cortex and putamen in two patients with aceruloplasminemia compared with those in controls. Immunohistochemical analysis with an antibody raised against HNE-modified protein showed a large number of immunoreactive neurons and glias in the brain of a patient. MDA and 4-HNE are good indicators of lipid peroxidation because they are generated in the process of oxidation of polyunsaturated fatty acids. The data strongly suggest that the increase of oxygen free radicals associated with excessive iron accumulation plays an important pathogenic role in the process of neuronal cell death in the brains of patients with aceruloplasminemia.

Aged↗

PubMed2000

Nuclear localization signals of the BRCA2 protein.

BRCA2 is a tumor suppressor gene whose germline mutations increase the lifetime risk of breast cancer. BRCA2 encodes a large nuclear protein involved in DNA repair, but the location of its functional domain has been unclear. Here, we report nuclear localization signals (NLSs) of the BRCA2 protein. By expressing various portions of the BRCA2 protein tagged with enhanced green fluorescent protein in HeLa cells, we show that the C-terminal domain is necessary for nuclear localization. Two regions in the C-terminal domain were identified with functional NLSs by site-directed mutagenesis analyses. The NLSs locate between the germline mutation found in the most downstream position and the polymorphic stop codon, suggesting that defects in the proper nuclear transport of the BRCA2 protein are causative of carcinogenesis. Our data thus provide a possible explanation for the high frequency of frame-shift and nonsense mutations in BRCA2 of hereditary breast cancer patients.

BRCA2 Protein↗

PubMed2000

Angiotensin II increases intracellular Ca(2+) concentration in folliculo-stellate cells of the rat anterior pituitary in primary culture.

It has been reported that pituitary gonadotrophs and lactotrophs contain angiotensin II (Ang II) and suggested that Ang II modulates hormone secretion from endocrine cells of the anterior pituitary through paracrine mechanism among the endocrine cells. However, there has been no report on the effect of Ang II on the folliculo-stellate cells (FSC) which are thought to play a regulatory role in the release of hormones from pituitary endocrine cells. We, therefore, examined the effect of Ang II on FCS in primary culture by Ca(2+) imaging technique. Certain proportion (42%) of FSC responded to 100 nM Ang II by increasing [Ca(2+)](i). In addition, Ang II elicited the Ca(2+) response in about 50% of the pituitary endocrine cells. The results indicate that Ang II functions as a paracrine factor among pituitary cells including FSC.

Angiotensin II↗

PubMed2000

Involvement of two different mechanisms in trigeminal ganglion-evoked vasodilatation in the cat lower lip: role of experimental conditions.

The present study was designed to examine the vasodilator mechanisms elicited by electrical stimulation of trigeminal ganglion (TG) in cat lower lip of the cats. When vago-sympathectomized cats were fixed into a stereotaxic frame by means of ear-bars, etc., the lip blood flow (LBF) increase evoked by lingual nerve (LN) stimulation (parasympathetic reflex response) was almost abolished in 15 out of 34 animals, but unaffected in the other 19. With the animal in the stereotaxic frame, electrical stimulation at sites within the TG evoked an LBF increase whether or not the LN stimulation-induced reflex response was intact. However, hexamethonium abolished the TG stimulation-induced LBF increase in animals whose brainstem parasympathetic reflex was intact, but reduced it by only 50% in animals whose reflex was impaired. This difference was seen in all experiments in which the electrode site was within the TG proper, regardless of its exact position. Although the underlying mechanism is unclear, these data suggest that when the TG is stimulated the LBF increase is entirely mediated via the parasympathetic reflex mechanism in animals whose brainstem reflex is intact, and that an antidromic vasodilatation occurs only in animals whose brainstem parasympathetic reflex is impaired.

Adrenergic Antagonists↗

PubMed2000

Smad6 is a Smad1/5-induced smad inhibitor. Characterization of bone morphogenetic protein-responsive element in the mouse Smad6 promoter.

Smad6 is an inhibitory Smad that is induced by bone morphogenetic proteins (BMPs) and interferes with BMP signaling. We have isolated the mouse Smad6 promoter and identified the regions responsible for transcriptional activation by BMPs. The proximal BMP-responsive element (PBE) in the Smad6 promoter is important for the transcriptional activation by BMPs and contains a 28-base pair GC-rich sequence including four overlapping copies of the GCCGnCGC-like motif, which is a binding site for Drosophila Mad and Medea. We generated a luciferase reporter construct (3GC2-Lux) containing three repeats of the GC-rich sequence derived from the PBE. BMPs and BMP receptors induced transcriptional activation of 3GC2-Lux in various cell types, and this activation was enhanced by cotransfection of BMP-responsive Smads, i.e. Smad1 or Smad5. Moreover, direct DNA binding of BMP-responsive Smads and common-partner Smad4 to the GC-rich sequence of PBE was observed. These results indicate that the expression of Smad6 is regulated by the effects of BMP-activated Smad1/5 on the Smad6 promoter.

Animals↗

PubMed2000

Tagged mutagenesis and gene-trap in the moss, Physcomitrella patens by shuttle mutagenesis.

The moss, Physcomitrella patens has been used as a useful material in many fields, because of its simple body plan, ease of gene targeting, and other reasons. Although many mutants have been reported, no method to isolate the corresponding genes was reported. We developed a gene tagging and gene-trap system in P. patens by using the shuttle mutagenesis technique, which has been used in the budding yeast. In 5264 tagged lines, 203 mutants with altered developmental or morphological phenotypes were obtained. In 129 of 4757 gene-trap lines, beta-glucuronidase (GUS) activity was detected in some tissue. Although multiple copies of a tag were detected in many tagged lines by Southern analyses, most copies are likely integrated at the same locus according to PCR analyses.

Blotting, Northern↗

PubMed2000

Establishment of fetal gonad/mesonephros coculture system using EGFP transgenic mice.

In developing mouse embryos, the Sertoli cells, Leydig cells, and seminiferous cords are differentiated in the XY gonads. The migration of mesonephric cells into the gonads is required during the developmental stage for seminiferous cord formation in the male gonads. In previous experiments, an organ coculture system has been used to examine morphologically developing gonads. However, by the process used in this system for fixing and staining the gonad/mesonephros complexes for examination, the kinetics of cell migration and the character of migrating cells cannot be observed. In the present study, we established an improved organ coculture system, using transgenic mice ubiquitously expressing Enhanced Green Fluorescent Protein (EGFP). In this system, time-dependent morphological changes in male-specific migration were observable in the gonad/mesonephros complex. The cell migration occurred at around 20 hr of coculture and began to spread at 25 hr with increases in the number of migrating cells occurring at 45 hr of coculture. No degenerative changes were detected at the end of coculture. Our results indicate that the present coculture system is very useful for investigating the mechanism of cell migration, as well as the characteristics of the migrating cells, in developing gonads. J. Exp. Zool. 286:320-327, 2000.

Animals↗

PubMed2000

Ligation of the T cell receptor complex results in phosphorylation of Smad2 in T lymphocytes.

TGF-beta modulates immune responses by regulating T cell function. The Smad family of proteins has been recently shown to transduce signals for the TGF-beta superfamily and Smad2 mediates TGF-beta signaling. Here, we showed that TGF-beta phosphorylated Smad2 and induced interaction between Smad2 and Smad4 in primary T cells and the Jurkat T cell line. Interestingly, ligation of the T cell receptor (TCR)/CD3 complex with anti-CD3 mAb also phosphorylated Smad2, but failed to induce interaction between Smad2 and Smad4 in the Jurkat T cell line. Phosphorylation of Smad2 via the TCR/CD3 complex was not abrogated by treatment with neutralizing antibody against TGF-beta. Furthermore, PD98059, a MEK inhibitor, suppressed Smad2 phosphorylation by stimulation with anti-CD3 mAb in Jurkat T cell line. These findings indicated that not only TGF-beta but also stimulation via the TCR/CD3 complex phosphorylated Smad2 through mitogen-activated protein (MAP) kinase cascades, suggesting that Smad2 may function in both TGF-beta- and TCR/CD3 complex-mediated signaling pathways in T cells.

Animals↗

PubMed2000

Inhibition of human plasma cholinesterase and erythrocyte acetylcholinesterase by nondepolarizing neuromuscular blocking agents.

PURPOSE: The kinetics of the inhibition of human plasma cholinesterase (ChE) and erythrocyte acetylcholinesterase (AChE) by alcuronium, atracurium, d-tubocurarine, pancuronium, pipecuronium, and vecuronium were studied in blood drawn from 35 surgical patients. METHODS: The activities of plasma ChE and erythrocyte AChE were determined by the calorimetric method of Ellman et al., using acetylthiocholine as the substrate. Lineweaver-Burk plots and Dixon plots were used for the analysis of the kinetics of both enzymes. RESULTS: The dissociation constants (K(m)) of plasma ChE and erythrocyte AChE were 5.00 x 10(-5) M and 5.28 x 10(-5) M, respectively, indicating that both enzymes have similar affinity to acetylthiocholine. Both Lineweaver-Burk plots and Dixon plots indicated that the six nondepolarizing neuromuscular blocking agents (NMBAs) at different concentrations induce linear mixed-type inhibition. The apparent inhibition constants (K(i)) of pancuronium (8.72 x 10(-8) M) and vecuronium (3.53 x 10(-7) M) for plasma ChE inhibition were lower than that of neostigmine (7.36 x 10(-7) M), whereas those of the six nondepolarizing NMBAs for erythrocyte AChE were markedly higher than that of neostigmine. CONCLUSIONS: Both plasma ChE and erythrocyte AChE were inhibited by six nondepolarizing NMBAs, and the pattern of inhibition of both enzymes was of mixed type. The inhibitory potencies of pancuronium and vecuronium for plasma ChE were larger than that of neostigmine, whereas those of the six nondepolarizing NMBAs for erythrocyte AChE were markedly lower than that of neostigmine. The rank order of relative potency for plasma ChE was pancuronium > vecuronium > pipecuronium > alcuronium > d-tubocurarine > atracurium.

Journal Article↗