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Biomedical subjects

S Hirota

Publications and source records attributed to S Hirota.

At least 145 records · Page 8Linked to original sources
PubMed1996

Interventricular septal dissection in a patient with an old myocardial infarction.

We observed an unusual case of interventricular septal wall dissection in a patient with a prior myocardial infarction. Echocardiography, magnetic resonance imaging, and left ventriculography revealed separation of the right-side and left-side walls of the interventricular septum with an accessory chamber between the two walls. Morphologic findings were consistent with interventricular septal dissection.

Diagnosis, Differential↗
PubMed1996

Ki-67 and p53 immunoreactive stain and early colorectal neoplasms.

The aim of this work was to conduct a histopathological study of the different pathways of colorectal tumorigenesis by using Ki-67 and p53 immunoreactive stains. Between 1987 and 1993, 14,023 patients were investigated by colonoscopy at Akita Red Cross Hospital and several affiliated hospitals. Five hundred and sixty-five cases of early colorectal neoplasms identified in this population were used in the present study. Specimens were cut in half: one half was cut along the vertical axis, the other half along the horizontal axis to analyze the structure of glands which opened to the surface. They were stained with hematoxylin-eosin, Ki-67 and p53 immunoreactive stains. macroscopically, early colorectal neoplasms were classified into two types: protruding type and depressed type. The protruding type was mainly composed of branching glands. In contrast, the depressed type was almost completely composed of straight glands which opened to the surface. The Ki-67 positive ratio was almost equal. However, the p53 positive ratio was significantly different in the protruding type and the depressed type. The results suggest the existence of at least two pathways of colorectal tumorigenesis: one with the process of branching structure and one without the process of branching structure. Furthermore, there were clinical and immunohistochemical indications that the depressed type invades into deeper layers more rapidly than does the protruding type.

Adolescent↗
PubMed1995

High incidence of ultraviolet-B-or chemical-carcinogen-induced skin tumours in mice lacking the xeroderma pigmentosum group A gene.

Xeroderma pigmentosum (XP) is an autosomal recessive disorder characterized by a high frequency of skin cancer on sun-exposed areas, and neurological complications. XP has a defect in the early step(s) of nucleotide-excision repair (NER) and consists of eight different genetic complementation groups (groups A-G and a variant). We established XPA (group-A XP) gene-deficient mice by gene targeting of mouse embryonic stem (ES) cells. The XPA-deficient mice showed neither obvious physical abnormalities nor pathological alterations, but were defective in NER and highly susceptible to ultraviolet-B- or 9,10-dimethyl-1,2-benz[a]anthracene-induced skin carcinogenesis. These findings provide in vivo evidence that the XPA protein protects mice from carcinogenesis initiated by ultraviolet or chemical carcinogen. The XPA-deficient mice may provide a good in vivo model to study the high incidence of skin carcinogenesis in group A XP patients.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1995

Characterization of c-kit-positive neurons in the dorsal root ganglion of mouse.

Previously, we showed that c-kit receptor tyrosine kinase is expressed by a subpopulation of dorsal root ganglion (DRG) neurons, and that the ligand for the c-kit receptor, stem cell factor (SCF), induces the neurite outgrowth and supports the survival of these neurons in culture [16]. However, it is unknown which class of DRG neurons express c-kit receptor and which factor regulates differentiation and survival of c-kit-positive neurons. In the present study, we attempted to characterize c-kit positive neurons in the mouse DRG. The c-kit-positive neurons were small or medium in size, and 44% of these neurons contained substance P. Central fibers of the c-kit-positive neurons terminated in laminae I and II of the gray matter of the spinal cord. These results suggest that c-kit-positive neurons in the DRG belong to a functional subpopulation. The c-kit receptor protein was presented on the membrane of processes and growth cones in neurons. When DRG cells of embryonic day 15.5 or 17.5 were cultured, the survival of c-kit-positive neurons was supported by SCF, nerve growth factor (NGF) or leukemia inhibitory factor. SCF and NGF synergistically supported the survival of c-kit-positive neurons at submaximal concentrations. c-kit-positive DRG neurons from neonatal mice survived without addition of any factor in culture, suggesting that the requirement for trophic support in c-kit-positive neurons changes during development.

Age Factors↗
PubMed1995

Infection with Nippostrongylus brasiliensis induces invasion of mast cell precursors from peripheral blood to small intestine.

Precursors of mast cells were defined as cells that formed mast-cell colonies in methylcellulose culture (CFU-mast). Mononuclear cells (MNC) were obtained from the bone marrow, peripheral blood, and small intestine of Ws/Ws rats with a small deletion at the tyrosine kinase domain of c-kit and of control normal (+/+) rats. In the culture containing concanavalin A-stimulated spleen cell conditioned medium (ConA-SCM) alone, the numbers of mast-cell colonies produced by Ws/Ws MNC were comparable with those of +/+ MNC. In the culture containing both ConA-SCM and stem cell factor (a ligand of c-kit), however, the numbers of mast-cell colonies produced by +/+ blood MNC were 107 times as great as that of Ws/Ws blood MNC. Using this culture condition, we investigated changes in concentration of CFU-mast in the marrow, blood, and intestine of +/+ rats after infection with Nippostrongylus brasiliensis (NB), which induced marked mast-cell accumulation in the small intestine. The concentration of CFU-mast in blood dropped to 21% of preinfection levels 1 week after the NB infection. In contrast, a sevenfold increase of CFU-mast occurred in the small intestine. The proportion of CFU-mast in S phase of the cell cycle remained at low levels in the marrow and blood after NB infection, but it increased significantly in the small intestine. The present result suggests that NB infection induces the invasion of CFU-mast into the intestine from blood and their subsequent proliferation in the tissue site.

Animals↗
PubMed1995

Osteoblasts are regulated by the cellular adhesion through ICAM-1 and VCAM-1.

The two major processes of bone metabolism--bone formation and resorption--are regulated by cellular interactions. Osteoblasts and osteoclasts play a significant role in bone metabolism, which is known to be regulated by local soluble factors and systemic hormones. Although bone is a heterogeneous tissue comprised of osteogenic and hematopoietic cells, cellular adhesion of osteoblasts and its regulation remains to be understood. We first demonstrate that cellular adhesion by which osteoblasts communicate with opposing cells in bone milieu is involved in the osteoblast activation: (a) purified human osteoblasts obtained from osteoarthritis patients expressed particular adhesion molecules, ICAM-1, VCAM-1, and LFA-3; (b) toe osteoblasts adhered to T cells which were used as representative adhesive partners, since T cells possess all the receptors to these adhesion molecules; (c) mRNA transcription and secretion of IL-1beta and IL-6 were induced in the osteoblasts by the cellular adhesion to T cells and they were reduced by interrupting the adhesion; (d) cross-linking of ICAM-1 and VCAM-1 on the osteoblasts induced IL-6 secretion from the osteoblasts. These results indicate that osteoblasts adhere to opposing cells through particular adhesion molecules on their surface and that the adhesion molecules on the osteoblasts not only function as glue with opposing partners but transduce activation signals that facilitate the production of bone-resorbing cytokines. We propose that cellular adhesion of osteoblasts as well as soluble factors is significant for the regulation of bone metabolism.

Base Sequence↗
PubMed1995

Clinical application of computed radiography in orthopedic surgery.

Since 1988, Fuji Computed Radiography (FCR) system (Fuji Medical Systems, Tokyo, Japan) has been used at Osaka Prefectural Hospital (Osaka, Japan) for all kinds of images. In this paper, we discuss the advantages and disadvantages of computed radiography (CR) images from the standpoint of an orthopedic surgeon. Contours, which can not be seen on conventional radiographs, are clearly visualized on the CR image. Adequate information for diagnosis can be obtained with a great reduction in x-ray exposure during the screening of scoliosis or congenital dislocation of hip joint. However, because the scale is reduced by one half in antero-posterior views of the bilateral hip joint, CR images are unsuitable for postoperative measurement of total hip arthroplasty (THA). Furthermore, caution is required because the clear zone after THA is emphasized on edge-enhanced CR image.

Absorptiometry, Photon↗
PubMed1995

Disturbed intestinal movement, bile reflux to the stomach, and deficiency of c-kit-expressing cells in Ws/Ws mutant rats.

BACKGROUND & AIMS: Interstitial cells of Cajal (ICCs) are believed to initiate the basic contractile activity of the gastrointestinal tract. Because ICCs in the intestine of mice express c-kit receptor tyrosine kinase and because rats are more commonly used than mice for pathophysiological investigations of the gastrointestinal tract, the number of the c-kit messenger RNA-expressing cells was compared with gastrointestinal movement in rats. METHODS: The c-kit messenger RNA-expressing cells were detected by in situ hybridization. The autonomous contraction of excised segments of the ileum was recorded. The function of the pyloric sphincter was evaluated by measuring the content of bile acids in the stomach. RESULTS: The c-kit messenger RNA-expressing cells were not detectable in the stomach of Ws/Ws mutant rats with a small deletion at the tyrosine kinase domain of c-kit, and the number of c-kit messenger RNA-expressing cells decreased to 7% that of normal control rats in the ileum of Ws/Ws rats. The contractile activity of the ileum was apparently impaired, and the content of bile acids in the stomach was significantly increased in Ws/Ws rats. CONCLUSIONS: The abnormalities in the ileal movement and pyloric sphincter function in Ws/Ws rats were attributable to the deficiency of c-kit messenger RNA-expressing cells.

Animals↗
PubMed1995

p53 immunoreactive stain and early colorectal adenocarcinomas.

565 cases of early colorectal adenocarcinomas were used in this study to examine mechanisms of carcinogenesis. Specimens were paraffin embedded and histological sections were stained with haematoxylin-eosin and p53. Macroscopically, early colorectal adenocarcinomas could be classified into two types: protruding and depressed. The former were composed of branching glands, while the latter were composed of straight glands which opened to the surface. The p53 positive ratio was similar for protruding tumours but was higher in depressed submucosal invasive adenocarcinomas than in depressed intramucosal adenocarcinomas. These results raise the possibility of at least two pathways for colorectal carcinogenesis, adenoma-carcinoma lesions and de novo carcinoma lesions.

Adenocarcinoma↗
PubMed1995

Clinical pilot study on high-dose intraarterial chemotherapy with direct hemoperfusion under hepatic venous isolation in patients with advanced hepatocellular carcinoma.

BACKGROUND: We recently developed a novel system of direct hemoperfusion under hepatic venous isolation in an attempt to achieve high-dose intraarterial chemotherapy for patients with malignant liver tumors. We report here the results of treatment of these patients with advanced hepatocellular carcinoma. METHODS: Adriamycin (100 to 150 mg/m2) was administered into the hepatic artery of 15 patients, under conditions of extracorporeal drug elimination by direct hemoperfusion under hepatic venous isolation. Hepatic venous isolation was accomplished mainly by the double-balloon technique with an occlusion catheter and a balloon catheter. The isolated hepatic venous blood was filtered by direct hemoperfusion and pumped to the left axillary vein. RESULTS: During 5 minutes of adriamycin infusion, the mean drug extraction ratios of the direct hemoperfusion filters were 91% +/- 9% (mean +/- SD). The amount of drug removed by the system was 26.4% +/- 16.0% of the amount of drug administered. Two patients died, one of necrotizing pancreatitis and the other of hepatic arterial thrombosis. Both deaths were related directly to the hepatic arterial catheter. Other side effects included hemolysis related to the system of hemoperfusion (87%), chemical hepatitis (80%), leukopenia less than 3000/mm3 (67%), alopecia (33%), and nausea and vomiting (20%). Nine (64%) of 14 evaluable patients had objective tumor responses, with a median duration of response of 6.2 months. CONCLUSIONS: This approach offers an effective therapeutic option for patients with advanced hepatocellular carcinoma.

Adult↗
PubMed1995

Simultaneous dietary supplementation of sodium cholate and beta-carotene markedly enhances accumulation of beta-carotene in mice.

This study evaluated whether simultaneous supplementation of sodium cholate and beta-carotene to a diet enhanced the accumulation of beta-carotene in mice. For 2 wk, male ICR mice were fed either a basal diet or a diet containing Dunaliella-bardawil beta-carotene 50 mg/100g that was or was not supplemented with sodium cholate (0.25 g/100 g). The concentrations of beta-carotene in liver and plasma were approximately 5 and 10 times higher, respectively. In the mice fed the beta-carotene diet with sodium cholate than in those fed the beta-carotene diet without sodium cholate. Beta-carotene was not detectable in the liver or plasma of mice fed either basal diet. The concentrations of vitamin E in the plasma and liver of mice fed either beta-carotene diet or the basal diet with sodium cholate were significantly lower than in those fed the basal diet. In a second study, mice were fed a diet containing 50 mg/100 g synthetic beta-carotene supplemented with various concentrations of sodium cholate (0, 0.05, 0.1, 0.25, 0.5 g/100 g) for 2 wk. The concentrations of beta-carotene and vitamin E in plasma, liver and bone marrow cells were higher in mice fed the beta-carotene diet supplemented with 0.05 g/100 g of sodium cholate than in those fed the unsupplemented diet. These findings show that simultaneous supplementation of sodium cholate and beta-carotene to a diet markedly enhances the accumulation of beta-carotene. This dietary protocol may be useful to introduce a high amount of beta-carotene in the tissue of mice in a short period of time.

Animals↗
PubMed1995

Expression of bone-related protein messenger RNA in human meningiomas: possible involvement of osteopontin in development of psammoma bodies.

Meningiomas often contain concentric calcified foci, referred to as psammoma bodies. Since calcium phosphate deposits in both psammoma bodies and bone tissues, we examined whether messenger (m) RNA of bone-related extracellular matrix proteins and bone morphogenetic proteins (BMP) were expressed in human meningioma tissues. Northern blotting demonstrated the expression of osteopontin (OPN), matrix Gla protein (MGP), osteonectin (ON) and BMP-4 mRNA but not bone sialoprotein, osteocalcin and BMP-2 mRNA. In situ hybridization revealed that most OPN mRNA-expressing cells were located around the psammoma bodies in meningothelial whorls. Moreover, combination of in situ hybridization and immunohistochemistry on serial sections showed that the OPN mRNA-expressing cells were CD68-positive, suggesting they were macrophages. Immunohistochemistry with anti-OPN antibody and von Kossa staining on the adjacent section showed that the deposition site of OPN protein was consistent with that of calcium phosphate. Neither MGP nor ON mRNA expression appeared to correlate with the calcification. The present result suggests that OPN produced by CD68-positive macrophages may play a significant role for development of psammoma bodies in meningiomas.

Antibodies, Monoclonal↗
PubMed1995

Possible role of osteopontin in deposition of calcium phosphate in human pilomatricomas.

Human pilomatricomas are benign epidermal appendage tumors composed of hair matrix-like basaloid cells and keratinized remnant cells referred to as shadow cells. Deposition of calcium phosphate usually occurs in the shadow cell nests. Because osteopontin is believed to be involved in the deposition of calcium phosphate in bones, we asked whether osteopontin messenger RNA also is expressed in pilomatricomas. Using Northern blotting and in situ hybridization we detected osteopontin messenger RNA in pilomatricoma tissues but not in normal skin tissue. By the combination of in situ hybridization and immunohistochemistry, osteopontin messenger RNA-expressing cells were identified as CD68-positive macrophages surrounding the shadow cell nests. Immunohistochemistry of anti-human osteopontin antibodies revealed that the localization of osteopontin protein was consistent with that of calcium phosphate. The present results suggest that osteopontin produced by macrophages may play a significant role in the deposition of calcium phosphate in the shadow cell nests of pilomatricomas.

Amino Acid Sequence↗
PubMed1995

Effects of methylxanthine derivatives on adriamycin concentration and antitumor activity.

We studied the mechanism whereby caffeine acts as a biochemical modulator of adriamycin, and examined various methylxanthine derivitives to determine whether they would be of value as biochemical modulators. In an in vitro study of adriamycin efflux in Ehrlich ascites carcinoma cells, theophylline, pentoxifylline, and theobromine inhibited this efflux, while caffeine metabolites did not. The effects of several methylxanthine derivatives on the antitumor activity of adriamycin and on adriamycin concentration in tissue were also examined in CDF1 tumor-bearing mice. Theobromine, which inhibited adriamycin efflux in vitro, increased the antitumor activity of adriamycin and the concentration of adriamycin in tumors. The caffeine metabolites, which had no effect on the adriamycin efflux, did not increase antitumor activity. These results suggest that the metabolism of caffeine may weaken its effect as a biochemical modulator, and that pentoxifylline and theobromine would be of value as biochemical modulators of adriamycin.

Animals↗
PubMed1995

Expression of vascular permeability factor (VPF/VEGF) messenger RNA by plasma cells: possible involvement in the development of edema in chronic inflammation.

Edema occurs in some types of chronic inflammation such as nasal polyps, uterine cervical polyps and gastric hyperplastic polyps. However, the factors or cellular components involved in the development of edema in chronic inflammation remain to be clarified. Recently, the gene encoding vascular permeability factor (VPF) or vascular endothelial growth factor (VEGF) and the genes encoding its receptors (kinase insert domain-containing receptor (KDR) and fms-like tyrosine kinase-1 [fit-1]) have been cloned. VPF/VEGF induces vascular hyperpermeability and vascular endothelial proliferation through KDR or fit-1 receptors. As there is a possibility that VPF/VEGF may play a role in the development of edema in chronic inflammation, we examined the messenger (m) RNA expression of VPF/VEGF and its receptors in nasal polyp tissues, which is an example of chronic inflammation with remarkable edema. Using northern blotting, all nasal polyp tissues examined expressed mRNA of VPF/VEGF and KDR. In situ hybridization revealed that VPF/VEGF mRNA-expressing cells were scattered in the edematous stroma of nasal polyps. In the adjacent sections, these cells showed the morphological features of plasma cells and expressed mRNA of immunoglobulin light chains. Human B cell leukemia and plasmacytoma cell lines expressed VPF/VEGF mRNA but human mast-cell leukemia and T cell leukemia cell lines did not. The alternatively spliced pattern of VPF/VEGF transcripts observed in nasal polyp tissues was consistent with that in plasmacytoma cell lines. Taken together, the VPF/VEGF mRNA-expressing cells in nasal polyps appeared to be plasma cells, suggesting that plasma cells may play an important role in the development of edema in chronic inflammation through the production of VPF/VEGF.

Base Sequence↗
PubMed1995

Alterations of bone matrix protein mRNA expression in rat aorta in vitro.

We examined the expression of matrix Gla protein (MGP), osteopontin (OPN), and osteonectin (ON) mRNAs in aortic rings excised from 3-month-, 10-month-, and 2-week-old rats during 72-hour incubations in serum-free media. In the aortic rings from 3-month-old rats, the expression of MGP mRNA was strong before incubation and increased during the 72-hour incubation. The expression of OPN mRNA was first detected after a 5-hour incubation and increased thereafter, and that of ON mRNA was strong before the incubation and decreased during the incubation. The expression of MGP and OPN mRNAs in 10-month- and 2-week-old rats was similar to that in 3-month-old rats. In contrast, expression of ON mRNA in 10-month-old rats and the expression of ON mRNA in 2-week-old rats was stronger than that in 3-month-old rats at every incubation period. In situ hybridization and immunohistochemistry identified the MGP, OPN, and ON mRNA-expressing cells as vascular smooth muscle cells. These results suggest that the expression of these mRNAs was regulated in incubation time-dependent and age-specific ways. We believe that this organ culture model is useful for further studies of the function of these bone matrix proteins and regulation of their expression in the vessel wall.

Animals↗