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Biomedical subjects

T Fukui

Publications and source records attributed to T Fukui.

At least 55 records · Page 3Linked to original sources
PubMed2001

Role of nitric oxide in regional blood flow in angiotensin II-induced hypertensive rats.

The present study was designed to evaluate the contribution of nitric oxide (NO) to regional hemodynamics during the early phase of angiotensin II (Ang II)-induced hypertension. The responses of regional blood flow to chronic NO synthase inhibition with N(G)-nitro-L-arginine methyl ester (L-NAME) were assessed using radioactive microspheres in conscious Ang II-infused hypertensive rats. Ang II-infused rats (270 ng/kg/min, subcutaneously for 12 days: n=11) showed higher mean arterial pressure (MAP: 153+/-4 mmHg) and total peripheral resistance (TPR: 1.61+/-0.06 mmHg/min/ml), and lower cardiac output (CO: 102+/-3 ml/min) than vehicle-infused normotensive rats (115+/-2 mmHg, 0.96+/-0.05 mmHg/min/ml and 130+/-7 ml/min, n=11, respectively). The blood flow rates in the brain, spleen, large intestine and skin were significantly reduced in Ang III-infused rats compared with vehicle-infused rats, while those in the lung, heart, liver, kidney, adrenal gland, small intestine, and skeletal muscle were similar. Treating Ang II-infused rats with L-NAME (75 mg/l in drinking water for 10 days, n=11) resulted in higher MAP (166+/-6 mmHg) and TPR (1.89+/-0.18 mmHg/min/ml) and lower CO (87+/-7 m/min) than untreated Ang II-infused rats. L-NAME-treated Ang II-infused rats showed widespread increases in regional vascular resistance and reduced blood flow rates in the kidney (3.81+/-0.27 ml/min/g) and skeletal muscle (0.20+/-0.03 ml/min/g) compared with untreated Ang II-infused rats (6.88+/-0.27 and 0.33+/-0.04 ml/min/g, respectively). However, there were no significant differences in the flow rates of other organs investigated between these animals. An NO donor, (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK409: 30 microg/kg/min, i.v.), significantly decreased MAP (110+/-6 mmHg) and TPR (1.23+/-0.18 mmHg/min/ml) without significant changes in CO (89+/-9 ml/min) in L-NAME-treated Ang II-infused rats. Furthermore, FK409 partially reversed blood flow rates in the kidney (4.72+/-0.40 ml/min/g) and skeletal muscle (0.25+/-0.02 ml/min/g)in these animals. These results suggest that NO counteracts, at least in part, the vasoconstrictor effects of elevated Ang II levels in renal and skeletal muscle vascular beds, and is an important modulator in the regulation of blood flow to these organs during the development of Ang II-induced hypertension.

Angiotensin II↗
PubMed2001

Benidipine dilates both pre- and post-glomerular arteriole in the canine kidney.

The aim of the present study was to determine the effects of benidipine on renal function and whether benidipine may dilate the efferent arteriole as well as the afferent arteriole of the canine kidney. The effects of benidipine on the renal segmental vascular resistance were estimated using Gomez's formula with some modification. The renal hemodynamic action of benidipine was also compared with that of amlodipine. Intrarenal arterial injection of benidipine at a dose of 3 microg/kg resulted in a significant increase in renal blood flow (RBF), urine flow and urinary excretion of sodium, but not in glomerular filtration rate (GFR). Amlodipine at a dose of 300 microg/kg also increased RBF, urine flow and urinary excretion of sodium to a significant degree equivalent to that by benidipine. However, in contrast to benidipine, amlodipine significantly increased GFR. After the administration of benidipine, autoregulation of RBF and GFR was relatively maintained and the renal perfusion pressure (RPP)-RBF relation shifted upward; that is, RBFs at 75 and 50 mmHg were maintained at a higher level than those of the control. In contrast to benidipine, amlodipine diminished the autoregulation of RBF and GFR. RBFs at 75 and 50 mmHg were not different from those of the control. The afferent and efferent arteriolar resistance (Ra and Re) were calculated based on the RPP-RBF and RPP-GFR relations. Benidipine reduced both Ra and Re, but amlodipine selectively reduced Ra. Benidipine increased RBF but not GFR via the dilation of both afferent and efferent arterioles. Thus, benidipine has unique renal hemodynamic actions which differ from those by most calcium antagonists.

Animals↗
PubMed2001

Cost-effectiveness analysis of dopamine agonists in the treatment of Parkinson's disease in Japan.

BACKGROUND: Dopamine agonists such as bromocriptine or pergolide are often used in Japan to treat Parkinson's disease. Dopamine agonists are relatively expensive drugs; economic evaluations are required. OBJECTIVE: To evaluate the cost effectiveness of dopamine agonists for the treatment of Parkinson's disease in Japan. DESIGN AND SETTING: We used a Markov model to simulate the course of Parkinson's disease and to compare the cost effectiveness of dopamine agonists added to levodopa with that of levodopa alone in Japan. The model assumed that 60-year-old men with Parkinson's disease in Hoehn-Yahr (HY) stages 2 to 5 using levodopa were administered dopamine agonists or continued on levodopa alone. The incremental cost effectiveness of dopamine agonists used for 10 years was then estimated. STUDY PERSPECTIVE: Societal. MAIN OUTCOME MEASURES AND RESULTS: In the patients in HY stage 2, the incremental cost effectiveness of dopamine agonists was 18,610,000 to 19,320,000 yen per quality-adjusted life-year (QALY) [$US 172,300 to $US 178,900/QALY; 1998 values] . In patients in HY stage 3 or higher, the use of dopamine agonists was dominant over levodopa alone mainly due to reduced cost for care. In sensitivity analyses, costs and effectiveness of dopamine agonists significantly influenced the results. The use of a generic formulation of bromocriptine was dominant over levodopa alone even in the patients with HY stage 2 disease. CONCLUSIONS: Dopamine agonists appear to be cost effective in advanced Parkinson's disease, although their use is sensitive to the costs and effectiveness of dopamine agonists. If factors discouraging the prescription of generic drugs in Japan were removed, the treatment of Parkinson's disease would become more cost effective.

Aged↗
PubMed2001

Factors related to biomedical research productivity in Asian countries.

By and large, biomedical research is not a priority sector in Asian countries due to many factors. Lack of resources and trained manpower are certainly among these factors. We investigated the factors related to biomedical research productivity in Asian countries based on Medline data. The number of biomedical articles published in the indexed journals from each country of Asia and Oceania during 1990-1998 was used as a surrogate of total biomedical research productivity. Multiple regression analysis revealed that low gross national product per capita (p<0.013), insufficient number of physicians (p<0.047), and inadequate public spending on the health sector (p<0.049) were responsible for the meager number of biomedical publications in Asian countries.

Asia↗
PubMed2001

The defibrillation system of basic emergency medical technicians in Japan: a comparison with other systems from a 14-year review of out-of-hospital cardiac arrest reports.

Although seven years have passed after basic emergency medical technician (EMT) defibrillation system was introduced in Japan, the overall survival for out-of-hospital cardiac arrest (OHCA) remains poor. We investigated factors leading to such an unanticipated result in Japan by comparing the data of OHCA in Japan with those in other countries. We obtained population-based OHCA data from three communities in Japan. We also performed a comprehensive literature and manual search to identify reports that included rates for incidence and survival or provided sufficient data for the calculation of these rates of OHCA. Statistical analysis was performed to compare survival and incidence rates between the communities. We identified 36 articles from 16 countries by a comprehensive literature search. There was no significant difference in incidence and survival rates among communities in Japan. Although the incidence rate of collapse-witnessed OHCA with ventricular fibrillation (VF) was much lower in Japan than western countries, the proportions of survival from it were comparable to those. Basic-EMT defibrillation system in Japan has yielded excellent result in terms of the survival of VF cases. However, much lower proportion of VF to all cases is responsible for lower overall rates of survival from OHCA in Japan.

Chi-Square Distribution↗
PubMed2001

The Nd-YAG laser is useful in prevention of dental caries during orthodontic treatment.

Plaque control during the course of orthodontic treatment is not an easy task, and dental caries are not an unlikely complication. We examined the possibility of controlling dental caries with Nd-YAG laser irradiation in orthodontic patients. As a preliminary experiment, we used the Nd-YAG laser to irradiate an extracted tooth and then left it to soak in lactic acid. The decay of the tooth was evaluated with a scanning electron microscope (SEM); tooth decay was inhibited by the action of the laser. Twenty patients undergoing orthodontic treatment for early decalcification of the teeth (white spot lesions) were selected, and photographs were taken of their oral cavities. White spot lesions on the four incisors and two canines of the maxilla were traced on tracing paper, and their areas were calculated by computer. Ten of the patients received laser treatment and acidulated phosphate fluoride solution (APF); the other ten acted as the control group. Between 11 and 12 months later, we photographed the oral cavity as we had previously; the white spot lesions were again traced and their areas calculated. The changes in the areas of the white spots of the laser-irradiated and control groups showed the following increases: laser-irradiated group, 1.41 times; controls, 2.87 times. The difference was statistically significant. These results demonstrate that Nd-YAG laser irradiation with application of APF acts as an effective method of caries control during orthodontic treatment.

Acidulated Phosphate Fluoride↗
PubMed2001

Aberrant BCR-ABL transcript with intronic insertion in a patient with philadelphia chromosome-positive chronic myeloid leukemia: implications for disease progression.

The BCR-ABL fusion gene is important for the leukemogenesis of chronic myeloid leukemia (CML). A relationship between types of BCR-ABL transcripts in CML and clinical features has been proposed. We present here a patient with CML who carried an aberrant BCR-ABL transcript with an intronic sequence insert. A 26-year-old woman was diagnosed as having Philadelphia chromosome (Ph) positive CML. Reverse transcription polymerase chain reaction detected an atypically large BCR-ABL mRNA transcript. Sequencing revealed a 589bp insertion consisting of a 5' portion of BCR intron b2 and a 3' portion of ABL intron 1b between BCR exon b2 and ABL exon a2. Although the typical b2a2 transcript was undetectable initially, it appeared after intensive chemotherapy. The aberrant transcript presumably arose as a result of a lack of splicing, and chemotherapy might modify the disease course by selecting the subpopulation of the CML clone expressing typical BCR-ABL mRNA dominantly.

Adult↗
PubMed2001

ATP-citrate lyase from the green sulfur bacterium Chlorobium limicola is a heteromeric enzyme composed of two distinct gene products.

The reductive tricarboxylic acid cycle functions as a carbon dioxide fixation pathway in the green sulfur bacterium, Chlorobium limicola. ATP-citrate lyase, one of the key enzymes of this cycle, was partially purified from C. limicola strain M1 and the N-terminal sequence of a 65-kDa protein was found to show similarity toward eukaryotic ATP-citrate lyase. A DNA fragment was amplified with primers designed from this sequence and an internal sequence highly conserved among eukaryotic enzymes. Using this fragment as a probe, we isolated a DNA fragment containing two adjacent open reading frames, aclB (1197 bp) and aclA (1827 bp), whose products showed significant similarity to the N- and C-terminal regions of the human enzyme, respectively. Heterologous expression of these genes in Escherichia coli showed that both gene products were essential for ATP-citrate lyase activity. The recombinant enzyme was purified from the cell-free extract of E. coli harboring aclBA for further characterization. The molecular mass of the recombinant enzyme was determined to be approximately 532--557 kDa by gel-filtration. The enzyme catalyzed the cleavage of citrate in an ATP(-), CoA- and Mg(2+)-dependent manner, where ATP and Mg(2+) could be replaced by dATP and Mn(2+), respectively. ADP and oxaloacetate inhibited the reaction. These properties suggested that ATP-citrate lyase from C. limicola controlled the cycle flux depending on intracellular energy conditions. This paper provides the first direct evidence that a bacterial ATP-citrate lyase is a heteromeric enzyme, distinct from mammalian enzymes.

ATP Citrate (pro-S)-Lyase↗
PubMed2001

[Neuropathology of longstanding subacute myelo-optico-neuropathy (SMON): an autopsy case of SMON with duration of 28 years].

The present case, 78-years-old female, had been troubled with SMON during 28 years, and was suddenly died from cerebral hemorrhage. The neuropathology characteristic for SMON could not be revealed in the spinal cord on routine histological preparations. There were decreasing number of immunopositive granules in the nucleus gracilis of medulla oblongata for synaptophysin, and in the marginal zone of the lumbar dorsal horn for substance P. These findings showed the presence of tractus gracilis degeneration and the disappearance of nociceptive fibers from the dorsal roots, respectively. To elucidate the histopathological changes of the spinal cord in long standing cases with SMON, the 11 cases reported were reviewed. The mean duration from the onset to death was 22.8 years(16 to 33 years). The mean age was 76.3 years old(54 to 92), and the 10 cases were female. All cases showed sensory impairment of the lower extremities, while deep tendon reflex exaggerated was seen in 7 cases. There were nine cases involving dorsal funiculi degeneration of the spinal cord, in contrast the lateral funiculi alternation were noticed in only two cases. It was considered that the corticospinal tract alteration becomes undiscernible during the long course, although the dorsal funiculi degeneration remained.

Aged↗
PubMed2001

Antitumor efficacy in vitro and in vivo of falconensones, a new type of polyene.

Falconensones A and B are new type of yellow pigment isolated from the mycelial extract of ascomycetous fungi, Emericella falconensis. To date, these falconensones and their derivatives, falconensone A p-bromophenylhydrazone and falconensone A dioxime are known to exhibit biological activities, which include growth inhibition and both induction of differentiation and apoptosis of HL60 human leukemia cells. The synthetic derivatives have been shown to be more potent than natural falconensone A and B in eliciting these activities. Herein, we investigate whether falconensones inhibit growth of other cancer cell lines in vitro, and we evaluate their ability to modify survival in C57 BL/6J mice using M5076 murine reticulosarcoma in vivo, which is established as the metastasis model. Falconensone A, falconensone A p-bromophenylhydrazone, and falconensone A dioxime inhibit growth of human myeloid leukemia cell lines, HL60 and HL60R, human hepatoma cell line HepG2, human prostate cancer cell line DU-145, and human breast cancer cell line MCF-7/Adr(R), whereas falconensone B, the 4'-nor-methyl derivative of falconensone A, shows extremely low or no activity. In contrast, all of the falconensones are active in growth inhibition of human breast cancer cell line MCF-7. Survival time of M5076-implanted mice was prolonged by treatment with falconensones, particularly falconensone A dioxime. These results indicate that falconensone A and its derivatives exhibit anticancer efficacy in a broad spectrum of cancer cell lines. These agents may have great potential for clinical use in the treatment of various cancers.

Animals↗
PubMed2000

Intrafractional tumor position stability during computed tomography (CT)-guided frameless stereotactic radiation therapy for lung or liver cancers with a fusion of CT and linear accelerator (FOCAL) unit.

PURPOSE: To evaluate intrafractional tumor position stability during computed tomography (CT)-guided frameless stereotactic radiation therapy (SRT) for lung or liver cancers, we checked repeated CT scanning, with a fusion of CT and linear accelerator (FOCAL) unit. METHODS AND MATERIALS: The FOCAL unit is a combination of a linear accelerator (Linac), CT scanner, X-ray simulator (X-S), and carbon table, and is designed to achieve CT-guided SRT with daily CT positioning followed by immediate irradiation while patients keep reduced shallow respirations. To evaluate intrafractional tumor position stability, 50 lung or liver lesions in 20 patients were checked by repeated CT scanning just before and after irradiation, and the obtained images were compared. RESULTS: There was no case with the intrafractional error judged to be greater than 10 mm. In 68% of cases, the intrafractional positioning errors were negligible (0-5 mm). CONCLUSIONS: Using the FOCAL unit, SRT for lung or liver cancers could be performed with intrafractional positioning errors not greater than 10 mm.

Equipment Design↗
PubMed2000

Dietary troglitazone decreases oxidative stress in early stage type II diabetic rats.

Oxidative stress is involved in the initiation and development of atherosclerosis in diabetes. We tested the hypothesis that oxidative stress is already increased in early stage type II diabetes, and that troglitazone may prevent the increase. Three groups of 20 week old rats were studied: untreated Otsuka Long-Evans Tokushima Fatty (OLETF) rats, as an animal model of type II diabetes, OLETF rats treated with troglitazone, and control Long-Evans Tokushima Otsuka (LETO) rats. Plasma lipid hydroperoxides (LOOH) concentration, as an indication of lipid peroxidation, and superoxide dismutase (SOD) activity in the thoracic aorta were measured. Plasma LOOH concentration was significantly higher in non-treated OLETF rats compared to LETO rats and treatment with troglitazone completely prevented this increase. SOD activity was significantly decreased in non-treated OLETF rats compared to LETO rats and troglitazone attenuated the diminution of it. These observations demonstrate oxidative stress is already increased in the early stage of type II diabetes and we confirmed troglitazone has the effect of an antioxidant in vivo.

Animals↗
PubMed2000

Volumetric study of lobar atrophy in Pick complex and Alzheimer's disease.

BACKGROUND: Lobar atrophy is an important neuroimaging feature of Pick complex (PiC). However, differences in patterns of focal brain atrophy between PiC and Alzheimer's disease (AD), and among PiC subgroups, have not been studied quantitatively. OBJECTIVE: To compare volumetric measures among primary progressive aphasia (PPA), frontotemporal dementia (FTD) and AD; to assess association between brain atrophy and cognition. PATIENTS: Seventeen patients with PPA, 11 with FTD and 24 with probable AD were studied. METHODS: We measured total and regional volume quantitatively using MRI and computerized volumetry. Contributing factors were controlled statistically or by adopting brain volume ratios. We investigated the classifying power of volumetry and correlated regional brain volume with cognitive and language test scores. RESULTS: The ratio for fronto-temporo-central region was smaller on the left in PPA and on the right in FTD. AD and some PPA patients had smaller parietal lobes. The frontal ratios correctly classified 93% of PPA and FTD patients, but only 50% of the entire PiC and AD patients. Language-dependent examinations correlated with the left fronto-temporal volume. CONCLUSIONS: Brain atrophy differs in PPA, FTD and AD, but there is some morphological overlap between PiC and AD in parietal volumes. Focal brain atrophy is most consistently associated with language impairments.

Aged↗