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Biomedical subjects

S Nakano

Publications and source records attributed to S Nakano.

At least 73 records · Page 4Linked to original sources
PubMed2001

Japan-specific subtype of hepatitis C virus genotype 1b, J subtype, has relatively low pathogenicity.

The prognostic implication of viral genotype 1b for hepatitis C virus (HCV) infection has been controversial, possibly due to the pathogenetic heterogeneity of genotype 1b. We analyzed two newly delineated subtypes of HCV genotype 1b subtypes with respect to progression of liver disease. Patients with chronic HCV 1b infection (113 total, including 18 with chronic persistent hepatitis, 60 with chronic active hepatitis, 19 with cirrhosis, and 16 with hepatocellular carcinoma with cirrhosis) were studied to elucidate the factors associated with progression of liver disease. Factors evaluated included sex, age at diagnosis, blood transfusion history, and HCV genotype 1b subtype (W subtype or J subtype). W subtype was identified more often in association with chronic active hepatitis than with chronic persistent hepatitis (P = 0.0089), and more often in patients with cirrhosis than in those without (P = 0.0044). The age-, sex-, and transfusion history-adjusted odds ratios with respect to histological activity and presence of cirrhosis for W subtype compared to J subtype were 6.966 (1.856 to 26.145) and 6.397 (1.506 to 27.179), respectively. Age at diagnosis was the most important risk factor for predicting development of cirrhosis and carcinoma. In conclusion, the W subtype of HCV 1b is associated closely with histologically active disease and development of cirrhosis, whereas the Japan-specific J subtype has relatively low pathogenicity. HCV genotype 1b, therefore, is heterogeneous in its pathogenicity.

Adult↗
PubMed2001

[Bacterial contamination of salvaged blood in open heart surgery: is that an airborne contamination or a normal skin flora contamination?].

We investigated sources of bacterial contamination of intraoperative salvaged blood producted by autologous transfusions device (CS; CELL SAVER 5, Heamonetics Corp., Braintree, MA). Eleven patients undergone open heart surgeries including 2 emergency operations with a median sternotomy enrolled in this study. Blood samples were drawn from salvaged blood bags. Airborne contaminants (AB) were collected by a blood agar plate put besides the operation bed for 30 minutes. The median wounds samples were collected by a swab. Bacterial growth was detected in 81.8% of salvaged blood samples. Twenty-nine bacterium were isolated from CS, 72.4% of those were Staphylococci. 9.1% of sample was positive in wound swabs. Forty bacterium were isolated from plate cultures. 65% of them were Staphylococci. Staphylococcus epidermidis and coagulase negative Staphylococcus isolated both CS and AB in the 2 cases had the same identify codes, and incubated from several AB cultures. Corynebacterium sp. is also isolated from both CS and AB cultures in other 2 same cases. In 7 out of 8 cases (87.5%), from which Staphylococci isolated in CS, the Staphylococci were cultured from AB in not the same but the other cases. In conclusion, highly incidence of the identification in identical code of Staphylococci indicated that the main source of CS contamination was highly suspected to AB.

Air Microbiology↗
PubMed2001

Donepezil hydrochloride preserves regional cerebral blood flow in patients with Alzheimer's disease.

UNLABELLED: The aim of this SPECT study was to investigate the effects of donepezil on regional cerebral blood flow (rCBF) in patients with mild to moderate Alzheimer's disease (AD) using statistical parametric mapping. METHODS: rCBF was noninvasively measured using (99m)Tc-ethyl cysteinate dimer in 35 AD patients with a Mini-Mental State Examination score > 16 on initial evaluation. Baseline and follow-up SPECT studies with a mean interval of 12 mo were performed on these patients. We used the adjusted rCBF images in the relative flow distribution (normalization of global cerebral blood flow for each patient to 50 mL/100 g/min with proportional scaling) to compare these groups through statistical parametric mapping. RESULTS: In the follow-up study, the adjusted rCBF was significantly preserved in the right and left anterior cingulate gyri, right middle temporal gyrus, right inferior parietal lobules, and prefrontal cortex of donepezil-treated AD patients, compared with placebo-treated AD patients. CONCLUSION: Treatment with donepezil for 1 y appears to reduce the decline in rCBF, suggesting preservation of functional brain activity.

Aged↗
PubMed2000

Apoptosis and cell proliferation in esophageal sqamous cell carcinoma treated by chemotherapy.

The p53 gene is associated with G1 arrest during the cell cycle and with apoptosis. To evaluate the preoperative chemotherapeutic effect in esophageal squamous cell carcinoma, we retrospectively investigated the apoptotic index (AI) and Ki-67 labeling index (Ki-67LI) in relation to the expression of p53. Thirty patients with esophageal carcinoma who had received chemotherapy prior to surgery were examined using the terminal deoxynucleotidyl-transferase-mediated in-situ end-labeling (TUNEL) method for evaluating AI and immunohistochemical staining with anti Ki-67 and anti p53 antibody for evaluating Ki-67LI and p53 expression, respectively. The histological response rate of chemotherapy was 20.0%. A significant correlation between p53-negative expression and response to chemotherapy was found (P<0. 01). The AIs and Ki-67LIs in p53-negative tumors with ineffective responses to chemotherapy were significantly higher than those in p53-positive tumors with ineffective responses (P<0.05). The AIs and Ki-67LIs were significantly lower in p53-negative tumors with effective responses to chemotherapy than those in p53-negative tumors with ineffective responses (P<0.05 and P<0.01, respectively). Furthermore, significant correlations were found between AIs and Ki-67LIs in p53 negative tumors (r=0.60, P<0.05). In esophageal carcinoma, p53-negative tumors with highly proliferative cells might be susceptible to apoptosis induced by chemotherapy.

Adult↗
PubMed2000

Thermodynamics-structure relationship of single mismatches in RNA/DNA duplexes.

Thermodynamics of 66 RNA/DNA duplexes containing single mismatches were measured by UV melting methods. Stability enhancements for rG. dT mismatches were the largest of all mismatches examined here, while rU.dG mismatches were not as stable. The methyl group on C5 of thymine enhanced the stability by 0.12 approximately 0.53 kcal mol(-)(1) depending on the identity of adjacent Watson-Crick base pairs, whereas the 2'-hydroxyl group in ribouridine stabilized the duplex by approximately 0.6 kcal mol(-)(1) regardless of the adjacent base pairs. Stabilities induced by the methyl group in thymine, the 2'-hydroxyl group of ribouridine, and an nucleotide exchange at rG.dT and rU.dG mismatches were found to be independent of each other. The order for the mismatch stabilities is rG.dT >> rU. dG approximately rG.dG > rA.dG approximately rG.dA approximately rA. dC > rA.dA approximately rU.dT approximately rU.dC > rC.dA approximately rC.dT, although the identity of the adjacent base pairs slightly altered the order. The pH dependence stability and structural changes were suggested for the rA.dG but not for rG.dA mismatches. Comparisons of trinucleotide stabilities for G.T and G.U pairs in RNA, DNA, and RNA/DNA duplexes indicate that stable RNA/DNA mismatches exhibit a stability similar to RNA mismatches while unstable RNA/DNA mismatches show a stability similar to that of DNA mismatches. These results would be useful for the design of antisense oligonucleotides.

Base Composition↗
PubMed2000

High-frequency oscillations in human somatosensory evoked potentials are enhanced in school children.

High-frequency oscillations (HFOs) in the range of 300-900Hz have been shown to occur simultaneously with the primary response (N20) of the human somatosensory cortex following median nerve stimulation. We studied the effects of development on somatosensory evoked HFOs. Somatosensory evoked potentials (SEPs) were recorded with a filter set at 10-2000Hz following median nerve stimulation in 15 normal adult subjects and 15 normal children (6-12years). The HFOs were obtained by digitally filtering the wide-band SEPs (10-2000Hz) using a band-pass of 300-900Hz. In children, the HFOs were significantly higher in amplitude, longer in duration and larger in number of negative peaks than adult subjects. In addition, the interpeak latency of HFOs in children was longer than that of adult subjects. These results suggest that the HFOs are influenced by development.

Adult↗
PubMed2000

Structure and functional analysis of the human STAT3 gene promoter: alteration of chromatin structure as a possible mechanism for the upregulation in cisplatin-resistant cells.

STAT3 is involved in the signal transduction activated by various cytokines and growth factors. We found that the STAT3 gene is overexpressed in cisplatin-resistant cells. We isolated a genomic fragment containing the 5'-portion of the human STAT3 gene using a bubble PCR method. Using the bubble PCR product as a probe, one genomic clone was isolated. The nucleotide sequence of the first exon and the 1800 base pairs (bps) preceding it was determined. The promoter region of the human STAT3 gene is highly homologous to the corresponding region of the mouse STAT3 gene; several potential factor binding sites such as CRE/ATF, SBE, and GC boxes are also well conserved between human and mouse. A transient expression assay using the luciferase reporter gene showed that the sequence from -403 to +102 possesses maximal promoter activity, and transcription of the STAT3 gene was significantly higher in cisplatin-resistant cells than in parental cisplatin-sensitive cells. Deletion of the region between -261 and -167 resulted in significant loss of promoter activity in both parental and cisplatin-resistant cells. In vivo footprint analysis revealed several protein bindings; however, no significant differences were observed between drug-sensitive and drug-resistant cells. MNase digestion revealed that several open or active nucleosomes were only detected in cisplatin-resistant cells. These results suggest that STAT3 promoter function in a highly structured chromatin environment requires a complex interaction of several transcriptional factors.

Base Sequence↗
PubMed2000

Novel ring chromosome composed of X- and Y-derived material in a girl with manifestations of Ullrich-Turner syndrome.

We present a female infant who has a novel genetic variant of Ullrich-Turner syndrome. Chromosome analysis on amniotic fluid cells obtained because of ultrasound observation of nuchal thickening showed 45,X in all cells. The infant was born with a low posterior hairline and moderate edema over hands and feet. Postnatal chromosome analysis demonstrated two cell lines-47% of the metaphases were 45,X, but 53% had a ring chromosome in addition to the normal X. FISH studies using alpha satellite probes, an X-whole-chromosome-paint (WCP) probe, and a Y-cocktail probe determined that the ring was composed of both X and Y sequences. FISH studies also determined that the KAL locus was present on the ring, but that XIST was absent. PCR-based analysis of lymphocyte DNA documented that the ring contained sequences from both the short and the long arm of the Y chromosome. X-chromosome analysis using a panel of highly polymorphic markers indicated that the ring contained material derived only from Xp22.1 to Xp21.3. No Xq material was identified on the ring, and androgen receptor-based X-inactivation studies suggested that the intact X chromosome was not subject to random X inactivation.

Dosage Compensation, Genetic↗
PubMed2000

Species-specific bird functions in a forest-canopy food web.

Bird functions in a forest-canopy food web were evaluated by a large-scale field experiment using 'canopy' enclosures. By controlling the presence of two bird species, great tits (Parus major; foliage gleaner) and nuthatches (Sitta europaea; trunk gleaner), in the enclosures, their effect on predatory insects (ants), herbivorous insects (Lepidoptera larvae) and producers (oak trees) was quantified. Great tits reduced the density of Lepidoptera larvae and, indirectly, leaf damage, but had no impact on ants. Nuthatches decreased the density of ants but did not influence either Lepidoptera larvae or leaf damage. These results highlight species-specific functions of birds in the maintenance of forest ecosystems.

Animals↗
PubMed2000

A role for upstream RNA structure in facilitating the catalytic fold of the genomic hepatitis delta virus ribozyme.

Hepatitis delta virus (HDV) has a circular RNA genome that replicates by a double rolling-circle mechanism. The genomic and antigenomic versions of HDV contain a ribozyme that undergoes cis-cleavage, thereby processing the transcript into unit-length monomers. A genomic HDV transcript containing 30 nucleotides immediately upstream of the cleavage site was found to have attenuated self-cleavage. Structure mapping and site-directed mutagenesis revealed an inhibitory stretch consisting of upstream nucleotides -24 to -15 that forms a long-range pairing, termed Alt 1, with the 3' strand of P2 (P2(3')) located at the very 3'-end of the ribozyme. Two other alternative pairings were found, Alt 2, which involves upstream nucleotide-ribozyme interactions, and Alt 3, which involves ribozyme-ribozyme interactions. Self-cleavage was rescued 2700 to 20,000-fold by adding DNA oligomers, which sequester the -24/-15 inhibitory stretch in trans. Surprisingly, co-transcriptional self-cleavage occurs when the number of upstream nucleotides is increased to 54. Computer prediction and structure mapping support the existence of an unusually stable upstream hairpin involving nucleotides -54 to -18, termed P(-1)/L(-1), which sequesters the majority of the -24/-15 inhibitory stretch in cis. This hairpin is followed by a stretch of single-stranded pyrimidine-rich nucleotides, termed J(-1/1). Sequence comparison suggests that the P(-1)/L(-1)/J(-1/1) motif is conserved among known genomic HDV isolates, and that the J(-1/1) stretch is conserved among antigenomic HDV isolates. Lastly, the secondary structure of the Alt 1-containing ribozyme provides insight into possible folding intermediates of the ribozyme.

Algorithms↗
PubMed2000

Determination of grepafloxacin in plasma and urine by a simple and rapid high-performance liquid chromatographic method.

A rapid, specific, sensitive and economical method has been developed and validated for the determination of grepafloxacin in human plasma and urine. The assay consisted of reversed-phase HPLC with UV detection. Plasma proteins were removed by a fast and efficient procedure that has eliminated the need for costly extraction and evaporation. For the urine samples, the only required sample preparation was dilution. Separation was achieved on a reversed-phase TSK gel column with an isocratic mobile system. The method had a quantification limit of 0.05 microg/ml in plasma and 0.5 microg/ml in urine. The coefficients of variation (C.V.) were less than 4% for within- and between-day analyses. The method was successfully applied to a pharmacokinetic study, and was proved to be simple, fast and reproducible.

Anti-Infective Agents↗
PubMed2000

General acid-base catalysis in the mechanism of a hepatitis delta virus ribozyme.

Many protein enzymes use general acid-base catalysis as a way to increase reaction rates. The amino acid histidine is optimized for this function because it has a pK(a) (where K(a) is the acid dissociation constant) near physiological pH. The RNA enzyme (ribozyme) from hepatitis delta virus catalyzes self-cleavage of a phosphodiester bond. Reactivity-pH profiles in monovalent or divalent cations, as well as distance to the leaving-group oxygen, implicate cytosine 75 (C75) of the ribozyme as the general acid and ribozyme-bound hydrated metal hydroxide as the general base in the self-cleavage reaction. Moreover, C75 has a pK(a) perturbed to neutrality, making it "histidine-like." Anticooperative interaction is observed between protonated C75 and a metal ion, which serves to modulate the pK(a) of C75. General acid-base catalysis expands the catalytic repertoire of RNA and may provide improved rate acceleration.

Base Pairing↗
PubMed2000

The effect of retreatment with interferon-alpha on the incidence of hepatocellular carcinoma in patients with chronic hepatitis C.

BACKGROUND: Interferon (IFN) has been reported to have beneficial long term effects that reduce the occurrence of hepatocellular carcinoma (HCC), even in patients who do not have complete responses to IFN. The authors evaluated the effect of retreatment with IFN-alpha on the long term prognoses of those with incomplete responses to their initial IFN-alpha treatment. METHODS: Among 271 patients with incomplete responses to initial IFN-alpha treatment who had received sufficient dose and duration (a total dose of more than 350 megaunits administered over a period longer than 12 weeks) between October 1989 and September 1997, 63 patients received retreatment and 208 did not. The authors retrospectively compared the incidence of HCC between patients who received retreatment and those who did not. RESULTS: There were no significant differences in the clinical characteristics between these two groups. The cumulative incidence of HCC was significantly lower among the patients who had retreatment, and retreatment with IFN-alpha was the only factor that correlated with the lower incidence of HCC in multivariate analysis. The results were similar when the 12 patients with complete responses to retreatment were excluded from the analysis. CONCLUSIONS: Retreatment with IFN-alpha appeared to have the additional effect of suppressing the development of HCC in patients who had incomplete responses to the initial treatment, even when the hepatitis C virus was not cleared (i.e., a complete response was not achieved) with retreatment. Further prospective study is required.

Adolescent↗
PubMed2000

Suppression of malignant growth potentials of v-Src-transformed human gallbladder epithelial cells by adenovirus-mediated dominant negative H-Ras.

Although Src transformation of NIH3T3 mouse fibroblasts has been shown to be dependent on Ras function, the signaling mechanism whereby Src induces malignant transformation of human epithelial cells still remains unclear. In the present study, we analyzed the functional role of Ras, which acts downstream of Src in intracellular signaling, in the acquisition of fully neoplastic potentials by v-Src-transformed human gallbladder epithelial cells (HAG/src3-1) by infecting these cells with replication-defective adenovirus vector expressing dominant negative H-Ras (AdCARasY57). High efficiency of gene transduction was demonstrated with the adenovirus vector containing beta-gal gene insert (AdCALacZ). On infection with AdCARasY57, the activity of mitogen-activated protein (MAP) kinase, a major downstream event triggered by Ras, was markedly inhibited over 7 days, indicating that the inhibition of Ras function by AdCARasY57 remains active during this period. AdCARasY57 did not inhibit the monolayer growth of HAG-1 cells transfected with activated H-ras, but inhibited the HAG/src3-1 cells by 30%, as compared with cells infected with AdCALacZ as a control. This growth inhibition by AdCARasY57 was strengthened nearly twofold on surfaces coated with an antiadhesive polymer (poly 2-hydroxyethylmethacrylate) that can quantitate anchorage-independent growth, and was much more pronounced up to 95% when assayed in soft agar. The HAG/src3-1 cells transfected with beta-gal gene produced tumors in nude mice within 4 weeks after implantation, whereas cells infected with AdCARasY57 failed to form tumors during this period. These findings show that Ras function is essential for v-Src-induced anchorage-independent growth in vitro as well as tumorigenesis in vivo, and that mitogenic activity driven by v-Src is not solely dependent on MAP kinase pathway. Because anchorage-independent growth correlates with tumor growth in vivo as well as metastatic potential, targeting Ras would be potentially useful for the treatment of human tumors with elevated Src tyrosine kinase activity.

Adenoviridae↗