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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↗
PubMed2003

Solid-solution reactions in As(V) sorption by schwertmannite.

Sorption behavior of As(V) by synthesized schwertmannite was examined under pH 3.3 as a function of As(V) concentration in the initial solution and interpreted in term of solid-solution reactions. Results showed that schwertmannite released 0.62 mmol of SO4(2-) for every 1 mmol of H2AsO4- and 0.24 mmol of OH- that has been sorbed. As(V) replaced SO4 up to half of the total SO4 in schwertmannite. The quantitative relationship among the three chemical compositions indicated that As(V)-sorbed schwertmannite would behave as a solid solution between the As(V) free schwertmannite and schwertmannite containing the maximum level of As(V). The equilibrium constant for the anion exchange in the solid-solution reaction estimated from the reacted solution chemistry depicts the As(V) content found in precipitates formed in acid mine drainage and laboratory experiments. Although schwertmannite is metastable with respect to goethite, the transformation is significantly inhibited by sorption of As(V). The solid-solution reactions also explain the stabilization of schwertmannite by sorption of As(V).

Adsorption↗
PubMed2003

Interaction between leukemic-cell VLA-4 and stromal fibronectin is a decisive factor for minimal residual disease of acute myelogenous leukemia.

Bone-marrow minimal residual disease (MRD) causes relapse after chemotherapy in patients with acute myelogenous leukemia (AML). We postulate that the drug resistance is induced by the attachment of very late antigen (VLA)-4 on leukemic cells to fibronectin on bone-marrow stromal cells. We found that VLA-4-positive cells acquired resistance to anoikis (loss of anchorage) or drug-induced apoptosis through the phosphatidylinositol-3-kinase (PI-3K)/AKT/Bcl-2 signaling pathway, which is activated by the interaction of VLA-4 and fibronectin. This resistance was negated by VLA-4-specific antibodies. In a mouse model of MRD, we achieved a 100% survival rate by combining VLA-4-specific antibodies and cytosine arabinoside (AraC), whereas AraC alone prolonged survival only slightly. In addition, overall survival at 5 years was 100% for 10 VLA-4-negative patients and 44.4% for 15 VLA-4-positive patients. Thus, the interaction between VLA-4 on leukemic cells and fibronectin on stromal cells may be crucial in bone marrow MRD and AML prognosis.

Animals↗
PubMed2003

Inhibition of type I procollagen production by tRNAVal CTE-HSP47 ribozyme.

BACKGROUND: Fibrosis characteristically occurs in the advanced stages of chronic inflammatory diseases, occasionally as the primary lesion, and frequently determines the disease prognosis. Fibrotic lesions consist mostly of collagen, and therefore it may be possible to prevent or treat fibrosis by inhibiting collagen production. Of the currently available therapeutic approaches, however, none is sufficiently effective and specific for inhibition of collagen. Heat shock protein 47 (HSP47) is a collagen-specific molecular chaperone that has been reported to play a pivotal role in secretion of procollagen molecules. Therefore, we have tried to suppress its function to inhibit these various types of collagen. METHODS: We have developed a novel type of ribozyme by ligating a hammerhead sequence to a tRNA(Val) promoter to facilitate displacing the ribozyme from nucleus to cytoplasm and to constitutive transport element, a binding motif of helicase which unwinds mRNA to render the target sequence on the mRNA accessible to the ribozyme. RESULTS: The ribozyme thus constructed showed strong activity to cleave HSP47 mRNA and suppress the secretion of type I procollagen in the human primary fibroblast. CONCLUSION: We suggest applicability of this ribozyme as a new modality for antifibrosis therapy.

Antisense Elements (Genetics)↗
PubMed2003

Jejunal varix with extrahepatic portal obstruction treated by embolization using interventional radiology: report of a case.

We report a case of relapsing jejunal varix with extrahepatic portal obstruction, which was successfully treated by embolization using interventional radiology. A 79-year-old woman suffered repeated episodes of tarry stools 2 years after undergoing jejunal resection for a jejunal varix. The bleeding point was inferred to be in the small intestine, and abdominal angiography revealed extrahepatic portal obstruction and the development of a jejunal varix around the hepaticojejunostomy. Because surgical obliteration of the varices or a shunt operation for portal decompression may have been very invasive due to severe adhesions, the jejunal varix was embolized with anhydrous ethanol and interlocking detachable coils. There were no changes in liver enzymes, the clearance rate of indocyanine green, or portal pressure, and there has been no sign of rebleeding for 13 months. Our experience shows that hemostasis can last, as long as the embolization can be done without aggravating portal hypertension. In conclusion, embolization using interventional radiology is a safe and useful method of treating intestinal varices.

Aged↗
PubMed2003

Two cases of hepatic artery interruption after hepatopancreatobiliary surgery treated by prostaglandin E(1) infusion via the superior mesenteric artery.

In two cases of hepatic arterial flow interruption after hepatopancreatic surgery, continuous PGE(1) infusion from the superior mesenteric artery (SMA) was applied to oxygenate the liver through the portal vein. Case 1 was a 69-year-old woman with a non-functioning islet cell tumor of the pancreas. She underwent pancreatic resection following hepatic arterial infusion of anticancer drugs. Serum alanine aminotransferase (ALT) was elevated to 5500 IU/l on postoperative day (POD) 2; angiography revealed complete celiac artery obstruction. Continuous PGE(1) was administered from SMA at a rate of 0.01 &mgr;g/kg/min for 7 days. Serum ALT was normalized within 2 weeks and the peak level of serum total bilirubin (T. Bil) was 4.5 mg/dl. Case 2 was a 66-year-old man suffering from metastatic liver cancer. Complete obstruction of the proper hepatic artery was noted at the time of liver resection after hepatic arterial chemotherapy. Serum ALT was elevated to 2930 IU/l on POD 1, and PGE(1) infusion from SMA was done for the succeeding 7 days. Necrotic area was so vast that serum T. Bil rose to 19 mg/dl. However, it decreased with time. Both cases required 3 months for necrotic liver shrinkage. Doppler ultrasonography revealed that PGE(1) infusion actually increased portal blood flow. In conclusion, based on the preceding experimental backgrounds and clinical experiences, continuous PGE(1) infusion via the SMA can be a useful measure to prevent severe liver damage after hepatic arterial flow interruption through portal blood oxygenation.

Journal Article↗
PubMed2003

Bacillus subtilis diacylglycerol kinase (DgkA) enhances efficient sporulation.

The sn-1,2-diacylglycerol kinase homologue gene, dgkA, is a sporulation gene indispensable for the maintenance of spore stability and viability in Bacillus subtilis. After 6 h of growth in resuspension medium, the endospore morphology of the dgkA mutant by standard phase-contrast microscopy was normal; however, after 9 h, the endospores appeared mostly dark by phase-contrast microscopy, suggesting a defect in the spores. Moreover, electron microscopic studies revealed an abnormal cortex structure in mutant endospores 6 h after the onset of sporulation, an indication of cortex degeneration. In addition, a significant decrease in the dipicolinic acid content of mutant spores was observed. We also found that dgkA is expressed mainly during the vegetative phase. It seems likely that either the DgkA produced during growth prepares the cell for an essential step in sporulation or the enzyme persists into sporulation and performs an essential function.

Bacillus subtilis↗
PubMed2003

[Biliary stenting for hepatobiliary-pancreatic disease].

Since 1990, expandable metallic stents (EMS) have been used in biliary obstruction, which are thinner than the plastic endoprosthesis and can secure sufficient biliary tract. EMS treatment improves the prognosis of patients with unresectable malignant biliary obstruction. Several types of stent are available, and each has its own characteristics of expansion, flexibility, visibility, shorting, and size variation. Those characteristics must be taken into account when selecting a stent for individual patients. In the case of hepatic hilar obstruction, more than one EMS is needed and the position of stent placement is important. For bile duct cancer, stents should be placed in a side-by-side or end-to-side position, because in these cases the tumor affects in-growth through the stent, so repeat biliary drainage and stenting would be needed. EMS treatment is sometimes used for stenosis of the portal vein, but stent placement is not effective for chronic stenosis with collateral circulation. With the development of stenting instruments, biliary endoprosthesis has become safer and easier. But we must not forget that stent treatment is a palliative treatment and consider the indications for and selection of the stent carefully.

Bile Duct Diseases↗
PubMed2002

Transgenic silkworms produce recombinant human type III procollagen in cocoons.

We describe the generation of transgenic silkworms that produce cocoons containing recombinant human collagen. A fusion cDNA was constructed encoding a protein that incorporated a human type III procollagen mini-chain with C-propeptide deleted, a fibroin light chain (L-chain), and an enhanced green fluorescent protein (EGFP). This cDNA was ligated downstream of the fibroin L-chain promoter and inserted into a piggyBac vector. Silkworm eggs were injected with the vectors, producing worms displaying EGFP fluorescence in their silk glands. The cocoons emitted EGFP fluorescence, indicating that the promoter and fibroin L-chain cDNAs directed the synthesized products to be secreted into cocoons. The presence of fusion proteins in cocoons was demonstrated by immunoblotting, collagenase-sensitivity tests, and amino acid sequencing. The fusion proteins from cocoons were purified to a single electrophoretic band. This study demonstrates the viability of transgenic silkworms as a tool for producing useful proteins in bulk.

Animals↗
PubMed2002

Ex vivo expansion of human umbilical cord hematopoietic progenitor cells using a coculture system with human telomerase catalytic subunit (hTERT)-transfected human stromal cells.

We developed a new human stromal cell line that could expand human hematopoietic progenitor/stem cells. Primary human bone marrow stromal cells were infected with retrovirus containing the human telomerase catalytic subunit (hTERT) gene, resulting in increased population doubling and the acquisition of cell immortalization. Characteristics of the hTERT-transduced stromal (hTERT-stromal) cells were identical with those of the primary stromal cells in terms of morphologic appearance and expression of surface antigens. Human cord blood (CB) CD34(+) cells were expanded by coculture with primary stromal or hTERT-stromal cells in the presence of stem cell factor, thrombopoietin, and Flk-2/Flt-3 ligand under serum-free condition. The degree of expansion of CD34(+) cells and total number of colony-forming units in culture (CFU-Cs) after 2 weeks' coculture with the hTERT-stromal cells were nearly the same as those after 2 weeks' coculture with primary stromal cells (CD34(+) cells, 118-fold +/- 8-fold versus 117-fold +/- 13-fold; CFU-Cs, 71-fold +/- 5-fold versus 67-fold +/- 5-fold of initial cell number). CB expansion on hTERT-stromal cells occurred at a similar rate through 7 weeks. In contrast, the rate of CB expansion on primary stromal cells had drastically declined at 7 weeks. In nonobese diabetic/severe combined immunodeficiency (SCID) mice, the degree of engraftment of SCID-repopulating cells that had been cocultured with hTERT-stromal cells for 4 weeks was significantly higher than that of precocultured CB cells. These results indicate that this hTERT-stromal cell line could be useful for ex vivo expansion of hematopoietic progenitor/stem cells and for analyzing the microenvironment of human bone marrow.

Animals↗
PubMed2002

Uptake of indocyanine green by hepatocytes under inflow occlusion of the liver.

BACKGROUND: It is not clear that hepatic venous backflow actually contributes to hepatic tissue oxygenation under inflow occlusion of the liver. In order to prove that substances delivered via the hepatic vein can be utilized and/or metabolized in hepatocytes during inflow occlusion, hepatic uptake in bile and excretion of indocyanine green (ICG) were investigated in pigs. MATERIALS AND METHODS: Animals were divided into two groups: an inflow occlusion (IO) group (N = 6) and a total hepatic vascular exclusion (THVE) group (N = 3) using a bypass. One milligram of ICG per kilogram body weight was administered at the beginning of blood flow occlusion, the retention rate in the blood (ICG R) measured, and the ICG in the hepatic tissue measured by near-infrared (NIR) spectroscopy. Furthermore, the ICG concentration was measured in bile excreted by intermittent perfusion of the liver. RESULTS: ICG R declined with time in both groups; however, ICG R in the IO group decreased much faster than in the THVE group. There were significant differences between the two groups after 30 min of occlusion (P < 0.05). ICG in the hepatic tissue could be detected as a peak at 805 nm 10 min after ICG injection, and the peak became steeper with time. On the other hand, ICG was not detected at all in the hepatic tissue after 180 min in the THVE group. ICG was excreted in the bile after 60 min under IO and increased with time. On the contrary, ICG was not excreted in the bile at all under THVE. There were significant differences between the two groups after 90 min (P < 0.05). CONCLUSION: These results indicate that ICG can be extracted in hepatocytes and excreted in bile under IO of the liver. Consequently, substances such as oxygen and drugs, which are delivered via the hepatic vein, can be utilized and/or metabolized in hepatocytes under IO.

Animals↗
PubMed2002

Induction of heat shock protein 47 synthesis by TGF-beta and IL-1 beta via enhancement of the heat shock element binding activity of heat shock transcription factor 1.

With most immunological reactions, tissue fibrosis, collagen overproduction caused by immune cytokines, is inevitably associated. Among the various immune cytokines, heat shock protein 47 (HSP47) is a procollagen-specific molecular chaperon and is essential for secretion of procollagen from cells. Induction of HSP47 by TGF-beta has been previously reported in rat skeletal myoblasts and mouse osteoblasts, but not in human diploid fibroblasts. As for IL-1beta, its effect on HSP47 has not been elucidated. In the present study, using human embryonic lung fibroblast cells, we first disclosed that both TGF-beta and IL-1beta induced HSP47 synthesis. We then revealed that the binding of the heat shock element (HSE) by heat shock transcription factor 1 (HSF1) was enhanced by both cytokines. We further demonstrated that trimer formation of HSF1, which is essential for its binding to HSE, was induced by these cytokines. The enhancement of HSP47 synthesis and their trimer formation of HSF1 were augmented by using a combination of both cytokines. Collectively, TGF- beta and IL-1beta were found to induce trimer formation of HSF1 which in turn bound to HSE of HSP47, resulting in the enhancement of HSP47 expression. Thus, HSP47 could well be a good candidate for molecular targeting in controlling tissue fibrosis, given that both principal fibrinogenetic cytokines (TGF-beta, IL-1beta) are commonly involved in its induction through HSF1 trimerization.

Cell Line↗
PubMed2002

Identification and characterization of the Bacillus subtilis D-glucarate/galactarate utilization operon ycbCDEFGHJ.

In the course of the Bacillus subtilis functional genomics project, an open reading frame called ycbG whose product is classified as a transcriptional regulatory protein with a helix-turn-helix motif in the putative D-glucarate/galactarate utilization operon (ycbCDEFGHJ) was initially screened as the gene disruptant that exhibits a defect that blocked the early stage of sporulation. However, the transcription of ycbCDEFG was extremely highly induced in response to nutrient exhaustion by the disruption of ycbG, but inactivation of the transcription from upstream ycbC in the ycbG mutant restored the sporulation efficiency, suggesting that the inappropriate over-production of the ycbCDEFG gene products inhibits efficient sporulation. We further analyzed the role of the ycbCDEFGHJ cluster and found that (i) a unit of ycbCDEFGHJ was induced by either D-glucarate or D-galactarate, and (ii) the cell growth was inhibited by the mutation of the ycbF and ycbH genes, that respectively encode the putative proteins, D-glucarate dehydratase and D-galactarate dehydratase on plates supplemented with D-glucarate and D-galactarate, respectively, as the sole carbon source. Our results indicate that the ycbCDEFGHJ genes are involved in the utilization of D-glucarate and D-galactarate in B. subtilis.

Bacillus subtilis↗
PubMed2002

Squalene-hopene cyclase: catalytic mechanism and substrate recognition.

Rapid progress on the catalytic mechanism and substrate recognition by squalene-hopene cyclase, which has occurred only in the last several years, is reported. A series of site-directed mutation experiments and some squalene analogues have provided deep insight into the polycyclization mechanism and catalytic sites in conjunction with the information from X-ray crystal data.

Amino Acid Sequence↗
PubMed2002

E1B-55K-deleted adenovirus expressing E1A-13S by AFP-enhancer/promoter is capable of highly specific replication in AFP-producing hepatocellular carcinoma and eradication of established tumor.

Here, we constructed a recombinant replication-competent adenovirus (rRCAd; AdAFPep/Rep) that expresses both E1A-13S driven by the alpha-fetoprotein (AFP) enhancer/promoter (AFPep) lacking any silencers in the 5'-flanking region of the AFP gene, and 55K-deleted E1B driven by the cytomegalovirus (CMV) promoter. We then examined the feasibility of gene therapy utilizing this virus for AFP-producing hepatocellular carcinoma (HCC). AdAFPep/Rep lysed all the AFP-producing HCC cell lines (HuH7, HepG2, PLC/PRF/5 (P5)) examined at a multiplicity of infection (MOI) as low as 0.1 and did not lyse primary human hepatocytes (Hc) at a MOI as high as 100, indicating that the rRCAd virus can lyse AFP-producing HCC cells with a higher specificity and potency than previously reported. Furthermore, this virus was capable of complete eradication of a preestablished HuH7-cell tumor by a single intratumoral injection of 10(8) plaque-forming units (pfu) of AdAFPep/Rep. Thus, AdAFPep/Rep may be applicable for clinical use.

Adenovirus E1A Proteins↗
PubMed2002

Management of pancreatic mass accompanying chronic pancreatitis.

We report two patients with focal, chronic pancreatitis that was diagnosed by dynamic computed tomography (CT) combined with intraoperative biopsy. In case 1, serum carbohydrate antigen (CA) 19-9 level rose to 160 U/ml. Abdominal ultrasonography, CT, and magnetic resonance imaging demonstrated a mass, of 4.5 cm in diameter, in the pancreatic head. On dynamic CT, the mass was enhanced similarly to the normal pancreatic parenchyma. In case 2, dynamic CT demonstrated a mass, of 3.0 cm in diameter, in the pancreatic head, which was enhanced similarly to the normal pancreatic parenchyma. From such characteristics of enhancement, both masses were suspected to be chronic pancreatitis rather than cancer, and the diagnosis was confirmed by intraoperative biopsy. Three years in case 1 and 2 years in case 2 have passed since their operations, and the size of each mass has not changed. With the use of dynamic CT combined with intraoperative biopsy, focal chronic pancreatitis could be diagnosed more accurately, and this may lead to a reduction in unnecessary pancreatic resection.

Biopsy↗
PubMed2002

Acute emphysematous cholecystitis preceded by symptoms of ileus: report of a case.

We herein describe a case of acute emphysematous cholecystitis in which the patient presented with symptoms of ileus. The patient was a 72-year-old man with no history of diabetes mellitus. He presented with epigastric pain, vomiting, and low-grade fever. Plain abdominal radiography showed some intestinal gas and niveau, and he was admitted to our hospital with a diagnosis of ileus. The next day, the abdominal pain increased and was accompanied by muscular defense. Plain radiography and computed tomography of the abdomen were carried out, and an emergency laparotomy was performed under a diagnosis of panperitonitis due to a perforation of the gallbladder caused by acute emphysematous cholecystitis. The patient made favorable progress after the operation and was discharged on postoperative day 14. Percutaneous transhepatic gallbladder drainage has been increasingly performed for the treatment of acute emphysematous cholecystitis. but when a perforation of the gallbladder is suspected, a laparotomy first should be considered.

Acute Disease↗