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Biomedical subjects

N Kato

Publications and source records attributed to N Kato.

At least 217 records · Page 12Linked to original sources
PubMed2000

Effects of skin pressure by clothing on digestion and orocecal transit time of food.

In order to reveal the influence of clothing skin pressure on digestion of food through the gastrointestinal tract, we examined the absorption of dietary carbohydrate and orocecal transit time of a test meal by means of a breath hydrogen test on 7 healthy young women. In this experiment, we collected breath samples from the participants wearing loose-fitting experimental garment on the second day of the experiment and from the same participants but wearing an additional tight-fitting girdle on the following day for 16 hours and 9 hours, respectively. Skin pressure applied by a girdle on participant's waist, abdomen and hip region was 15.5 +/- 0.4 mmHg (mean +/- SE), 11.0 +/- 0.2 mmHg, and 13.6 +/- 0.6 mmHg, respectively, and the values were 2-3 times larger than those of the experimental garment. The hydrogen concentration vs. time curve showed that breath hydrogen levels at its peaks (15:00, 15:30, 16:00, 16:30, and 17:00 hr) on the third day of the experiment were significantly higher than those of the corresponding time on the second day (p < 0.05 at 17:00 and 15:00, p < 0.01 at 15:00, 16:00 and 16:30). Consequently, significantly pronounced breath hydrogen excretion was observed under the "pressure" clothing condition (p < 0.01). On the other hand, the transit time of the test meal for the subjects wearing a girdle did not differ significantly from that for the subjects wearing the garment of less pressure (270 +/- 18 minutes and 263 +/- 21 minutes, respectively). These results indicate that the clothing skin pressure has an inhibitory effect on the absorption of dietary carbohydrate in the small intestine, but no effect on the orocecal transit time of a meal.

Adult↗
PubMed2000

Everyday breath hydrogen excretion profile in Japanese young female students.

A breath hydrogen test has been used widely as a noninvasive and simple method of detecting carbohydrate malabsorption as well as estimation of the small intestinal and orocecal transit time. By means of this method, we have examined the change in breath hydrogen concentration of young female students in their everyday life in order to reveal the breath hydrogen excretion profile under normal circumstances. In this survey, we have asked them to collect their own breath samples every one-hour as regularly as possible during one day from awakening until bedtime. We also asked them to complete the questionnaire concerning their dietary habit, dietary record and physical activities. Among the 43 subjects who gave the breath hydrogen records, 37 subjects excreted detectable hydrogen into their alveolar air. By comparing the changes in breath hydrogen concentration during the time of day, breath hydrogen excretions could be classified into two distinct patterns; more than half of the total hydrogen excretion occurred in the first half of the waking hours (designated as "pattern A", 18 cases) and in the latter half (designated as "pattern B", 19 cases). Taking into consideration the subjects' records of diets and physical activities, the early-pronounced breath hydrogen excretion observed among 18 "pattern A" students was probably resulted from the malabsorption of the dietary carbohydrate in the breakfast meals.

Adult↗
PubMed2000

Genetic analysis of the atrial natriuretic peptide gene in essential hypertension.

Atrial natriuretic peptide (ANP) plays an important role in the regulation of blood pressure through sodium-water homoeostasis. Accordingly, several investigators have raised the question of whether the gene encoding ANP is involved in the aetiology of essential hypertension or related phenotypes such as salt sensitivity. Most of the studies have used anonymous polymorphic markers of the gene, and made inconclusive claims about the disease relevance of ANP. Therefore, in order to find sequence variations with potential functional significance and to characterize the pattern of linkage disequilibrium between polymorphisms, we screened a 3368-bp genomic fragment of ANP. Subsequently we tested the association of detected polymorphisms with plasma ANP levels and with hypertension status. Two new polymorphisms were identified, in the 5'-untranslated region and exon 1 respectively, as well as three previously reported polymorphisms in intron 2 and exon 3. When analysed in 102 healthy normotensive subjects, none of the polymorphisms appeared to significantly affect plasma ANP levels. A case-control study in a Japanese population (255 hypertensive and 225 normotensive individuals) revealed a marginally significant association (P=0.026) between an ANP polymorphism located in the 5'-untranslated region (C-664G) and hypertension, but no association for the other polymorphisms. Each of the uncommon variants has an allele frequency of less than 10% in Japanese people, which may have hampered our detection of a significant association between ANP variants and hypertension status (and plasma ANP levels). The pathophysiological relevance of ANP, however, needs to be further defined in relation to hypertension-associated phenotypes, and also should be examined in different ethnic groups.

Aged↗
PubMed2000

Population pharmacokinetics and pharmacodynamics of TS-943 for selective nonpeptide platelet glycoprotein IIb/IIIa receptor antagonist in normal healthy subjects.

The pharmacokinetics and pharmacodynamics of TS-943 were evaluated with use of NONMEM in 36 healthy male subjects after constant infusion of five different single-dose regimens. Population analysis showed the plasma concentration-time profiles of TS-943 to be best-fit characterized by a two-compartment open model with constant infusion and first-order elimination. The pharmacodynamic model that best fitted the platelet aggregation was a sigmoid Emax model. The final estimates for baseline effect, 50% inhibitory concentration (IC50), and the Hill coefficient were 79.4%, 23.4 ng/mL and 1.63, respectively. The maximum effect (Emax) was fixed at 80% (submaximal aggregation response). In addition, correlations between TS-943 plasma concentration and extension of template bleeding time were examined by fitting with an exponential model. The model estimates that the TS-943 plasma concentration necessary to double template bleeding time is approximately 63 ng/mL (ie, 2.7-fold greater than the IC50). The population approaches for pharmacokinetic-pharmacodynamic investigation can be useful for the analysis of concentration-effect relationships and concentration-adverse event relationships for a platelet glycoprotein IIb/IIIa receptor antagonist.

Adult↗
PubMed2000

[Radiation induced glioblastoma: a case report].

We report a surgical case of a 54-year-old woman with a radiation induced glioblastoma. At the age of 34, the patient was diagnosed to have a non-functioning pituitary adenoma. It was partially removed followed by 50 Gy focal irradiation with a 5 x 5 cm lateral opposed field. Twenty years later, she suffered from rapidly increasing symptoms such as aphasia and right hemiparesis. MRI showed a large mass lesion in the left temporal lobe as well as small mass lesions in the brain stem and the right medial temporal lobe. These lesions situated within the irradiated field. Magnetic resonance spectroscopy revealed relatively high lactate signal and decreased N-acetyl aspartate, choline, creatine and phosphocreatine signals. Increased lactate signal meant anaerobic metabolism that suggested the existence of a rapidly growing malignant tumor. Thus, we planned surgical removal of the left temporal lesion with the diagnosis of a radiation induced malignant glioma. The histological examination revealed a glioblastoma with radiation necrosis. MIB-1 staining index was 65%. Postoperatively, her symptoms improved, but she died from pneumonia 1 month after the surgery. An autopsy was obtained. The lesion of the left temporal lobe was found to have continuity to the lesion in the midbrain, the pons and the right temporal lobe as well. High MIB-1 staining index suggested that a radiation induced glioblastoma had high proliferative potential comparing with a de novo and a secondary glioblastoma.

Adenoma↗
PubMed2000

[Intraaneurysmal embolization and parent artery trapping to treat a giant partial thrombosed vertebral artery aneurysm after surgical proximal clipping].

We encountered a case with a giant partially-thrombosed vertebral artery aneurysm successfully treated by endovascular trapping following a surgical parent artery clipping two years previously. The patient complained only of headache on her admission. Initial CT showed no subarachnoid hemorrhage, and MRI of the left anterior aspect of the pons showed flow void and hematoma. The angiogram showed fusiform dilatation of the left vertebral artery just proximal to the vertebral union. At first, the patient was treated by surgical proximal clipping of the left vertebral artery, under a diagnosis of arterial dissection. Her symptom improved and the angiogram showed a slight retrograde aneurysmal filling after the operation. Two years later, she complained of dysphasia, right hemiparesis, and hemidysesthesia caused by the compression of the brain stem. On MRI study, a partially-thrombosed giant aneurysm was detected in the left anterior aspect of the brain stem. The retrograde filling did not change remarkably on the angiogram. We performed the GDC embolization of the left distal vertebral artery and non-thrombosed residual neck with an assisting balloon positioned through the right vertebral artery to the basilar artery. After the embolization, the patient's neurological deficits caused by the compression of the brain stem disappeared. MRI study showed the mass volume reducing gradually over a two-years follow-up period. Treatment for a partially-thrombosed giant vertebral artery aneurysm is difficult and controversial. It is necessary to shut off the blood flow into the aneurysm completely, so we consider that endovascular trapping with intraaneurysmal embolization is the most effective procedure.

Embolization, Therapeutic↗
PubMed2000

Current and future therapies for ischemic cerebrovascular disease.

Stroke is the third leading cause of death in the adult population. It makes great demands on patients, who must not only survive the complications of the acute stages but also must cope with the great physical and economic costs of long-term disabilities. Therefore, there is an urgent need to establish generally useful treatments for ischemic stroke. Currently, there are three treatment approaches based on pathophysiologic concepts derived from basic research: (i) pharmacologic strategies for arterial recanalization, (ii) neuronal protection and (iii) the inhibition of undesirable damaging host responses. The key to current treatment is the emergent administration of tissue plasminogen activator (t-PA). Thrombolytic treatment improves outcome when given to carefully selected patients within 3 h of stroke onset. Numerous neuroprotective agents have been developed in the last decade, and a new wave of therapies is now on the horizon that could potentially minimize ischemic brain damage. This article highlights recent advances in pharmacological interventions for ischemic stroke.

Journal Article↗
PubMed1999

Electrophysiological evidence for sequential activation of multiple brain regions during the auditory selective attention process in humans.

In an attempt to examine dynamic involvement of multiple brain regions in the auditory selective attention process, negative difference wave (Nd) generators were assessed using a high-resolution EEG system (128ch) and scalp current density (SCD) analysis. Ten normal volunteers participated in the study. Event-related potentials were recorded during a selective attention task. Sequential SCD mappings revealed that current sinks were located in the bilateral temporal regions at 160 ms subsequent to the onset of stimuli, shifting the dipole orientation more tangentially to the scalp at around 220 ms. Moreover, a current sink was demonstrated in the midfrontal region at around 320 ms. These findings confirm that different cortical regions are sequentially involved in the auditory selective attention process.

Adult↗
PubMed1999

Enhancement of hepatitis C virus replication by Epstein-Barr virus-encoded nuclear antigen 1.

Based on our recent observation that Epstein-Barr virus (EBV) is detected in 37% of the tissues of hepatocellular carcinoma, and especially frequently in cases with hepatitis C virus (HCV), the effect of EBV infection on the replication of HCV was investigated. EBV-infected cell clones and their EBV-uninfected counterparts in cell lines MT-2 (a human T-lymphotropic virus type I-infected T-cell line), HepG2 (a hepatoblastoma cell line) and Akata (a Burkitt's lymphoma cell line) were compared in terms of their permissiveness for HCV replication following inoculation of HCV derived from patients who were HCV carriers. The results indicated that EBV-infected cell clones, but not their EBV-uninfected counterparts, promoted HCV replication. EBV-encoded nuclear antigen 1 (EBNA1), which is invariably expressed in EBV-infected cells, supported HCV replication. Deletion analysis of the EBNA1 gene showed good correlation between transactivation activity and the activity supporting HCV replication. The present findings suggest that EBV acts as a helper virus for HCV replication.

Base Sequence↗
PubMed1999

Production of fungal fructosyl amino acid oxidase useful for diabetic diagnosis in the peroxisome of Candida boidinii.

A high-level production of fructosyl amino acid oxidase (FAOD), whose production was toxic in Escherichia coli, was investigated through attempts to utilize the peroxisome of Candida boidinii as the place for protein accumulation. The alcohol oxidase-depleted strain (strain aod1Delta) produced FAOD at a four to five times higher level than the wild type strain in terms of protein amount and enzyme activity, although the transcriptional level was similar. As a result of this study, we could improve FAOD productivity approximately 47-fold from the original transformant, and FAOD accumulated within membrane-bound peroxisomes up to 18% of the total soluble proteins.

Amino Acid Oxidoreductases↗
PubMed1999

Alcohol oxidase hybrid oligomers formed in vivo and in vitro.

Cell-free extract prepared from methanol-grown cells of the methylotrophic yeast Pichia methanolica showed nine multiple alcohol oxidase (AOD) bands on active staining in native polyacrylamide gel electrophoresis. Their molecular basis was investigated and two AOD-encoding genes, MOD1 and MOD2, were cloned from P. methanolica genome. When the two genes were expressed in a heterologous host, an alcohol oxidase-depleted strain of Candida boidinii(aod1Delta strain), both MOD1 and MOD2 partially complemented growth defect of the host strain on methanol. While expression of either MOD1 or MOD2 in C. boidinii aod1Delta strain gave a single AOD band corresponding to the band with the largest and smallest mobility among the nine AOD bands, respectively, co-expression of MOD1 and MOD2 resulted in multiple band formation. Mixed oligomerization of Mod1p and Mod2p in vitro also gave nine multiple bands. From these results, we concluded that the nine multiple forms of AOD observed on native-PAGE represent two homo-octamers and seven hetero-octamers of Mod1p and Mod2p. Using this zymogram analysis, we also found that Mod1p was preferably produced at low methanol concentrations in the media, while Mod2p was produced at higher methanol concentrations. This shows distinct regulatory features of the two AOD-encoding genes in this methylotrophic yeast.

Alcohol Oxidoreductases↗
PubMed1999

Distinct temporal profiles of activity-dependent calcium increase in pyramidal neurons of the rat visual cortex.

1. Using fluo-3-based fluorometry, we studied variation in depolarization-induced calcium increases in the proximal dendrites or soma of pyramidal neurons in layer II/III of the rat visual cortex. 2. Depolarization for all durations tested (0.1-2 s; 0.5 nA) evoked a train of action potentials and a small increase in calcium signal (mean 26 %) which peaked within 1 s of the onset of depolarization. With depolarization for longer than 1 s, this small increase was often followed by a larger increase (73 %). This later phase of calcium increase occurred without sudden changes in action potential firing. 3. Application of ryanodine, which suppresses intracellular calcium release, abolished the second phase without affecting the early phase in a use-dependent manner. Meanwhile, no major changes were observed in the pattern of action potential firing. 4. In calcium-free medium, both the early and late phases were almost undetectable, although action potential firing was still evoked by injection of depolarizing currents. Since the late phase depended on intracellular calcium release, this effect of calcium-free medium on the late phase is likely to be indirect through an influence on the early phase. 5. This two-phase profile was observed with somatic depolarization or with antidromic action potentials induced by tetanization. Neocortical pyramidal neurons can thus recruit calcium from different sources, even without chemical sensitization, generating temporally diverse profiles of intracellular calcium signal in response to action potential firing. 6. Such variety in the mechanisms of calcium increase may be relevant to the role of calcium as a versatile second messenger for various types of synaptic plasticity.

Aniline Compounds↗
PubMed1999

Isothiazolone derivatives selectively inhibit telomerase from human and rat cancer cells in vitro.

The telomere hypothesis postulates stabilization of telomere length and telomerase activation as key events in cellular immortalization and carcinogeneses. Accordingly, telomerase has been suggested as a novel and highly selective target for design of antitumor drugs. Screening of a chemical library including 16 000 synthetic compounds yielded six that strongly inhibited telomerase activity in extracts of cultured human cells, including four isothiazolone derivatives and two unrelated compounds. The most potent inhibitor was 2-[3-(trifluoromethyl)phenyl]isothiazolin-3-one (TMPI), a concentration of 1.0 microM inhibited telomerase activity by 50% according to a telomere repeat amplification protocol (TRAP) assay. Analysis using partially purified telomerase from AH7974 rat hepatoma cells demonstrated noncompetitive inhibition with the telomere-repeat primer and mixed inhibition with the dNTPs; the inhibition constant was 2.5 microM. TMPI did not inhibit eukaryotic DNA polymerase alpha, beta, or human immunodeficiency virus reverse transcriptase (HIV RT). Thus, inhibition by TMPI was highly selective for telomerase. Inhibition by TMPI was quenched by 1 mM of dithiothreitol or glutathione, suggesting that TMPI inhibits telomerase by acting at a cysteine residue. TMPI inhibition of this enzyme may find application as an antineoplastic agent.

Animals↗
PubMed1999

Occurrence of dentate granule cell LTP without proximal dendritic Ca2+ increase.

We investigated activity-dependent calcium increases in proximal dendrites of dentate granule cells in the rat hippocampus, and its relationship with induction of LTP at perforant path synapses (PP-synapses). LTP was induced at PP-synapses by high-frequency stimulation (HFS; 100 Hz for 0.4 s), and the same HFS evoked a dendritic calcium increase in the proximal dendrite. However, bath-application of the L-type voltage-dependent calcium channel (VDCC) blocker nimodipine noticeably reduced this calcium increase without abolishing induction of LTP. This calcium increase mediated by high-threshold VDCCs is likely to be evoked by action potentials. LTP induction at PP-synapses is hence suggested to be independent of action potential-induced calcium increases in the proximal dendrite.

Animals↗
PubMed1999

Multiple generators in the auditory automatic discrimination process in humans.

To reveal the spatiotemporal characteristics of the auditory automatic discrimination process, mismatch negativity (MMN) generators were assessed with a high-resolution EEG system (128ch) and scalp current density (SCD) analysis. Ten normal volunteers participated in the study. Event-related potentials were recorded during a selective attention task. Sequential SCD mappings revealed that a current sink/source combination in the left temporal regions and a current sink in the right frontotemporal regions appeared around 200 msec irrespective of the ear of stimulation. Moreover, a parietal sink/source combination was demonstrated on the right hemisphere around 240 ms irrespective of the ear of stimulation. These findings demonstrate that the auditory automatic change detection process is, both spatially and temporally, a multiple-generated system.

Acoustic Stimulation↗
PubMed1999

Elevated neuropeptide Y and corticotropin-releasing factor in the brain of a novel epileptic mutant rat: Noda epileptic rat.

Noda epileptic rat (NER) is a new epileptic rat strain, which was developed by inbreeding rats with spontaneous tonic-clonic seizures in a stock of Crj:Wistar. In the present study, possible changes of two neuropeptides, neuropeptide Y (NPY) and corticotropin-releasing factor (CRF), in the brains of NER were investigated. Increased contents of immunoreactive (IR) NPY were found in the striatum and amygdala of 8-week NERs with partial seizure, while these changes extended to the limbic region including hippocampus in 16-week NERs with fully developed generalized tonic-clonic seizure. IR-CRF were elevated only in the entorhinal and pyriform cortex of both 8-week and 16-week NERs. Generalized tonic-clonic seizure in NERs induced a transient increase of NPY mRNA in the granular layer of dentate gyrus. These results suggest that NPY metabolism in the limbic brain contributes to the seizure susceptibility in this model of epilepsy.

Animals↗