Biomedical subjects

H Okabe

Publications and source records attributed to H Okabe.

At least 181 records · Page 10Linked to original sources

PubMed1996

Potentiation of carbon tetrachloride-induced liver damage by dibutylyl-3',5'-cyclic AMP in unstarved rats.

It has been reported that carbon tetrachloride-induced liver damage is potentiated by starvation partly due to fat accumulation in the liver and a decrease in hepatic reduced glutathione concentration and that dibutylyl-3',5'-cyclic AMP (DBcAMP) affects fuel metabolism and decreases hepatic reduced glutathione. We investigated the effects of DBcAMP on carbon tetrachloride-induced liver damage both in unstarved and starved rats. In unstarved rats, intraperitoneal administration of DBcAMP potentiated an increase in serum alanine aminotransferase activity and fatty vacuolization in the liver, both of which were induced by carbon tetrachloride. Hepatic reduced glutathione concentration was also reduced by DBcAMP, although the change was not significant. In contrast, the administration of DBcAMP in starved rats did not affect carbon tetrachloride-induced changes in serum alanine aminotransferase activity, histological alterations and hepatic reduced glutathione concentration. Administration of DBcAMP to control rats induced different responses in unstarved control rats compared with starved control rats: in unstarved rats, blood glucose concentration decreased but serum free fatty acid concentration increased, whereas in starved rats, blood glucose concentration increased and serum free fatty acid concentration decreased. It was suggested that DBcAMP potentiated carbon tetrachloride-induced liver damage in unstarved rats, probably due to hepatic fat accumulation and a decreased hepatic reduced glutathione concentration. The former could increase the affinity of the liver for carbon tetrachloride and the latter could accelerate carbon tetrachloride-induced lipid peroxidation. It was also suggested that DBcAMP failed to affect carbon tetrachloride-induced liver damage in starved rats, probably because starvation had already decreased hepatic glutathione concentration and DBcAMP had different effects on fuel metabolism compared with effects observed in unstarved rats.

Alanine Transaminase↗

PubMed1996

Attenuation of endotoxin-induced pulmonary vascular injury by antithrombin III.

We evaluated the effects of antithrombin III (AT III) on the pulmonary vascular injury induced by injecting rats with lipopolysaccharide (LPS) to investigate the possible usefulness of AT III as a treatment for acute respiratory distress syndrome. The intravenous administration of AT III prevented the pulmonary accumulation of leukocytes (as evaluated by myeloperoxidase activity) and the increase in pulmonary vascular permeability to 125I-bovine serum albumin induced by LPS. The increase in pulmonary vascular permeability induced by LPS administration was unaffected by various anticoagulants but was inhibited by the leukocytopenia induced by nitrogen mustard or by the administration of a granulocyte elastase inhibitor, ONO-5046. AT III given alone, but not heparin plus AT III or Trp49-modified AT III, which lacks affinity for heparin, significantly increased the plasma concentration of 6-keto-prostaglandin F1alpha, suggesting that the interaction of AT III with heparin-like substances at the endothelial cell surface promotes the release of prostacyclin from endothelial cells in vivo. Trp49-modified AT III failed to prevent the LPS-induced accumulation of leukocytes and vascular injury. The pulmonary accumulation of leukocytes and vascular injury induced by LPS were not prevented by administering AT III to rats that were pretreated with indomethacin. The continuous intravenous infusion of prostacyclin prevented the LPS-induced pulmonary accumulation of leukocytes and vascular injury. Findings suggest that AT III depends on its ability to promote the release of prostacyclin, a potent inhibitor of leukocyte activation, from endothelial cells to prevent pulmonary vascular injury induced by LPS.

6-Ketoprostaglandin F1 alpha↗

PubMed1996

Recombinant thrombomodulin prevents endotoxin-induced lung injury in rats by inhibiting leukocyte activation.

Acute respiratory distress syndrome (ARDS) is a serious complication of sepsis. Thrombomodulin, an important endothelial anticoagulant, binds thrombin to generate activated protein C (APC). We have previously demonstrated that APC prevents endotoxin (ET)-induced pulmonary vascular injury by inhibiting activated leukocytes. We therefore examined whether recombinant human soluble thrombomodulin (rhs-TM) prevents activated leukocyte-induced pulmonary vascular injury in rats receiving ET. Intravenous administration of rhs-TM prevented ET-induced pulmonary accumulation of leukocytes and increase in pulmonary vascular permeability, as well as ET-induced histological changes, such as leukocyte infiltration and pulmonary interstitial edema. Dansyl-Glu-Gly-Arg-chloromethyl ketone-treated factor Xa (DEGR-Xa), a selective inhibitor of thrombin generation, did not prevent these effects of ET. rhs-TM did not prevent ET-induced pulmonary accumulation of leukocytes and pulmonary vascular injury in rats pretreated with DEGR-Xa. These results suggest that rhs-TM prevents ET-induced pulmonary vascular injury by inhibiting pulmonary accumulation of leukocytes and that this effect may be mediated primarily by APC generation.

Animals↗

PubMed1996

Direct inhibitory effect of thyrotropin-releasing hormone on isolated cecal circular smooth muscle cells of guinea pig.

Smooth muscle cells isolated from cecal circular smooth muscle of the guinea pig were used to determine whether thyrotropin-releasing hormone (TRH) can inhibit the contractile response produced by 10(-6) M carbachol by exerting a direct action on muscle cells. In addition, the inhibitory effect of 2',5'-dideoxyadenosine (an inhibitor of adenylate cyclase), phorbol 12-myristate 13-acetate (an inhibitor of particulate guanylate cyclase), 6-anilinoquinoline-5,8-quinone (an inhibitor of nitric oxide synthase) on the TRH-induced relaxation of cecal circular smooth muscle cells was examined. TRH inhibited the contractile response produced by 10(-6) M carbachol in a concentration-dependent manner, with an IC50 value of 4 nM, 2',5'-Dideoxyadenosine and phorbol 12-myristate 13-acetate did not have any significant effect on the TRH-induced relaxation. On the other hand, 6-anilinoquinoline-5,8-quinone and N omega-nitro-L-arginine methyl ester significantly inhibited the relaxation produced by TRH. Our findings show that TRH has a direct inhibitory effect on the isolated cecal circular smooth muscle cells via activation of nitric oxide synthase and soluble guanylate cyclase.

Aminoquinolines↗

PubMed1996

The difference between the changes in systemic oxygen consumption during orthotopic liver transplantation and those during extracorporeal hepatic resection.

Every organ in the body requires oxygen to perform its function. In liver transplantation and extracorporeal hepatic resection, oxygen utilization by the graft or the re-implanted liver is a prerequisite for restoration of liver function. We compared the changes in systemic oxygen consumption in a patient who underwent orthotopic liver transplantation with those in two patients who underwent extracorporeal hepatic resection. The pre-anhepatic systemic oxygen consumption in the patient who underwent orthotopic liver transplantation seemed to be lower than that in the patients who underwent extracorporeal hepatic resection, possibly due to the depressed oxygen utilization which sometimes occurs in cirrhotic patients. The increase in oxygen consumption or the overconsumption of oxygen after reperfusion was more significant in the patient who underwent orthotopic liver transplantation than in the patients who underwent extracorporeal hepatic resection. The possible causes might be the greater hepatic oxygen debt, an associated intestinal oxygen debt, and/or the greater ischemia/reperfusion-induced overproduction of superoxide anion in the patient who underwent orthotopic liver transplantation. The differences between the changes in systemic oxygen consumption during orthotopic liver transplantation and those during extracorporeal hepatic resection further support the usefulness of systemic oxygen consumption to predict the immediate restoration of blood flow and oxygen utilization in the graft or the re-implanted liver. These findings also support the importance of evaluating oxygen consumption to confirm whether the critically ill or unconscious patient can utilize oxygen on demand or not.

Female↗

PubMed1996

Severe anemia in a patient with isolated adrenocorticotropin deficiency.

A 64-year-old man was referred to our hospital for evaluation of progressive anemia. On admission, he had a severe normocytic normochromic anemia [hemoglobin 7.5 g/dl] requiring a blood transfusion. Endocrinological studies demonstrated an isolated ACTH deficiency. After receiving glucocorticoid replacement therapy, his anemia was rapidly corrected, his hematocrit and hemoglobin remained elevated for approximately 4 months. We present evidence that glucocorticoid plays an important role in the physiological regulation of human erythropoiesis.

Adrenocorticotropic Hormone↗

PubMed1996

[Plasma allantoin in patients undergoing maintenance hemodialysis].

Recently, it has been noted that radical molecules participate in the pathogenesis of some of the complications associated with long-term dialysis therapy, such as amyloidosis. Since allantoin is produced from uric acid almost exclusively by the hydroxy radical, we investigated the plasma concentrations of allantoin in 71 patients with chronic renal failure who were on maintenance hemodialysis. Our specific objective was to investigate the relation of allantoin to the plasma concentrations of beta2-microglobulin and methylguanidine to evaluate the potential of allantoin as a significant parameter of the radical reaction. Although plasma allantoin was not detected in 15 healthy controls, plasma concentrations of allantoin increased markedly in all of the hemodialysis patients (42.6 +/- 37.7 nmol/mL) and wide variation was observed from 4.3 to 185.2 nmol/mL. In addition, we confirmed significant correlations between plasma concentrations of allantoin and beta2-microglobulin as well as serum concentrations of methylguanidine/creatinine and hyaluronic acid (r - 0.456, p < 0.0005, r = 0.313, p < 0.005, r = 0.368, p < 0.01, respectively). Although evidence for a direct link between plasma allantoin levels and amyloidosis was not obtained, the increase in the plasma concentrations of allantoin suggested its clinical significance as a parameter of the radical reaction that is thought to participate closely in the pathogenesis of dialysis-related amyloidosis. From a practical point of view, the measurement of plasma allantoin can be expected to become a significant method of measuring radical members which may be useful in the prophylaxis of some of the complications induced by free radicals.

Adolescent↗

PubMed1996

[Anomalous origin of the left coronary artery from the pulmonary artery coronary revascularization under normothermic coronary perfusion in an infant].

A 5-months-old baby was hospitalized with congestive heart failure. Anomalous origin of the left coronary artery from the pulmonary artery was diagnosed on echo cardiography and coronary angiogram. Preoperative examination revealed severe left ventricular dysfunction (left ventricular end-diastolic pressure was 32 mmHg, left ventricular ejection fraction was 16%). Coronary revascularization was performed by anastomosis of the neo-left coronary artery to the aorta using an autologous pulmonary arterial roll under normothermic coronary perfusion. Although postoperative CPK-MB was within normal limits, the patient died on the 12th postoperative day due to ventricular arrythmia. Autopsy revealed severe endomyocardial fibroelastosis.

Cardiac Surgical Procedures↗

PubMed1996

A novel platelet activating factor antagonist, SM-12502, attenuates endotoxin-induced disseminated intravascular coagulation and acute pulmonary vascular injury by inhibiting TNF production in rats.

Adult respiratory distress syndrome and disseminated intravascular coagulation are important pathologic conditions affecting the outcome of patients with sepsis. To elucidate the possible therapeutic efficacy of SM-12502, a novel platelet activating factor antagonist, on acute lung injury and disseminated intravascular coagulation in sepsis, we investigated the effect of SM-12502 on an endotoxin (ET)-induced septic model in rats. SM-12502 prevented ET-induced increases in pulmonary vascular permeability and ET-induced histologic changes, such as leukocyte infiltration and pulmonary interstitial edema, 6 h following the administration of ET (5 mg/kg). SM-12502 also inhibited the decrease in fibrinogen and the increase in fibrin and fibrinogen degradation products observed following ET administration. SM-12502 prevented increases in the serum concentration of tumor necrosis factor (TNF) 90 min following ET administration in vivo, and significantly inhibited the production of TNF-alpha by ET-stimulated monocytes in vitro. These findings suggest that SM-12502 attenuates the actions of endotoxin by the inhibition of TNF production.

Animals↗

PubMed1996

[Long-term patency after the Blalock-Taussig operation--comparison between classic and modified shunts].

There is still a need for Blalock-Taussig shunt (BTS) in some situations involving complex heart diseases. This study demonstrates the long-term patency after shunt procedure in classic and modified BTS of different calibers using cineangiographic evaluation. Between January 1980 and December 1994, 150 patients 236 BTS including classic BTS (cBTS) in 62, modified in 174 procedures (GS: Golaski microknit graft in 112, EPTFE: expanded polytetrafluoroethylene graft in 62). Cineangiographic Evaluation for graft patency and freedom from stenosis (less than 50% in diameter) was performed a mean interval of 35 months after BTS. The five-year patency of cBTS was significantly superior to that of mBTS (EPTFE, p < 0.001). There was a significant superiority of three-year actuarial freedom from graft stenosis in cBTS compared to that after mBTS with GS (p < 0.01) and in mBTS with EPTFE compared to mBTS with GS (p < 0.05). In cases receiving small caliber grafts (4 mm or less), cBTS showed significantly better patency after five years compared to mBTS with GS (p < 0.05) and showed significant advantages in three-year actuarial freedom from graft stenosis compared to that after mBTS (p < 0.05). This study demonstrated the superior patency and freedom from stenosis after cBTS compared to that after mBTS, especially in cases receiving GS grafts. MBTS with GS graft and with small caliber EPTFE grafts could not be expected to maintain freedom from stenosis for three years.

Adolescent↗

PubMed1996

Analysis of the presence of osteocalcin, S-100 protein, and proliferating cell nuclear antigen in cells of various types of osteosarcomas.

Osteosarcomas are characterized by different histologic subtypes that are composed of heterogeneous tumor cells. Although the histological origin of the malignant cells is unknown, it has been speculated that osteoblasts lead to the malignant cells. In the current study, the osteosarcoma cells in 27 lesions were assessed by means of immunohistochemical staining for osteocalcin (OC), S-100 protein (S-100) and proliferating cell nuclear antigen (PCNA). PCNA labeling indices were the highest in osteoblastic and stromal areas, and significantly lower in chondroblastic areas (p < 0.01). Cells that were positive for both PCNA and OC were abundant in osteoblastic and stromal areas, while cells that were positive for both PCNA and S-100 were rarely observed. These results were almost similar for conventional, parosteal and periosteal osteosarcomas. In contrast, OC reactivity was poor in fibroblastic osteosarcoma, in osteosarcoma with giant cells, and in telangiectatic osteosarcoma. Pulmonary metastatic osteosarcoma lesions weakly expressed OC (p < 0.01), but showed high values for the PCNA labeling indices. In conclusion, immunohistochemical staining for OC, S-100, and PCNA are useful to analyze the proliferating cells in osteosarcomas. The main proliferating cells in most osteosarcomas are mature osteoblast-like cells. OC-negative tumor cells predominate in some of osteosarcoma subtypes, and these tumors therefore probably represent a distinct osteosarcoma variant. OC expression in pulmonary metastatic lesions may be suppressed.

Adolescent↗

PubMed1996

[Biochemistry of risk factors for cardiovascular diseases in laboratory medicine].

This paper provides a broad overview of biochemical risk factors such cholesterol and triglyceride in atherosclerotic cardiovascular diseases from the perspective of clinical laboratory medicine, since additional knowledge is needed in the genetic, biochemical, clinical and epidemiological spheres. Lipids play an important role in cell metabolism. Fatty acids and triglycerides, their storage form, are a high energy metabolic fuel. Cholesterol and phospholipids are essential components of cell membranes and cholesterol is a precursor of steroids. Cholesterol is delivered to the liver either from the intestine following dietary intake or is transported from extrahepatic tissues. It is removed from the liver through incorporation into lipoproteins by conversion into bile acids, and by secretion into bile. Lipoproteins are transported between tissues and organs in the form of particles. Lipoproteins are metabolically inert and apolipoproteins involve enzyme activation and inhibition of lipoprotein lipase, hepatic triglyceride lipase and lecithin-cholesterol acyltransferase. There is an exchange of components between lipoprotein particles facilitated by the cholesterol ester transfer protein. Lipoprotein receptors control the rate of cellular uptake and degradation and indirectly the rate of de novo cholesterol synthesis and individual subclasses of major lipoprotein species as well as the apolipoproteins and even the products of oxidative damage inflicted on the lipoprotein. This paper summarizes the relevant physiological and clinical knowledge and reviews a series of very practical data that must be understood to accurately quantify laboratory parameters.

Arteriosclerosis↗

PubMed1996

[Aprotinin reduces homologous blood transfusions when pediatric cardiac surgery must be redone].

The hemostatic effect of aprotinin in pediatric cardiac surgery is controversial. This study demonstrated the usefulness of aprotinin in cases undergoing additional surgery. In a retrospective study, three groups of children were investigated. In group I (n = 10), no aprotinin or Cell saver was used (control). In group II (n = 12), Cell saver was used intraoperatively. In group III (n = 14), aprotinin 30,000 KIU/kg was added to the prime of cardiopulmonary bypass, and another 10,000 KIU/kg was given every hour during extracorporeal circulation. Both blood loss and use of homologous blood during operation were significantly (p < 0.01) reduced in group III compared to those in the other two groups. In group III, blood loss both 12 and 48 hours postoperatively were one-third less than those in group I (no significant difference). The use of homologous blood 48 hours postoperatively was significantly reduced in group III compared to that in group I (p < 0.01) or group II (p < 0.05). We conclude that aprotinin administration during cardiopulmonary bypass reduced blood loss and homologous blood requirements both operatively and postoperatively when pediatric cardiac surgery must be redone.

Aprotinin↗

PubMed1996

Expression of heat shock protein 70 (HSP70) and EBV latent membrane protein 1 (LMP1) in Reed-Sternberg cells of Hodgkin's disease.

Tissue sections embedded in paraffin and fixed in formalin from 65 patients with Hodgkin's disease (HD) were examined for the presence of heat shock protein 70 (HSP70) and Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) using avidin-biotin immunoperoxidase complex technique. The staining results in Reed-Sternberg (R-S) cells and their variants were evaluated independently. HSP70 expression was found in R-S cells in 55 cases (85%) of HD examined and the frequency of HSP70 positive cases was significantly higher than that of HSP70 negative cases (P < 0.01). This protein was present in pathogenic cells in 9/12 cases (75%) of lymphocyte predominant Hodgkin's disease (LPHD), 21/27 cases (78%) of mixed cellularity Hodgkin's disease (MCHD), 10/10 cases (100%) of lymphocyte depleted Hodgkin's disease (LDHD) and 15/16 cases (94%) of nodular sclerosing Hodgkin's disease (NSHD). The association between HSP70 expression and HD thus appeared to be more frequent in patients wish LDHD and NSHD subtypes, although examples of HSP70-positive tumors were found in all histological subtypes. Studies of non-neoplastic lymphoid tissues demonstrated that centroblasts (large lymphocytes in germinal centers) were constantly positive; occasional histiocytes revealed variable reactivity for.

HSP70 Heat-Shock Proteins↗

PubMed1996

[The role of xanthine dehydrogenase (xanthine oxidase) in ischemia-reperfusion injury in rat kidney].

Xanthine dehydrogenase (XDH) and xanthine oxidase (XO) are enzymes involved in the metabolism of purines in various organisms. XO produces superoxide radicals, suggesting that is responsible for tissue ischemia-reperfusion injury. To test this notion further studies were performed on rat kidneys and the time course of changes in purine nucleotides, oxypurines and XDH and XO activity was determined. At 24 hours after reperfusion subsequent to 30-minute ischemia, serum creatinine increased to 0.83 +/- 0.74 mg/dl from 0.28 +/- 0.06 mg/dl (the level prior to ischemia, the control). Renal ATP and ADP contents were reduced after ischemia lasting for 30 minutes and restored 10 minutes after reperfusion following 30 minutes of ischemia. The renal AMP content increased after 30 minutes of ischemia and recovered within 10 minutes after reperfusion. The total adenine nucleotide (TAN) content was reduced gradually during ischemia-reperfusion in the rat kidney. Although the energy charge was reduced following 30 minutes of ischemia, it was restored to the control level 10 minutes following reperfusion. Hypoxanthine (HX) and xanthine (X), which had accumulated at 30 minutes after ischemia, were reduced to the control levels 10 minutes after reperfusion. There were no significant changes in the pre-ischemia values of total XDH and XO activities or XDH/XO ratio during the period nor at various time intervals (up to 24 hours) during reperfusion. It was shown that HX and X accumulate without significant conversion of XDH to XO during ischemia. Therefore the putative role of XO in ischemia-reperfusion injury seems to more complex than initially predicted.

Animals↗

PubMed1996

Immunohistochemical findings of arterial fibrinoid necrosis in major and lingual minor salivary glands of primary Sjögren's syndrome.

Arterial fibrinoid lesions in major salivary glands and lingual minor salivary glands from four autopsied patients with primary Sjögren's syndrome were studied histologically and immunohistochemically. On a morphological basis, the preceding arterial fibrinoid necrosis was regarded as medial damage, particularly of smooth muscle cells. The medial smooth muscle cells underwent vacuolated degeneration and disappeared, and resulted in full-blown fibrinoid arteritis. By means of the immunoperoxidase method the distribution of the immunoglobulins, fibrin, complement (C3), transferrin, ferritin, vimentin and lysozyme was studied. The normal arterial wall reacted with the lambda light chain of immunoglobulin, transferrin and vimentin Vacuolated degeneration of medial smooth muscle cells, regarded as the initial change in cases of vascular fibrinoid lesion, was positive for IgG, C3 and vimentin. We suggest that IgG antibody is a useful marker to detect the initial phase of arterial fibrinoid necrosis. In the foci of fibrinoid necrosis, fibrin, C3 and vimentin were detected. Among these three antibodies, only fibrin was negative in the normal arterial wall and vacuolated degenerates of medial smooth muscle cells. Mononuclear cells surrounding areas of fibrinoid necrosis stained strongly with antisera to immunoglobulins, transferrin, ferritin and vimentin, and negatively with fibrin, C3 and lysozyme antibodies.

Adult↗

PubMed1995

Effects of antithrombin III (AT III) and Trp49-modified AT III on plasma level of 6-keto-PGF1 alpha in rats.

We evaluated the effect of antithrombin III (AT III) on the plasma level of 6-keto-PGF1 alpha in rats to determine whether AT III may promote the release of prostacyclin (PGl2) from endothelial cells in vivo. The intravenous administration of AT III (250 U/kg) significantly increased the plasma levels of 6-keto-PGF1 alpha, with a peak seen 90 min post-administration. Neither Trp49-modified AT III, which lacks affinity for heparin but retains an inhibitory capacity for thrombin, nor heparin plus AT III, increased the plasma level of 6-keto-PGF1 alpha 90 min after administration. Indomethacin pretreatment inhibited the increase in plasma levels of 6-keto-PGF1 alpha produced by AT III. Observations suggest that AT III may promote the release of PGl2 from endothelial cells by interacting with heparin-like glycosaminoglycans in vivo, consistent with previous observations in cultured endothelial cells.

6-Ketoprostaglandin F1 alpha↗

PubMed1995

Liquid chromatography combined with thermospray and continuous-flow fast atom bombardment mass spectrometry of glycosides in crude plant extracts.

In crude plant extracts, constituents of biological or pharmaceutical interest often exist in the form of glycosides. Off-line mass spectral investigations of these metabolites require soft ionisation techniques such as desorption chemical ionisation (DCI) or fast atom bombardment (FAB) if information on molecular mass or sugar sequence is desired. In LC-MS, glycosides can be ionised by using thermospray (TSP), continuous-flow fast atom bombardment (CF-FAB) or other interfaces. These techniques are thus potentially applicable to the on-line analysis of glycosides and can be applied to plant extract analysis. Thermospray (TSP) used with ammonium acetate as buffer provides mass spectra similar to those obtained with DCI-MS using NH3 and is potentially applicable to the on-line analysis of relatively small glycosides bearing no more than three sugar units. CF-FAB provides cleaner MS spectra than static FAB due to the lower concentration of the matrix used and can be applied to more polar compounds such as glycosides with a larger number of sugars. The use of a special setup involving post-column addition of the buffer or the matrix and splitting allows LC-UV, TSP LC-MS and CF-FAB LC-MS to be performed with the same standard HPLC conditions. Different crude plant extracts containing various types of glycosides with one to eight sugar units have been analysed by both TSP and CF-FAB. Cardenolides from Nerium odorum (Apocynaceae) and saponins from Swarzia madagascariensis (Leguminosae), Aster scaber and Aster tataricus (Asteraceae) have been studied by LC-MS. The combination of these two interfaces for the HPLC screening of crude plant extracts is discussed.

Cardenolides↗