Search PubMed⌕ Search

Biomedical subjects

K Nakano

Publications and source records attributed to K Nakano.

At least 235 records · Page 13Linked to original sources
PubMed1998

Extension of in vitro life-span of gamma-irradiated human embryo cells accompanied by chromosome instability.

We studied the effect of repeated irradiation with a low dose rate (about 0.0012 cGy per min) of 60Co gamma-rays on the in vitro life-span of human embryo (HE) cells. HE cells were cultured in an incubator that was set in a 60Co gamma-ray-irradiation room, and the irradiation was repeated throughout the life-span of the HE cells (for about 150 to 160 days) on every day base. During this period, the cells accumulated 106 to 123 cGy. The life-span of the irradiated cells prolonged 1.14 to 1.35 times when compared to that of non-irradiated cells. The incidence of cells with chromosome bridge and micronuclei significantly increased in the irradiated cells. Although the number of chromosomes gradually changed with repetition of culture in both non-irradiated and irradiated cells, the frequencies of aneuploid cells in irradiated cells were about two times higher than that in non-irradiated cells. These results indicate that repeated irradiation with a low dose of gamma-rays produces chromosome instability, and it may be a cause of numerical chromosome abnormalities and life-span extension of irradiated cells.

Aneuploidy↗
PubMed1998

Stimulation by histamine of TPA-dependent hepatocyte growth factor production in promyelocytic leukemia HL-60 cells.

Hepatocyte growth factor (HGF) is most likely a physiological hepatotrophic factor that triggers regeneration of the injured liver. Histamine may also be important in the pathophysiology of the injured liver. Previously we showed that histamine production was increased in liver macrophages of mice injected with CCI4, a well-known hepatotoxin. Therefore, it is likely that the biological actions of histamine in repairing processes of the injured liver are mediated by HGF. This study was aimed at examining the effects of histamine on production of HGF using, as a model, the human promyelocytic leukemia cells, HL-60. 12-o-Tetradecanoylphorbol-13-acetate (TPA) markedly stimulated HGF production and release from the cells; the maximal amount of HGF was released at a concentration of 3 ng/ml of TPA. Histamine significantly stimulated the TPA-induced HGF production and release in these cells, depending on incubation time and its dose. These actions of histamine were abrogated by a H2 receptor antagonist, ranitidine.

Dose-Response Relationship, Drug↗
PubMed1998

Ratio of motor nerve conduction velocity to F-wave conduction velocity in diabetic neuropathy.

OBJECTIVE: To investigate the usefulness of a new parameter, the ratio of motor nerve conduction velocity to F-wave conduction velocity (M/F ratio), for the differential diagnosis of diabetic neuropathy. RESEARCH DESIGN AND METHODS: Nerve conduction studies were conducted in 95 patients with diabetic neuropathy, 44 nondiabetic patients with peripheral neuropathy, and 24 normal control subjects. Nondiabetic patients with neuropathy were grouped by clinical diagnosis as follows: segmental demyelination (n = 15), axonal neuropathy (n = 11), alcoholic polyneuropathy (n = 4), and other polyneuropathy (n = 14). Motor nerve conduction velocity (MCV) of post-tibial nerves, sensory nerve conduction velocity (SCV) of sural nerves, and F-wave conduction velocity (FWCV) of post-tibial nerves were measured by standardized techniques. The M/F ratio was calculated from these measurements. RESULTS: The MCV and SCV of diabetic patients were significantly slower and the M/F ratio was significantly lower than those of normal subjects: MCV, 43.7 +/- 5.4 vs. 47.1 +/- 2.9 m/s, P < 0.001; SCV, 44.7 +/- 11.1 vs. 48.3 +/- 5.7 m/s, P < 0.05; M/F ratio, 0.84 +/- 0.09 vs. 0.90 +/- 0.06, P < 0.001. The FWCV of nondiabetic patients with neuropathy was significantly slower (40.0 +/- 6.3 vs. 48.3 +/- 4.0 m/s, P < 0.001) and the M/F ratio was significantly higher (1.04 +/- 0.12, P < 0.001) than that of normal subjects, respectively. Although MCV, SCV, and FWCV were correlated with age in normal control subjects, the M/F ratio was independent of age in the diabetic as well as the nondiabetic patients with neuropathy. CONCLUSIONS: Results suggest that the M/F ratio, which is influenced by the neuronal damages in the distal segment of peripheral nerves, is useful in the differential diagnosis of diabetic neuropathy.

Diabetic Neuropathies↗
PubMed1998

Preclinical antitumor efficacy of S-1: a new oral formulation of 5-fluorouracil on human tumor xenografts.

S-1 is a new oral formulation of 5-fluorouracil (5-FU) consisted of 1M tegafur, 0.4M 5-chloro-2,4-dihydroxypyridine that inhibits a degradation of 5-FU, and 1M potassium oxonate that regulates the phosphorylation of 5-FU in the gastrointestinal tract, and has shown excellent antitumor efficacy against various murine tumors in rodents, compared to the oral tegafur-based antitumor drug, UFT (1M tegafur plus 4M uracil), which is used clinically in Japan. To assess the possibility of clinically using S-1, we investigated the antitumor effect of S-1 on various human solid tumor xenografts in athymic rats and mice. In the nude rat system, S-1 was significantly effective against all 12 tumor xenografts tested when its minimum toxic dose (15 mg/kg) was administered for 14 days. Three tumors, stomach (H-81), colon (KM12C) and breast (H-31) markedly regressed in response to treatment with S-1 but not with UFT. The antitumor potency of S-1 was weak against human tumors xenografted into nude mice and likely similar to that of UFT. The reason of the discrepancy in the efficacy of S-1 between rats and mice was found to be that the 5-FU levels in the blood and tumor tissue of rats after oral administration of S-1 persisted much longer than in mice, and this prolonged maintenance of plasma 5-FU levels was significantly related to the potent antitumor activity of S-1. In conclusion, the results of this study suggested that based on its biological and pharmacokinetic characteristics, oral S-1 should be active against various human cancers.

Administration, Oral↗
PubMed1998

[Surgical treatment for prosthetic valve endocarditis].

From April 1993 to May 1997, 21 patients underwent surgical treatment for prosthetic valve endocarditis (PVE). There were 13 males and eight females aged from 46 to 79 years old (mean 62 years). There were four cases of early PVE (onset of PVE within 60 days from previous valve replacement), and 17 cases of late PVE (after 60 days). The predominant organisms were Staphylococcus epidermidis (eight cases), Staphylococcus aureus (two cases), MRSA (one case), streptococcal species (three cases), Candida (two cases), Pseudomonas cepacia (one case) and Enterococcus (one case). The predominant organisms were identified in 16 of 20 cases by preoperative blood culture, and in 11 of 20 cases by intraoperative tissue culture, and in 19 cases in all. There were four cases of preoperative cerebral complications, and three cases resurged. The hospital mortality rate was 24% (five patients). Reoperation was required in four patients for recurrence of PVE. Autopsy was performed in four of five patients. Intramyocardial abscess was detected in three patients. Earlier diagnosis and earlier surgical treatment could prevent emboli due to vegetations, which might cause catastrophic results, and could achieve better outcomes. Identification of the predominant organisms, especially from operative tissue cultures, is required.

Aged↗
PubMed1998

[A novel approach for cancer chemoprevention referred to as "gene-regulating chemoprevention"].

We examined the effect of butyrate on the expression of WAF1, a potent inhibitor of cyclin-dependent kinases, and its relation to growth arrest in a p53-mutated human colon cancer cell line WiDr. Five millimolar butyrate completely inhibited the growth of WiDr and caused G1-phase arrest. WAF1 mRNA was rapidly induced by treatment with 5.0 mM butyrate, and significant WAF1 protein induction was detected. Using several mutant WAF1 promoter fragments, we found that the butyrate responsive elements are specific Sp1 sites. These findings suggest that butyrate arrests the growth of WiDr by activating the WAF1 promoter through specific Sp1 sites in a p53-independent fashion. Based on our results, we propose a novel approach for cancer chemoprevention, which we term "gene-regulating chemoprevention". Our strategy is to activate the potent function of growth-inhibitory genes, which are preserved in cancer cells. WAF1 is a good candidate, because it rarely appears to be mutated in common human tumors, while the p53 gene is frequently mutated. Therefore the p53-independent activation of WAF1 by butyrate could be applied to the prevention of cancer when p53 is mutated.

Butyrates↗
PubMed1998

[MR diagnosis of internal derangement of the knee by SE T1 and GRE T2* weighted images: evaluation of 300 arthroscopically proven knees].

To evaluate whether or not the combination of sagittal and coronal spin-echo (SE) T1 and sagittal gradient echo (GRE) T2* weighted imaging is adequate to diagnose internal derangement of the knee, a study was done in 300 knees of 293 consecutive patients who underwent both MR imaging of the knee and arthroscopy. In prospective analysis, the MR imaging had an accuracy, sensitivity and specificity of more than 90% in the evaluation of medial meniscus (MM) and of 97% in the evaluation of anterior cruciate ligament (ACL). In the evaluation of lateral meniscus (LM), accuracy was 83%, sensitivity 76%, and specificity 88%. In a review of false-negative MR diagnoses (n = 42) of menisci, the most significant lesion was not in the meniscus but in the ACL in 32 knees (76%). Conservative treatment was selected in 25 knees (60%), rather than partial meniscectomy (n = 13) or meniscoresis (n = 4). There were 21 false-positive MR diagnoses of menisci even in retrospective analysis, and 17 of them (81%) had findings of tear in the posterior zone, which is known to be a difficult area for arthroscopic examination. The results were similar to those of other authors' with SE T1 and/or proton density and T2 weighted images. The combination of sagittal and coronal SE T1 and sagittal GRE T2* weighted images could be sufficient as a routine MR protocol for diagnosing the internal derangement of the knee.

Adolescent↗
PubMed1998

[Our challenge in Kagoshima University Hospital--development of more useful clinical laboratory].

In 1995, we newly developed a clinical laboratory system equipped with an expert system, which was named HIPOCLATES (Hospital Intelligent POwers of Clinical Laboratory Automation Technology with Expert System). Since this system includes an expert system, we have been able to support diagnostic and therapeutic procedure in clinics and begin developing a "zonal verification method" and "early-stage DIC diagnosis support system". The former is one of the individual quality control methods and we have attempted to develop a test assurance system in HIPOCLATES using this method. The latter system is to diagnosis DIC in the early phase. Here, we introduce the detail of our project using HIPOCLATES. Following the introduction HIPOCLATES, we attempted to develop a highly integrated system in physiological examinations, and succeeded in establishment PLATON (Physiological LAboratory TOtal Network system) in 1997. Thereafter, we planned a graphic reporting system named GALIREO (Graphic Assistant Laboratory Informational REport Operating system). In GALIREO, we attempted to connect the Department of Clinical Laboratory, Ultrasonic waves test room, Fiberscope test room, Department of Pathology and Surgical center by computer network. Developing these computer network system in our clinical laboratory we want to create electronic medical record linking with THINK (HIS in our hospital). We plan to make these expert system and electronic medical record available to clinical staff via a network to realize evidence-based medicine (EBM) and utilize these to support treatment and education.

Clinical Laboratory Information Systems↗
PubMed1997

Identification of Myo3, a second type-II myosin heavy chain in the fission yeast Schizosaccharomyces pombe.

We cloned the myo3+ gene of Schizosaccharomyces pombe which encodes a type-II myosin heavy chain. myo3 null cells showed a defect in cytokinesis under certain conditions. Overproduction of Myo3 also showed a defect in cytokinesis. Double mutant analysis indicated that Myo3 genetically interacts with Cdc8 tropomyosin and actin. Myo3 may be implicated in cytokinesis and stabilization of F-actin cables. Moreover, the function of Myo2 can be replaced by overexpressed Myo3. We observed a modest synthetic interaction between Myo2 and Myo3. Thus, Myo2 and Myo3 seem to cooperate in the formation of the F-actin ring in S. pombe.

Actins↗
PubMed1997

A polypeptide derived from mitochondrial dihydrolipoamide succinyltransferase is located on the plasma membrane in skeletal muscle.

Dihydrolipoamide succinyltransferase (DLST) is the core-enzyme of 2-oxoglutarate dehydrogenase complex which is located in mitochondria. In this study, several tissues from rat and human were immunostained with an affinity-purified anti-DLST antibody. Of the tissues examined, the plasma membrane of skeletal muscle was immunostained with the antibody besides mitochondria. Furthermore, subcellular fractionation analysis coupled with Western blotting demonstrated that the antigen of the anti-DLST antibody is distributed on the plasma membrane fraction in addition to the mitochondria fraction in skeletal muscle and that it is free from the complex. The molecular weight of the polypeptide bound to the plasma membrane was about 20 kilodaltons (kDa). The polypeptide was purified by immunoprecipitation and its N-terminal amino-acid sequence was determined. The amino-acid sequence exactly corresponded to a part of DLST. Northern blots revealed the presence of mRNA corresponding to the 20 kDa protein. We are the first to report that a mitochondrial protein is also present on the plasma membrane in skeletal muscle as well as in mitochondria.

Acyltransferases↗
PubMed1997

Histone deacetylase inhibitor activates the WAF1/Cip1 gene promoter through the Sp1 sites.

Treatment of cultured cells with trichostatin A (TSA), a specific histone deacetylase inhibitor, induces the histone hyperacetylation and modulates expression of some mammalian genes. We examined the effects of TSA on cell growth arrest, and its relation to expression of the WAF1/Cip1 gene, a potent inhibitor of cyclin-dependent kinases, in a p53-mutated human osteosarcoma cell line MG63. TSA at 500 ng/ml induced growth arrest at both G1 and G2/M phases, and the expressions of the WAF1/Cip1 mRNA and protein. We also examined the changes of acetylated isoforms of histone H4. Dose-response and kinetic analysis suggest a close correlation between the level of histone acetylation and the induction of the WAF1/Cip1 expressions. Using several mutant WAF1/Cip1 promoter fragments, we found that the TSA responsive elements are two Sp1 sites at -82 and -69 relative to the transcription start site. These findings indicate that TSA induces the WAF1/Cip1 promoter through the typical Sp1 sites, in a p53-independent fashion. Furthermore, the Sp1-luc plasmid, containing SV40 promoter-derived three consensus Sp1 binding sites, was markedly activated by TSA, compared to the mutant Sp1-luc plasmid. These results demonstrate that transcriptional activation through the Sp1 sites of the WAF1/Cip1 promoter by TSA coincides with induced hyperacetylation of histone H4.

Animals↗
PubMed1997

Stimulation of NGF production by tryptophan and its metabolites in cultured mouse astroglial cells.

Effects of various amino acids and tryptophan metabolites on the synthesis of nerve growth factor (NGF) in cultured mouse astroglial cells were evaluated. L-Tryptophan stimulated NGF production in a dose-dependent manner. Serotonin and quinolinic acid slightly increased NGF synthesis. L-Kynurenine had a marked stimulatory effect on NGF production at a dose of 10 microM. In contrast, kynurenic acid had no effect on the reaction. L-Glutamine, L-glutamic acid, L-phenylalanine and L-methionine produced no significant change in NGF synthesis. These results were discussed in relation to the treatment of Alzheimer's diseases.

Animals↗
PubMed1997

Long-term stress degenerates, but imipramine regenerates, noradrenergic axons in the rat cerebral cortex.

Exposed to a forced walking stress for 2 weeks, some rats became persistently inactive (depression-model rats), whereas others gradually recovered from exhaustion (spontaneous recovery rats). We also studied rats exposed to short-term stress, rats without stress, and the model rats treated with imipramine or saline. We examined the density of noradrenergic axons in the frontal cortex using retrograde labeling of the locus coeruleus with horseradish peroxidase injected into the cortex and immunohistochemical staining of cortical axons with dopamine beta-hydroxylase antiserum. The density was significantly lower in the depression-model rats, but tended to be higher in the recovery rats and short-term stressed rats. Chronic treatment with imipramine significantly increased the density in the model rats. There was also a correlation between the density of noradrenergic axons and the recovery rate of activity. Our results suggest that cortical noradrenergic degeneration is involved in the pathogenesis of depression.

Adrenergic Uptake Inhibitors↗
PubMed1997

Protein synthesis inhibitor transiently reduces neuronal death in the thalamus of spontaneously hypertensive rats following cortical infarction.

Using stroke-prone spontaneously hypertensive rats with permanent occlusion of the middle cerebral artery (MCA), we investigated whether the secondary thalamic degeneration following cortical infarction is related to apoptosis, and whether the protein synthesis inhibitor cycloheximide (CHX) ameliorates this degenerative process. TdT-mediated dUTP-biotin nick end labeling (TUNEL staining) revealed a distinct pattern of nuclear staining in many ventroposterior (VP) thalamic nucleus neurons on the lesioned side at 1 week after MCA occlusion. In rats with a single or continuous intraventricular infusion of CHX, starting just after brain ischemia, in the VP thalamic neurons were significantly more numerous than those in the thalamic nucleus of rats with vehicle infusion at 1 week after MCA occlusion. However, at 2 weeks after MCA occlusion, the numbers of VP thalamic neurons were similar in the CHX- and vehicle-treated groups. These findings suggest that the secondary thalamic degeneration following cortical infarction is an event reminiscent of apoptosis and that CHX prevents the secondary thalamic neuronal death transiently.

Animals↗
PubMed1997

Butyrate activates the WAF1/Cip1 gene promoter through Sp1 sites in a p53-negative human colon cancer cell line.

Butyrate is a well known colonic luminal short chain fatty acid, which arrests cell growth and induces differentiation in various cell types. We examined the effect of butyrate on the expression of WAF1/Cip1, a potent inhibitor of cyclin-dependent kinases, and its relation to growth arrest in a p53-mutated human colon cancer cell line WiDr. Five millimolar butyrate completely inhibited the growth of WiDr and caused G1-phase arrest. WAF1/Cip1 mRNA was rapidly induced within 3 h by treatment with 5.0 mM butyrate, and drastic WAF1/Cip1 protein induction was detected. Using several mutant WAF1/Cip1 promoter fragments, we found that the butyrate-responsive elements are two Sp1 sites at -82 and -69 relative to the transcription start site. We also found that a TATA element at -46 and two overlapping consensus Sp1 sites at -60 and -55 are essential for the basal promoter activity of WAF1/Cip1. These findings suggest that butyrate arrests the growth of WiDr by activating the WAF1/Cip1 promoter through specific Sp1 sites in a p53-independent fashion.

Base Sequence↗