Search PubMed⌕ Search

Biomedical subjects

S Hirota

Publications and source records attributed to S Hirota.

At least 109 records · Page 6Linked to original sources
PubMed1998

Impaired expression of noncollagenous bone matrix protein mRNAs during fracture healing in ascorbic acid-deficient rats.

In scorbutic patients, fractures are slow to heal because of impaired collagen synthesis. To investigate the influence of impaired collagen synthesis on the differentiation and proliferation of osteogenic and chondrogenic cells, we examined the expression of genes encoding bone matrix proteins, including osteonectin (ON), osteopontin (OPN), osteocalcin (OC), and matrix Gla protein (MGP), as differentiation markers for osteogenic and chondrogenic cells during fracture healing in Osteogenic Disorder Shionogi (ODS) rats, which have a hereditary defect in the ability to synthesize ascorbic acid (Asc). In ODS rats without Asc supplementation, intramembranous ossification was completely inhibited. Although a few fibroblast-like cells expressing ON mRNA were observed, no OPN mRNA-expressing cells were detected. During endochondral ossification, a small amount of metachromatic staining cartilage appeared at the fracture site, but there was no provisional calcification zone in the cartilage. Chondrocytes expressed ON and MGP mRNAs, but not OPN mRNA. When Asc was given to these rats, callus formation was soon detected around the fracture site, while OPN mRNA was expressed by differentiated osteoblasts and hypertrophic chondrocytes. Our data indicate that impaired collagen synthesis due to Asc deficiency inhibited the increase of ON and MGP mRNA-expressing cells as well as the appearance of OPN mRNA-expressing cells. Since OPN is considered to play an important role in normal and pathological mineralization, lack of OPN mRNA expression accompanying impaired collagen synthesis may have a role in defective mineralization and delayed fracture healing in scurvy.

Animals↗
PubMed1998

Expression of bone matrix proteins mRNA during distraction osteogenesis.

Distraction osteogenesis is a recently advanced principle of bone lengthening in which a bone separated by osteotomy is subjected to slow progressive distraction using an external fixation device. Appropriate mechanical tension-stress is believed not to break the callus but rather to stimulate osteogenesis. To study the molecular features of this process, the expression and localization of the mRNAs encoding osteopontin (OPN), osteocalcin (OC), matrix Gla protein (MGP), osteonectin (ON), and collagen type I and I during distraction osteogenesis were examined by in situ hybridization and Northern blot analysis. The process can be divided into three distinct phases: the lag phase for 7 days between osteotomy and the beginning of distraction, the distraction phase for 21 days, and the consolidation phase for several weeks. The histologic and molecular events taking place during the lag phase were similar to those observed in fracture healing. The osteotomy site was surrounded by external callus consisting of hyaline cartilage. As distraction started at the rate of 0.25 mm/12 h, the cartilaginous callus was elongated, deformed, and eventually separated into proximal and distal segments. The chondrocytes were stretched along the tension vector and became fibroblast-like in shape. Although morphologically these cells were distinguishable from osteogenic cells, they expressed OPN, OC, and alkaline phosphatase mRNAs. As distraction advanced, the cartilaginous callus was progressively replaced by bony callus by endochondral ossification and thereafter new bone was formed directly by intramembranous ossification. OPN mRNA was detected in preosteoblasts and osteoblasts at the boundary between fibrous tissue and new bone. ON, MGP, and OC mRNAs appeared early in the differentiation stage. The variety of cell types expressing mRNA encoding bone matrix proteins in distraction osteogenesis was much greater than that detected in the embryonic bone formation and fracture healing process. Moreover, the levels of OPN, ON, MGP, and OC mRNA expression markedly increased during the distraction phase. These results suggested that mechanical tension-stress modulates cell shape and phenotype, and stimulates the expression of the mRNA for bone matrix proteins.

Animals↗
PubMed1998

Modulation of cancer chemotherapy by green tea.

Biochemical modulation has played an important role in the development of cancer chemotherapy. We have directed our attention to the intake of common beverages and investigated the effects of green tea and tea components on the antitumor activity of doxorubicin. We carried out the combined treatment of toxorubicin and green tea on Ehrlich ascites carcinoma tumor-bearing mice. The oral administration of green tea enhanced 2.5-fold the inhibitory effects of doxorubicin on tumor growth. The Doxorubicin concentration in the tumor was increased by the combination of green tea with doxorubicin. In contrast, the increase in doxorubicin concentration was not observed in normal tissues after green tea combination. Furthermore, the enhancement of antitumor activity of doxorubicin induced by green tea was observed in M5076 ovarian sarcoma, which has low sensitivity to doxorubicin. These results suggest that drinking green tea can encourage cancer chemotherapy and may improve the quality of life of clinical patients.

Animals↗
PubMed1998

Expression of the 150-kd oxygen-regulated protein in human breast cancer.

Tumor cells subjected to environmental stress, such as oxygen deprivation followed by reoxygenation, redirect biosynthetic pathways to express oxygen-regulated proteins (ORPs) and heat-shock proteins (HSPs). The 150-kd oxygen-regulated protein (ORP150) is a novel endoplasmic reticulum-associated polypeptide in the HSP70 family. In view of links between expression of HSPs/ORPs and tumor properties, especially tumor invasiveness and resistance to therapeutic regimens, expression of ORP150 in human breast cancers was examined. Western and Northern blotting demonstrated elevated expression of ORP150 in breast cancer, regardless of estrogen receptor status, compared with normal breast tissue. Immunohistochemical and in situ hybridization techniques revealed that infiltrating cancer cells in the stroma expressed ORP150 more strongly than large nests of cancer cells. Furthermore, pancreatic and thyroid carcinomas also displayed greater ORP150 expression. These results suggest that ORP150 is up-regulated in tumors and, in breast tumors, may be associated with tumor invasiveness.

Adenocarcinoma, Mucinous↗
PubMed1998

[Endoscopic findings of esophagitis in concurrent chemo-radiotherapy for lung cancer].

We performed esophageal endoscopy with concurrent chemo-radiotherapy for lung cancer in 19 patients. Endoscopical examination proved that seven patients (36.8%) had esophageal erosion or coating (grade 2), four patients (21.1%) had ulcer or bleeding (grade 3) confined to the radiation field, and only one patient (5.3%) had severe symptoms (WHO grade 3). There was a discrepancy between patients' symptoms and endoscopical findings. Endoscopically proven esophagitis, that is, erosion or coating (grade 2), and ulcer or bleeding (grade 3), was more frequent in the daily low-dose chemotherapy group (5/5) than in the full dose chemotherapy group (5/14) (p < 0.05). One patient with grade 3 endoscopial damage showed less recovery in spite of three months medication. In concurrent radiochemotherapy in which the radiation field includes the esophagus, careful attention should be given to radiation esophagitis, which may be underestimated when assessed on the basis of subjective symptoms alone. Therefore, endoscopy is recommended even if patients have few complaints, and once the esophageal ulcer is proven (grade 3), it should be closely followed up using endoscopy.

Adult↗
PubMed1998

[The long-term results of percutaneous isolated hepatic perfusion for patients with advanced hepatocellular carcinoma].

We studied the long-term outcome of percutaneous isolated hepatic perfusion (PIHP) for patients with hepatocellular carcinoma. This study included 31 patients with Stage IVA and 5 with IVB disease treated by PIHP until December, 1997. The mean age and tumor diameter were 55 and 7.7 cm, respectively. Twenty-two had portal vein invasion, 13 had hepatic vein invasion, and all patients had multiple intrahepatic metastases of more than 5 tumor foci. The PIHP with adriamycin or cisplatin was undertaken in a total of 50 treatments in these 36 patients. CR was observed in 6 and PR in 13 with an overall response rate of 59%, excluding 4 patients who were not evaluable. Five of 6 patients with CR remain free of disease at 7 to 54 months after the first treatment. The overall survival rate was 67% at 1 year and 32% at 5 years. The survival rates of Stage IVA patients (1-year = 71%, 5-year = 36%) were higher than Stage IVB patients (1-year = 20%, 5-year = 0%). The 5-year survival rates of patients with vascular invasion (Vp1-3 = 23%, Vv1-3 = 8%) were lower than those without it (Vp0 = 47%, Vv0 = 51%). These results indicated that PIHP achieved a 5-year survival rate of approximately 40% in patients with multiple advanced hepatocellular carcinoma in the absence of distant organ metastases and marked vascular invasion, and yielded complete long-term remission in some of these patients.

Antibiotics, Antineoplastic↗
PubMed1998

Increase of mast cells in the liver and lung may be associated with but not a cause of fibrosis: demonstration using mast cell-deficient Ws/Ws rats.

Tissue fibrosis is frequently associated with an increase of mast cells, and mast cells are regarded as playing a role in the induction of tissue fibrosis. We attempted to examine whether mast cells influenced the induction of fibrosis using Ws/Ws mast cell-deficient rats. The mast cell deficiency of Ws/Ws rats is due to a 12-base pair deletion of the c-kit gene. The activity of c-kit receptor tyrosine kinase is remarkably reduced in Ws/Ws rats. Liver fibrosis was induced by the repeated injections of pig serum, and lung fibrosis was induced by the instillation of bleomycin. Marked fibrosis in the liver and lung did occur in the Ws/Ws rats, and the magnitude of fibrosis was more severe in Ws/Ws rats than in control normal (+/+) rats. The mast cell increase was observed in the liver of +/+ and Ws/Ws rats and in the lung of +/+ rats. However, the number of mast cells in the liver of treated Ws/Ws rats with marked fibrosis was comparable to that observed in the liver of nontreated +/+ rats without fibrosis. Histamine content increased in the liver and lung of +/+ rats after the treatment, but it remained in low levels even after the treatment in Ws/Ws rats. Mast cells and histamine did not appear to play important roles in the induction of fibrosis. Thus, an increase in mast cell number and histamine content may be associated with but not a cause of fibrosis.

Animals↗
PubMed1998

[Basic study of MR-dacryocystography].

We developed MR-dacryocystography as a non-invasive, safer imaging technique for canaliculi, the nasolacrimal duct and lacrimal sac by dropping saline solution and diluted Gd-DTPA solution into the eye. The diluted Gd-DTPA solution was found to create no local irritation in the eyes of rabbits and normal volunteers. Lacrimal sacs and ducts were well visualized in all of 10 normal volunteers by using the saline solution or the diluted Gd-DTPA solution. Canaliculi were visualized in 4-7 cases on thin-slice axial images. MR-dacryocystography was suggested to be a useful screening examination for lacrimal outflow disorders.

Adult↗
PubMed1998

Possible relation of osteopontin to development of psammoma bodies in human papillary thyroid cancer.

BACKGROUND: Psammoma bodies are often observed in papillary carcinomas of the thyroid. Recently we reported that osteopontin (OPN) appears to play an important role in the development of psammoma bodies in meningiomas. Because the morphology and components of psammoma bodies in papillary carcinoma of the thyroid are similar to those of psammoma bodies in meningioma, we examined whether OPN was related to the psammoma bodies in papillary carcinoma of the thyroid. METHODS: Expression of OPN mRNA was examined by Northern blotting and in situ hybridization. Immunohistochemistry was performed to localize the deposition of OPN protein and to identify the type of OPN mRNA-expressing cells. RESULTS: The expression of OPN mRNA was detected in papillary thyroid carcinomas but not in normal thyroid tissue. Osteopontin mRNA-expressing cells were present around the psammoma bodies, and the localization of OPN protein was consistent with that of psammoma bodies. The OPN mRNA-expressing cells were identified as CD68-positive macrophages. CONCLUSION: Osteopontin produced by macrophages may play a significant role in the development of psammoma bodies in papillary carcinoma of the thyroid.

Blotting, Northern↗
PubMed1997

Resonance Raman, infrared, and EPR investigation on the binuclear site structure of the heme-copper ubiquinol oxidases from Acetobacter aceti: effect of the heme peripheral formyl group substitution.

Acetobacter aceti produces two different terminal ubiquinol oxidases (cytochromes a1 and o) depending on the culture conditions. Two types of oxidases share a common protein moiety but with different heme components at the binuclear center (heme A for cytochrome a1 and heme O for cytochrome o). We investigated the structure of the binuclear site of the two oxidases using resonance Raman, Fourier transform-infrared (FT-IR), and EPR spectroscopies to clarify the interactions of heme A formyl group with protein moiety. We found that the overall architecture and the electronic configuration at the binuclear center in the oxidized state seem to be well conserved irrespective of the heme peripheral group at position 8, except for the azide-inhibited state. In contrast, we observed great variations in the C-N stretching frequency and cyanide-binding affinity in the CN-reduced state, in addition to multiple C-O stretching bands in the CO-reduced state. Present and previous studies suggest that the conformational flexibility of the binuclear center in the reduced ligand-bound state may be a common feature among the heme-copper oxidase superfamily. In the CN-reduced state, a hydrogen bond network may be formed among the formyl group, water molecule(s), and the surrounding amino acid residue(s). This network may be very important to maintain proper orientations of the distal amino acid residues and/or the CuB1+ ion relative to the cyanide ion bound to the ferrous heme iron and could play a critical role for the high affinity in cyanide binding.

Acetobacter↗
PubMed1997

Protective effect of flavonoids on doxorubicin-induced cardiotoxicity.

We have examined the effect of alpha G-Rutin and luteolin on doxorubicin (DOX) toxicity in mice. In the heart, the lipid peroxide level, increased to 1.5 times of the normal level induced by DOX, decreased to the normal level after treatment with alpha G-Rutin or luteolin (i.p.). Glutathione peroxidase (GSHpx) activity, decreased to 73% of normal activity after DOX treatment, was shown to recover by the combined flavonoids. The lipid peroxide level in bone marrow cells increased to 5.9 times of the normal level by DOX treatment, whereas this level in the extra bone marrow cells did not change by treatment with DOX. The combination of alpha G-Rutin and luteolin with DOX significantly inhibited the DOX induced-increment of the lipid peroxide level in bone marrow cells. Flavonoids have also reduced the effect of DOX toxicity by oral administration. It is suggested that it is possible to reduce DOX toxicity by the intake of food including flavonoids. In NADPH-dependent lipid peroxidation, alpha G-Rutin and luteolin showed concentration-dependent inhibition. Therefore, we considered that the reduction effect of DOX toxicity by flavonoids was caused by antioxidative action and other effect of the flavonoids.

Administration, Oral↗
PubMed1997

Biodistribution of liposomes containing synthetic galactose-terminated diacylglyceryl-poly(ethyleneglycol)s.

We describe the synthesis of biodegradable poly(ethyleneglycol)-coupled galactolipids in which the galactose moiety is separated from a diacylglyceride lipid anchor by poly(ethylene glycol) chains of 10, 20 or 40 oxyethylene residues (PEG10/20/40). These Gal-PEG lipids (Gal-PEG-Lip) were incorporated in the bilayer of liposomes. The surface exposure of the galactose was investigated by aggregation experiments with ricinus communis agglutinin 120. Only the liposomes containing the PEG10 galactolipid aggregated with the lectin. Therefore liposomes were prepared containing Gal-PEG10-Lip and a trace amount of [3H]cholesteryl oleyl ether with an average diameter of approximately 100 nm and injected intravenously into rats. The Gal-PEG10-Lip liposomes were cleared from plasma with a T1/2 of 0.3 h. Identically sized and composed control liposomes without the Gal-PEG10-Lip had a T1/2 of approximately 12 h. The rapid plasma elimination of the Gal-PEG10-Lip liposomes could be attributed entirely to increased uptake by the liver amounting to more than 90% of injected dose. Uptake by the spleen was decreased to less than 1% of injected dose. A single injection of N-acetylgalactosamine 1 min prior to Gal-PEG-Lip liposome administration reduced the initial rate of plasma clearance to control levels. The increased liver uptake was almost entirely attributable to increased uptake by the Kupffer cells. Incorporation of PEG-DSPE in the Gal-PEG10-Lip liposomes only partially reversed the effect of the galactolipid with respect to liver and spleen uptake as well as intrahepatic distribution. These experiments demonstrate that liposome surface-exposed galactose residues, even if attached at the distal end of a poly(ethyleneglycol) chain anchored in the liposomal bilayer are effectively recognized by the galactose particle receptor on the Kupffer cells but fail to achieve significant targeting to the asialoglycoprotein receptor on the hepatocytes.

Acetylgalactosamine↗
PubMed1997

Emergence of osteoblast-like cells in a neoplastic human salivary cancer cell line after treatment with 22-oxa-1alpha, 25-dihydroxyvitamin D3.

A neoplastic clonal cell line, which was prepared by 5-azacytidine treatment of a neoplastic human salivary intercalated duct cell line, was cultivated in the presence of 22-oxa-1alpha, 25-dihydroxyvitamin D3 and 3 mM beta-glycerophosphate. Major alterations, such as expression of type I collagen and alkaline phosphatase as well as of human osteopontin and osteonectin, were observed in these cells with a phenotype similar to osteoblasts. In addition, formation of bone nodule was observed in the cultured cells. The tumors produced by transplantation into nude mice of the clonal cells were treated with 22-oxa-1alpha, 25-dihydroxyvitamin D3 and examined for tumor growth and morphology. Consequently, growth of the treated tumor was significantly suppressed. Moreover, it was found that bone formation was induced in the treated tumor, in which the tumor cells around bone formation expressed human osteopontin and osteonectin mRNA as could be detected by in situ hybridization. The above findings indicate that the emergence of osteoblast-like cells in the human salivary cancer cells occurs in the presence of 22-oxa-1alpha, 25-dihydroxyvitamin D3 and beta-glycerophosphate.

Animals↗
PubMed1997

Effects of administered route on tissue distribution and antitumor activity of polyethyleneglycol-coated liposomes containing adriamycin.

Tissue distribution, antitumor activity and side effects after intraperitoneal administration of polyethyleneglycol-coated liposomes containing adriamycin (PEG-LADR) were examined and compared to that after intravenous treatment. Plain liposomes (PLADR) and PEG-LADR appeared to maintain blood circulation by intraperitoneal injection and suggested usefulness in passive targeting. Because of the accumulation of ADR in the pancreas found after intraperitoneal treatment, this administered route of PLADR and PEG-LADR was expected to be useful as a method of targeting the pancreas. The side effects of ADR in the heart and liver were suppressed by the liposomalization and PEG-modification. The antitumor effect of ADR was increased by the liposomalization, and PEG-modification after intraperitoneal administration was superior to that after intravenous administration. The slowly disappearing pattern of PLADR and PEG-LADR from the abdominal cavity was similar. It is suggested that PLADR and PEG-LADR were absorbed intact from the abdominal cavity and transferred into the blood circulation.

Animals↗
PubMed1997

Technetium-99m methoxyisobutylisonitrile single-photon emission tomography in hepatocellular carcinoma.

Nine lesions in eight patients with hepatocellular carcinoma (HCC) were studied using single-photon emission tomography (SPET) and technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) to evaluate the pattern of uptake of 99mTc-MIBI in the lesions and the relation between the uptake pattern and the histopathology of HCC. All the lesions were diagnosed as HCC by percutaneous needle biopsy. Four of the nine lesions showed positive uptake of 99mTc-MIBI, while the other five showed negative uptake. All of the lesions which showed positive uptake were of the compact type. Of the five lesions that showed negative uptake, four were of the trabecular type while one was of the compact type. These results suggest that the patterns of 99mTc-MIBI accumulation in HCC are divided into positive and negative types and that these uptake patterns are associated with the tissue structure of HCC.

Aged↗
PubMed1997

Ultrastructural identification of the c-kit-expressing interstitial cells in the rat stomach: a comparison of control and Ws/Ws mutant rats.

Interstitial cells in the circular muscle layer of the stomach of the Ws/Ws mutant rat, which lacks c-kit-expressing cells, and its siblings have been studied by electron microscopy. In the sibling control rats, two types of interstitial cells are found lying in close association with nerve bundles. Cells of the first type are characterized by electron-dense cytoplasm containing abundant mitochondria, granular endoplasmic reticulum, and Golgi apparatus. Intermediate filaments are richly distributed throughout the perinuclear region and the cell processes. Caveolae, subsurface cisterns, and indistinct basal lamina are observed along the cell membrane. The most conspicuous feature of this cell type is the existence of many large gap junctions that interconnect with the same type of cell, smooth muscle cells, or cells of the second type. Cells of the second type show an ultrastructure similar to fibroblasts, viz., a well-developed Golgi apparatus and granular endoplasmic reticulum whose cisterns often show a dilated form and contain flocculent material. Unlike typical fibroblasts, however, cells of this type also form many gap junctions with cells of the first type and smooth muscle cells. Both types of cells are observed in close apposition to nerve varicosities. Since cells of the first type are absent in the Ws/Ws mutant rat, we concluded that they correspond to c-kit-expressing cells and to interstitial cells of Cajal.

Animals↗
PubMed1997

Possibility of defense against colorectal tumor by foamy cells.

To investigate the difference between colorectal adenocarcinomas with white spots (foamy cells) and those without white spots, clinically and histopathologically, we examined 112 cases of colorectal adenocarcinomas in this study. Thirty-two cases were diagnosed as submucosal invasive adenocarcinoma and 80 as advanced adenocarcinoma. They were classified into two groups: with white spots and without white spots. Submucosal tumors and squamous epithelial-origin tumors were excluded. In each case we looked for evidence of lymph node and liver metastases. Immunoreactive staining for macrophages, foamy cells, T cells, and B cells was also performed. We found a significant difference in the incidence of lymph node metastasis between the two groups with advanced carcinoma. White spots (foamy cells) were present at some distance from carcinoma cells. We conclude that foamy cells might have a beneficial role. From a histopathological viewpoint they can be considered a possible physical defense wall, an index of immune response activation. Clinically, it is important not to overlook any lesion.

Adenocarcinoma↗