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Biomedical subjects

M Goto

Publications and source records attributed to M Goto.

At least 253 records · Page 14Linked to original sources
PubMed1999

A mechanism for shock following stomach rupture in the newborn.

BACKGROUND: Stomach rupture often leads to shock and death within a short period, but the mechanism for this is not well-known. Shock may be due, in part, to endotoxin translocation and endotoxemia. METHODS: Sterile, endotoxin-free HCl (0.1 mol/L), with or without endotoxin-feeding, was injected intraperitoneally into 10-day-old rats, simulating stomach rupture in the newborn. The plasma endotoxin concentration was measured. Plasma glucose and lactate concentrations were monitored to assess physiologic response to endotoxemia and shock. RESULTS: Endotoxin feeding alone caused endotoxemia (0.49 +/- 0.12 ng/mL; P < 0.05) in 10-day-old rats, while plasma endotoxin concentration in controls was less than 0.04 ng/mL. However, the endotoxemia did not cause disruption of glucose regulation or death. Injection of HCl alone did not increase plasma endotoxin concentrations and did not alter glucose regulation. However, HCl injection into endotoxin-fed rats induced endotoxemia (211.1 +/- 70.5 ng/mL; P < 0.05), hypoglycemia, lactacidemia and mortality (45%; P < 0.05). CONCLUSION: Early development of shock following stomach rupture may be in part due to endotoxin translocation and endotoxemia.

Animals↗
PubMed1999

Roles of prostaglandin E receptors in mesangial cells under high-glucose conditions.

BACKGROUND: High glucose reportedly stimulates prostaglandin (PG) E2 production and DNA synthesis in mesangial cells (MCs). However, the pathophysiological significance of PGE2 in MCs has remained unclear. METHODS: The effects of prostanoids on [3H]-thymidine uptake and cAMP production in rat MCs cultured with 5.6 mM glucose, 25 mM glucose, or 5.6 mM glucose supplemented with 19.4 mM mannitol were examined. The gene expression of PGE2 receptor (EP) subtypes in MCs was analyzed with Northern blotting techniques. RESULTS: Northern blotting indicated EP1 and EP4 gene expression in MCs. EP1 agonists and PGE2 stimulated [3H]-thymidine uptake in MCs. EP1 antagonists dose dependently attenuated high-glucose-induced [3H]-thymidine uptake, which suggests EP1 involvement, by an increase in intracellular Ca2+, in DNA synthesis of MCs. On the other hand, forskolin, db-cAMP, and 11-deoxy-PGE1, an EP4/EP3/EP2 agonist, significantly decreased DNA synthesis in MCs. These inhibitory effects are thought to be mediated via EP4 as a result of an increase in cAMP synthesis. The effects via EP4 seem to be particularly important because PGE2-induced cAMP synthesis was significantly attenuated in the high-glucose group compared with the mannitol group, in which [3H]-thymidine uptake did not increase in spite of augmented PGE2 production. CONCLUSION: The increase in DNA synthesis in MCs under high-glucose conditions can be explained, at least in part, by the high-glucose-induced inhibition of cAMP production via EP4, which augments EP1 function in conjunction with the overproduction of PGE2.

1-Methyl-3-isobutylxanthine↗
PubMed1999

Gestational changes in endothelin-1-induced receptors and myometrial contractions in rat.

The present experiments were performed to characterize the gestational changes in endothelin (ET)-1-induced myometrial contractions and ET receptors in rat. ET-1-induced contractions were composed of two types: increases in resting tone and rhythmic contractions. The increase in resting tone was decreased at 7 days of gestation, but increased at 20 days. The increase in amplitude and frequency of rhythmic contractions remained unchanged during days 7-14 of gestation. Continuous rhythmic contractions were not produced by ET-1 near the term. Both contractions were inhibited by the antagonists BQ 123 and Ro 46-2005 but not by RES 701-1 or BQ 788. In binding studies, total binding sites of [1251]-ET-1 were unchanged, however higher affinity binding sites appeared during pregnancy in addition to the lower affinity sites. The specific [125I]-ET-1 binding in non-pregnant and pregnant myometrium was completely inhibited by unlabelled ET-1 and Ro 46-2005. In contrast, the proportion which was inhibited by BQ 123 was decreased during pregnancy. In conclusion, characteristic gestational changes were the augmentation of ET-1-induced increased resting tone near term, and the appearance of high affinity ET-1 binding sites and an increase in BQ 123-resistant ET-1 binding sites during pregnancy. Further investigations are needed to understand the physiological role of these changes.

Animals↗
PubMed1999

Insulin-like growth factor-1 content and pattern of expression correlates with histopathologic grade in diffusely infiltrating astrocytomas.

Studies of experimental tumorigenesis have strongly implicated signaling of the insulin-like growth factor 1 (IGF-1) as a key component in astrocytic neoplasia; however, its role in the growth of low-grade and malignant human tumors is not well understood. Correlative analyses of IGF-1, p53, and Ki-67 (MIB-1) immunohistochemistry and IGF-1 receptor (IGF-1R) mRNA expression were performed to examine the cellular pattern of IGF-1 signaling in 39 cases of astrocytoma (World Health Organization grades II-IV). Tumor cells expressing IGF-1 and IGF-1R were present in all tumor grades. The proportion of tumor cells that expressed IGF-1 correlated with both histopathologic grade and Ki-67 labeling indices, while expression of IGF-1R mRNA correlated with Ki-67 indices. In cases where stereotactic tissue sampling could be identified with a specific tumor area by neuroimaging features, the numbers of IGF-1 immunoreactive cells correlated with the tumor zones of highest cellularity and Ki-67 labeling. In glioblastomas, the localization of IGF-1 immunoreactivity was notable for several features: frequent accentuation in the perivascular tumor cells surrounding microvascular hyperplasia; increased levels in reactive astrocytes at the margins of tumor infiltration; and selective expression in microvascular cells exhibiting endothelial/pericytic hyperplasia. IGF-1R expression was particularly prominent in tumor cells adjacent to both microvascular hyperplasia and palisading necrosis. These data suggest that IGF-1 signaling occurs early in astroglial tumorigenesis in the setting of cell proliferation. The distinctive correlative patterns of IGF-1 and IGF-1R expression in glioblastomas also suggest that IGF-1 signaling has an association with the development of malignant phenotypes related to aberrant angiogenesis and invasive tumor interactions with reactive brain.

Astrocytoma↗
PubMed1999

Three-dimensional coronary magnetic resonance angiography with injection of extracellular contrast medium.

RATIONALE AND OBJECTIVES: To evaluate serial changes of the signal intensity and the contrast-to-noise ratios of the coronary arteries on three-dimensional (3D) coronary magnetic resonance angiography (MRA) after an injection of extracellular contrast medium, and to demonstrate the feasibility of this method for the diagnosis of coronary artery abnormalities. METHODS: Five healthy volunteers and two patients with Kawasaki disease and an anomalous coronary artery were studied. Coronary MRAs of the left anterior descending artery and the right coronary artery were obtained using a fat-suppressed 3D MRA sequence before and 0 to 5, 10 to 15, 20 to 25, and 30 to 35 minutes after administration of Gd-DTPA-BMA. RESULTS: Administration of the contrast agent provided a significant increase in the signal intensity and contrast-to-noise ratio. Aneurysm of the left anterior descending artery in Kawasaki disease and the proximal course of the anomalous right coronary artery, which were not well depicted on precontrast 3D MRA, were clearly demonstrated after contrast injection. CONCLUSIONS: The current study demonstrated that the use of an extracellular gadolinium contrast agent can significantly improve the clinical usefulness of 3D coronary MRA.

Adolescent↗
PubMed1999

A case of Werner's syndrome associated with osteosarcoma.

We described a case of Werner's syndrome associated with osteosarcoma. A 37-year-old Japanese man was diagnosed as having Werner's syndrome by the presence of juvenile cataracts, skin sclerosis and hyperpigmentation of the feet, high-pitched voice, characteristic bird-like appearance of the face with beak-shaped nose, thinning of the entire skin and hyperkeratoses on soles, hyperlipemia, hyperuricemia, diabetes melitus, and the mutated responsible gene (WRN). He had a 3-month history of a tumor on his left forearm. Histologically, the tumor included four histological patterns; a malignant fibrous histiocytoma-like, a desmoid-like, a dermatofibrosarcoma protuberans-like, and a chondrosarcoma-like pattern. Tumoral osteoid formation was also found in the tumor. Therefore, the tumor was diagnosed as osteosarcoma.

Adult↗
PubMed1999

Purification and identification of p68 RNA helicase acting as a transcriptional coactivator specific for the activation function 1 of human estrogen receptor alpha.

The estrogen receptor (ER) regulates the expression of target genes in a ligand-dependent manner. The ligand-dependent activation function AF-2 of the ER is located in the ligand binding domain (LBD), while the N-terminal A/B domain (AF-1) functions in a ligand-independent manner when isolated from the LBD. AF-1 and AF-2 exhibit cell type and promoter context specificity. Furthermore, the AF-1 activity of the human ERalpha (hERalpha) is enhanced through phosphorylation of the Ser(118) residue by mitogen-activated protein kinase (MAPK). From MCF-7 cells, we purified and cloned a 68-kDa protein (p68) which interacted with the A/B domain but not with the LBD of hERalpha. Phosphorylation of hERalpha Ser(118) potentiated the interaction with p68. We demonstrate that p68 enhanced the activity of AF-1 but not AF-2 and the estrogen-induced as well as the anti-estrogen-induced transcriptional activity of the full-length ERalpha in a cell-type-specific manner. However, it did not potentiate AF-1 or AF-2 of ERbeta, androgen receptor, retinoic acid receptor alpha, or mineralocorticoid receptor. We also show that the RNA helicase activity previously ascribed to p68 is dispensable for the ERalpha AF-1 coactivator activity and that p68 binds to CBP in vitro. Furthermore, the interaction region for p68 in the ERalpha A/B domain was essential for the full activity of hERalpha AF-1. Taken together, these findings show that p68 acts as a coactivator specific for the ERalpha AF-1 and strongly suggest that the interaction between p68 and the hERalpha A/B domain is regulated by MAPK-induced phosphorylation of Ser(118).

Adenocarcinoma↗
PubMed1999

Desensitization to LPS after ethanol involves the effect of endotoxin on voltage-dependent calcium channels.

Hepatic macrophages are sensitized to alcohol in 24 h due to increases in the endotoxin receptor, CD14; however, desensitization to lipopolysaccharide (LPS), which occurred earlier, could not be explained by changes in CD14. Therefore, the purpose of this work was to attempt to understand factors responsible for ethanol-induced desensitization to LPS in hepatic macrophages. Rats were given ethanol (5 g/kg body wt) intragastrically, and hepatic macrophages were isolated 2 h later. After addition of endotoxin, intracellular Ca(2+) concentration ([Ca(2+)](i)) was measured using fura 2 and tumor necrosis factor (TNF)-alpha was measured by ELISA. Ethanol given 2 h before injection of LPS totally prevented liver injury and blunted LPS-induced increases in [Ca(2+)](i) and TNF-alpha in hepatic macrophages. Furthermore, the protein kinase C (PKC) agonist phorbol 12-myristate 13-acetate and acute ethanol treatment both activated PKC and largely prevented the influx of [Ca(2+)](i) caused by LPS. Sterilization of the gut with antibiotics completely blocked all effects of ethanol on [Ca(2+)](i) and TNF-alpha release. Thus ethanol-induced desensitization of hepatic macrophages correlates with gut-derived endotoxin after ethanol and involves the effect of PKC on voltage-dependent Ca(2+) channels.

Animals↗
PubMed1999

Transmural microcirculatory blood flow distribution in right and left ventricular free walls of rabbits.

Within-layer regional myocardial flows in the left and right ventricles (LV, RV) and in LV with increased myocardial workload (beta(1)-adrenoceptor stimulation) were studied transmurally in anesthetized rabbits. Myocardial flow distribution was visualized with resolutions between 0.1 x 0.1- and 1 x 1-mm(2) pixels, using digital radiography combined with the (3)H-labeled desmethylimipramine deposition technique. The spatial pattern of flow distribution was quantitated by the coefficient of variation of regional flows (CV, related to global flow heterogeneity) and the correlation between adjacent regional flows (CA, inversely related to local flow randomness). CV was lower in LV than in RV [P < 0.05, nonparametric 2-way analysis of variance (NANOVA)]. When resolution was lowered from 0.1 x 0.1- to 1 x 1-mm(2) pixels, CV decreased by 70% in both LV and RV. CA was higher in LV than in RV (P < 0.05, NANOVA); the interventricular difference in CA was large over the resolutions between 0.4 x 0.4- and 1 x 1-mm(2) pixels. In LV, both CV and CA increased with depth of myocardium (P < 0.05, NANOVA); in subendocardium CV was high comparable with CV in RV (P = 0.47, NANOVA). The enhancement of myocardial workload decreased CV and tended to decrease CA in LV subendocardium (P < 0.05, P = 0.06, respectively; NANOVA). We conclude that 1) microregional flow distribution is less heterogeneous and less random in LV than in RV; 2) transmurally, in LV subendocardium global flow heterogeneity was the highest whereas local flow randomness was the lowest, so that clusters of low- or high-flow regions exist in this LV layer; and 3) global flow heterogeneity decreased and local flow randomness tended to increase (flow homogenizing occurred) in LV subendocardium with increasing myocardial workload. Thus the distributed pattern of myocardial microregional flows may be adaptable to local myocardial metabolic change.

Animals↗
PubMed1999

No evidence for extraocular photoreceptors in the circadian system of the Syrian hamster.

Campbell and Murphy reported recently that 3 h of bright light (13,000 lux) exposure to the area behind the knee caused phase shifts of the circadian rhythms of both body temperature and saliva melatonin in humans. The authors tested the hypothesis that extraocular photoreception is also involved in the circadian system of the Syrian hamster. Hamsters were bilaterally enucleated (eyes removed), and their backs were shaved. Hamsters with stable free-running rhythms in constant darkness were exposed to direct sunlight for 1 or 3 hours during their subjective night. Intact (control) animals showed phase shifts as expected, but the locomotor activity of enucleated animals was unaffected by the exposure to sunlight. The authors also measured the pineal melatonin content after exposure to sunlight. Pineal melatonin content in intact animals declined markedly as expected, but no decline was observed in the enucleated hamsters. The authors conclude that extraocular phototransduction is not capable of shifting the phase of the hamster's locomotor activity rhythm or of suppressing pineal melatonin synthesis.

Animals↗
PubMed1999

ATZ1993, an orally active and novel nonpeptide antagonist for endothelin receptors and inhibition of intimal hyperplasia after balloon denudation of the rabbit carotid artery.

The present experiments were designed to investigate the effect of ATZ1993 [3-carboxy-4,5-dihydro-1-[1-(3-ethoxyphenyl)propyl]-7-(5-pyrimidinyl)met hoxy-[1H]-benz[g]indazole] on the intimal hyperplasia after balloon endothelial denudation of the rabbit carotid artery. ATZ1993 inhibited the specific [125I]endothelin (ET)-1 binding not only to ET-receptor subtype A (ET(A)) with a pKi value of 8.69+/-0.02, but also to ET-receptor subtype B (ET(B)) with a pKi value of 7.20+/-0.03. Counterscreening in the binding assay (30 different receptors) confirmed that ATZ1993 had a high selectivity for ET receptors. Increases in intima:media ratio and DNA content in the vessel wall were significantly (P < 0.005) inhibited by ATZ1993 in a daily dose of 30 mg x 200 ml(-1) x kg(-1) for 1 week before and 6 weeks after balloon denudation. Inhibition of the intimal hyperplasia with ATZ1993 was determined as approximately 77% for increases in intima:media ratio and DNA content. Plasma concentrations of ATZ1993 ranged between 121.6+/-26.6 and 131.7+/-20.9 nM throughout experimental periods. Mean arterial blood pressure, heart rate and body weight gain remained unaffected by administering ATZ1993. These results demonstrate that ATZ1993 is a novel nonpeptide and nonselective ET(A)/ET(B)-receptor antagonist, and the agent when administered orally inhibits effectively intimal hyperplasia after balloon denudation of the rabbit carotid artery.

Administration, Oral↗
PubMed1999

Heterologous expression and characterization of endoglucanase I (EGI) from Trichoderma viride HK-75.

Endoglucanase I (EGI) secreted from Trichoderma viride HK-75 has a unique transglycosylation activity. The genomic and cDNA clones encoding EGI (egl1) of T. viride HK-75 were isolated and characterized. The coding region of egl1, composed of 1392 bp, was found to encode a polypeptide of 464 amino acids that has extensive similarity (93.8%) with EGI of T. reesei. Expression of the egl1 gene in E. coli as a fusion protein (with N-terminal thioredoxin and C-terminal histidine tag) led to a large production of a nonglycosylated protein of 62.5 kDa. However, it formed an insoluble inclusion body. Upon denaturation with 8 M urea followed by dialysis and successive purification, the enzymatically active recombinant EGI (rEGI) was obtained at a level as high as 18.3 mg/l of 1,000 ml of culture. The rEGI had 67.8% activity for carboxymethyl cellulose (CMC), compared to native EGI (nEGI). The optimum pH and optimum temperature of rEGI were lower than those of nEGI by 0.5 and 5 degrees C, respectively. The rEGI also had narrower CMCase ranges than nEGI in pH and temperature stabilities. However, the catalytic and transglycosylation abilities against cellotriose of rEGI were comparable to those of nEGI. These results suggest that the glycosylation is important for the stabilities of EGI but not critical for the essential enzymatic capacity.

Amino Acid Sequence↗
PubMed1999

A competitive enzyme-linked immunosorbent assay-like method for the measurement of urinary hyaluronan.

A highly sensitive method for measurement of urinary hyaluronan with a minimum molecular mass of 2,000 Da was developed without using HPLC or radioisotopes. This competitive enzyme-linked immunosorbent assay-like method, used competitive binding of free hyaluronan in the sample and biotin-labeled standard hyaluronan to hyaluronan binding protein in solid phase. A total of 150 healthy individuals from both sexes at ages from 0 to 100 years was examined by the established method. Hyaluronan of 384 +/- 80 ng/mg creatinine (mean +/- SD) was constantly excreted into urine of 24-40-year-old healthy adults. The urinary hyaluronan levels were significantly higher before age 1 (p < 0.001) and rather high after 90 years compared to the other groups. The average molecular weight of urinary hyaluronan (5,500 Da) was constant through all generations. Sex difference of urinary hyaluronan was not observed both quantitatively or qualitatively.

Adolescent↗
PubMed1999

Immunological characterization of circulating osteoprotegerin/osteoclastogenesis inhibitory factor: increased serum concentrations in postmenopausal women with osteoporosis.

Osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor (OCIF) is a soluble member of the tumor necrosis factor receptor family of proteins and plays an important role in the negative regulation of osteoclastic bone resorption. Whether OPG/OCIF circulates in human blood and how its level changes under pathological conditions is not known. To address these issues, a panel of monoclonal antibodies was generated against recombinant OPG/OCIF and screened for reactivity with solid-phase monomeric and homodimeric forms of the recombinant protein. Antibodies that showed high affinity for both forms of OPG/OCIF and those that selectively recognized the homodimer were identified, enabling development of two types of sensitive enzyme-linked immunosorbent assay (ELISA): one that detects both forms of OPG/OCIF equally and one specific for the homodimer. Characterization of circulating OPG/OCIF with these ELISAs revealed that the protein exists in human serum mainly in the monomeric form. The serum concentration of OPG/OCIF increased with age in both healthy Japanese men and women, and was significantly higher in postmenopausal women with osteoporosis than in age-matched controls. Within the osteoporotic group, serum OPG/OCIF concentrations were higher in patients with low bone mass. Serum OPG/OCIF concentrations were also significantly increased in those postmenopausal women with a high rate of bone turnover, as determined by increased serum bone-specific alkaline phosphatase and urinary excretion of pyridinoline and deoxypyridinoline. The results suggested that circulating OPG/OCIF levels are regulated by an age-related factor(s) and that the increased serum concentration may reflect a compensative response to enhanced osteoclastic bone resorption and the resultant bone loss rather than a cause of osteoporosis.

Adult↗
PubMed1999

Calcitonin stimulates lysosomal enzyme release and uptake in LLC-PK1 cells.

Renal tubular targeted hormones increase urinary excretion of a lysosomal enzyme, N-acetyl-beta-D-glucosaminidase (NAG). To elucidate the mechanism of this event, the calcitonin effect on NAG handling by LLC-PK1 cells was examined. Calcitonin (1 nM to 1 microM), phorbol myristate (10 nM to 1 microM), and ionomycin (1 to 10 microM) promoted NAG release without any increase in lactate dehydrogenase release or any reduction of mitochondrial dehydrogenase activity. Treatment with 100 nM calphostin C or 50 microM KN-93 partially reversed the calcitonin effect on NAG release. Calcitonin promoted secretion of fluorescence ceramide, a reporter of protein transport from Golgi apparatus to cell surface. Calcitonin-stimulated NAG release was partially inhibited by 10 microg/ml brefeldin A, a blocker of protein transport through the Golgi apparatus. Calcitonin accelerated cellular uptake of exogenous NAG, which was inhibited by low temperature, 0.1 mM monodansyl cadaverine (receptor-mediated endocytosis inhibitor), and 10 mM mannose-6-phosphate. Furthermore, calcitonin promoted progression of intracellular membranes stained by a fluorescence membrane marker, styryl pyridinium dye, from cell periphery to perinuclear regions (commonly referred to as recycling vesicles) and increased dye release from preloaded cells. Fluorescence release from the cells pre-loaded with FITC-labeled NAG or albumin was also stimulated by calcitonin. These calcitonin effects on endocytotic and re-exocytotic pathways were inhibited by 100 nM cytochalasin D, 100 nM nocodazole, 0.1 to 1 microM bafilomycin A1, or 0.1 mM monodansyl cadaverine. Increased urinary NAG excretion has been considered to reflect renal tubular damage. However, it was demonstrated here that stimulation of secretory and recycling pathways may be an alternative mechanism for calcitonin-induced enzymuria, which will become a new indicator of renal tubular response to this hormone.

Acetylglucosaminidase↗
PubMed1999

Helicobacter heilmannii associated erosive gastritis.

The spiral bacteria, Helicobacter heilmannii (H. heilmannii), distinct from Helicobacter pylori (H. pylori), was found in the gastric mucosa of a 71-year-old man without clinical symptoms. The endoscopic examination revealed erosive gastritis. Rapid urease test from the antral specimen was positive, but both culture and immunohistological staining for H. pylori were negative. Touch smear cytology showed tightly spiral bacteria, which were consistent with H. heilmannii. At the second endoscopy after medication regimen for eradication of H. pylori, inflammation was decreased and the rapid urease test was negative. The second cytology showed no evidence of H. heilmannii. Anti-H. pylori therapy may be a useful medication for H. heilmannii.

Abietanes↗