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Biomedical subjects

S Miyamoto

Publications and source records attributed to S Miyamoto.

At least 217 records · Page 12Linked to original sources

Increased plasma levels of adrenomedullin in patients with systemic inflammatory response syndrome.

We measured the plasma levels of adrenomedullin (AM), a novel vasodilating peptide, in 89 patients with various forms of systemic inflammatory response syndrome (SIRS) and 13 healthy volunteers serving as controls. Plasma levels of AM in SIRS (burns: 20.5 +/- 3. 2 fmol/ml [mean +/- SEM]; pancreatitis: 13.8 +/- 3.8 fmol/ml; trauma: 14.9 +/- 2.5 fmol/ml; traumatic shock: 41.1 +/- 7.8 fmol/ml; severe sepsis: 59.9 +/- 11.2 fmol/ml; septic shock: 193.5 +/- 30.1 fmol/ml) were significantly increased over those of controls (5.1 +/- 0.2 fmol/ml). The patients with traumatic shock or septic shock especially had higher levels of plasma AM than those with trauma or severe sepsis, respectively. These data showed that in patients with SIRS, plasma AM levels increased in proportion to the severity of illness. Subsequently, we measured the plasma levels of mediators such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, plasminogen activator inhibitor (PAI)-1, and thrombomodulin (TM) in patients with traumatic shock and septic shock. A significant correlation was observed between plasma AM and TNF-alpha levels in patients with septic shock, suggesting an important role for AM as well as of TNF-alpha in the pathophysiology of inflammation. Plasma AM and IL-8 levels correlated positively with Acute Physiology and Chronic Health Evaluation (APACHE) II score, peak multiple organ failure (MOF) score during the first month and prognosis in patients with septic shock, as did plasma IL-6 levels in patients with traumatic shock. The plasma AM level might serve as a useful marker for evaluating the severity of disease and as an early predictor of subsequent organ failure and outcome in septic shock.

APACHE↗

Effect of clarithromycin and other macrolides on the sulfoxidation and 5-hydroxylation of lansoprazole in dogs.

The purpose of this study was to evaluate a possible interaction between lansoprazole and clarithromycin as well as other macrolides in dogs. Lansoprazole (30 mg) was orally administered to male beagle dogs, with or without oral pretreatment with 200-mg clarithromycin twice a day for 5 d. The experiments had a randomized cross-over design with a two-week washout period between dosing regimens. Clarithromycin pretreatment for 5 d resulted in a significant increase in the area under the serum lansoprazole concentration-time curve (AUC), whereas the area for a lansoprazole metabolite, lansoprazole sulfone, was significantly reduced, as was the maximum serum concentration (Cmax) of lansoprazole sulfone. When the effects of clarithromycin on the metabolism of lansoprazole were studied using dog liver microsomes, it was found that clarithromycin significantly inhibited the formation of lansoprazole sulfone but not another metabolite, 5-hydroxylansoprazole. These results suggest that co-medication of lansoprazole with clarithromycin may produce a synergistic effect caused by the increased serum levels of lansoprazole of benefit in Helicobacter pylori eradication.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Effects of activin on hormone secretion by single female rat pituitary cells: analysis by cell immunoblot assay.

We investigated the effect of activin A on secretion of LH, FSH, and prolactin (PRL) by female cultured rat pituitary cells at the single-cell level by means of the cell immunoblot assay. Anterior pituitary cells from 8-week-old female rats were preincubated with or without activin A for 24 h, after which they were monodispersed and immediately used for cell immunoblot assay. The percentages of LH-, FSH- and PRL-immunoreactive cell blots detected were 5.5, 5.3 and 43.1%, respectively, of all pituitary cells applied to the transfer membrane. The percentage of LH-secreting cells and mean LH secretion per cell did not change after treatment with activin. In contrast, activin significantly increased the percentage of FSH-secreting cells and mean FSH secretion per cell to 136.0 and 114. 5% respectively. In addition, activin significantly decreased the percentage of PRL-secreting cells and mean PRL secretion per cell to 52.2 and 72.0% respectively. These results suggest that (1) activin A has effects on female rat pituitary cells that increase not only the amount of FSH secretion per cell but also the number of FSH-secreting cells, and (2) activin A decreases both the amount of PRL secretion per cell and the number of PRL-secreting cells.

Activins↗

Moyamoya disease showing atypical angiographic findings--two case reports.

A 7-year-old boy and a 10-year-old girl presented with moyamoya disease showing atypical angiographic findings. In these cases, the internal carotid artery (ICA) had a tapering occlusion just distal to the origin of the ophthalmic artery, whereas the top of the ICA was not occluded and was retrogradely supplied through the posterior communicating artery from the posterior circulation. Surgical treatment resolved the symptoms in both patients. Moyamoya disease may include a number of variant types not showing all the characteristic angiographic findings of moyamoya disease.

Carotid Artery, Internal↗

Skull bone regeneration in primates in response to basic fibroblast growth factor.

OBJECT: The feasibility of using a biodegradable hydrogel incorporating basic fibroblast growth factor (bFGF) to induce bone regeneration at the site of a skull defect in monkeys was investigated. METHODS: Basic fibroblast growth factor was incorporated into a bioabsorbable hydrogel, which was prepared through glutaraldehyde crosslinking of gelatin. Following treatment of monkey skull defects measuring 6 mm in diameter (six defects/experimental group) with gelatin hydrogel incorporating bFGF, skull bone regeneration was evaluated using soft x-ray studies, dual x-ray absorptometry, and histological examinations. The water content of the hydrogels varied according to the glutaraldehyde concentration in the hydrogel preparation. Gelatin hydrogels incorporating 100 microg of bFGF significantly promoted bone regeneration and the skull defect was completely closed 21 weeks after implantation. This is in marked contrast with the effect of the same dose of bFGF in solution form. Bone mineral density (BMD) measured at the sites of skull defect was enhanced by the bFGF-incorporating hydrogels. The BMD enhancement was more prominent at lower water contents of hydrogel. Empty gelatin hydrogels neither induced nor interfered with skull bone regeneration. CONCLUSIONS: The findings of this study indicate that bFGF coupled with bioabsorbable hydrogel is a very promising tool to assist in the regrowth of bone at the site of a skull defect, which clinically has been recognized as almost impossible.

Absorptiometry, Photon↗

[Thoraco-abdominal impalement injury with diaphragmatic injury: a case report].

A 60-year-old man was admitted to our hospital because of impalement injury due to traffic accident. Chest X-ray on admission revealed normal lung field. CT scans of the chest and abdomen revealed slight pneumothorax and intra-abdominal organ protruding from abdominal cavity. An emergency operation was performed. Diaphragmatic injury was not detected during the abdominal procedure. On exploring the back wound, we found a laceration of 8 cm in diameter in the diaphragm and repaired it. Impalement injuries which have aspects of both blunt and penetrating trauma are uncommon. Accordingly, wound exploration and debridement of fistulous tract are necessary. In the case of thoraco-abdominal injuries by impalement, one should bear in mind the existence of diaphragmatic injury even with normal diaphragmatic shadow on chest X-ray.

Abdominal Injuries↗

[Decreased plasma soluble P-selectin level in coronary sinus after successful coronary angioplasty in patients with unstable angina].

P-selectin, an adhesion molecule, is involved in the alpha-granules of platelets with several factors such as platelet factor 4 (PF-4) and in Weibel-Parade bodies of endothelial cells with von Willebrand factor. The levels of the soluble form of P-selectin increase after angina episodes in patients with unstable angina, indicating that soluble P-selectin is associated with platelet activation and thrombogenesis in the coronary circulation. To evaluate the effect of successful coronary angioplasty on platelet activation or thrombogenesis in the coronary circulation, plasma soluble P-selectin, PF-4 and von Willebrand factor antigen levels were measured in blood obtained from the coronary sinus before and after successful coronary angioplasty in 15 patients with unstable angina. Fifteen patients with normal coronary angiograms served as controls. Plasma P-selectin, PF-4 and von Willebrand factor antigen levels were determined by sandwich enzyme-linked immunosorbent assays. Increased plasma soluble P-selectin (159.7 +/- 74.5 vs 78.7 +/- 26.4 ng/ml, p < 0.01) and PF-4 (456.5 +/- 87.0 vs 118.7 +/- 62.3 IU/ml, p < 0.01) levels were found in patients with unstable angina compared with those in controls, and were significantly decreased after angioplasty (147.8 +/- 69.6 ng/ml, p < 0.05; 401.6 +/- 108.5 IU/ml, p < 0.05), whereas von Willebrand factor antigen was unchanged. The ratio of plasma soluble P-selectin levels after and before angioplasty correlated with the corresponding ratio of plasma PF-4 levels (r = 0.53, p < 0.05), but not with the ratio of plasma von Willebrand factor antigen levels. The plasma levels of soluble P-selectin, which increase in the coronary circulation in patients with unstable angina, decrease after successful coronary angioplasty. Such data indicate that soluble P-selectin is associated with platelet activation and the therapeutical procedure improves the thrombogenic state in the coronary circulation.

Aged↗

[Incidence of recurrence after hepatic resection and prophylactic hepatic arterial infusion chemotherapy for liver metastases from colon cancer].

We studied recurrence after hepatic resection and prophylactic hepatic arterial infusion chemotherapy for liver metastases from colon cancer, retrospectively. Eighty-six patients underwent curative hepatic resection for liver metastases, and 41 of them received arterial infusion chemotherapy. Eight patients (20%) developed only remnant liver metastases, 6 patients (15%) had hepatic and extrahepatic recurrences, and 10 patients (24%) developed only extrahepatic recurrences. Regional therapy including hepatic resection for residual liver metastases should be indicated for recurrences after hepatic arterial infusion chemotherapy.

Antineoplastic Agents↗

Seizure with prominent tonic initial signs followed by psychomotor features: a case report clinically manifesting an unusual ictal evolution.

A clinically tonic seizure phase, immediately followed by psychomotor features (right hand dystonic posture, left hand and oral automatisms), was recorded by video and EEG, in a patient who had gliosis of the left temporal lobe and left hippocampal atrophy. Interictal epileptiform discharges were frequently seen in the left temporal area, and at the time of the tonic seizure phase, ictal spike discharges were continuously observed at the left posterior temporal area, which was recognized only by applying a high frequency filter (HFF) of 15 Hz to the digitally recorded EEG because EMG artifacts totally obscured the EEG with a HFF of 60 Hz. It is most likely that tonic seizure can occur in an adult patient with temporal lobe epilepsy, and it is speculated that an epileptogenic focus might activate a certain brain area which is regarded as a symptomatogenic zone for tonic seizures. If the tonic seizure phase is immediately followed by psychomotor features as seen in the present patient, the former could be due to focal epilepsy.

Adult↗

Long-term efficacy of low-density lipoprotein apheresis on coronary heart disease in familial hypercholesterolemia. Hokuriku-FH-LDL-Apheresis Study Group.

Familial hypercholesterolemia (FH) is characterized by severe hypercholesterolemia and premature coronary heart disease (CHD). The lower the plasma cholesterol level, the more likely it is that CHD can be prevented or retarded; aggressive cholesterol-lowering therapies may be indicated for FH patients with CHD. This study describes the long-term (6 years) safety and efficacy of intensive cholesterol-lowering therapies with low-density lipoprotein (LDL) apheresis in heterozygous FH patients with CHD. One hundred thirty heterozygous FH patients with CHD documented by coronary angiography had been treated by cholesterol-lowering drug therapy alone (n=87) or LDL apheresis combined with cholesterol-lowering drugs (n=43). Serum lipid levels and outcomes in each treatment group were compared after approximately 6 years. Both treatment groups had significant reductions in serum cholesterol, LDL cholesterol, and high density lipoprotein cholesterol levels. LDL apheresis significantly reduced LDL cholesterol levels from 7.42+/-1.73 to 3.13+/-0.80 mmol/L (58%) compared with group taking drug therapy, from 6.03+/-1.32 to 4.32+/-1.53 mmol/L (28%). With Kaplan-Meier analyses of the coronary events including nonfatal myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, and death from CHD, the rate of total coronary events was 72% lower in the LDL-apheresis group (10%) than in drug therapy group (36%) (p=0.0088). It is concluded that LDL-apheresis is effective as treatment of CHD in FH heterozygotes, and may become the therapy of choice in severe types of FH.

Aged↗

Long-term outcome after STA-MCA anastomosis for moyamoya disease.

A long-term assessment was performed to determine the posttreatment clinical course of 113 patients with moyamoya disease. All patients sustained cerebral ischemic attacks and underwent superficial temporal artery-middle cerebral artery anastomosis with or without temporal muscle grafting. The follow-up duration was 3 to 24 years (mean 14.4 +/- 5.8 [standard deviation]). Complete cessation of the ischemic episodes was obtained in 110 of 113 patients. One hundred patients were able to return to independent acitvities of daily living. Intellectual delays prevented 24 patients from engaging in an independent social life . Although intracranial bleeding is one of the common manifestations in moyamoya disease, hemorrhage was not detected in the 113 patients who underwent cerebral revascularization.

Journal Article↗

Fibronectin and integrins in cell adhesion, signaling, and morphogenesis.

Fibronectin and integrins play crucial roles in a variety of morphogenetic processes, in which they mediate cell adhesion, migration, and signal transduction. They induce hierarchical transmembrane organization of cytoskeletal and signaling molecules into multimolecular complexes of more than 30 proteins. Organization of these complexes is a synergistic process dependent on integrin aggregation and occupancy, as well as tyrosine phosphorylation. Integrins also cooperate with growth-factor receptors to enhance signaling. Fibronectin and integrins induce a variety of downstream effects, including enhanced transcription factor activity, induction of over 30 genes (> half novel), and altered expression of over 100 proteins. Fibronectin and integrins therefore trigger a hierarchy of signaling responses involved in regulating processes crucial for normal morphogenesis, including cell adhesion, migration, and specific gene expression.

Animals↗

Reduced susceptibility to collagen-induced arthritis in mice deficient in IFN-gamma receptor.

Collagen-induced arthritis (CIA) is an arthritic model that was developed after immunization with type II collagen (CII). Apparently, contradictory results have been reported regarding the role of IFN-gamma in the development of CIA. Therefore, we employed IFN-gamma R-deficient mice to study the role of IFN-gamma. To introduce the CIA susceptibility gene (H-2q), IFN-gamma R-deficient (H-2b/b/IFN-gamma R-/-) mice were mated with DBA/1 (H-2q/q/IFN-gamma R+/+) mice; next, the F1 mice were interbred to yield F2 offspring bearing different combinations of H-2 (H-2q/q, H-2q/b, and H-2b/b) and IFN-gamma R (IFN-gamma R+/+, IFN-gamma R+/-, and IFN-gamma R-/-) genes. Although the H-2q allele appeared to confer susceptibility to CIA, mice that were homozygous for the IFN-gamma R mutation showed a substantially decreased incidence and severity of CIA. The CII-specific IgG levels of serum samples, which are known to be involved in the development of CIA, were remarkably reduced in IFN-gamma R-/- mice. Furthermore, the anti-CII IgG2a levels controlled by IFN-gamma R were significantly reduced in IFN-gamma R-/- F2 mice compared with those seen in IFN-gamma R+/+ and IFN-gamma R+/- mice, although the levels of all IgG subclass Abs examined were lower in IFN-gamma R-/- mice than in IFN-gamma R+/+ mice. No clear evidence of the imbalance of Th1/Th2 cytokines was observed in CII-immunized, IFN-gamma R-deficient mice. Taken together, these results suggest that IFN-gamma exacerbates CIA by affecting, at least, levels of CII-specific IgG Ab rather than the imbalance of Th1/Th2 cells.

Animals↗

Large-scale preparation of human thrombin: polyethylene glycol potentiates the factor Xa-mediated activation of prothrombin.

We investigated the ability of polyethylene glycol 4000 to accelerate thrombin generation in a mixture of prothrombin and factor X at concentrations of 1-30%. In the presence of 5 mM of CaCl2, polyethylene glycol 4000 promoted prothrombin activation at concentrations above 1%. The peak of activation was seen at levels of 14 and 20% of polyethylene glycol 4000. The effect of the polyethylene glycol was remarkably dependent on its molecular weight; molecular weights greater than 2000 were required for accelerating thrombin generation. Under optimal conditions, polyethylene glycol 4000, in the presence of CaCl2, promoted conversion of all of the prothrombin into thrombin and its derivatives. We conclude that polyethylene glycol 4000, at concentrations ranging from 14 to 20%, effectively accelerates thrombin generation in the presence of 5 mM of CaCl2. This new method for preparing thrombin is based on the use of polyethylene glycol 4000 and CaCl2 and is applicable to the manufacture of thrombin.

Calcium Chloride↗

Isochronous storage ring of the New SUBARU project.

The aims of the New SUBARU project are to promote industrial applications in the VUV and soft X-ray region and to develop research and development towards new light sources. The main facility of the New SUBARU project is the 1.5 GeV electron storage ring which is under construction at the SPring-8 site in Harima Science Garden City, Japan. The storage ring is quasi-isochronous and has variable momentum dispersion for the deep study of beam dynamics in very short bunches.

Journal Article↗

A kinetic analysis of the interaction of human recombinant tissue factor pathway inhibitor with factor Xa utilizing and immunoassay and the effect of antithrombin III/heparin on the complex formation.

We have recently shown that a complex formation of tissue factor pathway inhibitor (TFPI) and factor Xa (Xa) promotes a clearance of proteoglycans-associated TFPI. In the current studies, the interaction between human recombinant TFPI (h-rTFPI) and Xa were kinetically analyzed by utilizing both a protease inhibitor, p-(amidophenyl) methanesulfonyl fluoride hydrochloride, and a specific enzyme-linked immunosorbent assay for the complex of h-rTFPI with Xa. We further investigated the effect of antithrombin III on the complex formation between h-rTFPI and Xa. We found that the h-rTFPI/Xa complex formed in a time-dependent manner: the second-order rate constant (K1) for the complex formation was calculated to be 0.86x10(6) M(-1)s(-1). The addition of antithrombin III to the h-rTFPI solution modestly reduced the rate of the complex formation between h-rTFPI and Xa. Heparin strikingly enhanced antithrombin III's inhibition of Xa and resulted in complete abrogation of the complex formation between h-rTFPI and Xa in the absence or presence of acidic phospholipids. Furthermore, antithrombin III induced dissociation of the preformed h-rTFPI/Xa complex in the presence of heparin. These results suggest that in the presence of heparin, antithrombin III interferes with the catabolism of TFPI mediated via Xa.

Antithrombin III↗

Human recombinant tissue factor pathway inhibitor induces apoptosis in cultured human endothelial cells.

Tissue factor pathway inhibitor (TFPI) is mainly synthesized in vascular endothelial cells and exhibits a strong and specific inhibitory activity against tissue factor-mediated blood coagulation. In the present study, we demonstrate that human recombinant TFPI (h-rTFPI) inhibits the growth of cultured human umbilical vein endothelial cells (HUVECs) by inducing apoptosis. In a growth-rate assay of HUVECs, the growth of the cultured HUVECs is completely abolished by the addition of 1 microM h-rTFPI to the culture medium containing fetal bovine serum (FBS), basic fibroblast growth factor, and epidermal growth factor. In addition, h-rTFPI and h-rTFPI-C which lacks the carboxyl-terminal basic region prevent the survival of growth-arrested HUVECs which are starved in a medium containing 2%, FBS alone, suggesting that h-rTFPI directly induces the death of these HUVECs. This hypothesis is supported by the finding that h-rTFPI does not inhibit the synthesis of DNA in HUVECs during proliferation, as shown by a 5-bromo-2'-deoxyuridine (BrdU) incorporation assay. Furthermore, Giemsa staining and a gel electrophoretic analysis of DNA fragmentation show that the HUVEC death mediated by h-rTFPI has the typical characteristics of apoptosis. However, the apoptosis in HUVECs is considerably inhibited in the presence of 1 microg/ml of the protein synthesis inhibitor, cycloheximide. Therefore, the process of apoptosis triggered by h-rTFPI is, at least in part, actively conducted by the cells.

Adaptor Proteins, Signal Transducing↗