Search PubMed⌕ Search

Biomedical subjects

M Kato

Publications and source records attributed to M Kato.

At least 271 records · Page 15Linked to original sources
PubMed2001

[A case of multiple liver metastases from breast cancer successfully treated with intra-arterial administration of paclitaxel].

A 57-year-old woman underwent modified radical mastectomy for left breast cancer (T4bN1M1: stage IV) in September 1999. Four-cycle CAF therapy had been administered as adjuvant therapy, but multiple recurrent tumors in the liver had grown bigger and the tumor marker (CEA) increased in value. Because CAF therapy was not effective, we tried to treat the patient with systemic and intra-arterial chemotherapy using paclitaxel. The side effects of this treatment were mild nausea and appetite loss, which required no treatments. This treatment reduced the multiple liver metastases on an abdominal CT and was thought to produce a partial response (PR). The time to response was the 101st day and PR has been continued.

Antineoplastic Agents, Phytogenic↗
PubMed2001

[Prefrontal lobes and the attentional control: a neuropsychological study using modified Stroop test].

The prefrontal lobes may play an important role in attentional and cognitive control. The modified Stroop test can detect the disorder of this regulatory function in the brain-damaged patients. The Stroop conflict task was given to 35 prefrontal damaged patients (prefrontal group) and 20 subjects with temporal or parietal lesions (posterior group). The prefrontal subjects were further divided into the three subgroups, which consisted of 17 dorsolateral, 6 medial and 12 orbitofrontal patients. There were no significant differences between the prefrontal and posterior group on the Stroop test. However, the dorsolateral prefrontal damaged subgroup and the medial prefrontal damaged subgroup had significantly poor performances than the posterior group on the incongruent condition of the Stroop test. This findings indicated that the impairment of attentional control between the word reading and color naming resulted from the lesions of dorsolateral and medial part of prefrontal lobes. The cognitive control of visual attention may be supported by the neural substrates including dorsolateral prefrontal lobe, supplementary motor area and anterior cingulate cortex.

Attention↗
PubMed2000

Effect of YM-126414 on glucose uptake and redistribution of glucose transporter isotype 4 in muscle cells.

We discovered a novel compound, YM-126414 [1,3, 3-trimethyl-2-(2-phenylaminovinyl)-3H-indolium perchlorate], which stimulates glucose uptake in skeletal muscle cells in vitro. This compound increased the rate of consumption of glucose by C2C12 mouse myoblast cells in a dose-dependent manner (EC(50)=10 nM). To investigate the mechanism of this stimulation, we determined the redistribution of insulin-regulatable glucose transporter isotype 4 (Glut4). When fully differentiated C2C12 cells stably expressing myc-tagged Glut4 protein were treated with YM-126414, redistribution was dramatically increased in a dose-dependent manner (EC(50)=21 nM). These results indicate that YM-126414 is a novel glucose uptake stimulator for muscle cells by causing up-regulation of Glut4 redistribution in differentiated muscle cells. Our findings for the in vitro effects of YM-126414 suggest a direction for the development of new drugs for the treatment of type 2 diabetes.

Animals↗
PubMed2000

Sympathetic activation by sildenafil.

BACKGROUND: Sildenafil citrate is an effective and widely prescribed therapy for erectile dysfunction. Little is known about the effects of sildenafil on neural control of the circulation or about the effects of sildenafil on neurocirculatory stress responses. METHODS AND RESULTS: We studied 14 normal volunteers (age 32+/-7 years) who were randomized in a double-blind crossover fashion to receive a single oral dose of sildenafil 100 mg or placebo on 2 separate study days. Blood pressure, heart rate, forearm vascular resistance, muscle sympathetic nerve activity, and plasma catecholamines were measured at baseline and at 30 and 60 minutes after sildenafil and after placebo administration. The effects of sildenafil and placebo on neural and circulatory responses to stressful stimuli (sustained handgrip, maximal forearm ischemia, mental stress, and the cold pressor test) were also evaluated. Blood pressure, heart rate, and forearm vascular resistance after sildenafil and placebo were similar. However, muscle sympathetic nerve activity increased strikingly after sildenafil (by 141+/-26%, mean+/-SEM) compared with placebo (3+/-8%) (P=0.006); plasma norepinephrine levels also increased by 31+/-5% after sildenafil administration (P=0.004). Sympathetic nerve traffic during mental, physical, and cold stresses was 2- to 8-fold higher after sildenafil than with placebo (P<0.05). CONCLUSIONS: Sildenafil causes a marked increase in sympathetic activation, evident both at rest and during stressful stimuli. Sympathetic activation by sildenafil may have implications for understanding cardiovascular events associated with sildenafil use.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2000

Recovery of brain dysfunction after methylmercury exposure in rats.

We studied the time course of central nervous system (CNS) involvement after the termination of methylmercury exposure to rats, in order to investigate whether or not the involvement still progresses even after the termination of exposure. Methylmercury chloride (MMC), at a dose of 2 mg/kg/day, was subcutaneously injected for 25 consecutive days in 12 adult male Sprague-Dawley rats. Six of them were sacrificed on the final day of exposure (group A) after completing the observations of behavioral changes and determining the local cerebral glucose utilization (LCGU) as an indicator of cerebral neuronal activities. Histological examinations of the brain and the sciatic nerve were done. The other six rats were further followed up for 90 days after the termination of exposure (group B). In addition, six rats that received physiological saline served as a control. Group A showed a significant reduction of LCGU without any accompanying cerebral histological alterations and a moderate loss of myelinated fibers in the sciatic nerve. Group B showed normal LCGU rates while severe axonal degeneration of the sciatic nerve was found on the final day of the 90-day follow-up period. The present results demonstrate that a transient involvement of the CNS can occur after MMC exposure. In addition, a complete recovery may occur when the process is mild enough not to cause histological alterations. In contrast, the involvement of the peripheral nerve is much more severe than that of the CNS and it was observed to progress even after the cessation of MMC exposure. Therefore, it seems unlikely, at least in rats, that a steadily progressive course occurs in the CNS but not in the peripheral nerves over a long period of time after MMC exposure.

Animals↗
PubMed2000

Expression of CD40 in the brain of Alzheimer's disease and other neurological diseases.

We have investigated immunohistochemically the expression of CD40 in post-mortem human brain tissues. In control brain, the blood vessels were stained weakly for CD40. Vascular expression of CD40 was enhanced in the lesions of Alzheimer's disease and some other neurological diseases. In such diseases, reactive microglia were also positive for CD40. The results of this study suggest that CD40 expression by microglia is up-regulated upon a variety of brain insults and is not limited to lesions with amyloid beta-protein deposits.

Alzheimer Disease↗
PubMed2000

A deubiquitinating enzyme UBPY interacts with the Src homology 3 domain of Hrs-binding protein via a novel binding motif PX(V/I)(D/N)RXXKP.

Hrs-binding protein (Hbp) is a Src homology 3 (SH3) domain-containing protein that tightly associates with Hrs. Hbp together with Hrs is thought to play a regulatory role in endocytic trafficking of growth factor-receptor complexes through early endosomes. Association of Hbp with a binding partner(s) via the SH3 domain seems to be essential for Hbp to exert its function. In this study, we searched for Hbp-binding proteins by a far Western screening and isolated a mouse cDNA clone encoding a deubiquitinating enzyme mUBPY as an Hbp SH3-binding protein. mUBPY has two Hbp-SH3 domain binding sites. Mutagenic analysis identified a consensus sequence PX(V/I)(D/N)RXXKP as the Hbp-SH3 domain binding motif. It is a novel SH3-binding motif and does not contain the canonical proline-rich consensus binding motif, PXXP. Ubiquitination of growth factor receptors is thought to regulate their intracellular degradation. Thus, UBPY may play a regulatory role in the degradation by interaction with the SH3 domain of Hbp via the novel SH3-binding motif.

3T3 Cells↗
PubMed2000

Impairment of endothelium-dependent vasodilation of resistance vessels in patients with obstructive sleep apnea.

BACKGROUND: Patients with obstructive sleep apnea (OSA) experience repetitive episodic hypoxemia with consequent sympathetic activation and marked blood pressure surges, each of which may impair endothelial function. We tested the hypothesis that patients with OSA have impaired endothelium-dependent vasodilation, even in the absence of overt cardiovascular disease. METHODS AND RESULTS: We studied 8 patients with OSA (age 44+/-4 years) and 9 obese control subjects (age 48+/-3 years). Patients with OSA were newly diagnosed, never treated for OSA, on no medications, and free of any other known diseases. All obese control subjects underwent complete overnight polysomnographic studies to exclude occult OSA. Resistance-vessel function was tested by use of forearm blood flow responses to intra-arterial infusions of acetylcholine (a vasodilator that stimulates endothelial release of nitric oxide), sodium nitroprusside (an exogenous nitric oxide donor), and verapamil (a calcium channel blocker). Conduit-vessel function was also evaluated by ultrasonography. Brachial artery diameter was measured under baseline conditions, during reactive hyperemia (with flow increase causing endothelium-dependent dilatation), and after sublingual administration of nitroglycerin (an endothelium-independent vasodilator). Patients with OSA had a blunted vasodilation in response to acetylcholine (P:<0.007), but responses to sodium nitroprusside and verapamil were not significantly different from those of control subjects. No significant difference in conduit-vessel dilation was evident between OSA patients and obese control subjects. CONCLUSIONS: Patients with OSA have an impairment of resistance-vessel endothelium-dependent vasodilation. This may be implicated in the pathogenesis of hypertension and heart failure in this condition.

Acetylcholine↗
PubMed2000

Predictive variables of interictal psychosis in epilepsy.

OBJECTIVE: To evaluate which variables predict interictal psychosis in epilepsy. METHODS: The authors reviewed the biological backgrounds, clinical characteristics, and EEG findings in 246 patients with epilepsy and interictal psychosis and in 658 control patients with epilepsy and no psychotic history. With a logistic regression approach, the significance of each variable for the development of interictal psychosis was evaluated. RESULTS: There are significant differences in family history of psychosis, age at onset of epilepsy, type of epilepsy, lateralization of epileptiform discharges, and level of intelligence between patients with interictal psychosis and those without it. Subsequent logistic regression analysis with all variables demonstrated that family history of psychosis, age at onset of epilepsy, type of seizures, and level of intelligence significantly correlated with psychosis. CONCLUSIONS: A family history of psychosis, earlier age at onset of epilepsy, complex partial seizures or generalized tonic clonic seizures, and borderline intellectual functioning were the most important predictors for development of interictal psychosis.

Adolescent↗
PubMed2000

Arsenite induces apoptosis of murine T lymphocytes through membrane raft-linked signaling for activation of c-Jun amino-terminal kinase.

Because of its dual roles in acute toxicity and in therapeutic application in cancer treatment, arsenic has recently attracted a renewed attention. In this study, we report NaAsO(2)-induced signal cascades from the cell surface to the nucleus of murine thymic T lymphocytes that involve membrane rafts as an initial signal transducer. NaAsO(2) induced apoptosis through fragmentation of DNA, activation of caspase, and reciprocal regulation of Bcl-2/Bax with the concomitant reduction of membrane potential. We demonstrated that NaAsO(2)-induced caspase activation is dependent on curcumin-sensitive c-Jun amino-terminal kinase and barely dependent on SB203580-sensitive p38 kinase or PD98059-sensitive extracellular signal-regulated kinase. Additionally, staurosporine, which severely inhibited the activation of mitogen-activated protein (MAP) family kinases and c-Jun, partially blocked the NaAsO(2)-mediated signal for poly(ADP-ribose) polymerase (PARP) degradation. Potentially as the initial cell surface event for intracellular signaling, NaAsO(2) induced aggregation of GPI-anchored protein Thy-1 and superoxide production. This Thy-1 aggregation and subsequent activation of MAP family kinase and c-Jun and the degradation of PARP induced by NaAsO(2) were all inhibited by DTT, suggesting the requirement of interaction between arsenic and protein sulfhydryl groups for those effects. beta cyclodextrin, which sequestrates cholesterol from the membrane rafts, inhibited NaAsO(2)-induced activation of protein tyrosine kinases and MAP family kinases, degradation of PARP, and production of superoxide. In addition, beta cyclodextrin dispersed NaAsO(2)-induced Thy-1 clustering. These results suggest that a membrane raft integrity-dependent cell surface event is a prerequisite for NaAsO(2)-induced protein tyrosine kinase/c-Jun amino-terminal kinase activation, superoxide production, and downstream caspase activation.

Animals↗
PubMed2000

Correlation of telomere lengths in normal and cancers tissue in the large bowel.

The hypothesis that telomeres in colorectal cancer cells exhibit age-related shortening, as in normal cells of the colorectal epithelium, was tested with samples of non-cancerous mucosa and cancer tissue from 124 patients (aged 29-97 years). Shortening with aging could be demonstrated for both normal and cancer tissues; regression analysis showed rates for length reduction of 44 and 50 base pair/year, respectively. Straight, essentially parallel, lines were obtained for the two cases, normal tissue values being about 2 kilobase pairs (kbp) higher, with a significant correlation between data at the individual patient level.

Adult↗
PubMed2000

Preparation of non-fouling surface through the coating with core-polymerized block copolymer micelles having aldehyde-ended PEG shell.

A new type of surface modification with reactive polymeric micelle was carried out for the creation of non-fouling surface. Amphiphilic poly(ethylene glycol)-b-poly(D,L lactide) (PEG/PLA) copolymers possessing acetal group at PEG-end and methacryloyl group at PLA-end were quantitatively synthesized via an anionic polymerization technique. A micelle of narrow distribution was prepared from the block copolymer. Acetal groups on the micelle surface were quantitatively converted into aldehyde group by an acid treatment. The methacryloyl group located in the core of the micelle was polymerized via radical polymerization to form core-polymerized micelle having reactive aldehyde groups on the surface. The core-polymerized reactive micelle was coated to a primary amino-containing polypropylene (PP) plate that was prepared by a plasma treatment. A reductive amination reaction was employed for a conjugation of the reactive core-polymerized micelle on the surface via a covalent linkage. The coating was evaluated by X-ray photoelectron spectroscopy, zeta-potential measurement, and the adsorption of bovine serum albumin, and compared with the PEG-coating under the same condition. The ratio of peak from &Cmacr;&z.sbnd;O bond to C&z.sbnd;&Cmacr;&z.sbnd;C bond indicated that the density of PEG on the surface was higher for the micelle coating than the linear PEG-coating. This is also confirmed by the zeta-potential measurement. By coating the amino-PP surface with micelle, the zeta-potential was remarkably decreased while the PEG-coating under the same condition decreased only appreciably, indicating that micelle coating efficiently masked the surface charge. Further, micelle-covered surface exhibited reduction of protein adsorption. The reduction of protein adsorption along with remarkably masked surface charge implies the high applicability of the micelle coatings to biomedical and bioanalytical applications.

Journal Article↗
PubMed2000

Effect of interferon therapy on the incidence of hepatocellular carcinoma and mortality of patients with chronic hepatitis C: a retrospective cohort study of 738 patients.

The effect of interferon on the long-term clinical outcome of patients with chronic hepatitis C remains unclear. This study included 594 patients with chronic hepatitis C who received interferon-alpha therapy (Interferon group) and 144 patients with chronic hepatitis C who did not receive interferon (Control group). The patients in the Interferon group were classified into the following three groups based on the response of the serum aminotransaminase level of the patient during and after completion of the therapy protocol: sustained responders (n = 175), transient responders (n = 165), and non-responders (n = 254). The age, sex, serum aminotransaminase level, platelet count, histological staging, hepatitis C virus (HCV) subtype, and HCV concentration at baseline were adjusted with the Cox proportional hazards model. The length of follow-up for assessment of the risk for developing hepatocellular carcinoma (HCC) was 57.2 +/- 13.9 months in the Interferon group and 67.7 +/- 28.7 months in the Control group. Multivariate analysis showed that interferon therapy decreased the risk for developing HCC by 48% compared with that in the Control group (P = 0.064). The older the age, being male, having a low platelet count, and higher histological stage were independent factors associated with the development of HCC. The hazard rate ratio for development of HCC in the sustained responders, transient responders, and non-responders was 0.16 (95% confidence interval [CI]: 0.04-0.62), 0.27 (95% CI: 0. 09-0.79), and 0.74 (95% CI: 0.37-1.48), respectively. During follow-up, 18 patients in the Interferon group died (10 from liver-related diseases) and 17 patients in the Control group died (10 from liver-related diseases). No sustained responder or transient responder in the Interferon group died of liver-related disease. The cumulative survival rates of the Interferon and Control groups were nearly identical during the first 5 years following diagnosis. Thereafter, the cumulative survival rate of the Control group declined, resulting in an 8-year survival rate in the Interferon and Control groups of 97% and 81%, respectively (P = 0. 061). Similar trends were seen in the survival analysis of those who had died of liver disease: the 8-year survival rates of the Interferon and Control groups were 98% and 88%, respectively (P = 0. 32). Our study demonstrated that interferon therapy significantly lowered the incidence of HCC among patients with chronic hepatitis C who showed sustained normalization and among patients who showed transient normalization of the serum aminotransferase level after completion of interferon therapy. The survival analyses and determination of cause of death suggested that interferon therapy improves the long-term survival of chronic hepatitis C patients who respond to this therapy, possibly by decreasing mortality from liver-related diseases.

Antiviral Agents↗
PubMed2000

Isolation of novel mouse genes differentially expressed in brain using cDNA microarray.

The major issue in the post-genome sequencing era is determination of gene expression patterns in variety of biological systems. A microarray system is a powerful technology for analyzing the expression profile of thousands of genes at one experiment. In this study, we identified highly expressed genes in mouse brain using the cDNA microarray carrying 2304 cDNAs derived from oligo-capped mouse cDNA library. Nine genes were highly expressed in adult mouse brain compared to kidney, liver, and skeletal muscle. Tissue distribution analysis by reverse transcription-coupled polymerase chain reaction (RT-PCR) revealed that consistent with the microarray data, all of the selected 9 genes were predominantly expressed in the brain. A database search showed that 5 of the 9 genes, MBP, SC1, HiAT3, S100 protein-beta, and SNAP25, were previously known to be expressed at high level in the brain and in the nervous system. One gene was highly sequenced similar to rat S-Rex-s/human NSP-C, suggesting that the gene is a mouse homologue. The remaining three genes did not match to known genes in the GenBank/EMBL database, indicating that these are novel genes highly expressed in the brain. Taken together, our cDNA microarray system can be an excellent tool for identifying differentially expressed genes in mouse brain.

Animals↗
PubMed2000

Crystal structure of glycosyltrehalose trehalohydrolase from the hyperthermophilic archaeum Sulfolobus solfataricus.

The crystal structure of glycosyltrehalose trehalohydrolase from the hyperthermophilic archaeum Sulfolobus solfataricus KM1 has been solved by multiple isomorphous replacement. The enzyme is an alpha-amylase (family 13) with unique exo-amylolytic activity for glycosyltrehalosides. It cleaves the alpha-1,4 glycosidic bond adjacent to the trehalose moiety to release trehalose and maltooligo saccharide. Unlike most other family 13 glycosidases, the enzyme does not require Ca(2+) for activity, and it contains an N-terminal extension of approximately 100 amino acid residues that is homologous to N-terminal domains found in many glycosidases that recognize branched oligosaccharides. Crystallography revealed the enzyme to exist as a homodimer covalently linked by an intermolecular disulfide bond at residue C298. The existence of the intermolecular disulfide bond was confirmed by biochemical analysis and mutagenesis. The N-terminal extension forms an independent domain connected to the catalytic domain by an extended linker. The functionally essential Ca(2+) binding site found in the B domain of alpha-amylases and many other family 13 glycosidases was found to be replaced by hydrophobic packing interactions. The enzyme also contains a very unusual excursion in the (beta/alpha)(8) barrel structure of the catalytic domain. This excursion originates from the bottom of the (beta/alpha)(8) barrel between helix 6 and strand 7, but folds upward in a distorted alpha-hairpin structure to form a part of the substrate binding cleft wall that is possibly critical for the enzyme's unique substrate selectivity. Participation of an alpha-beta loop in the formation of the substrate binding cleft is a novel feature that is not observed in other known (beta/alpha)(8) enzymes.

Amino Acid Sequence↗