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Biomedical subjects

K Fukuda

Publications and source records attributed to K Fukuda.

At least 91 records · Page 5Linked to original sources
PubMed2001

Anaesthetic management of 27 cases of boron neutron capture therapy for glioblastoma.

Twenty-seven patients received boron neutron capture therapy during craniotomy at our research reactor from 1991 to 1999. This is a form of intra-operative radiation therapy, which uses neutrons from a nuclear reactor. There are three additional major problems to anaesthetists: boron neutron capture therapy must be given beside the nuclear reactor, with no hospital facilities; neutrons cannot be shielded effectively by ordinary protectors; and neutrons are detrimental to metal devices and especially to electrical appliances. Boron neutron capture therapy has been adopted as an effective therapy for glioblastoma/astrocytoma, but special considerations are required for anaesthesia.

Anesthesia, General↗
PubMed2001

Comparison of real-time quantitative polymerase chain reaction with three other assays for quantitation of hepatitis C virus.

BACKGROUND AND AIMS: Evaluation of serum levels of hepatitis C virus (HCV) is important for predicting the response to interferon treatment and monitoring its therapeutic efficacy. The aim of this study was to evaluate real-time quantitative polymerase chain reaction (PCR) as a method for the measurement of HCV-RNA. METHODS: The subjects were 50 patients with chronic hepatitis C: 36 with genotype 1b, eight with genotype 2a, and six with genotype 2b. Samples were tested for HCV-RNA by using real-time quantitative PCR with the ABI Prism 7700 sequence detection system, a branched DNA signal amplification assay, and an Amplicor monitor test; and for HCV core protein by using a fluorescent enzyme immunoassay. RESULTS: The detection range of the real-time quantitative PCR was between 10(1)-10(8) copies/mL of HCV-RNA. Hepatitis C virus RNA was detectable in all 50 samples by the use of real-time quantitative PCR, but was undetectable in 14 samples by the use of a branched DNA assay and in two samples by using the Amplicor monitor test; HCV core protein was undetectable in three samples. A significant correlation was found between the results of real-time quantitative PCR and those of the three other assays: branched DNA assay (r = 0.837, P < 0.0001), Amplicor monitor test (r = 0.853, P < 0.0001), and HCV core protein concentrations (r = 0.549, P < 0.0001). CONCLUSIONS: Our results showed that the real-time quantitative PCR was a highly sensitive assay for the measurement of HCV-RNA.

Adult↗
PubMed2001

Age-related changes of sleeping pattern during adolescence.

A questionnaire concerning sleep-related lifestyle, and physical and mental health was administered to the students of junior high schools (12-15 years), high schools (15-18 years), and universities. While bedtime linearly delayed with age throughout the adolescence (from junior high school to university age), rise time remained constant until high school ages. As a result, total nocturnal sleep time considerably decreased during this period. Rise time then delayed with age in the university sample. Daytime sleepiness increased with age peaking at high school age, then decreased gradually during university age. Several physical and mental health conditions got worse during high school and university ages. Compared with the adolescent samples, daytime sleepiness and mental health complaints were very low in the adult samples.

Adolescent↗
PubMed2001

Development of regenerative cardiomyocytes from mesenchymal stem cells for cardiovascular tissue engineering.

We have isolated a cardiomyogenic (CMG) cell line from murine bone marrow stroma. Stromal cells were immortalized, treated with 5-azacytidine, and spontaneous beating cells were repeatedly screened for. The cells showed a fibroblast-like morphology. However, this morphology changed after 5-azacytidine treatment in about 30% of the cells, which connected with adjoining cells after 1 week, formed myotube-like structures and began spontaneous beating after 2 weeks, and beat synchronously after 3 weeks. These cells expressed atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). Electron microscopy revealed a cardiomyocyte-like ultrastructure including typical sarcomeres and atrial granules. They had sinus node-like or ventricular cell-like action potentials. Analysis of the isoform of contractile protein genes, such as myosin and alpha-actin, indicated that their phenotype was similar to fetal ventricular cardiomyocytes. These cells expressed Nkx2.5, GATA4, TEF-1, and MEF2-C mRNA before 5-azacytidine treatment, and expressed MEF2-A and MEF2-D after treatment. This new cell line provides a powerful model for the study of cardiomyocyte transplantation.

Actins↗
PubMed2001

Hepatitis C virus core protein enhances the activation of the transcription factor, Elk1, in response to mitogenic stimuli.

Mitogen-activated protein kinase (MAPK) pathways play key roles in cell proliferation, transformation of mammalian cells, and the stress response. We and other investigators showed that hepatitis C virus (HCV) core protein has an oncogenic potential, but its mechanism has remained unknown. We previously demonstrated that the MAPK-extra-cellular signal-regulated kinase (ERK) kinase (MEK)-ERK pathway and its downstream target, the serum response element (SRE), is activated in BALB/3T3 cells producing HCV core protein. To elucidate the precise mechanism by which HCV core protein activates the MEK-ERK pathway, we transiently expressed HCV core protein in several cell lines and studied the signal transduction of the pathway, using Gal4-Elk1 luciferase assay, in vitro kinas assay of MAPK, and Western blotting analysis. We discovered that, in the presence of mitogenic signal, HCV core protein enhanced Elk1 activation working downstream of MEK without affecting ERK activity and Elk1 phosphorylation. Our data suggest that HCV core protein may activate Elk1 through a pathway alternative to the typical phosphorylation cascade. These findings might give new insights into the role of HCV in hepatocarcinogenesis.

3T3 Cells↗
PubMed2001

Method to detect substitutions in the interferon-sensitivity-determining region of hepatitis C virus 1b for prediction of response to interferon therapy.

Substitutions deduced by direct sequencing in the interferon-sensitivity-determining region (ISDR) of hepatitis C virus (HCV) are related to patients' responses to interferon (IFN), but sequencing is time consuming and results are only for the dominant virus. We developed a rapid method to detect such changes. With serum from 50 patients with chronic hepatitis C (genotype 1b) given IFN-alpha, a way to detect changes in ISDR by hybridization with oligonucleotide probes that had a prototype nucleotide sequence of HCV-J was established. Hybridization intensity was expressed as optical density (OD(NS5A)). The method was checked with serum from 100 more patients. In the study of 50 patients, all 21 with the prototype sequences had a high OD(NS5A) (> or = 0.4), and all 8 patients with a mutant-type sequence had low values (< or = 0.2). Twelve (95% confidence interval, 36-81%) of 20 patients with OD(NS5A) of <0.4 and 2 (1%-22%) of 30 patients with OD(NS5A) > or = 0.4 had complete responses (CR). All nine (66%-100%) patients with OD(NS5A) <0.4 and little HCV RNA (<100 kIU/mL) had CR, but none (0%-14%) of the 24 patients with high values from both predictors had CR. In the study of 100 patients, OD(NS5A) and the HCV RNA level were independent predictors of the effects of IFN. By multivariate analysis, the odds ratio for a CR in patients with OD(NS5A) of > or = 0.4 was 0.015 (0. 001-0.190) compared with the other patients (P =.001). In conclusion, our method should be useful in identification of prototype strains, which generally resist IFN therapy.

Amino Acid Substitution↗
PubMed2001

Proper use of MR imaging for evaluation of low back pain (radiologist' view).

Magnetic resonance (MR) imaging has been recognized as a modality of choice in the evaluation of the spine. However, morphological abnormalities demonstrated by MR imaging do not always reflect low back pain (LBP). MR imaging should be interpreted with consideration of full clinical signs, symptoms, and other relevant background. At the same time, MR findings potentially relevant to LBP, such as morphological abnormalities of the disc, presence or absence of high intensity zone, abnormalities of the end plate and adjacent marrow signal, degree of nerve root compression, and degeneration of the facet joint, should be described without omission.

Humans↗
PubMed2001

Dialysis-related amyloidosis.

Dialysis-related amyloidosis (DRA) is a well-recognized complication in patients on long-term hemodialysis. It occurs secondary to the deposition of beta(2)-microglobulin, preferentially in the musculoskeletal tissues. Plain radiography demonstrates advanced DRA findings such as bone erosions and cystic lesions, but it is not suitable for the demonstration of earlier changes. Magnetic resonance imaging and ultrasound are sufficient for the detection of amyloid deposition in the periarticular soft tissues and in the evaluation of spinal complications.

Aged↗
PubMed2001

Knowledge representation of signal transduction pathways.

MOTIVATIONS: Signal transduction is the common term used to define a diverse topic that encompasses a large body of knowledge about the biochemical mechanisms. Since most of the knowledge of signal transduction resides in scientific articles and is represented by texts in natural language or by diagrams, there is the need of a knowledge representation model for signal transduction pathways that can be as readily processed by a computer as it is easily understood by humans. RESULTS: A signal transduction pathway representation model is presented. It is based on a compound graph structure and is designed to handle the diversity and hierarchical structure of pathways. A prototype knowledge base was implemented on a deductive database and a number of biological queries are demonstrated on it.

Amino Acid Motifs↗
PubMed2001

Characteristics of human ovulation in natural cycles correlated with age and achievement of pregnancy.

BACKGROUND: The aim of this study was to evaluate whether characteristics of human ovulation correlate with age and pregnancy potential. METHODS: Two groups of women with regular menstrual cycles were included (i.e. one fertile and one infertile group), which were divided into four age groups (< or =29, 30-34, 35-39, > or = 40 years). Monitoring included observations of follicular phase length, whether ovulations occurred from the left or right ovary, the pattern of ovulations in succeeding natural cycles and, in a subset of women, early follicular phase FSH concentrations. RESULTS: Ovulation moving from one ovary to the other in two consecutive cycles (i.e. contralateral ovulation) was inversely correlated with age, showing a ratio of contralateral ovulation per contra plus ipsilateral ovulations (C/C+I) of 62% in women <29 years, gradually decreasing to 42% in women >40 years. The ratio of right-sided ovulation per right plus left-sided ovulations (R/R+L) was unrelated to age and remained almost constant at a level of approximately 55%. The follicular phase length was inversely correlated with age, being 16.2 +/- 2.9, 15.4 +/- 2.9, 14.8 +/- 2.8 and 13.7 +/- 1.3 days in women < 29, 30-34, 35-39 and >40 years of age respectively. The follicular phase length was similar when comparing ovulations occurring from the right and left ovary, but comparing two successive cycles, the length of the follicular phase of the second cycle, showing contralateral ovulation, was shorter than ipsilateral ovulation with two consecutive ovulations in the same ovary. The pregnancy rate of the four groups decreased with age, being 14, 12, 5 and 3% respectively. The C/C+I ratio correlates with pregnancy rate and follicular phase length, and inversely correlates with basal FSH, whereas R/R+L is unrelated to age and pregnancy rate. CONCLUSIONS: Human ovulation shows characteristics related to age. The interaction between the two ovaries seems to be most pronounced in the younger years, where ovulations jump from one ovary to the other more frequently than later on in life. The C/C+I ratio shows a clear correlation with age and pregnancy rate.

Adult↗
PubMed2001

Construction of the dual-functional RNA ligand against HCV NS3 protease and helicase.

Non-structural protein 3 (NS3) of hepatitis C virus (HCV) contains two distinct activities, protease and helicase which are essential for the HCV replication. In the previous study, we succeeded to obtain RNA aptamers, G9-I, G9-II and G9-III specific for the NS3 protease domain (delta NS3) by in vitro selection (1). As the result of mutational analysis in G9-I, we could obtain the minimum length of RNA structure, delta NEO-III maintaining the full inhibitional activity as shown in G9-I. Furthermore, we created a bi-functional novel RNA ligand, NEO-III-14U which was constructed by connecting delta NEO-III with (U)14 at the 3' terminal. NEO-III-14U was able to inhibit the unwinding of duplex DNA catalyzed by the Full-NS3 helicase activity as well as the protease activity in vitro. Consequently, we could obtain the dual-functional RNA ligand which could inhibit both NS3 protease and helicase activities essential for the HCV proliferation.

Base Sequence↗
PubMed2001

Activation of mu-opioid receptor induces expression of c-fos and junB via mitogen-activated protein kinase cascade.

BACKGROUND: Opioid-induced long-term functional alterations of the nervous system, such as tolerance, addiction, and dependence, conceivably involve changes in gene expression. The authors have previously reported that opioid receptors are functionally coupled to extracellular signal-regulated kinase, a class of the mitogen-activated protein kinase. To address whether activation of the opioid receptor induces changes in gene expression through the activation of extracellular signal-regulated kinase, the authors examined mu-opioid receptor (MOR)-induced immediate early gene expression. METHODS: Chinese hamster ovary cells stably expressing MOR were used. Cells were stimulated by MOR agonists after 24-h serum starvation. Expression of c-fos and junB genes was analyzed by RNA blot hybridization. To explore the mechanism of MOR-mediated c-fos and junB expression, activity of a transcription factor, Elk-1, was assessed by reporter assay. Furthermore, to investigate the functional consequences of c-fos and junB induction, MOR-mediated formation of the functional transcription factor complex AP-1 was examined by reporter assay and electrophoretic mobility shift assay. RESULTS: Mu-opioid receptor activation induced c-fos and junB messenger RNAs, which were inhibited by pretreatment of the cells with pertussis toxin and PD98059, an inhibitor of extracellular signal-regulated kinase cascade. MOR stimulation elevated Elk-1-mediated transcriptional activity by about 10-fold. AP-1-mediated transcriptional activity was stimulated by MOR agonists by about twofold. Electrophoretic mobility shift assay revealed that AP-1 binding activity in the nuclear extract was elevated by MOR activation and further showed that products of c-fos and junB genes are involved in formation of AP-1 complex. CONCLUSIONS: Mu-opioid receptor activation induces c-fos and junB expression and elevates AP-1-mediated transcriptional activities via the mitogen-activated protein kinase cascade.

Animals↗
PubMed2001

Anti-tumor effect of gallic acid on LL-2 lung cancer cells transplanted in mice.

We previously reported that gallic acid (3,4,5-trihydroxybenzoic acid), a naturally occurring plant phenol, can induce apoptosis in four kinds of human lung cancer cell lines in vitro. The present study further investigated the in vivo anti-tumor effects of orally administered gallic acid. Gallic acid reduced cell viability of LL-2 mouse lung cancer cells in vitro dose dependently, with a 50% inhibitory concentration (IC50) value of around 200 microM. C57Black mice were transplanted with LL-2 cells, and administered gallic acid (1 mg/ml in drinking water, ad libitum) and/or cisplatin (4 mg/kg i.p. injection, once a week). The average weight of the transplanted tumors, obtained at 29 days after transplantation, in the mice of control, gallic acid-treated cisplatin-treated and cisplatin plus gallic acid-treated groups was 4.02, 3.65, 3.19 and 1.72 g, respectively. The average tumor weight of the mice treated with cisplatin combined with gallic acid was significantly smaller than that of the control group (p<0.05). The amount of apoptotic cells in the tumor tissues of mice treated with gallic acid and/or cisplatin was significantly higher than those of the control mice. Combination of gallic acid and cisplatin increased the tumor cell apoptosis compared with the treatment with cisplatin alone. The present findings suggest that the combination of gallic acid with an anti-cancer drug, including cisplatin, may be an effective protocol for lung cancer therapy.

Animals↗
PubMed2001

Detection and cloning of a protein recognized by anti-human prostate-specific antigen (PSA) antibody in the rat ventral prostate.

Prostate-specific antigen (PSA), a 33 kDa glycoprotein produced in the epithelium of the human prostate, has become established as a useful tumor marker for prostate cancer in man. Since reports of homologous proteins in animals other than primates have been lacking, the present investigation was carried out to identify any PSA-like protein in rats. Immunoblot analysis using a specific monoclonal anti-human PSA antibody detected a 32 kDa immunoreactive protein in the ventral lobe of the rat prostate, but not in other lobes or in other tissues. Positive immunostaining was observed only for the luminal surface of the glandular epithelium and the intraductal fluid in the ventral prostate. Sequence analysis of a cDNA for the rat PSA-like protein, cloned by immunoscreening of an expression cDNA library prepared from the ventral lobe, revealed identity to the rat submaxillary gland S3 kallikrein. Human PSA also belongs to the kallikrein family. Thus, this protein produced in the rat ventral prostate was suggested to be a possible counterpart of human PSA.

Amino Acid Sequence↗
PubMed2001

Immunological and PCR analyses for Borna disease virus in psychiatric patients and blood donors in Japan.

The involvement of Borna disease virus (BDV) in psychiatric diseases in humans remains controversial. T-cell memory response and seroprevalence of BDV in patients with psychiatric disorders and blood donors in Japan were evaluated collectively by Western blot (WB) analysis with inhibition test, electrochemiluminescence immunoassay, immunofluorescence assay, and T-cell proliferative response as well as detection of BDV p24 RNA in peripheral blood mononuclear cells (PBMCs). Positive proliferative responses to both BDV p40 and p24 proteins were detected in 9% of patients with mood disorders (4 of 45), 4% of schizophrenic patients (2 of 45), and 2% of blood donors (1 of 45). By WB analysis, the antibody to BDV p40 was detected only in 2% of patients with mood disorders (1 of 45). The BDV p24 antibody was detected in 2% of patients with mood disorders (1 of 45) and 9% of schizophrenic patients. (4 of 45) No plasma reacted with both BDV proteins. The finding of a lower seroprevalence than previously reported suggests the presence of false-positive cases in the previous report. BDV RNA was detected only in 2% of patients with mood disorders (1 of 45). In these three serological assays, T-cell responses, and PCR analysis, there was no significant difference in the prevalence among the three groups. However, we found three psychiatric patients who were positive for both BDV antibodies and T-cell proliferative responses and one patient who was positive for BDV RNA in PBMCs. These findings suggest the usefulness of the proliferative T-cell response and that certain individuals are infected with BDV or a BDV-related virus.

Adolescent↗
PubMed2001

Treatment with sheng-mai-san reduces myocardial infarct size through activation of protein kinase C and opening of mitochondrial KATP channel.

Sheng-mei-san (SMS), a traditional Chinese formulation comprising Radix Ginseng, Radix Ophiopogonis and Fructus Schisandrae, has long been used for more than 700 years for patients with coronary heart disease. We attempted to clarify 1) whether SMS reduces myocardial infarct size, and 2) whether the infarct size-reducing effect of SMS is related to activation of protein kinase C and the opening of the mitochondrial KATP channels in Japanese white rabbits without collateral circulation. The results indicate that three days treatment but not acute treatment with SMS reduces myocardial infarct size through activation of protein kinase C and opening of the mitochondrial KATP channels.

Analysis of Variance↗