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Biomedical subjects

K Nozawa

Publications and source records attributed to K Nozawa.

At least 19 recordsLinked to original sources
PubMed2005

Smart control of monodisperse Stöber silica particles: effect of reactant addition rate on growth process.

Control over the synthesis of monodisperse silica particles up to mesoscopic scale is generally made difficult due to intrinsic limitation to submicrometric dimensions and secondary nucleation in seeded experiments. To investigate this issue and overcome these difficulties, we have implemented single step processing by quantifying the effects of the progressive addition of a diluted tetraethyl orthosilicate solution in ethanol on the size and monodispersity of silica particles. Contrary to particles grown in seeded polymerization, monodisperse particles with size up to 2 microm were synthesized. Moreover, the particles exhibit a final diameter (d(f)), which varies with V(-1/3) over more than 2 orders of magnitude in rate of addition (V). On the basis of a kinetic study in the presence of addition showing that particle growth is limited by the diffusion of monomer species, we developed a diffusion-limited growth model to theoretically explain the observed d(f)(V) behavior and quantitatively retrieve the measured amplitude and exponent. Using a single parameter procedure, we can therefore predict and generate in the room temperature range, monodisperse particles of a targeted size by simply adjusting the rate of addition.

Journal Article↗
PubMed2003

Vascular anatomy for right colon lymphadenectomy.

Since the superior mesenteric artery (SMA) mostly originates on the left side of the superior mesenteric vein (SMV), the ileocolic artery (ICA) and the right colic artery (RCA) cross the SMV. Understanding the three-dimensional relation of these vessels is important for dissecting these arteries to their origin. Hence, we conducted a study of the vascular anatomy of the right colon in 27 cadavers. The RCA was separate from the SMA in eight cases (30%). The RCA passed the SMV either anteriorly (5 cases, 63%) or posteriorly (3 cases, 38%). In seven (88%) of these eight cases, the ICA was posterior to the SMV. The ICA was identified in all 27 cases, and passed the SMV anteriorly in nine cases (33%) and posteriorly in 18 cases (67%). Thus, the ICA and the RCA may pass on either side of the SMV. The surgeon must dissect the arteries with the SMV, being aware of both possibilities.

Aged↗
PubMed2003

Response to ADP-ribose by activation of TRPM2 in the CRI-G1 insulinoma cell line.

The response to intracellular ADP-ribose in the rat CRI-G1 insulinoma cell line was studied using a patch-clamp method. Dialysis of ADP-ribose into cells induced a response in a dose-dependent manner. The reversal potentials in various solutions showed that the ADP-ribose-gated channel was a Ca2+-permeable nonselective cation channel. In inside-out recordings, ADP-ribose and b-NAD induced responses in the same patch. The single-channel current-voltage relationships for ADP-ribose- and b-NAD-induced responses were almost identical, indicating that ADP-ribose and b-NAD activated the same channel. The physiological properties of the ADP-ribose-gated channel are similar to those we reported previously for the cloned transient receptor potential channel TRPM2. Moreover, RT-PCR analysis showed that TRPM2 was abundantly expressed in CRI-G1 cells, suggesting that the ADP-ribose-gated channel represents the native TRPM2 channel in CRI-G1 cells. These results suggest that ADP-ribose can be an endogenous modulator of Ca2+ influx through the TRPM2 channel into CRI-G1 cells.

Adenosine Diphosphate Ribose↗
PubMed2002

The role of posterior guidances under the altered anterior guidance.

In five subjects, bilateral condylar movement was assessed during lateral excursions with different tooth guidance angles without changing the intercuspal position. Statistical analysis of anova (P < 0.01) revealed that when the incisal path angle became steeper than the natural tooth guidance, distances of the non-working side condyle paths (centre of condyle) decreased significantly, while distances of the working side condyle paths (centre of condyle) remained unchanged. Directions of the working side condyle paths were random, while directions of the non-working side condyle paths remained stable. By analysing six points around the centre of the condyle, it was not possible to confirm any affect on the working side condyle movement by changing the tooth guidance angle. It was revealed that the non-working side condyle had an 'active' role during lateral excursions, and that the working side condyle moved as a result of mandibular movement that was changed because of a steepening of the incisal path angle during lateral excursions. This suggests the possibility that the working side condyle movements were affected 'passively' by altering the tooth guidance.

Adult↗
PubMed2001

Preferential blockade of CD8(+) T cell responses by administration of anti-CD137 ligand monoclonal antibody results in differential effect on development of murine acute and chronic graft-versus-host diseases.

We investigated the effect of CD137 costimulatory blockade in the development of murine acute and chronic graft-vs-host diseases (GVHD). The administration of anti-CD137 ligand (anti-CD137L) mAb at the time of GVHD induction ameliorated the lethality of acute GVHD, but enhanced IgE and anti-dsDNA IgG autoantibody production in chronic GVHD. The anti-CD137L mAb treatment efficiently inhibited donor CD8(+) T cell expansion and IFN-gamma expression by CD8(+) T cells in both GVHD models and CD8(+) T cell-mediated cytotoxicity against host-alloantigen in acute GVHD. However, a clear inhibition of donor CD4(+) T cell expansion and activation has not been observed. On the contrary, in chronic GVHD, the number of CD4(+) T cells producing IL-4 was enhanced by anti-CD137L mAb treatment. This suggests that the reduction of CD8(+) T cells producing IFN-gamma promotes Th2 cell differentiation and may result in exacerbation of chronic GVHD. Our results highlight the effective inactivation of CD8(+) T cells and the lesser effect on CD4(+) T cell inactivation by CD137 blockade. Intervention of the CD137 costimulatory pathway may be beneficial for some selected diseases in which CD8(+) T cells are major effector or pathogenic cells. Otherwise, a combinatorial approach will be required for intervention of CD4(+) T cell function.

Acute Disease↗
PubMed2001

Mechanism for the reduction of telomerase expression during muscle cell differentiation.

Telomerase, the reverse transcriptase that maintains telomere DNA, is usually undetectable in adult human tissues, but is positive in embryonic tissues and in cancers. However, in rodents, several organs of normal adult animals express substantial amounts of telomerase activity. To elucidate relevant control mechanisms operating on the tissue-specific expression of telomerase in rodents, we examined the transcriptional regulation of telomerase reverse transcriptase (mTERT) gene in muscle cell differentiation. Reverse transcriptase-polymerase chain reaction analysis showed that the reduction of telomerase activity was caused by the decrease of mTERT mRNA level during myogenesis. Transfections of mTERT promoter showed that the proximal 225-base pair region is the core promoter responsible for basal transcriptional activity and also participates in the reduced transcription after muscle differentiation. Electrophoretic mobility shift assays showed that this region contained the GC-boxes, which bind to Sp1 family proteins, and the E-box, which binds to c-Myc. Furthermore, DNA binding activities of Sp1, Sp3, and c-Myc were down-regulated during myogenesis. These data suggest that Sp1, Sp3, and c-Myc have critical roles of TERT transactivation in mouse, and the lack of these transcription factors cause down-regulation of mTERT gene expression in muscle cells differentiation.

3T3 Cells↗
PubMed2001

The increased interleukin-13 in patients with systemic lupus erythematosus: relations to other Th1-, Th2-related cytokines and clinical findings.

The levels of interleukin-13 (IL-13) in patients with systemic lupus erythematosus (SLE) were examined and related to other Th1-/Th2- related cytokines, clinical manifestations and other markers. Serum levels of IL-13 and other cytokines, soluble markers were measured by enzyme-linked immunosorbent assay (ELISA). Patients with active SLE had a significantly increased level of IL-13. Most patients with high levels of IL-13 had higher levels of IL-6, and some patients had high levels of gammaIFN. These patients were divided into two groups according to the patterns of these increased cytokines; one with a high level of only Th2 related cytokines (IL-13 or IL-6) and another with high levels of both Th2 related and Th1 related cytokines (gammaIFN or IL-2). The latter patients had high levels of soluble CD8 and CD23, and some of them had hemolytic anemia or pulmonary involvement, while most of the former patients had nephropathy. Thus, in SLE, the levels of IL-13 were increased, and the heterogeneity of increased Th2- and Th1-related cytokines was related to that of activation markers and clinical manifestations.

Adult↗
PubMed2000

In vitro expansion of mammalian telomere repeats by DNA polymerase alpha-primase.

Among the polymerases, DNA polymerase alpha-primase is involved in lagging strand DNA synthesis. A previous report indicated that DNA polymerase alpha-primase initiates primer RNA synthesis with purine bases on a single-stranded G-rich telomere repeat. In this study, we found that DNA polymerase alpha-primase precisely initiated with adenosine opposite the 3'-side thymidine in the G-rich telomere repeat 5'-(TTAGGG)(n)-3' under rATP-rich conditions. Then, DNA polymerase alpha-primase synthesized the nascent DNA fragments by extending the primer. It was remarkable that DNA polymerase alpha-primase further expanded the product DNA far beyond the length of the template DNA, as ladders of multiple hexanucleotides on polyacrylamide gel electrophoresis. Using an oligomer duplex 5'-A(GGGTTA)(5)-3'/5'-(TAACCC)(5)T-3' as a template-primer, we show that both the Klenow fragment of Escherichia coli DNA polymerase I and HIV reverse transcriptase could expand telomere DNA sequences as well, giving products greater than the size of the template DNA. The maximum product lengths with these polymerases were approximately 40-90 nt longer than the template length. Our data imply that DNA polymerases have an intrinsic activity to expand the hexanucleotide repeats of the telomere sequence by a slippage mechanism and that DNA polymerase alpha uses both the repeat DNA primers and the de novo RNA primers for expansion. On the other hand, a plasmid harboring a eukaryotic telomere repeat showed remarkable genetic instability in E.coli. The telomere repeats exhibited either expansions or deletions by multiple hexanucleotide repeats during culture for a number of generations, suggesting involvement of the slippage mechanism in the instability of telomeric DNA in vivo.

Animals↗
PubMed2000

Differential suppression of liver-specific genes in regenerating rat liver induced by extended hepatectomy.

BACKGROUND/AIMS: The function of the remnant liver is critical to survival of patients following an extended hepatectomy. The aim of this study was to determine whether proliferating hepatocytes in the remnant liver preserve the expression of liver-specific genes. METHODS: Using regenerating rat livers after 30, 70, and 90% partial hepatectomy (PHx), Northern blot analyses were performed with probes for seven liver-specific genes, six growth-related genes, two housekeeping genes and two acute phase reactant protein genes. RESULTS: During the regeneration after 90% PHx, the transcription of liver-specific genes showed three chronological patterns: transcription of serum albumin and cytochrome P450 2B decreased rapidly and reached a nadir at 6 to 24 h after PHx; those of apolipoprotein A-1, phosphoenolpyruvate carboxykinase and ornithine transcarbamylase decreased gradually until 24 to 48 h; those of UDP-glucuronosyltransferase and hepatocyte nuclear factor 4 did not show any changes until 48 h after PHx. In contrast, expression levels of all the growth-related genes and of housekeeping genes increased rapidly after PHx. After 30 and 70% PHx, expression of these genes changed in a similar manner to the 90% PHx case but to a lower extent. CONCLUSIONS: Based upon the fractions of Ki-67 positive hepatocytes in remnant livers, we could estimate the degree of expression of each liver-specific gene in the proliferating hepatocytes. The serum albumin gene was completely suppressed, while that encoding UDP-glucuronosyltransferase was not affected. These results correlated well with the patterns of albumin and bilirubin in rat serum after PHx. Other liver-specific genes were moderately suppressed in proliferating hepatocytes. Thus, expression of liver-specific gene is differentially suppressed when hepatocytes enter a proliferation cycle. Those that are unaffected may be indispensable for maintaining the homeostasis of the living organism.

Animals↗
PubMed2000

Antifungal substances against pathogenic fungi, talaroconvolutins, from talaromyces convolutus.

The dichloromethane extract of Talaromyces convolutus cultivated on barley exhibited antifungal activity against Candida albicans. In the course of a search for the active compounds, four new tetramic acid derivatives, talaroconvolutins A (1), B (2), C (3), and D (4), were isolated along with ZG-1494alpha (5), and mitorubrin derivatives. The structures of talaroconvolutins A-D (1-4) were established on the basis of spectroscopic and chemical investigations and chemical correlations. The antifungal activity of the talaroconvolutins against the pathogenic fungi Aspergillus fumigates, Aspergillus niger, C. albicans, and Cryptococcus neoformans was determined.

Antifungal Agents↗
PubMed2000

[Recent advances is surgical adjuvant chemotherapy for colorectal cancer].

To evaluate the significance of surgical adjuvant chemotherapy, randomized controlled trials (RCTs) of adjuvant chemotherapy after curative resection for colorectal cancer were reviewed. Several multi-drug systemic chemotherapies (MOF, MMC/FT, 5-FU, UFT p.o.) were useful as adjuvant treatment to improve survival or disease-free survival of patients with colorectal cancer. Moreover, a worldwide meta-analysis suggested that continuous intraportal 5-FU infusion improves survival. Combination chemotherapy trials utilizing 5-FU and levamisol (LEV) demonstrated a survival advantage in patients with high risk colon cancer. Recently, many RCTs have substantiated the benefits of treatment with 5-FU/Leucovorin (LV) and this treatment is widely used as adjuvant treatment for the patients with Dukes C resected colon cancer in Europe and the U.S.A. Now, with the increasing use of oral chemotherapy drugs, new trials comparing oral UFT/LV with intravenous 5-FU/LV are being implemented to investigate these drugs in terms of QOL, toxicity and cost. Furthermore, the new drug irinotecan (CPT-11) is now under investigation to see if it brings added efficacy to 5-FU/LV. In Japan, two major groups (N-SAS-CC and TAC-CR) are comparing surgery alone and UFT alone in patients with Dukes C colon and rectal cancer. From these results, surgical adjuvant chemotherapy seems to be effective in the treatment of patients with high risk colon cancer and those with rectal cancer.

Antineoplastic Combined Chemotherapy Protocols↗
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

Active form of human hepatocyte growth factor is excreted into bile after hepatobiliary resection.

BACKGROUND/AIMS: We have shown that hepatocyte growth factor is excreted into bile after hepatectomy in patients with biliary tract carcinoma. However, it is not certain whether hepatocyte growth factor in bile is an active molecule or degradation products. METHODS: Bile was obtained from five patients after hepatobiliary resection. Bile hepatocyte growth factor was purified on a heparin-Sepharose column and subjected to Western blotting. It was also tested for growth-stimulating activity with rat primary cultured hepatocytes. Biles from 50 patients who underwent various types of hepatobiliary resections were examined with respect to hepatocyte growth factor by an enzyme-linked immunosorbent assay. RESULTS: Upon Western blotting following nonreducing electrophoresis, the purified bile hepatocyte growth factor showed an 85 kDa peptide corresponding to native hepatocyte growth factor. Under reducing conditions, it showed bands of a-subunit at 69 kDa and beta-subunit at 34 kDa with corresponding monoclonal antibodies. The purified bile hepatocyte growth factor stimulated the [3H]thymidine incorporation into primary cultured hepatocytes with a specific activity comparable to recombinant human hepatocyte growth factor. It was observed that the levels of bile hepatocyte growth factor increased after the various types of hepatobiliary resections, including bile duct resection without hepatectomy. CONCLUSIONS: The human bile obtained after hepatobiliary resection contains active hepatocyte growth factor that can stimulate hepatocyte growth. Bile hepatocyte growth factor increased not only in hepatectomy but in bile duct resection. These results suggest that the biliary tract system may play an important role in the production of bile hepatocyte growth factor.

Adult↗
PubMed1999

Mitorubrin derivatives on ascomata of some talaromyces species of ascomycetous fungi

Two groups, producers of (+)- and (-)-mitorubrin derivatives, coexist in the series Lutei of the genus Talaromyces. The optical rotations of mitorubrins from T. emodensis, T. hachijoensis, and T. wortmannii var. sublevisporus, which produced mitorubrinol acetate (5), were all positive, whereas those from T. austrocalifornicus and T. convolutus, which produced mitorubrinal (3) and mitorubrinic acid (4), were all negative.

Journal Article↗
PubMed1999

Isolation of a new potent cytotoxic pigment along with indigotin from the pathogenic basidiomycetous fungus Schizophyllum commune.

An indole derivative, schizocommunin, was isolated along with indigotin (indigo), indirubin, isatin, and tryptanthrin, from the liquid culture medium in which a culture of Schizophyllum commune, isolated from the bronchus of a human patient with allergic bronchopulmonary mycosis, had been grown. The structure of schizocommunin was established by spectroscopic investigation. Schizocommunin showed the strong cytotoxicity against murine lymphoma cells. The assignments of the 1H- and 13C-NMR signals of indigotin were also listed.

Animals↗
PubMed1999

Apolipoprotein E polymorphism and plasma lipid levels in Native Mongolian sheep.

Apolipoprotein E (apoE) phenotypes were determined in 199 unrelated native sheep (Khalkhas line) of Central Mongolia, using a polyacrylamide gel isoelectric focusing-immunoblotting technique, and the plasma lipid levels in different phenotypes were assayed enzymatically. Twenty-eight phenotypes were identified in this sheep. In addition to all the previously detected seven apoE variants composing the phenotypes, four new variants were discovered, which were called E8, E9, E10, and E11. From the population data, these were found to be genetically controlled by four codominant alleles, designated APOE8, APOE9, APOE10, and APOE11, based on the same mode of inheritance as in the seven variants. These alleles were detected at a low frequency, in the range of 0.005 to 0.0126. The Khalkhas sheep differed most significantly from the Baruwal and Lampuchhre sheep of Nepal and the Vietnamese sheep with respect to the allele frequencies found in some Asian local sheep previously examined. Type 1/1 and/or 2/7 sheep had significantly higher plasma levels of total cholesterol and low-density lipoprotein cholesterol than type 7/7 sheep (P < 0.05 and/or P < 0.02).

Animals↗