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Biomedical subjects

R Ito

Publications and source records attributed to R Ito.

At least 37 records · Page 2Linked to original sources
PubMed2001

Increased expression but not genetic alteration of BRG1, a component of the SWI/SNF complex, is associated with the advanced stage of human gastric carcinomas.

BRG1, a component of the SWI/SNF complex, regulates gene transcription through chromatin remodeling. Certain human cancer cell lines have been shown to contain homozygous deletions or mutations, half of which are concentrated in exons 4 and 10, resulting in aberrant BRG1 expression. We examined the expression of BRG1 in 38 gastric carcinomas and corresponding nonneoplastic mucosa by using the quantitative real-time RT-PCR method. Twenty-three carcinomas (61%) showed increased BRG1 expression in tumor tissue in comparison with that in nonneoplastic mucosa. The T/N ratio (the expression level of BRG1 mRNA in tumor tissues relative to those in corresponding nonneoplastic mucosa) in advanced cases of gastric carcinoma (stages III and IV) was significantly higher than that in cases of stage I and II carcinoma (p = 0.029). Furthermore, gastric carcinomas with lymph node metastasis showed a tendency to express BRG1 at a higher level than gastric carcinomas without metastasis (p = 0.097). We also searched for genetic alterations of the BRG1 gene in 8 gastric carcinoma cell lines and 33 primary gastric carcinomas by PCR-SSCP analysis. No SSCP variants in exons 4, 10 and 16 of the BRG1 gene were found in both gastric carcinoma cell lines and primary gastric carcinomas. These results suggest that, although genetic abnormality of BRG1 might be rare, an increased expression of BRG1 might be associated with the development and progression of gastric carcinoma.

Carcinoma↗
PubMed2001

Role of cellulose-binding domain of exocellulase I from white rot basidiomycete Irpex lacteus.

The core fragment (designated P-42), devoid of the cellulose-binding domain (CBD) in the C-terminus and prepared from Irpex lacteus exocellulase I (Ex-1), was isolated by limited proteolysis using papain. Both the hydrolytic activity and binding ability of the isolated P-42 toward insoluble cellulose were lower than those of the native Ex-1, whereas Ex-1 and P-42 showed similar hydrolytic activities toward soluble substrates. These results indicate that the CBD of I. lacteus Ex-1 is the important domain which could enhance hydrolytic activity and binding ability of the enzyme toward insoluble cellulose. In addition, the isolated P-42 was different from the native Ex-1 in terms of enzymatic properties such as pH and temperature stabilities. These differences in stability, with regard to pH and temperature, between P-42 and the native Ex-1 are probably due to the O-linked sugar chains existing in the linker region.

Journal Article↗
PubMed2001

A Utstein-style analysis of prognostic factors related to survival in out-of-hospital cardiac arrests in Akita-City, Japan.

To analyze the epidemiology of out-of-hospital cardiac arrests and to elucidate modifiable factors affecting survival, we conducted a prospective cohort study in a middle-sized urban city served by a single emergency medical service (EMS) system in which emergency medical technicians use an automated external defibrillator. Data were collected from out-of-hospital cardiac arrests occurring between 1 January, 1994 and 31 December, 1998 by applying the Utstein style. The main outcome measure was survival at 1 year after hospital discharge. The overall incidence of out-of-hospital cardiac arrest was 71.7/100 000 inhabitants/year. Resuscitations were attempted in 762 of 1118 patients with confirmed cardiac arrest. Of the 762 patients, 37 (4.86%) survived. The cause of cardiac arrest was presumed to be cardiac in 340 (44.6%). Of the 340 cardiac arrests, 180 (52.9%) were witnessed by bystanders. Ventricular fibrillation (VF) was recorded as an initial rhythm in 56 (31.1%) of the 180 patients, and cardiopulmonary resuscitation (CPR) was performed by bystanders in 89 (49.4%). The survival rate was 39.2% (22/56) when cardiac arrest was bystander-witnessed and of cardiac origin with VF as an initial rhythm. VF as an initial rhythm, age of the patients and intervals of call-to-first CPR attempt and collapse-to-arrival at patient's side were major factors relating to survival in the witnessed cardiac arrests of cardiac origin. The age, and gender of the patients, place of collapse and intervals of collapse-to-first CPR and collapse-to-arrival at patient's side were representative factors affecting the incidence of VF as an initial rhythm. The survival rate in Akita-City from bystander-witnessed cardiac arrests of cardiac origin with VF as an initial rhythm was comparable to those in other regions with advanced EMS systems. However, the incidence of VF as an initial rhythm is extremely low. Reduction of intervals of call (collapse)-to-first CPR attempt and collapse-to-arrival at patient's side or authorization of use of automated external defibrillator in basic life support may increase the incidence of VF as an initial rhythm and improve the survival from witnessed cardiac arrests with cardiac origin.

Cardiopulmonary Resuscitation↗
PubMed2001

[EEG findings in a case of acute necrotizing encephalopathy of childhood associated with influenza A virus infection].

We reported here a case of symptomatic partial epilepsy following acute necrotizing encephalopathy of childhood associated with influenza A virus infection. This 2-year-old boy underwent repeated EEG recordings, which at the acute stage was dominated by diffuse 1-2 Hz slow waves. The background activity was 5 Hz theta waves on the 49th day. Paroxysmal activities appeared after the 89th day of illness. On the 231st day, EEG showed spike-and-waves on the left and right frontal areas. Interestingly, paroxysmal activities preceded the onset of epileptic seizures by 7 months, and spike-and-waves by 2 months. After 10 months, he had generalized seizures with fever, and partial seizures on awakening without fever. Interictal EEG showed spike-and-waves on the bilateral frontal areas, and diffuse polyspikes and slow waves were occasionally seen. Though the background activity improved, his consciousness level did not recover probably because the thalamus, basal ganglia, brainstem were damaged more severely than the cerebral cortex.

Child, Preschool↗
PubMed2001

Tentorial enhancement on MR images is a sign of cavernous sinus involvement in patients with sellar tumors.

BACKGROUND AND PURPOSE: This study was undertaken to analyze enhancement patterns of the dura around sellar tumors and to compare the results with tumor invasion or compression of the cavernous sinuses. Postoperative enhancement patterns on MR images were compared with preoperative findings. METHODS: Contrast-enhanced coronal and sagittal MR images were examined prospectively in 96 patients with sellar tumors (65 macroadenomas, 15 microadenomas, 14 Rathke cleft cysts, and two chordomas at the sella). All patients underwent surgical treatment, and pre- and postsurgical features on MR images were compared. RESULTS: Presurgical MR images showed dural enhancement in 36.5% of the patients: asymmetric tentorial enhancement in 24 patients, symmetric tentorial enhancement in seven, and sphenoidal ridge or clivus enhancement in four. Asymmetric tentorial enhancement disappeared after surgical decompression in seven patients. For evaluation of cavernous sinus invasion ipsilateral to the enhancement, sensitivity and specificity of the asymmetric tentorial enhancement sign were 81.3% and 86.3%, respectively. Sensitivity and specificity of the sign were 42.9% and 93.6% for cavernous sinus involvement, including compression and invasion. CONCLUSION: Asymmetric tentorial enhancement is a useful sign in the diagnosis of invasion or severe compression of the cavernous sinus by sellar tumor. The sign may represent venous congestion or collateral flow in the tentorium due to obstructed flow in the medial portion of the cavernous sinus.

Adenoma↗
PubMed2001

Prospective study of Ki-67 labeling index in the mucosa adjacent to cancer as a marker for colorectal cancer metastasis.

Multivariate regression analysis has shown that Ki-67 labeling index in the mucosa adjacent to cancer was the most significant marker for colorectal cancer metastasis among several metastasis-related parameters according to our previous retrospective data base (7). We have performed a prospective study to ascertain whether Ki-67 labeling index in the mucosa adjacent to cancer is a useful preoperative diagnostic marker for colorectal cancer metastasis. In 182 registered cases colonoscopically biopsied, we performed surgical resection of the cancer in 37 adenocarcinoma cases, which were registered in the study. In 31 out of the 37 cases except for 6 cases with an insufficient amount of non-neoplastic mucosa, preoperative diagnosis for metastasis was performed using the Ki-67 cutoff line. The cutoff line was set at 15% according to our previous retrospective database. The preoperative diagnosis for metastasis was compared to the pathological findings of the resected specimen. The incidences of correct diagnosis for metastasis was 81% (25/31). There were 3 false positive cases and 3 false negative cases in Dukes' A-B and Dukes' C, respectively. The mean Ki-67 labeling index in the mucosa adjacent to cancer of Dukes' A-B and Dukes' C-D cases, except for the 6 misdiagnosed cases, was 7.4+/-5.0% and 29.9+9.8%, being significant at p<0.0001 by unpaired Mann-Whitney U test. These results suggest that Ki-67 labeling index in the mucosa adjacent to cancer might be a good marker for metastasis in colorectal cancer.

Adenocarcinoma↗
PubMed2000

Dissociation in conditioned dopamine release in the nucleus accumbens core and shell in response to cocaine cues and during cocaine-seeking behavior in rats.

The dopaminergic innervation of the nucleus accumbens is generally agreed to mediate the primary reinforcing and locomotor effects of psychostimulants, but there is less consensus on conditioned dopamine (DA) release during drug-seeking behavior. We investigated the neurochemical correlates of drug-seeking behavior under the control of a drug-associated cue [a light conditioned stimulus (CS+)] and to noncontingent presentations of the CS+ in the core and shell subregions of the nucleus accumbens. Rats self-administered cocaine under a continuous reinforcement schedule in which a response on one of two identical levers led to an intravenous cocaine infusion (0.25 mg/infusion) and a 20 sec light CS+. Response requirements for cocaine and the CS+ were then progressively increased until stable responding was established under a second-order schedule of reinforcement. During microdialysis, rats were presented noncontingently with a set of 10 sec CS+ and neutral tone stimuli (CS-) before and after a 90 min period during which they responded for cocaine under a second-order schedule. Results showed the following: (1) nucleus accumbens DA increased in both the core and shell during intravenous cocaine self-administration; (2) noncontingent presentations of a cocaine-associated CS+ led to increased DA release selectively in the nucleus accumbens core; and (3) extracellular DA levels were unaltered in both core and shell during a protracted period of drug-seeking behavior under the control of the same cocaine-associated cue. These results indicate that the mesolimbic dopamine system is activated after exposure to drug-associated stimuli under specific conditions.

Acoustic Stimulation↗
PubMed2000

A missense mutation in the RING finger motif of PEX2 protein disturbs the import of peroxisome targeting signal 1 (PTS1)-containing protein but not the PTS2-containing protein.

SK24 and PT54 mutant cells, which are peroxisome-deficient Chinese hamster ovary (CHO) cells isolated using peroxisomal forms of green fluorescent protein (GFP), were found to be defective in the PEX2 gene. The nucleotide sequences of PEX2 cDNA from the mutant cells were determined to identify mutation sites in the mutant cells. The mutation in SK24 cells changed cysteine to tyrosine at amino acid position 258, which is a component of the RING finger (C(3)HC(4)) motif in the carboxyl terminus of the protein. PT54 cells contained a nonsense mutation in the codon for glutamine at position 101, resulting in premature termination. The immunocytochemical analyses revealed distinct phenotypes between mutant cells defective in the PEX2 gene. Both mutant cells exhibited cytosolic mislocalizations on catalase and urate oxidase containing PTS1. On the other hand, on 3-ketoacyl-CoA thiolase containing PTS2, PT54 cells exhibited cytosolic mislocalization, but SK24 cells exhibited peroxisomal localization. When wild-type or mutant-type PEX2 cDNA was transfected into both mutant cells, the stable transformants restored the phenotype in accordance with the transfected cDNA. These observations indicate that an amino acid substitution, cysteine-258 to tyrosine, in the RING finger motif of PEX2 protein, whose function is required for peroxisomal localizations of both PTS1- and PTS2-containing proteins, results in a complete defect in the PTS1 pathway but not in the PTS2 pathway.

Amino Acid Sequence↗
PubMed2000

Rapid isolation and characterization of CHO mutants deficient in peroxisome biogenesis using the peroxisomal forms of fluorescent proteins.

We isolated and characterized CHO mutants deficient in peroxisome assembly using green fluorescent protein (GFP) and blue fluorescent protein (BFP) as the fluorescent probes to study the molecular mechanism of peroxisome biogenesis. We used stable transformants of CHO cells expressing GFP appending peroxisome targeting signal-1 (PTS1) and/or peroxisome targeting signal-2 (PTS2) as the parent strains for rapid isolation of the mutants. We have obtained six peroxisome-deficient mutants by visual screening of the mislocalizations of the peroxisomal GFPs. Mutual cell fusion experiments indicated that the six mutants isolated were divided into four complementation groups. Several of the mutants obtained possessed defective genes: the PEX2 gene was defective in SK24 and PT54; the PEX5 gene in SK32 and the PEX7 gene in PT13 and PT32. BE41, which belonged to the fourth complementation group, was not determined. When peroxisomal forms of BFP were transiently expressed in mutant cells, the peroxisomal BFPs appending both PTS1 and PTS2 appeared to bypass either the PTS1 or PTS2 pathway for localization in SK32. This observation suggested that other important machinery, in addition to the PTS1 or PTS2 pathway, could be involved in peroxisome biogenesis. Thus, our approach using peroxisomal fluorescent proteins could facilitate the isolation and analysis of peroxisome-deficient CHO mutants and benefit studies on the identification and role of the genes responsible for peroxisome biogenesis.

Animals↗
PubMed2000

Studies on cytotoxicity of nickel ions using C3H10T1/2 fibroblast cells.

Cytotoxicity of Ni ions were examined using C3H mouse derived 10T1/2 fibroblast cells. It became evident that Ni ions had dose-dependent cytotoxicity. The cell number incubated in DME medium containing 0.04 mM/L Ni ion for 6 days was reduced to half that in control DME medium without Ni. The cell totally disappeared in DME medium containing 2 mM/L Ni ion. The dissolution of Ni ions from Ni-containing metallic restorations must be lower than these concentration levels so that oral tissues might not be damaged. No neoplastic transformation was found on all cells examined.

Animals↗
PubMed2000

Effects of bright light on cognitive and sleep-wake (circadian) rhythm disturbances in Alzheimer-type dementia.

Twenty-seven patients with Alzheimer-type dementia (ATD) were treated with bright light therapy in the morning for four consecutive weeks. The cognitive state of each patient was evaluated with the Mini-Mental-State Examination (MMSE) and circadian rhythm with actigram before and after therapy for all of the patients and those of two groups divided by the severity criteria of the Clinical Dementia Rating. The therapy improved the circadian rhythm disturbances. Although the therapy caused no remarkable effects on dementia severity, it improved the MMSE scores, especially in the early stages of ATD. These results suggest that bright light therapy improved the circadian rhythm disturbances and then bettered the cognitive state in early-stage ATD.

Aged↗
PubMed2000

BodyMap: a collection of 3' ESTs for analysis of human gene expression information.

BodyMap is a collection of site-directed 3' expressed sequence tags (ESTs) (gene signatures, GSs) that contains the transcript compositions of various human tissues and was the first systematic effort to acquire gene expression data. For the construction of BodyMap, cDNA libraries were made, preserving abundance information and histologic resolutions of tissue mRNAs. By sequencing 164,000 randomly selected clones, 88,587 GSs that represent chromosomally coded transcripts have been collected from 51 human organs and tissues. They were clustered into 18,722 independent 3' termini from transcripts, and more than 3000 of these were not found among ESTs assembled in UniGene (Build 75). Assessment of the prevalence of polyadenylation signals and comparison with GenBank cDNAs indicated that there was no significant contamination by internally primed cDNAs or genomic fragments but that there was a relatively high incidence (12%) of alternative polyadenylation sites. We evaluated the sensitivity and resolution of expression information in BodyMap by in silico Northern hybridization and selection of tissue-specific gene probes. BodyMap is a unique resource for estimation of the absolute abundance of transcripts and selection of gene probes for efficient hybridization-based gene expression profiling.

3' Untranslated Regions↗
PubMed2000

Azuki bean cells are hypersensitive to cadmium and do not synthesize phytochelatins.

Suspension-cultured cells of azuki bean (Vigna angularis) as well as the original root tissues were hypersensitive to Cd (<10 microM). Repeated subculturings with a sublethal level of Cd (1-10 microM) did not affect the subsequent response of cells to inhibitory levels of Cd (10-100 microM). The azuki bean cells challenged to Cd did not contain phytochelatin (PC) peptides, unlike tomato (Lycopersicon esculentum) cells that have a substantial tolerance to Cd (>100 microM). Both of the cell suspensions contained a similar level of reduced glutathione (GSH) when grown in the absence of Cd. Externally applied GSH to azuki bean cells recovered neither Cd tolerance nor PC synthesis of the cells. Furthermore, enzyme assays in vitro revealed that the protein extracts of azuki bean cells had no activity converting GSH to PCs, unlike tomato. These results suggest that azuki bean cells are lacking in the PC synthase activity per se, hence being Cd hypersensitive. We concluded that the PC synthase has an important role in Cd tolerance of suspension-cultured cells.

Aminoacyltransferases↗
PubMed2000

UV-B irradiation increases susceptibility of mice to malarial infection.

We here examined whether exposure of mice to UV-B affected their susceptibility to the murine malaria parasite Plasmodium chabaudi. When BALB/c mice with depilated skin were irradiated with UV-B and subsequently infected with the parasite, 80 to 100% of the UV-B-irradiated mice died within 12 days of infection with a sublethal dose. In addition, UV-B irradiation of C57BL/10 (B-10) mice, which are otherwise naturally resistant to the parasites, rendered them susceptible, and 100% of irradiated B-10 mice died within 11 days postinfection. The level of plasma gamma interferon (IFN-gamma) in unirradiated B-10 mice at 5 days after infection increased to 566 pg/ml, whereas the UV-B exposure of mice impaired the production of IFN-gamma, which showed a maximum level of 65 pg/ml in response to the parasite infection. The maximum level of plasma interleukin-10 in UV-B-irradiated mice in response to the parasite infection was approximately 1,100 pg/ml, which was approximately fourfold higher than the maximum level in unirradiated control mice. When UV-B-irradiated B-10 mice were administered murine recombinant IFN-gamma after infection, the mice regained parasite resistance. These results demonstrated that the UV-B exposure of mice enhances the susceptibility to the malaria parasites and suggested that the enhanced susceptibility following UV-B exposure was mediated by impairment of IFN-gamma production in response to the parasite infection.

Animals↗
PubMed2000

[2-(O-Phenylalkyl)phenoxy]alkylamines III: Synthesis and selective serotonin-2 receptor binding (2).

A series of 12-(2-phenylethyl)phenoxy]ethylpyrrolidine derivatives were synthesized, and their affinity for serotonin-2 (5-HT2) and dopamine-2 (D2) receptors was examined. Among them, compound 17, (2R,4R)-4-hydroxy-2-[2-[2-[2-(3-methoxyphenyl)ethyl]phenoxylethyl] -1-methylpyrrolidine hydrochloride, showed high 5-HT2 receptor affinity in vitro. This compound was a more potent inhibitor of ex vivo 5-HT-induced platelet aggregation than compound 3, which was previously shown to be more potent than ketanserin (1) and sarpogrelate (2a). However, compound 17 produced gastric irritation in rats. Therefore, we carried out a further derivatization of 17, and compound 45 (R-102444), a lauryl ester prodrug of compound 17, was found to be a promising candidate as an antithrombotic agent. Oral administration of R-102444 produced a marked inhibition of 5-HT-induced ex vivo platelet aggregation, and R-102444 did not cause any gastric irritation. The antiaggregatory effects of R-102444 were more potent than those of sarpogrelate (2a) and its active metabolite, M-1 (2b). In addition, R-102444 exhibited more potent antithrombotic effects than sarpogrelate in a rat photochemically-induced thrombosis model.

Acylation↗
PubMed2000

[2-(omega-phenylalkyl)phenoxy]alkylamines.II: Synthesis and selective serotonin-2 receptor binding.

A series of [2-(omega-phenylalkyl)phenoxy]alkylamines was synthesized and their receptor binding affinity was examined in vitro. These compounds showed an affinity for serotonin-2 (5-HT2) and dopamine-2 (D2) receptors. [2-(2-phenylethyl)phenoxy]alkylamine derivatives with a pyrrolidine or piperidine moiety in the structure showed higher affinity for 5-HT2 receptors but lower affinity for D2 receptors. Among these compounds, (S)-2-[2- [2-[2-(3-methoxyphenyl)ethyl]phenoxy]ethyl]-1-methylpyrrolidine, (S)-27, exhibited the most potent and selective affinity for 5-HT2 receptors. Furthermore, (S)-27 was effective in inhibiting 5-HT-induced vasoconstriction in vitro and platelet aggregation both in vitro and ex vivo.

Animals↗
PubMed2000

Isolation of peroxisome-defective CHO mutant cells using green fluorescent protein.

The authors constructed a recombinant green fluorescent protein (GFP) (PTS-GFP), which carries peroxisome targeting signal (PTS1 or PTS2) as an additional sequence, by polymerase chain reaction. The gene encoding for the recombinant GFP was constructed into an eukaryotic expression vector, and stable transformant of CHO cell expressing PTS-GFP was isolated, following the transfection of the plasmid encoding for the GFP. Each expressed PTS-GFP appeared to be localized in peroxisomes, because the GFP was observed in cellular structures, as was catalase. The observation proposed a visual screening procedure for isolating peroxisome-defective mutant. Following an enrichment of mutant cells by use of 9-(1'-pyrene)nonanol/ultraviolet irradiation (P9OH/UV) method, five peroxisome-defective mutants were isolated by pursuing the fluorescent signals from GFP. Two mutants (SK24 and SK32) were isolated from CHO cells expressing PTS1-GFP, and three mutants (PT13, PT32, and PT54) were isolated from cells expressing PTS2-GFP. Four mutants, except for PT13, showed cytosolic distributions of both PTS-GFP and catalase. On the other hand, mutant PT13 showed a cytosolic distribution on PTS2-GFP, but a peroxisomal distribution on catalase. Cell fusion analysis between SK24 mutant and other mutants indicated that PT54 mutant is in the same complementation group (CG) as SK24, but that SK32, PT13, and PT32 mutants are in different complementation group(s) from SK24.

Animals↗