Biomedical subjects

Tsutomu Sato

Publications and source records attributed to Tsutomu Sato.

At least 19 recordsLinked to original sources

PubMed2025

Efficacy of Repeated Administration of Cultured Human CD34+ Cells Against Streptozotocin-Induced Diabetic Nephropathy in Rats.

To date, no clinical trial has investigated the potential of CD34+ cells to treat diabetic nephropathy. This study examined the efficacy of human CD34+ cells against diabetic nephropathy in rats. Rats were administered streptozotocin (STZ) intraperitoneally and divided into three groups: normal control, STZ control, and STZ plus cell therapy. The STZ-plus-cell-therapy group was administered human umbilical cord blood-derived CD34+ cells weekly for three weeks. At eight weeks, the rats' renal function, pathology, and transcriptome profiles were assessed. Although blood glucose levels did not differ between the STZ-administered groups, urinary albumin excretion was significantly lower at 6 weeks in the STZ-plus-cell-therapy group than in the STZ control group (p < 0.001). Serum creatinine levels tended to be higher in the STZ control group and lower in the STZ-plus-cell-therapy group. Cell therapy significantly improved mesangial expansion, interstitial fibrosis, peritubular capillary rarefaction, and glomerular macrophage infiltration compared with the STZ control (p < 0.0001). Kidney transcriptomics revealed significant upregulation of genes related to M2 macrophage markers, cell homing, and angiogenesis in the STZ-plus-cell-therapy group. In rats with STZ-induced diabetic nephropathy, human CD34+ cells ameliorated renal injury through their anti-inflammatory and pro-angiogenic effects.

Animals↗

PubMed2007

Cytological analysis of the mother cell death process during sporulation in Bacillus subtilis.

We have identified the following events during the late stage in the mother cell in Bacillus subtilis: spore detachment from the polar site of the mother cell, membrane rupture, cell wall collapse, and release of the free spore. The membrane rupture was followed by mother cell lysis. Moreover, we found that NucB, an extracellular nuclease, is involved in DNA degradation after mother cell lysis.

Bacillus subtilis↗

PubMed2006

Function analysis of steA homolog in Aspergillus oryzae.

The asexual ascomycete Aspergillus oryzae has an steA homolog in its genome. The steA homolog of A. oryzae was transcribed in the wild-type strain but steA disruption did not affect the phenotype of the disruptant strain. On the other hand, the steA-overexpressing strain showed the restriction of vegetative hyphal growth and conidiation, and the formation of balloon-shaped structures. The restriction of vegetative hyphal growth and conidiation were partially rescued by high osmolarity. In addition, the hyphal growth of the steA-overexpressing strain was inhibited by Calcofluor white, and the strain was found to be sensitive to cell-wall-degrading reagents. Increase of secretory cell-wall-degrading enzymes of the steA-overexpressing strain was detected. These results indicate that SteA regulates cell-wall-degrading enzymes and that the phenotypes of A. oryzae steA-overexpressing strain may be due to cell wall abnormalities. steA may participate in cell wall metabolism.

Aspergillus oryzae↗

PubMed2006

Caenorhabditis elegans mutants having altered preference of chemotaxis behavior during simultaneous presentation of two chemoattractants.

Upon presentation of two distinct chemoattractants such as sodium acetate and diacetyl simultaneously, the nematode Caenorhabditis elegans was preferentially attracted by one of these chemoattractants. We isolated two mutants having altered preference of chemotaxis behavior toward simultaneous presentation of sodium acetate and diacetyl. The chep-1(qr1) (CHEmosensory Preference) mutant preferred sodium acetate to diacetyl, while the chep-2(qr2) mutant preferred diacetyl to sodium acetate in simultaneous presentation of these chemoattractants. The chemotaxis behavior of chep-2(qr2) mutant in simultaneous presentation suggests a function of chep-2 gene products within the chemosensory informational integration pathway as well as in the chemosensory pathway.

Animals↗

PubMed2006

Ex vivo large-scale generation of human platelets from cord blood CD34+ cells.

In the present investigation, we generated platelets (PLTs) from cord blood (CB) CD34(+) cells using a three-phase culture system. We first cultured 500 CB CD34(+) cells on telomerase gene-transduced human stromal cells (hTERT stroma) in serum-free medium supplemented with stem cell factor (SCF), Flt-3/Flk-2 ligand (FL), and thrombopoietin (TPO) for 14 days. We then transferred the cells to hTERT stroma and cultured for another 14 days with fresh medium containing interleukin-11 (IL-11) in addition to the original cytokine cocktail. Subsequently, we cultured the cells in a liquid culture medium containing SCF, FL, TPO, and IL-11 for another 5 days to recover PLT fractions from the supernatant, which were then gel-filtered to purify the PLTs. The calculated yield of PLTs from 1.0 unit of CB (5 x 10(6) CD34(+) cells) was 1.26 x 10(11) - 1.68 x 10(11) PLTs. These numbers of PLTs are equivalent to 2.5-3.4 units of random donor-derived PLTs or 2/5-6/10 of single-apheresis PLTs. The CB-derived PLTs exhibited features quite similar to those from peripheral blood in morphology, as revealed by electron micrographs, and in function, as revealed by fibrinogen/ADP aggregation, with the appearance of P-selectin and activated glycoprotein IIb-IIIa antigens. Thus, this culture system may be applicable for large-scale generation of PLTs for future clinical use.

Antigens, CD34↗

PubMed2006

Size distribution and anthropogenic sources apportionment of airborne trace metals in Kanazawa, Japan.

Aerosol samples were collected from Kanazawa, Japan to examine the size distribution of 12 elements and to identify the major sources of anthropogenic elements. Key emission sources were identified and, concentrations contributed from individual sources were estimated as well. Concentrations of elements V, Ca, Cd, Fe, Ba, Mg, Mn, Pb, Sr, Zn, Co and Cu in aerosols were determined with ICP-MS. The results showed that Ca, Mg, Sr, Mn, Co and Fe were mainly associated with coarse particles (>2.1 microm), primarily from natural sources. In contrast, the elements Zn, Ba, Cd, V, Pb and Cu dominated in fine aerosol particles (<2.1 microm), implying that the anthropogenic origin is the dominant source. Results of the factor analysis on elements with high EF(Crust) values (>10) showed that emissions from waste combustion in incinerators, oil combustion (involving waste oil burning and oil combustion in both incinerators and electricity generation plants), as well as coal combustion in electricity generation plants were major contributors of anthropogenic metals in the ambient atmosphere in Kanazawa. Quantitatively estimated sum of mean concentrations of anthropogenic elements from the key sources were in good agreement with the observed values. Results of this study elucidate the need for making pollution control strategy in this area.

Air Pollutants↗

PubMed2006

Human herpesvirus-6 hepatitis associated with cyclosporine-A encephalitis after bone marrow transplantation for chronic myeloid leukemia.

A 31-year-old man referred to our hospital for treatment of his chronic myeloid leukemia (CML) in the first chronic phase by bone marrow transplantation. We pretreated him with cyclophosphamide and total body irradiation and bone marrow transplantation (BMT) was carried out. On day 31, the engraftment was confirmed and on day 52, acute graft versus host disease (GVHD) was observed. On day 189, he lost consciousness due to cyclosporine A-induced leukoencephalopathy and 375 mg cyclosporine A was changed to 100 mg prednisolone. On day 199, liver dysfunction (AST 410 IU/L, ALT 557 IU/L, gammaGTP 385 IU/L, ALP 363 IU/L, D-Bil 0.3 mg/dl) developed and a liver biopsy was performed. PCR analysis of DNA from the liver biopsy specimen was positive for HHV-6 and immunostaining using anti-HHV-6 and anti-HHV-6b antibodies showed positive staining in the cytosol of hepatocytes. No other viruses were found to induce hepatitis. From these results, he was diagnosed as having HHV-6 hepatitis and it was successfully treated with gancyclovir (GCV) administration.

Adult↗

PubMed2006

The forespore line of gene expression in Bacillus subtilis.

Endospore formation by Bacillus subtilis involves three differentiating cell types, the predivisional cell, the mother cell, and the forespore. Here we report the program of gene expression in the forespore, which is governed by the RNA polymerase sigma factors sigma(F) and sigma(G) and the DNA-binding proteins RsfA and SpoVT. The sigma(F) factor turns on about 48 genes, including the gene for RsfA, which represses a gene in the sigma(F) regulon, and the gene for sigma(G). The sigma(G) factor newly activates 81 genes, including the gene for SpoVT, which turns on (in nine cases) or stimulates (in 11 cases) the expression of 20 genes that had been turned on by sigma(G) and represses the expression of 27 others. The forespore line of gene expression consists of many genes that contribute to morphogenesis and to the resistance and germination properties of the spore but few that have metabolic functions. Comparative genomics reveals a core of genes in the sigma(F) and sigma(G) regulons that are widely conserved among endospore-forming species but are absent from closely related, but non-spore-forming Listeria spp. Two such partially conserved genes (ykoU and ykoV), which are members of the sigma(G) regulon, are shown to confer dry-heat resistance to dormant spores. The ykoV gene product, a homolog of the non-homologous end-joining protein Ku, is shown to associate with the nucleoid during germination. Extending earlier work on gene expression in the predivisional cell and the mother cell, we present an integrated overview of the entire program of sporulation gene expression.

Bacillus subtilis↗

PubMed2006

A phase I/II study of nedaplatin and 5-fluorouracil with concurrent radiotherapy in patients with esophageal cancer.

PURPOSE: To determine the recommended dose (RD) of cis-diammine-glycolatoplatinum (nedaplatin) when given concurrently with 5-FU and high dose radiation therapy in the treatment of esophageal cancer. The purpose of the phase II trial is to determine efficacy and further define the side effect profile. METHODS: Twenty-six patients with clinical stage I to IVA squamous cell carcinoma of the esophagus were enrolled in a non-surgical treatment comprised of a fixed dose of fluorouracil (400 mg/m2 administered as continuous intravenous infusion on days 1-5 and days 8-12) plus escalating doses of nedaplatin (40 mg/m2 in level 1, 50 mg/m2 in level 2, or 60 mg/m2 in level 3 on days 1 and 8), repeated twice every 3 weeks with concurrent radiotherapy (60 Gy). RESULTS: Between July 1998 and February 2004, a total of 26 patients entered this trial, all of whom were considered evaluable for toxicity assessment. In phase I of the study, 12 patients were treated in sequential cohorts of three to six patients per dose level. The maximum tolerated dose was reached at level 3 with two grade 4 neutropenia and one grade 4 thrombocytopenia. Thus, the recommended dosing schedule is level 2. Of the 20 patients treated at the RD level 2, including 6 patients of the RD phase I portion, 8 out of 20 patients (40%) had grade 3-4 neutropenia, 5 patients (25.0%) had grade 3-4 thrombocytopenia, 4 patients (20.0%) had grade 3 anemia and 4 patients (20.0%) had grade 3-4 esophagitis. Other toxicities were relatively mild and usually of grade 2 or less. Objective responses were noted in the 26 patients (overall response rate, 88.5%) including 11 (42.3%) complete remissions. The 1- and 3-year survival rates were 65.1 and 37.2%, respectively, with a median survival time of 21.2 months. CONCLUSIONS: The combination of nedaplatin and 5-FU with radiation is a feasible regimen that shows promising antitumor activity with an acceptable safety profile in patients with esophageal cancer.

Aged↗

PubMed2006

Superoxide stress decreases expression of srfA through inhibition of transcription of the comQXP quorum-sensing locus in Bacillus subtilis.

During the course of screening for competence-deficient mutants in the mutant collection constructed by the Japan Consortium of Bacillus Functional Genomics, a disruption mutant of sodA encoding superoxide dismutase was identified as a mutant with decreased transformation efficiency. In fact, in the sodA mutant we observed a severe decrease in the expression of srfA required for the development of genetic competence. Northern and primer extension analyses revealed inhibition of the transcription of the comQXP quorum-sensing locus in the sodA mutant, thereby preventing srfA expression. Furthermore, an excess amount of superoxide anion induced by the addition of paraquat also resulted in a decrease in comQXP transcription. Thus, it was concluded that high levels of superoxide are able to inhibit specifically the transcription of the comQXP operon. In support of this conclusion, the effect of added paraquat was significantly alleviated in a comX-independent srfA expression system.

Bacillus subtilis↗

PubMed2006

Amelioration of murine dextran sulfate sodium-induced colitis by ex vivo extracellular superoxide dismutase gene transfer.

BACKGROUND: Although the etiology of inflammatory bowel disease has not been fully clarified, reactive oxygen species is speculated to be involved. Extracellular superoxide dismutase (EC-SOD), an isozyme of SODs, is known to function mainly in body fluids. We investigated the efficacy of an ex vivo EC-SOD gene transfer into dextran sulfate sodium (DSS)-induced colitis mice. MATERIALS AND METHODS: Experimental colitis was induced by providing Balb/c mice with DSS in sterile distilled water provided as desired. The syngenic fibroblasts were obtained from Balb/c mice embryos and retrovirally transduced with the hEC-SOD gene. These engineered cells were confirmed to secrete EC-SOD in culture medium by enzyme-linked immunosorbent assay and were inoculated subcutaneously in the backs of DSS-treated mice. Mucosal injury of the colon was evaluated by the disease activity index (DAI: body weight, rectal bleeding, and stool consistency), grading of histologic disease severity, and levels of cytokine (tumor necrosis factor-alpha, interleukin-1beta) production. 8-Hydroxydeoxyguanosine (8-OHdG) levels in the mucosal tissue were assessed by immunohistochemical staining. Malondialdehyde (MDA) was measured using a colorimetric assay. RESULTS: A significant improvement was observed in DAI score and histologic severity as well as in mucosal tissue levels of inflammatory cytokines, 8-OHdG, and MDA of mice treated with the EC-SOD gene as compared with those without gene therapy, not only in a mild colitis model but also in a severe colitis model. Survival of treated mice in these models was significantly prolonged. CONCLUSIONS: Ex vivo transfer of the EC-SOD gene was feasible for treatment of DSS-induced colitis.

Animals↗

PubMed2006

The putative ABC transporter YheH/YheI is involved in the signalling pathway that activates KinA during sporulation initiation.

The primary kinases that control the supply of phosphate to the phosphorelay are KinA and KinB, although it is not yet known what type of signal(s) activates these kinases. Our systematic study of protein-protein interactions using yeast two-hybrid analysis revealed an interaction between KinA and YheH. YheH with the preceding gene product YheI is categorized as an ABC transporter. Overexpression of yheH/yheI in the kinB mutant resulted in a reduced sporulation efficiency. Moreover, reporter assays using Spo0A approximately P dependent promoters revealed that the deficiency in sporulation is probably due to a failure in the activation of Spo0A. Our results further suggest that the N-terminal region of YheH may play an important role in sensing the signal to be delivered to the C-terminally bound KinA.

ATP-Binding Cassette Transporters↗

PubMed2006

Regulatory loop between redox sensing of the NADH/NAD(+) ratio by Rex (YdiH) and oxidation of NADH by NADH dehydrogenase Ndh in Bacillus subtilis.

NADH dehydrogenase is a key component of the respiratory chain. It catalyzes the oxidation of NADH by transferring electrons to ubiquinone and establishes a proton motive force across the cell membrane. The yjlD (renamed ndh) gene of Bacillus subtilis is predicted to encode an enzyme similar to the NADH dehydrogenase II of Escherichia coli, encoded by the ndh gene. We have shown that the yjlC-ndh operon is negatively regulated by YdiH (renamed Rex), a homolog of Rex in Streptomyces coelicolor, and a redox-sensing transcriptional regulator that responds to the NADH/NAD(+) ratio. The ndh gene regulates expression of the yjlC-ndh operon, as indicated by the fact that mutation in ndh causes a higher NADH/NAD(+) ratio. An in vitro study showed that Rex binds to the downstream region of the yjlC-ndh promoter and that NAD(+) enhances the binding of Rex to the putative Rex-binding sites in the yjlC-ndh operon as well as in the cydABCD operon. These results indicated that Rex and Ndh together form a regulatory loop which functions to prevent a large fluctuation in the NADH/NAD(+) ratio in B. subtilis.

Bacillus subtilis↗

PubMed2006

Screening of periodontitis with salivary enzyme tests.

The purpose of this study was to determine the usefulness of salivary biochemical markers for the screening of periodontal disease and examine the agreement between the results of saliva enzyme tests and those of probing depth. The present study included a total of 187 subjects who underwent annual medical check-ups at the Comprehensive Health Care Center, Honjo, Saitama Prefecture, Japan. Periodontal pocket probing was performed with a WHO probe, and various enzymes and biochemical parameters in saliva were measured. For lactate dehydrogenase (LDH), the proportions of the five isoenzymes were calculated. To decide the cut-off point for each enzymatic activity, receiver operating characteristic curves (ROC curves) were constructed and the points of minimum difference between sensitivity and specificity were decided. Among the biochemical markers tested, salivary LDH level had the highest sensitivity and specificity (sensitivity 0.66, specificity 0.67), while salivary levels of aspartate aminotransferase (AST) and blood urea nitrogen (BUN) also had sensitivity and specificity above 0.60. Among the LDH isoenzymes, LDH4 and LDH5 dominated in whole saliva samples. Salivary LDH may be a feasible and useful parameter for the screening of periodontal disease, while salivary AST and BUN also appear to be potentially useful for this purpose.

Adult↗

PubMed2006

[Low-dose weekly paclitaxel therapy proved useful for a case of recurrent gastric cancer with clinically latent hepatic cirrhosis].

The patient was a 68-year-old-man who suffered from recurrent peritoneal gastric cancer. He was initially treated with TS-1 as an outpatient. However, his serum CEA level elevated in March 2004, and he complained of epigastric pain in June. A chest and abdominal CT revealed lung and local recurrence. He began weekly paclitaxel as second-line chemotherapy in September. Paclitaxel was infused once a week for two weeks as one cycle, at a dose of 60 mg because of the clinically latent hepatic cirrhosis. One month after the first infusion therapy, epigastric pain was greatly reduced. A CT scan showed the lung metastasis had disappeared and the size of the tumor around the anastomosis was reduced to 50% after 2 months. The toxic events were appetite loss (grade 2) and alopecia (grade 2).

Aged↗

PubMed2006

[Enteropathy-type T-cell lymphoma with CD8 and CD56 expression].

A 54-year-old male presented at a previous hospital with abdominal pain, where the patient was diagnosed as having abdominal and retroperitoneal lymphadenopathies by CT scan, then, he was referred to our hospital for further examination. Upper gastrointestinal endoscopy showed a tumor formation in the second portion of the duodenum, and there were medium sized atypical lymphocytes in biopsy specimens of the tumor. Since the atypical lymphocytes in the biopsy specimens were positive for CD3, CD8, CD56 and CD103 by immunostain, and had a rearrangement of the T-cell receptor 7-chain, the patient was diagnosed as having enteropathy-type T-cell lymphoma (ETL). Although ETL usually occurs as a complication of celiac disease, malabsorption and anti-gliadin antibodies, which are normally present in celiac disease, were not observed in this patient.

CD3 Complex↗

PubMed2006

[Clinical efficacy and safety of weekly paclitaxel therapy as second-line chemotherapy for patients with advanced and recurrent gastric cancer who were previously treated with TS-1 therapy].

The clinical efficacy and safety of weekly paclitaxel therapy were studied retrospectively in 17 patients with advanced and recurrent gastric cancer who had previously been treated with TS-1 therapy. The overall response rate was 0%, but MST was 495 days. The adverse effects observed were grade 3 leukopenia in 2 patients (11.8%) and grade 1 and 2 alopecia in 13 patients (76.5%). However, weekly paclitaxel therapy was performed for all outpatients. Weekly paclitaxel therapy could be useful and safe as second-line chemotherapy.

Aged↗

PubMed2006

[A case of recurrent biliary cystadenocarcinoma successfully treated with 5FU/CDDP systemic chemotherapy].

We report a case of biliary cystadenocarcinoma which recurred 41 months postoperatively. A 60-year-old woman was admitted for further examination of multiple metastatic tumors and a large amount of ascites. Systemic administration of 5FU and CDDP caused her CEA level to decrease gradually and abdominal computed tomography revealed considerable reduction of the metastatic tumors and ascites. Since her general condition had improved, chemotherapy was continued in the outpatient clinic.

Antineoplastic Combined Chemotherapy Protocols↗