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Biomedical subjects

Y Sugano

Publications and source records attributed to Y Sugano.

At least 19 recordsLinked to original sources
PubMed2004

Features of bacterial cellulose synthesis in a mutant generated by disruption of the diguanylate cyclase 1 gene of Acetobacter xylinum BPR 2001.

The diguanylate cyclase 1 (DGC1) (dgc1) gene in Acetobacter xylinum BPR 2001--a bacterial cellulose (BC) producer--was cloned and sequenced, and a DGC1 gene-disrupted mutant, strain DD, was constructed. The production and structural characteristics of the BC formed by DD were compared with those of the parental strain BPR 2001. BC production by DD was almost the same as that by BPR 2001 in static cultivation and in shake flask cultivation. However, in a jar fermentor DD produced about 36% more BC than the parental strain. DD produced suspended particle materials that cannot aggregate owing to their random structural characteristics in static cultivation; more uniformly dispersed BC pellicles and smaller BC pellets are produced on average in a jar fermentor, as reflected by the higher BC production by DD than by the parental strain in a jar fermentor. Micrographs of BC produced by DD revealed that the width of cellulose ribbons assemblies decreased as a result of differences in the ultrastructure and mechanism of formation of BC between the two strains. These results reveal that disruption of the dgc1 gene, which catalyzes synthesis of c-di-GMP (an effector of BC synthase), is not fatal for BC synthesis, although it affects BC structure.

Cellulose↗
PubMed2003

Utilization of the buffering capacity of corn steep liquor in bacterial cellulose production by Acetobacter xylinum.

Acetobacter xylinum BPR2001 produces water-insoluble bacterial cellulose (BC). Using a pH sensor for the accurate control of pH, which is one of the most critical factors for efficient BC production, is difficult especially in a baffled shake-flask and an airlift reactor. The buffering capacity of corn steep liquor (CSL) was estimated by measuring beta (buffering capacity) values in advance and was used to maintain the pH within the optimal range during the production of BC. When CSL was added to either a shake-flask, a stirred-tank reactor or an airlift reactor, BC production was almost the same as that in cultivations where pH was controlled manually or by a pH sensor.

Bioreactors↗
PubMed2001

Acute rhabdomyolysis following administration of high-dose cyclophosphamide: case report.

Rhabdomyolysis is an unusual complication of hematopoietic stem cell transplantation (HSCT). Cyclophosphamide has been one of the key drugs in the most common preparative regimen for HSCT. We present here a rare case of acute rhabdomyolysis following administration of high-dose cyclophosphamide. A 47-year-old woman with adult T-cell leukemia in remission was treated with high-dose cyclophosphamide as a preparative regimen for allogeneic bone marrow transplantation. Nineteen hours later, general convulsions and acidosis suddenly occurred. Levels of serum creatine kinase (skeletal muscle type), myoglobin, and aldolase were markedly elevated to 32870 IU/l, 640 ng/ml, and 240.3 IU/l, respectively. Rhabdomyolysis caused by high-dose cyclophosphamide was diagnosed, and the preparative chemotherapy was discontinued. Subsequently, her muscular signs and symptoms improved, and the results of laboratory examinations returned to normal after 2 weeks. She had previously been treated with conventional doses of cyclophosphamide, doxorubicin, vincristine, and prednisolone without evidence of rhabdomyolysis. Acute rhabdomyolysis may be an adverse effect specific to high-dose cyclophosphamide therapy.

Acute Disease↗
PubMed2001

Bacterial cellulose production under oxygen-enriched air at different fructose concentrations in a 50-liter, internal-loop airlift reactor.

Bacterial cellulose (BC) production by Acetobacter xylinum subsp. sucrofermentans BPR2001 was carried out in a 50-1 internal-loop airlift reactor in air at an initial fructose concentration of 40 g/l. The BC production rate was 0.059 g/l per h. When oxygen-enriched air was supplied instead of air, the BC production rate increased to 0.093 g/l per h, and the BC yield was enhanced from 11% in air to 18%. When the initial fructose concentrations were varied from 30 to 70 g/l, the highest BC yield (35%) the highest production rate (0.22 g/l x per h), and the highest concentration of BC produced (10.4 g/l) were observed at 60-70 g/l fructose. From the carbon mass balance calculated at the final stage of cultivation, it was observed that enhanced BC production was reflected as a decrease in both CO2 evolution and the concentration of other unknown substances, suggesting the efficient utilization of energy for BC synthesis despite O2 limitation.

Acetobacter↗
PubMed2001

Efficient production of a heterologous peroxidase, DyP from Geotrichum candidum Dec 1, on solid-state culture of Aspergillus oryzae RD005.

The productivity of a peroxidase (DyP) originating from Geotrichum candidum Dec 1 was enhanced in the solid-state culture using Aspergillus oryzae RD005. When the humidity, water content, and temperature were adjusted to 60%, 50% and 27 degrees C, respectively, the productivity of DyP reached 5.3 g per kilogram wheat bran, which was used as the solid medium. The yield of 5.3 g per kg wheat bran corresponded to the yield of a 56 kg submerged culture. The productivity per gram carbon of the medium in the solid-state culture was 4.1-fold that in the submerged culture.

Journal Article↗
PubMed2000

Bacterial cellulose production by Acetobacter xylinum in a 50-L internal-loop airlift reactor.

Bacterial cellulose (BC) production was realized in a batch cultivation of Acetobacter xylinum subsp. sucrofermentans BPR2001 in a 50-L internal-loop airlift reactor. When the bacterium was cultivated with air supply, 3.8 g/L of BC was produced after 67 hours. When oxygen-enriched gas was supplied, the concentration of BC was doubled and the production rate of BC was 0.116 g/L. h, which was two times higher than that of air-supplied culture and comparable to that in a mechanically agitated stirred-tank fermentor. Bacterial cellulose produced by the airlift reactor formed a unique ellipse pellet (BC pellet), different from the fibrous form which was produced in an agitated stirred-tank fermentor. The BC-pellet suspension was demonstrated to have a higher volumetric oxygen transfer coefficient than the fibrous BC suspension in a 50-L internal-loop airlift reactor. The mixing time of BC-pellet suspension in the airlift reactor was also shorter than that in water.

Air↗
PubMed2000

Effect of molasses on the production and activity of dye-decolorizing peroxidase from Geotrichum candidum Dec1.

The production of dye-decolorizing peroxidase (DyP) was investigated by cultivating Geotrichum candidum Dec1 using molasses as a carbon source. Molasses at concentrations greater than 10 g.l(-1) was found to increase the decolorization activity of the culture broth toward dye, reactive blue 5 mainly because the amount of enzyme produced was enhanced. However, complete inhibition of DyP activity by molasses was observed at the concentration of 20 g.l(-1), indicating that the inhibitory effect of molasses on the culture broth activity to decolorize the dye was involved. When the culture broth was diluted 25 times, the dye-decolorizing activity was 7 times as much as that of non-diluted culture broth. The molasses fractions separated by gel chromatography (300-400 ml and 400-500 ml fractions) completely inhibited the purified DyP. On the basis of these results, we propose a scheme to control both positive and negative effects of molasses on the dye decolorization process.

Journal Article↗
PubMed2000

Removal of a high load of ammonia gas by a marine bacterium, Vibrio alginolyticus.

A newly isolated marine bacterium, Vibrio alginolyticus was used to remove a high load of ammonia gas. By a stepwise increase in ammonia supply over the concentration range of 120-2000 ppm (v/v), complete removal of ammonia was observed from the start of the experiment in a suspended culture of the bacterium in basal medium containing 3% NaCl. When cells were inoculated onto an inorganic packing material in a biofilter, and a high load of ammonia was introduced continuously under nonsterile conditions, the average percentage of gas removed exceeded 85% for a 61-d operation. The maximum removal capacity and the complete removal capacity were 22.8 g-N/kg-dry packing material/d and 18.6 g-N/kg-dry packing material/d, respectively, which were about four times larger than those obtained in nitrifying sludge inoculated onto the same packing material. During this operation, the nonsterile air supply had no adverse effect on the removability of ammonia by V. alginolyticus.

Journal Article↗
PubMed2000

Regulatory mechanisms for transforming growth factor beta as an autocrine inhibitor in human hepatocellular carcinoma: implications for roles of smads in its growth.

Transforming growth factor beta (TGF-beta) initiates signaling through heteromeric complexes of transmembrane type I and type II serine/threonine kinase receptors. Activated TGF-beta type I receptor phosphorylates receptor-regulated Smads (2 and 3). Antagonistic Smad 7 forms stable association with the activated TGF-beta type I receptor, blocking phosphorylation of receptor-regulated Smads. On the other hand, elevated serum concentration of TGF-beta along with resistance to its growth-inhibitory effect is commonly observed in human hepatocellular carcinoma (HCC) patients. In this study, we investigated the mechanisms of resistance to tumor-derived TGF-beta in human HCC and hepatoblastoma-derived cell lines, focusing on the roles of receptor-regulated Smads and antagonistic Smad 7. HuH-7 and HepG2 cells showed poor response to TGF-beta-mediated growth inhibition. Because neutralization of TGF-beta in the medium or blockage of signal transduction pathway by inductions of dominant negative Smad 2/3 resulted in a stimulation of cell growth, tumor-derived TGF-beta signal acts on cell growth negatively. However, Smad 7 induced by TGF-beta negatively regulated Smad 2 action and rendered most Smad 2 proteins in the cytoplasm. Taken together, these results indicate that endogenous TGF-beta-mediated induction of Smad 7 results in a higher "threshold" for the antiproliferative signals mediated by receptor-regulated Smads, and can be involved in reduced responsiveness to the cytokine in some human HCC cells.

Carcinoma, Hepatocellular↗
PubMed2000

Efficient heterologous expression in Aspergillus oryzae of a unique dye-decolorizing peroxidase, DyP, of Geotrichum candidum Dec 1.

Efficient expression of the dye-decolorizing peroxidase, DyP, from Geotrichum candidum Dec 1 in Aspergillus oryzae M-2-3 was achieved by fusing mature cDNA encoding dyp with the A. oryzae alpha-amylase promoter (amyB). The activity yield of the purified recombinant DyP (rDyP) was 42-fold compared with that of the purified native DyP from Dec 1. No exogenous heme was necessary for the expression of rDyP in A. oryzae. From the N-terminal amino acid sequence analyses of native DyP and rDyP, the absence of a histidine residue in both DyPs, which was considered to be important for heme binding of DyP, was confirmed. These results suggest that rDyP without a typical heme-binding region produced by A. oryzae exhibits a function similar to that of native DyP.

Amino Acid Sequence↗
PubMed1999

cDNA cloning and genetic analysis of a novel decolorizing enzyme, peroxidase gene dyp from Geotrichum candidum Dec 1.

A novel decolorizing peroxidase gene (dyp) was cloned from a cDNA library of a newly isolated strain of fungus Geotrichum candidum Dec 1. The open reading frame of 1494 nucleotides which corresponds to dyp predicts a primary translation product of 498 amino acids, M(r) 53,306. The deduced amino acid sequence of DyP does not contain the typical conserved motif which is characteristic of heme-containing peroxidases in the plant peroxidase superfamily. Comparison of the deduced amino acid sequence of DyP with that of a peroxidase from Polyporaceae sp. suggests that these proteins share highly homologous regions.

Journal Article↗
PubMed1999

[Evaluation of the efficacy and the cost-effectiveness of proton pump inhibitor-based dual and triple therapy regimens for H. pylori eradication in peptic ulcer disease].

To evaluate the efficacy and the cost-effectiveness of H. pylori eradication for the treatment of peptic ulcer disease, a randomized controlled trial to compare the efficacy of proton pump inhibitor-based dual and triple regimens was conducted. A decision analysis was also performed to assess H. pylori eradication compared to the conventional maintenance strategy. Two hundred and thirty-four peptic ulcer patients suffering from H. pylori infection were randomly treated with either omeprazole 20 mg bid + amoxicillin 500 mg qid + clarithromycin 400 mg bid (OAC) or with omeprazole 20 mg bid + clarithromycin 400 mg bid (OC) for 14 days. The eradication rate with OAC was 87.6% (92/105) (95% Confidence Interval (CI): 81-94%), which was significantly higher than that with OC (61.9% (60/97) (95% CI: 52-72%)) (p < 0.001, chi 2 test). Both regimens were safe and well tolerated. H. pylori eradication was more effective and less costly than conventional strategy in a long term perspective. OAC was more cost-effective than OC. In conclusion, H. pylori eradication is a cost-effective alternative to conventional treatment. We recommend 2 weeks triple regimen with omeprazole 20 mg bid + amoxicillin 500 mg qid + clarithromycin 400 mg bid (OAC) as a first-line treatment in all patients with peptic ulcers associated with H. pylori infection.

Amoxicillin↗
PubMed1999

Comparison of 1-week and 2-week triple therapy with omeprazole, amoxicillin, and clarithromycin in peptic ulcer patients with Helicobacter pylori infection: results of a randomized controlled trial.

This study was a comparison of 1-week and 2-week triple therapies with omeprazole, amoxicillin, and clarithromycin (OAC) in patients with peptic ulcer disease and Helicobacter pylori infection. A total of 147 peptic ulcer patients with H. pylori infection assessed by histology and culture were randomly treated with omeprazole 20mg bid + amoxicillin 1000mg bid + clarithromycin 400mg bid for either 1 week (OAC1w) or 2 weeks (OAC2w). Both groups then received omeprazole 20mg daily for 2 weeks followed by ranitidine 300mg daily for 4 weeks. Eradication of H. pylori was assessed by histology, culture, and the 13C-urea breath test (13C-UBT) at least 6 weeks after cessation of antimicrobial therapy. Intention-to-treat eradication rates were 78.2% (95%CI 69%-87%) with OAC1w and 88.4% (95%CI 81%-96%) with OAC2w. Per-protocol eradication rates were 86.0% (95%CI 78%-94%) with OAC1w, 97.0% (95%CI 93%-100%) with OAC2w. There was no significant difference in the eradication rates between OAC1w and OAC2w. Side effects were mild and self-limiting in both groups. In conclusion, both 1- and 2-week triple therapy with OAC are well tolerated and provide good eradication rates in peptic ulcer patients in Japan. The eradication rate of the 2-week regimen was higher than that of the 1-week regimen, but the difference was not statistically significant. Further studies including long-term economic considerations are required to determine the optimal duration of treatment.

Adolescent↗
PubMed1997

[Antigenic epitopes recognized by autoantibodies to calpastatin in patients with rheumatoid arthritis and their clinical significance].

We have previously described that novel autoantibodies to calpastatin (endogenous inhibitor for calcium-dependent neutral protease, calpain) were detected in patients with rheumatoid arthritis (RA) and other disorders. Since calpain is thought to mediate inflammatory process and cartilage destruction, autoantibodies to its inhibitor protein, calpastatin, may be involved in the pathogenic mechanism of rheumatoid arthritis. In the present study, we analyzed antigenic epitopes reactive with autoantibodies to calpastatin and their clinical correlation. cDNA encoding the C-terminal 178 amino acids of human calpastatin (RA-6) was digested by restriction enzymes and ligated in to pEX expression vectors. These recombinant plasmids were tranfected into E. coli POP2136 and screened by colony blots using RA sera containing anticalpastatin antibodies and a mouse monoclonal antibody. RA patient sera recognized the C-terminus of domain IV (epitope C1 ; aa. 647-673) and C-terminus of domain III (epitope C2 ; aa. 496-571), whereas the mouse monoclonal antibody recognized an entirely different region containing the calpain-binding site (epitope B2 ; aa. 572-625). To evaluate epitope reactivity of patient autoantibodies, 15 RA sera containing anti-calpastatin were reacted with epitope fusion proteins. In immunoblotting, most RA sera recognized either C1 or C2 epitopes (67% and 40%, respectively), and only one patient recognized both epitopes. B2 epitope a more progressed and sever state of arthritis than those not reacting with C1. These results suggests that anti-calpastatin antibodies may play a role in the pathogenic mechanisms of RA and their epitope reactivity may be important for disease progression.

Adult↗
PubMed1996

Mapping catechol-O-methyltransferase in vivo: initial studies with [18F]Ro41-0960.

Ro41-0960 is a potent, fluorine containing COMT inhibitor which has be en reported to cross the blood brain barrier and to inhibit COMT in the brain. It is structurally similar to Ro40-7592 which is currently undergoing clinical trials in Parkinson's disease. Positron emission tomographic (PET) studies in baboon using F-18 labeled Ro41-0960 demonstrated a negligible uptake in the brain both at tracer doses and with the addition of unlabeled drug (1.5 mg/kg) at all times through a 90 min experimental interval. The brain to plasma ratios of F-18 averaged about 0.025. Region of interest analysis of the brain tissue area suggests that most of F-18 in the brain was due to the blood in the brain and not the brain tissue itself. However, high uptake was observed in the kidneys and in other organs which are known to have high COMT activity. Studies in mice showed that at 30 min after injection of tracer, F-18 in kidneys was largely as unchanged [18F]Ro41-0960 and that it could be displaced with unlabeled Ro41-0960. The fact that the average brain to blood ratio for mice (n=12) was 0.04, and that similar HPLC metabolite patterns were observed for brain and blood, provides consistent evidence that nearly all the F-18 in the brain represents F-18 in the cerebral blood vessels. These studies raise the question of whether the central pharmacological effects of Ro41-0960 are due to its presence in the brain. They also provide the first example of a positron emitter labeled radiotracer for COMT, and provide initial encouraging evidence that [18F]Ro41-0960 may be used to examine COMT in peripheral organs in vivo.

Animals↗
PubMed1996

[LGL lymphoma].

We reported in this article two patients with large granular lymphocytic lymphoma (abbreviated as LGL lymphoma). One was the patient with LGL leukemia/lymphoma (patient 1) and other was the patient with NK-LGL lymphoma (patient 2). Because the gene of TCR delta was rearranged in the patient 1, the clonality of the LGL leukemia/lymphoma was confirmed. However, it is not determined yet whether the lineage of tumor cells is T cells or NK cells. The cytochemical features of the lymphoma cells of the patient 2 were studied. It was found that NK cell-derived lymphoma cells of the patient were positively stained with these two monoclonal antibodies that are reactive with T cell; one is anti-CD45RO (UCHL-1) and other is anti-CD3. Judging from the result, malignant NK-LGL cells in some patients are cytoplasmic CD3+ and UCHl-1+. It is emphasized that May-Grünwald-Giemsa stain of biopsied specimen of the lymphoma is required for making the diagnosis of LGL lymphoma.

Adult↗
PubMed1995

Binding of d-threo-[11C]methylphenidate to the dopamine transporter in vivo: insensitivity to synaptic dopamine.

The regional distribution of [11C]d-threo-methylphenidate in mouse brain was very similar to that of [3H]WIN 35,428 ((-)-2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane), and the two radioligands were displaced from striatum similarly after administration of the potent cocaine analog RTI-55 ((-)-2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane). However, while striatal [3H]WIN 35,428 increased between 5 and 30 min, striatal [11C]d-threo-methylphenidate halved. Thus [11C]d-threo-methylphenidate binds similarly to but more reversibly than [3H]WIN 35,428. The methyl ester of L-DOPA (L-3,4-dihydroxyphenylalanine; 200 mg/kg) plus benserazide plus clorgyline, which markedly elevates rat striatal extracellular dopamine (Wachtel and Abercrombie, 1994, J. Neurochem. 63, 108), decreased the mouse striatum-to-cerebellum ratio for [11C]d-threo-methylphenidate at 30 min by 13% (P < 0.05). In positron emission tomographic (PET) baboon studies [11C]d-threo-methylphenidate binding was insensitive to drugs expected to lower endogenous dopamine. These experiments suggest that normal synaptic dopamine does not compete for binding with [11C]d-threo-methylphenidate, and will not affect PET measures of dopamine transporter availability.

Animals↗