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Biomedical subjects

T Sugimoto

Publications and source records attributed to T Sugimoto.

At least 577 records · Page 32Linked to original sources

Stimulation of prostaglandin E2 release from cultured rabbit gastric cells by sodium deoxycholate.

Although bile salts are irritants in the gastric mucosa, their effects on prostaglandin (PG) release have not been well studied. We investigated the effects of bile salts on PGE2 release and the possible mechanisms involved. Cultured rabbit gastric mucous epithelial cells were studied. PGE2 was measured by radioimmunoassay. Intracellular free Ca2+ concentration was measured with Ca2+ fluorescent dye indo-1 AM. Dihydroxy bile salts, such as chenodeoxycholate and deoxycholate (DC), dose-dependently increased PGE2 release, while non-dihydroxy bile salts did not. Since agents involved in the cellular signal transduction system have been reported to play important roles in PG release, the possible involvement of Ca2+, calmodulin, and protein kinase C (PKC) in DC-induced PGE2 release was studied. Deprivation of Ca2+ from the medium blocked DC-induced PGE2 release. Lanthanum (La3+), which displaced surface-bound Ca2+, suppressed DC-induced PGE2. However, BAPTA (a chelator of intracellular Ca2+) did not decrease it. Neither calmodulin inhibitors nor PKC inhibitors altered DC-induced PGE2 release. DC increased intracellular free Ca2+ concentrations. This effect was blocked by deprivation of Ca2+ from the medium. Quinacrine (a phospholipase A2 inhibitor) blocked DC-induced PGE2 release. These results suggest that in cultured rabbit gastric cells, deoxycholate stimulates PGE2 release mainly through the influx of extracellular Ca2+.

Animals↗

Mu opioid receptor: expression and vagotomy-induced depletion of the mRNA in medullary preganglionic neurons.

By in situ hybridization with digoxigenin-labeled RNA probes, distinct expression of mu opioid receptor mRNA was found in rat medullary preganglionic neurons for vagal parasympathetic outflow. Two days or more following unilateral vagotomy, the expression was almost completely abolished on the operated side. The results, taken together with previous findings indicating proximodistal axonal transport of radioligand-labeled opioid receptors, suggest that the medullary preganglionic neurons thus identified are the source for mu opioid receptor acting in cardiorespiratory and gastrointestinal tissues.

Animals↗

Clinical significance of periportal tracking on computed tomographic scan in patients with blunt liver trauma.

This study was undertaken to evaluate the clinical significance of periportal tracking on computed tomography (CT) in patients with blunt liver trauma. The clinical records and CT findings of 88 patients were reviewed. Angiographic study revealed potential injury to portal triads in patients with periportal tracking on CT. Extrahepatic injuries beneath the liver were associated in 22 of 28 patients with periportal tracking and in 2 of 17 without periportal tracking (P < 0.01, chi-square = 16.38). Hepatic complications such as bile leak, biloma, hemobilia, and infected hematoma were evaluated separately in 43 patients treated conservatively and 45 patients treated surgically. The incidence of complications in patients with periportal tracking was significantly higher in both groups (nonoperative; P < 0.01, chi-square = 8.46 and operative; P < 0.01, chi-square = 8.48). We conclude that periportal tracking on CT implies injury to the subhepatic region and intrahepatic portal triads and that it requires careful examination for extrahepatic injuries in the initial management and late hepatic complications in the follow-up management.

Adolescent↗

Radial bone mineral content of normal Japanese infants and prepubertal children: influence of age, sex and body size.

The present study was performed to measure appendicular bone mass of Japanese infants and children, and to assess the influence of age, sex and body size on bone mass during the period of bone growth. The bone mineral content (BMC) and bone width (BW) at the distal third of the radius were measured by single photon absorptiometry (SPA) in 229 healthy Japanese infants and children aged 0-12 years, and the BMC/BW ratio was calculated to give the bone mineral density (BMD). BMC and BW increased with age until 2 years, while BMD did not obviously change until 2 years. After 2 years of age, the overall effect of aging appeared more prominent in BMC and BMD than in BW. There were no significant differences in BMC, BW and BMD between males and females aged 0-12 years. Age, body height, and body weight were strongly correlated with three parameters of bone mass (BMC, BW, and BMD). Among the three parameters of bone mass, BMC showed the highest Pearson coefficient of correlation with age (r = 0.955), body height (r = 0.957) and body weight (r = 0.966), as compared with BW and BMD. The present cross-sectional study provides normative data of the appendicular bone mass in healthy Japanese children, which may serve as a standard for assessment of bone mineralization in Japanese infants and children with medical problems.

Absorptiometry, Photon↗

Giant tumor formed by nodular fasciitis of the pharynx: a case report.

Nodular fasciitis caused a benign tumor which is composed of fibrous tissue. The most commonly affected site is the upper extremity, which accounts for half of all cases. Ten to 20% of the lesions occur in the head and neck area, most of which are subcutaneous. We report a case of nodular fasciitis, which presented as an unusually large submucosal tumor of the pharynx. The tumor was extended from the retropharyngeal to the parapharyngeal space, and it was measured 8 x 4 x 3 cm in size. Since nodular fasciitis is known for the spontaneous regression, the tumor was transorally debulked by the use of YAG laser.

Adult↗

Coexistence of MALT-type lymphoma and squamous cell carcinoma of the larynx.

A 66-year-old Japanese man was diagnosed as having a MALT-type lymphoma by histopathological examination. The lesion involved the vocal folds bilaterally, occupying the larynx and extending beyond it, as shown by computed tomography (CT). A course of radiation therapy with moderate doses was given. Six months later, a squamous cell carcinoma was found in the larynx and total laryngectomy was then performed. The patient remained well, without recurrence, 46 months after the operation. thus, MALT-type lymphoma may coexist with a squamous cell carcinoma of the larynx.

Aged↗

Congenital adrenal hyperplasia with 47, XXY Klinefelter syndrome.

We describe here a unique case of congenital adrenal hyperplasia (CAH) accompanied by Klinefelter syndrome. A Japanese boy was diagnosed as having CAH caused by 21-hydroxylase deficiency at birth, but was untreated thereafter until age 10. In the meantime he showed marked acceleration in somatic growth with sexual precocity by age 9, at which time growth completely stopped. During regular follow-ups at our clinic and steroid treatment after age 10, he was recognized as having bilateral small and firm testes. A chromosomal examination and a testicular biopsy revealed a complication of 47, XXY Klinefelter syndrome with CAH. Association of these two diseases has not been reported so far, and the present case is the first one to our knowledge.

Adrenal Hyperplasia, Congenital↗

Attenuation of antifibrillatory effects of lidocaine by its metabolite, glycylxylidide: application of modulated receptor hypothesis.

Lidocaine, one of the drugs effective in treating ventricular arrhythmias in acute myocardial infarction (AMI), sometimes loses its efficacy after prolonged administration, possibly owing to the counteraction of glycylxylidide, one of the metabolites of lidocaine, through modulation of binding of lidocaine to sodium channels. To determine whether glycylxylidide interferes with the antiarrhythmic action of lidocaine, we compared the antifibrillatory effects of lidocaine, glycylxylidide, and their combination in 14 anesthetized open-chest dogs. Although glycylxylidide alone prolonged intraventricular conduction time (CT) and did not affect ventricular effective refractory period (VERP), it had different effects when added to lidocaine; i.e., it had no effect on intraventricular conduction time but shortened VERP. Although glycylxylidide alone did not change ventricular fibrillation threshold (VFT), the increase in VFT induced by lidocaine was decreased by addition of glycylxylidide, possibly as a result of competition for the same cardiac sodium channels between lidocaine and glycylxylidide with similar onset but different offset kinetics, which may explain, at least in part, the drug-resistance phenomena that ensue from prolonged lidocaine administration.

Animals↗

Delayed rupture of the spleen caused by an intrasplenic pseudoaneurysm following blunt trauma: case report.

The delayed rupture of the spleen in a 12-year-old boy is reported. He was admitted with an isolated blunt splenic injury. Successive echograms revealed an enlarging hypoechogenic region in the spleen. A magnetic resonance imaging (MRI) scan showed that this hypoechogenic region was a splenic pseudoaneurysm. On his 7th hospital day the pseudoaneurysm ruptured. An emergency laparotomy with splenorrhaphy was performed. His subsequent clinical course was uneventful and the pseudoaneurysm was replaced by a hematoma that eventually resolved.

Aneurysm, False↗

Increased expression of trk proto-oncogene by gamma-interferon in human neuroblastoma cell lines.

Three human neuroblastoma cell lines were examined to determine the effect of recombinant gamma-interferon (IFN-gamma) treatment on the expression of trk proto-oncogene. Increased levels of trk proto-oncogene mRNA were observed in two neuroblastoma cell lines (KP-N-RT and KP-N-SI(FA)) after IFN-gamma treatment. The levels of trk mRNA increased with growth inhibition and morphological change in a time- and dose-dependent manner. The decreased level of N-myc mRNA after IFN-gamma treatment in KP-N-RT was inversely correlated with trk mRNA. Our results suggest that IFN-gamma can modulate the signal transduction of nerve growth factor in human neuroblastoma cells.

Blotting, Northern↗

Constitutive c-fos expression in osteoblastic MC3T3-E1 cells stimulates osteoclast maturation and osteoclastic bone resorption.

The effect of culture supernatants of c-fos-transfected MC3T3-E1 osteoblastic cells on osteoclastic bone resorption was studied. Human c-fos cDNA was integrated in the expression vector pH8, and the cells were transfected using the calcium phosphate precipitation technique. Osteoclastic bone resorption was quantified by the pit formation assay, and the osteoclast maturation from precursor was assessed by the generation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNC). The culture supernatants of MC3T3-E1 transfectants constitutively expressing c-fos gene enhanced osteoclast-like MNC formation from haematopoietic blast cells compared with those of control transfectants (P < 0.01). The culture supernatants also promoted osteoclastic bone resorption: the pit number, 118.7 +/- 38.5, was significantly higher than 19.0 +/- 10.1 of the control (P < 0.05). The absorption area, 12,394 +/- 3145 mm2, was significantly larger than 1646 +/- 314 mm2 of the control (P < 0.05). The culture supernatants also promoted bone resorption by purified chick osteoclasts (P < 0.05). The results show that constitutive expression of c-fos gene in osteoblastic MC3T3-E1 cells stimulates osteoclast maturation and osteoclastic bone resorption by releasing humoral mediator(s).

Animals↗

Differential alpha-smooth muscle actin expression in a gastric epithelioid leiomyosarcoma in a 14 year old girl.

Leiomyosarcoma in childhood is very rare. This report describes the immunohistochemical study of a gastric epithelioid leiomyosarcoma in a 14 year old girl. Microscopically, the tumor showed two distinct histological patterns within the same tumor: small epithelioid cells forming a lobular pattern and spindle-shaped cells forming interlacing fascicles, but no distinct border divided the two types of cells. Immunohistochemically, vimentin was positive in all tumor cells; alpha-smooth muscle actin, however, was negative in small epithelioid cells and positive in spindle-shaped cells. The data revealed that the tumor had components showing two stages of morphological and biochemical differentiation. This case indicates that leiomyosarcomas might lose smooth muscle actin during malignant transformation; or, alternatively, they might arise from a primitive type of smooth muscle cell and some of them could spontaneously differentiate into mature smooth muscle cells, expressing this actin.

Actins↗

Close correlation of the cardioprotective effect of FK409, a spontaneous NO releaser, with an increase in plasma cyclic GMP level.

FK409 ((+/-)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexeneamide) , which has been reported by us to be a new spontaneous nitric oxide (NO) releaser, prevented myocardial infarction following occlusion and reperfusion in rat coronary artery and increased plasma cyclic GMP level in rats, dose-dependently and significantly at 32 mg kg-1. Isosorbide dinitrate (ISDN), which is the most popular orally active NO donor used in the treatment of ischaemic cardiovascular diseases, did not show significant effects at 32 mg kg-1 in either experiment. Therefore, it is suggested that FK409 can attenuate myocardial injury during ischaemia and reperfusion in contrast to ISDN and a change in plasma cyclic GMP level may serve as an indicator of the cardioprotective effect of NO-releasing drugs.

Animals↗

Antianginal effects of FK409, a new spontaneous NO releaser.

1. The aim of this study was to compare antianginal effects of (+/-)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexeneamide (FK409), a new spontaneous nitric oxide releaser, with those of isosorbide dinitrate (ISDN). We used two types of rat angina model; methacholine- and arginine vasopressin (AVP)-induced coronary vasospasm models. 2. In the in vitro study, FK409 showed 80 times more potent vasorelaxant effect in dog isolated coronary artery than ISDN (EC50 = 16.7 +/- 4.8 and 1340 +/- 320 nM, respectively). 3. In the rat methacholine-induced coronary vasospasm model, FK409 suppressed the elevation of ST segment dose-dependently and significantly at 0.1 mg kg-1, i.d. On the other hand, ISDN suppressed it significantly at 3.2 mg kg-1, i.d. In addition, the efficacy of 3.2 mg kg-1 ISDN in the model was almost the same as that of 0.1 mg kg-1 FK409. 4. In the above experiments, FK409 and ISDN decreased mean blood pressure significantly at the maximum dose tested (1.0 mg kg-1, i.d. and 3.2 mg kg-1, i.d., respectively) but did not change heart rate at these doses. Therefore, the hypotensive effect of FK409 was 10 times weaker than the antianginal effect of the compound, while those of ISDN were almost the same. 5. In the rat AVP-induced coronary vasospasm model, 32 mg kg-1 FK409 significantly inhibited the depression of ST segment 60 min after oral administration. On the other hand, 32 mg kg-1 ISDN did not inhibit it at 60 and 120 min after oral administration. 6. In conclusion, FK409 inhibits coronary vasospasm more potently in two types of rat angina models than ISDN. In addition, FK409 shows an antianginal effect more selectively that a hypotensive effect,compared with ISDN.

Angina Pectoris, Variant↗

Clinical evaluation of a new type of centrifugal pump.

The major problems with existing centrifugal pumps are leakage, mechanical trauma, and thrombus formation. In consideration of these problems, a new compact centrifugal pump system was developed. The purpose of this study was to evaluate the new centrifugal pump system clinically. Ten patients underwent open heart surgery with a centrifugal pump or a roller pump. During surgery, hemodynamic and hematological data were obtained. A pulsatile assist device in the pump circuit was used in patients with severe heart disease. There was neither operative death nor hospital mortality, and there was no difference with regard to hemodynamic data between the two groups. The centrifugal pump groups, however, had significantly lower hemolysis, especially during prolonged cardiopulmonary bypass. This centrifugal pump could also create sufficient pulsatile flow with a pulsatile assist device. Postoperative macroscopic and microscopic findings demonstrated the smooth surface of the pump without thrombus formation. This centrifugal pump system might be useful for prolonged cardiopulmonary bypass.

Adolescent↗

IGF-I mediates the stimulatory effect of high calcium concentration on osteoblastic cell proliferation.

Since our recent study revealed that an increase in extracellular calcium ([Ca2+]e) but not magnesium enormously stimulated DNA synthesis in osteoblastic MC3T3-E1 cells at the minimal and maximal effective concentration of 3 and 5 mM, respectively, the present study was performed to clarify how an increase in [Ca2+]e caused a stimulation of DNA synthesis of these cells. Neither calcium channel blockers (verapamil, diltiazem, and nifedipine) and dantrolene, an inhibitor of Ca release from intracellular Ca pool, nor indomethacin, an inhibitor of prostaglandin synthesis, affected the high [Ca2+]e-induced increase in DNA synthesis. DNA synthesis first increased after a 12-h exposure to 5 mM [Ca2+]e, and cycloheximide eliminated the stimulatory effect of high [Ca2+]e on DNA synthesis, suggesting that this stimulatory effect of high [Ca2+]e was dependent on new protein synthesis. There is recent evidence that MC3T3-E1 cells constitutively produce and secrete insulin-like growth factor I (IGF-I) and possess IGF-I receptors. IGF-I antiserum (1:10,000 to 1:100) blocked the high [Ca2+]e-induced increase in DNA synthesis in a concentration-dependent manner. A neutralizing abolished DNA synthesis stimulated by high [Ca2+]e, indicating that IGF-I mediated the high [Ca2+]e-induced effect. Furthermore, high [Ca2+]e significantly increased the secretion of immunoreactive IGF-I into the medium as well as the expression of IGF-I mRNA. Present findings indicate that an increase in [Ca2+]e stimulated DNA synthesis of osteoblasts through the mechanism of an increase in the production and secretion of IGF-I.

3T3 Cells↗

Role of interleukin-6 and prostaglandins in the effect of monocyte-conditioned medium on osteoclast formation.

There is evidence suggesting some role of mononuclear cells at the resorptive site in bone remodeling. The possibility was therefore postulated that these cells might provide some signal for osteoclast formation. We examined the effects of human monocyte-conditioned medium (CM) on the formation of osteoclast-like cells from hemopoietic blast cells in the absence of stromal cells and unfractionated bone cells in the presence of stromal cells. In both culture systems, the osteoclast-like cell formation induced by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] or human parathyroid hormone (PTH)-(1-34) was significantly inhibited by adding 20% CM. The effects of monocyte-derived local regulators of bone turnover on osteoclast-like cell formation induced by 1,25(OH)2D3 or PTH were determined. Interleukin-6 (IL-6) inhibited osteoclast-like cell formation in both culture systems, whereas prostaglandin (PG) E2 significantly inhibited the formation only in the hemopoietic blast cell culture. The inhibitory effect of CM on osteoclast-like cell formation from hemopoietic blast cells was not observed when CM was prepared from monocytes pretreated with indomethacin. The inhibitory effect of CM and IL-6 on osteoclast-like cell formation in both culture systems was blocked by adding neutralizing IL-6 antibody. The present study demonstrated that CM inhibited osteoclast-like cell formation induced by 1,25(OH)2D3 and PTH presumably through the action of local regulators of bone turnover, such as IL-6 and PG. Our findings thus provide additional evidence that mononuclear cells play an important role at the resorptive site in bone remodeling.

Acid Phosphatase↗