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Biomedical subjects

K Satoh

Publications and source records attributed to K Satoh.

At least 631 records · Page 35Linked to original sources

Reversibility of cerebral ischaemia. Dynamic and xenon computed tomography study on ischaemic cerebrovascular disease.

Flow studies using dynamic CT and xenon (Xe) CT were carried out in 25 patients with ischaemic stroke in the territory of the middle cerebral artery to define the clinical characteristics of cerebral ischaemia at a chronic stage. The parameter of peak height/mean transit time (PH/MTT) obtained from dynamic CT can provide an accurate index for blood circulation in the cerebral vascular bed. Xe CT measurements revealed various kinds of ischaemia around the infarction even in the chronic stages. In mild ischaemia of more than 30 ml/100 g/min, reduction of cerebral blood flow (CBF) was well correlated to the PH/MTT. However, in severe ischaemia between 20 and 30 ml/100 g/min, changes of CBF were no longer correlated with the PH/MTT. There were cases showing severe reduction of CBF but which showed sufficient blood circulation (moderate value of PH/MTT). Mild reductions of CBF in parallel with decreased blood supply were often found in the peri-infarct area of infarctions in the centrum semiovale. On the other hand, infarctions in the cortico-subcortical region showed severe ischaemia, in even where blood circulation was relatively well sustained.

Adult↗

Bilateral giant bullae with rapidly increasing fluid in the right bulla following operation: report of a case.

A 33-year-old Japanese male was admitted to our hospital for the treatment of left pneumothorax. He was found to have bilateral giant bullae. Retention of fluid was observed in the right giant bulla. The fluid accumulated rapidly directly after bullectomy and excision of the left giant bullae. This suggested the existence of some mechanisms of fluid retention other than an infection of the bulla alone after operation.

Adult↗

Infrequent stromal expression of gelatinase A and intact basement membrane in intraductal neoplasms of the pancreas.

BACKGROUND/AIMS: Basement membrane disruption is a characteristic of invasive carcinoma. Gelatinases (also called type IV collagenases) that degrade type IV collagen are believed to play an important role in tumor invasion and metastasis. Intraductal neoplasm (IDN) of the pancreas is a unique tumor that grows intraductally with an infrequent stromal invasion. However, in IDN, basement membrane anomaly and gelatinase expression have not been clarified. The aim of this study was to examine the relationships between basement membrane disruption and the expression of gelatinase A in relation to the biological behavior of IDN or pancreatic duct cell carcinoma (DCC). METHODS: Disruption of basement membrane and expression of gelatinase A were immunohistochemically investigated in 14 cases of IDN and 16 cases of DCC. RESULTS: Basement membrane was intact in all cases of IDN, whereas focal to severe disruption was observed in DCC. Stromal expression of gelatinase A was higher in DCC than in IDN, and the intensity of expression was related to the degree of disruption of the basement membrane in DCC. CONCLUSIONS: Stromal expression of gelatinase A and disruption of basement membrane, common characteristics of invasive cancer, were not prominent in IDN. This may be related to the benign biological behavior of IDN.

Aged↗

Phosphatase inhibitors suppress Ca2+ influx induced by receptor-mediated intracellular Ca2+ store depletion in human platelets.

The effects of three phosphatase inhibitors including okadaic acid, calyculin A and tautomycin were evaluated on platelet Ca2+ mobilization. Calyculin A and tautomycin at appropriate concentrations appeared to have a selective inhibitory effect on thrombin-induced Ca2+ influx, but not on [Ca2+]i release from intracellular Ca2+ storage sites. In contrast, pretreatment with okadaic acid at concentrations that effectively lowered Ca2+ influx also suppressed Ca2+ release from intracellular Ca2+ stores. In a system that specifically evaluates the effects of agents on Ca2+ influx induced by the Ca(2+)-depleted state of intracellular Ca2+ storage sites, the three phosphatase inhibitors attenuated Ca2+ influx in a dose dependent manner and showed complete inhibition at appropriate concentrations. These findings suggest that protein phosphorylation/dephosphorylation plays an important role in mediating signals to open Ca2+ channels when Ca2+ depletion in intracellular Ca2+ stores is caused by thrombin. In contrast, Ca2+ influx induced by thapsigargin, a Ca(2+)-ATPase inhibitor, was only partially suppressed by pretreatment with each of the three phosphatase inhibitors. Based on these findings, we suggest that the Ca(2+)-depleted state of intracellular Ca2+ stores by thapsigargin induces the opening of Ca2+ channels via phosphatase inhibitor-insensitive pathways. All the phosphatase inhibitors, at the highest concentrations tested in the present study, only partially inhibited Mn2+ entry induced by thrombin. These findings suggest that there are at least two types of divalent ion channels on platelet plasma membranes and that one of them, that preferentially allows Mn2+ entry, is resistant to the inhibitory effects of phosphatase inhibitors.

Antifungal Agents↗

Hospital-wide PACS with a digital image intensifier TV system.

Tokyo Hitachi Hospital, Hitachi Ltd., has used a hospital-wide PACS for over 1 year. The system runs a 100 Mb/s optical fiber network over the whole hospital including wards and outpatient clinic rooms, with 11 image workstations. The network links digital imaging modalities such as X-CT, MRI, computed radiography (CR) and digital radiography (DR) with a 2048 x 2048 (2k x 2k) matrix image intensifier television (I.I.-TV) system. These modalities generate about 200 images/day. The system has managed over 300,000 images of about 8000 patients so far. Although being still under improvement, the system has really been used for routine work. The hospital-wide PACS of a small hospital has been proved to be very useful for both image diagnosis and image management.

Computer Terminals↗

Technology assessment of PACS in Osaka University Hospital.

This paper describes a methodology of PACS technology assessment and gives examples of the results of measurement of 24 items of PACS-related situations of image diagnosis systems in Osaka University Hospital before a PACS is installed. These data are to be compared with the data which will be measured after PACS is installed in the new Osaka University Hospital, in order to complete our technology assessment. We propose common variables, units, and conditions of measurement, in order to establish a standard method of data comparison between before and after PACS installation in hospitals at large. We designed our PACS taking technology assessment into account. We do not stop the technology assessment at the efficacy evaluation, because PACS must be more than a tool for radiological practice. We extend the technology assessment into the effectiveness evaluation, so that PACS is a part of radiological practice itself, and diagnostic accuracy, economy and efficiency are the results of PACS operation.

Diagnostic Imaging↗

Sclerodermatous renal crisis in a patient with mixed connective tissue disease.

We report a patient with mixed connective tissue disease who developed accelerated hypertension, acute renal insufficiency, and microangiopathic hemolytic anemia. A renal biopsy specimen showed marked vascular changes in small arteries consisting of laminated endothelial cell proliferation and luminal thrombosis, which were similar to those of scleroderma renal crisis. This patient was successfully treated with an angiotensin-converting enzyme inhibitor as well as analogues of prostaglandin E1 and prostaglandin I2. In patients with mixed connective tissue disease, a fatal complication like scleroderma renal crisis should be considered when the blood pressure rapidly increases. The combined administration of angiotensin-converting enzyme inhibitors and analogues of prostaglandin E1 and prostaglandin I2 may be an effective treatment for this complication.

Acute Kidney Injury↗

c-Jun expression in single cells and preneoplastic foci induced by diethylnitrosamine in B6C3F1 mice: comparison with the expression of pi-class glutathione S-transferase.

Expression of the oncogene product c-Jun was examined and compared with that of class pi glutathione S-transferase (GST-II) during chemical hepatocarcinogenesis in female and male mice. A single i.p. injection of diethylnitrosamine (DEN) (10 mg/kg) was administered to B6C3F1 mice and livers were immunohistochemically investigated with anti-c-Jun and anti-GST-II antibodies at various time points thereafter. In females, almost all foci detected by hematoxylin and eosin staining were positive for c-Jun 3, 6, 9 and 11 months after the DEN administration. Seventy-one and 82% of c-Jun-positive foci at 9 and 11 months respectively, were also positive for GST-II, while this was the case for only 15% at 6 months. In males almost all foci were also positive for c-Jun at 3 and 6 months, but 23% of foci were negative at 9 months. Unlike the foci in females, 96 and 79% of those in males expressing c-Jun were negative for GST-II at 6 and 9 months respectively. Both GST-II expression in foci of females and its lack in those of males were highly correlated with c-Jun expression. Furthermore, single cells expressing c-Jun were also observed in both sexes at 3 months and thereafter, but not at 2 or 4 weeks. Alterations in the numbers of c-Jun-positive single cells, minifoci and foci followed sequentially revealed the number of such single cells to decrease, while foci increased, the sum being relatively constant. On the other hand, while a large number of GST-II-positive single cells were detected in female livers 2 and 4 weeks after the DEN administration, they markedly decreased thereafter, suggesting that the majority were unlikely to give rise to foci. Thus, c-Jun may be a better positive marker not only for preneoplastic foci, but also putative precursor single cells in both female and male mice and therefore be useful for analysis of hepatocarcinogenic processes.

Animals↗

Simultaneous stereoinversion and isomerization at specific aspartic acid residues in alpha A-crystallin from human lens.

We characterized the primary structure of alpha A-crystallin from the lens of the human eye by detailed analyses of the amino acid sequence, mass, and stereoisomers, and found the biologically uncommon D- and beta-aspartic acid (Asp) residues in the protein. The stereoconfiguration of the Asp151 and Asp58 residues in alpha A-crystallin from old subjects (mean age: 80 years) was inverted to the D-isomer, and the residues were simultaneously isomerized to beta-aspartyl residues, which may occur via a succinimide intermediate. This is thought to be the first observation of stereoinversion of amino acids in protein in vivo. It is noteworthy that similar stereoinversion was observed in the same residues of alpha A-crystallin from young subjects (age: 11 months), with simultaneous isomerization, although the extent of isomerization was low compared with that in the aged. The conversion may take place in the early life of the lens and the resulting isomers may accumulate with aging. We also found that terminal serine173 was cleaved in aged alpha A-crystallin. Since the cleavage was not observed in young alpha A-crystallin, it may result from the in vivo aging process. The present findings also make it necessary to revise the amino acid sequence of human alpha A-crystallin presented previously: human alpha A-crystallin is composed of 173 (formerly reported as 172) amino acid residues, and the sequence from residues 153 to 155 is THA (formerly reported as -HT).

Aging↗

Improved method of preparation of inflated-fixed lung for radiologic-pathologic correlation.

The technique of inflation and fixation of the lung with polyethylene glycol is useful for specimen radiography and radiologic-pathologic correlation, but it is limited by poor histologic staining of the fixed tissue. To improve staining we used formalin to distend and fix the lung before standard fixation with a polyethylene glycol mixture. In this preliminary study, canine and infant lungs, and lungs from three cases of lung cancer were examined. The modified technique provided high-quality staining and satisfactory specimen radiography in all cases except one of the lung cancers; in this case excessive shrinkage occurred and degraded radiographic quality. We conclude that the new method of preparation permits both specimen radiography and high quality staining of the fixed tissue.

Adult↗

Restriction fragment length polymorphism of the human CYP2E1 (cytochrome P450IIE1) gene and susceptibility to lung cancer: possible relevance to low smoking exposure.

Polymorphic metabolism of certain chemical carcinogens may result in differences in susceptibility to cancers. Human CYP2E1 (cytochrome P450IIE1) is an enzyme involved in the metabolic activation of precarcinogens such as nitrosamines. We detected a restriction fragment length polymorphism (RFLP) of the human CYP2E1 gene for the restriction endonuclease Dra I. The distribution of this polymorphism was examined among lung cancer patients (n = 91), patients with cancer of the digestive tract (n = 45) and controls (n = 76). A significant difference in the distribution was observed between lung cancer patients and controls (chi 2 = 11.4 with 2 df; p < 0.005). On the other hand, there was no significant difference between patients between cancer of the digestive tract and controls (chi 2 = 4.87 with 2 df; NS). This finding suggests that the Dra I polymorphism of the CYP2E1 gene is associated with susceptibility to lung cancer. In addition, an association was found between the amount of lifelong smoking exposure and the distribution of the genotypes of the RFLP among lung cancer patients. The distribution pattern seemed deviated from that of controls especially in the population of low smoking exposure. Our Northern blot analysis data using RNA from human liver autopsy samples suggest that the Dra I polymorphism might be associated with the gene expression of CYP2E1 at mRNA level.

Aged↗

Effects of induced hypotension on arterial blood-gases under spontaneous breathing.

The effects of deliberate hypotension on both PaO2 and PaCO2 were investigated under isoflurane anaesthesia with spontaneous breathing from a laryngeal mask. Lumbar epidural block was introduced; anaesthesia was induced with thiamylal (4 mg.kg-1) and maintained with 0.5% isoflurane in nitrous oxide (4 l.min-1) and oxygen (2 l.min-1) under spontaneous breathing. After that nitroglycerin, trimetaphan or prostaglandin E1 were used to induce a hypotension of 70% of control. All three drugs significantly decreased PaO2, from 19.9 +/- 3.3, 19.2 +/- 2.7, and 19.6 +/- 3.1 kPa to 14.6 +/- 1.9, 16.6 +/- 2.2, and 16.2 +/- 2.4 kPa (mean +/- s.d.), respectively; none of them increased PaCO2. In spite of the sparing of functional residual capacity under spontaneous breathing, the levels of reduction of PaO2 were the same as levels reported in paralyzed and mechanically ventilated subjects. In conclusion, under deliberate hypotension PaO2 decreases to a considerable degree, even under spontaneous breathing, presumably not because of alveolar hypoventilation, but because of the suppression of hypoxic pulmonary vasoconstriction by the drugs used in this study.

Adult↗

Activities of phospholipase A2, cyclooxygenase, and PGI2 synthase of umbilical venous endothelial cells in preeclamptic women.

To elucidate the cause of low prostacyclin (PGI2) production in severe preeclampsia (PE), we studied the activities of phospholipase A2, cyclooxygenase, and PGI2 synthase in umbilical venous endothelial cells obtained from healthy pregnant women and from patients with mild or severe PE. Umbilical venous endothelial cells homogenized in a buffer solution were analysed by calculating the apparent Vmax (mean +/- SEM: p mol/min mg protein) and Km (mean +/- SEM: microM) values for phospholipase A2 activity by the release of arachidonic acid from phosphatidylcholine, for the activity of a complex of cyclooxygenase and PGI2 synthase by the conversion of arachidonic acid to PGI2, and the activity of PGI2 synthase by conversion of PGH2 to PGI2. The phospholipase A2 activity of normal-pregnancy cells (Vmax: 17.0 +/- 2.7 Km: 0.26 +/- 0.04) (n = 10) significantly exceeded that of cells from women with either mild PE (5.8 +/- 0.5, 0.12 +/- 0.02) (n = 4) or severe PE (6.3 +/- 2.0, 0.08 +/- 0.03) (n = 5). The apparent combined activity of cyclooxygenase and PGI2 synthase in mild PE (552 +/- 142, 0.29 +/- 0.07) (n = 8) significantly exceeded that of a normal pregnancy (176 +/- 42, 0.76 +/- 0.25) (n = 7), whereas that in severe PE (326 +/- 36, 3.26 +/- 0.78) (n = 3) was significantly lower than that of a normal pregnancy. PGI2 synthase activity in mild PE (305 +/- 50, 0.12 +/- 0.07) (n = 4) exceeded that of a normal pregnancy (220 +/- 45, 0.13 +/- 0.06) (n = 5), whereas that in severe PE (55 +/- 12, 0.16 +/- 0.04) (n = 3) was lower than that of a normal pregnancy. The phospholipase A2 activity in cells of normal pregnant women exceeded that of cells of women with mild or severe PE. The combined activity of cyclooxygenase and PGI2 synthase in a normal pregnancy was lower than in mild PE, but higher than in severe PE. Similar results were found for PGI2 synthase activity; in normal pregnancy the activity was less than in mild PE, but higher than in severe PE.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Pyrazolopyridine derivative acts as a novel cyclooxygenase inhibitor: antiplatelet effect in aged patients with ischemic stroke.

OBJECTIVE: To examine the antiplatelet effect of a novel pyrazolopyridine derivative (KC-764) in geriatric patients with ischemic stroke. DESIGN: Randomized clinical trial of three graded dose levels. SETTING: A geriatric clinic attached to a nursing home. PATIENTS: Fifteen patients with a history of cerebral infarction with a mean age of 75 +/- 5 years (range, 65-83). Patients were divided into three groups and administered 10, 20, or 40 mg/day KC-764 for 8 weeks. MEASUREMENTS: Platelet aggregation induced by arachidonate, ADP, collagen and platelet-activating factor. Plasma or serum levels of thromboxane B2 and 6-ketoprostaglandin F1 alpha. MAIN RESULTS: Platelet aggregation was inhibited by KC-764 administration and returned to the control level after discontinuation. Although plasma thromboxane B2 levels were markedly decreased, plasma 6-ketoprostaglandin F1 alpha was not affected. However, the dose of 10 mg/day was not sufficient to maintain an effective plasma level of KC-764. There were no side effects or changes in laboratory findings. CONCLUSIONS: We confirmed that KC-764 at a dose of 20 to 40 mg/day is an effective antiplatelet agent and a good candidate for a trial to see if it is feasible for long-term use for the prevention of ischemic stroke in high-risk patients.

6-Ketoprostaglandin F1 alpha↗

Proliferation-dependent changes in release of arachidonic acid from endothelial cells.

Stimulation of endothelial cells resulted in release of arachidonic acid from phospholipids. The magnitude of this response decreased as the cells became confluent and the change coincided with a decrease in the percentage of cells in growth phases (G2+M); this was not a consequence of time in culture or a factor in the growth medium. Preconfluent cells released approximately 30% of arachidonic acid; confluent cells released only 6%. The decreasing release of arachidonic acid was demonstrated using metabolic labeling, mass measurements of arachidonic acid, and measurement of PGI2. The decrease was not due to a changing pool of arachidonic acid, and mass measurements showed no depletion of arachidonic acid. Release from each phospholipid and from each phospholipid class decreased with confluence. Conversion of confluent cells to the proliferative phenotype by mechanical wounding of the monolayer caused increased release of arachidonic acid. Potential mechanisms for these changes were investigated using assays of phospholipase activity. Phospholipase A2 activity changed in concert with the alteration in release, a consequence of changes in phosphorylation of the enzyme. The increased release of arachidonic acid from preconfluent, actively dividing cells may have important physiologic implications and may help elucidate mechanisms regulating release of arachidonic acid.

Animals↗

Prostacyclin (PGI) receptor binding and cyclic AMP synthesis activities of PGI1 analogues, SM-10906 and its methyl ester, SM-10902, in mastocytoma P-815 cells.

The prostacyclin I1 (PGI1) analogue, SM-10906 and its methyl ester, SM-10902, have been compared with the PGI2 analogue, iloprost, with respect to binding to the PGI2 receptor, stimulation of adenylate cyclase activity and inhibition of thrombin-induced Ca2+ mobilization in mastocytoma P-815 cells. SM-10906 displaced [3H]iloprost binding to the membrane fraction, the IC50 value being 100 nM, but showed very low affinity for the prostaglandin E (PGE) receptor. SM-10906 dose-dependently stimulated GTP-dependent adenylate cyclase activity in the membrane fraction, the EC50 value being 35 nM. Furthermore, SM-10906 prevented a thrombin-induced increase in the intracellular Ca2+ concentration, the IC50 value being 300 nM. These IC50 and EC50 values are much lower than those of SM-10902. These results demonstrate that SM-10906, a stable PGI1 derivative, is an agonist for the [3H]iloprost-binding (PGI2) receptor, and that it prevents thrombin-induced Ca2+ mobilization through stimulation of the adenylate cyclase system in mastocytoma cells. On the other hand, a methyl ester derivative of PGI1, SM-10902, was inactive in the binding assay, but it seems to be a partial agonist for adenylate cyclase activity [corrected].

Adenylyl Cyclases↗