Biomedical subjects

A Morimoto

Publications and source records attributed to A Morimoto.

At least 73 records · Page 4Linked to original sources

PubMed1994

[Arterial infusion chemotherapy with human tumor necrosis factor (TNF): an experimental study using rabbits bearing VX2 tumor].

To evaluate the direct effects of TNF on tumor vessels, three groups of Japanese white rabbits bearing VX2 tumor received 5000 U, 25000, U, and 5000 U of TNF respectively. Angiograms were obtained before, and at 1, 15 and 30 minutes after arterial TNF injection. At 1 minute after TNF injection, dilated tumor vessels and dense tumor stains, depending on the dose of TNF, were demonstrated. At 30 minutes after injection these findings had disappeared However, there were no changes in normal vessels. It is suggested that arterial TNF injection influenced tumor vessels without damaging on normal vessels, indicating that it is effective as cancer therapy.

Animals↗

PubMed1994

Interleukin-1 beta production in the rabbit brain during endotoxin-induced fever.

Interleukin-1 beta (IL-1 beta) production in the brain and the spleen was investigated in rabbits made febrile by intravenous (I.V.) injection of endotoxin, or human recombinant IL-1 beta (hIL-1 beta). The endotoxin used in the present study was the lipopolysaccharide (LPS) of Salmonella typhosa endotoxin. Monophasic fever was induced by I.V. injection of a low dose of LPS (0.02 micrograms kg-1) and biphasic fever by I.V. injection of a large dose of LPS (4 micrograms kg-1), a sublethal dose of LPS (40 micrograms kg-1) or hIL-1 beta (2 micrograms kg-1). In situ hybridization and immunohistochemical studies revealed that, although no IL-1 beta production was observed in the brain at 1 and 3 h after injection of a low dose of LPS (0.02 micrograms kg-1) or of hIL-1 beta (2 micrograms kg-1), IL-1 beta production was demonstrated in organum vasculosum laminae terminalis (OVLT) and some cells around the blood vessels in the parenchyma 1 h after 4 micrograms kg-1 LPS. IL-1 beta production was detected throughout the brain after 40 micrograms kg-1 LPS. Pretreatment with indomethacin, an inhibitor of prostaglandin synthesis, did not affect IL-1 beta production in the brain induced by 4 micrograms kg-1 LPS. The cell type which produces IL-1 beta in the OVLT following LPS injection was confirmed to be a macrophage by electron microscopy. The cells producing IL-1 beta in the parenchyma were determined to be microglial cells. In the spleen, each dose of LPS induced a significant increase in IL-1 beta production in polymorphonuclear cells and macrophages in the red pulp 1 h after injection. However, 2 micrograms kg-1 hIL-1 beta did not induce IL-1 beta production in the spleen. The present results show clearly that systemic administration of LPS induces IL-1 beta production in the OVLT which may be responsible for induction of the second phase of biphasic fever. The production of IL-1 beta in the OVLT was not attributable to the action of peripherally synthesized IL-1 beta or prostaglandins.

Animals↗

PubMed1994

ACTH response induced in capsaicin-desensitized rats by intravenous injection of interleukin-1 or prostaglandin E.

1. We investigated whether afferent nerves are involved in the development of adrenocorticotrophic hormone (ACTH) responses induced either by systemic administration of interleukin-1 beta (IL-1 beta) and prostaglandin E2, or by psychological stress. The capsaicin desensitization method was used to impair afferent C fibres and we compared the ACTH responses between capsaicin desensitized and vehicle pretreated control rats. 2. The present results showed that the capsaicin desensitized rats had significantly smaller increases in plasma ACTH than the control rats in response to intravenous injection of IL-1 beta or prostaglandin E2. 3. There were no significant differences between the capsaicin desensitized and control rats in the ACTH responses induced by cage switch stress. 4. The capsaicin desensitized rats responded to intravenous injection of corticotrophin releasing factor (CRF) with a greater increase in the plasma level of ACTH than the control rats, indicating that capsaicin pretreatment resulted in augmentation of pituitary gland sensitivity to CRF. 5. These results suggest that afferent neurons play an important role in the ACTH responses induced by systemic injection of IL-1 beta or prostaglandin E2.

Adrenocorticotropic Hormone↗

PubMed1994

Cooperative roles of hepatocyte growth factor and plasminogen activator in tubular morphogenesis by human microvascular endothelial cells.

Epidermal growth factor (EGF) or transforming growth factor-alpha (TGF-alpha) stimulated cell migration, chemotaxis, and the expression of tissue-type plasminogen activator (t-PA) in human omental microvascular endothelial (HOME) cells. Hepatocyte growth factor (HGF) stimulated cell proliferation, but had a negligible stimulatory effect on cell migration, the expression of t-PA and tube-like formation into collagen gel in HOME cells. Basic fibroblast growth factor stimulated cell proliferation, cell migration, tubulogenesis and the expression of urokinase-type plasminogen activator (u-PA) in bovine aortic endothelial (BAE) cells. HOME and BAE cells had both high- and low-affinity receptors for HGF. In BAE cells, u-PA activity and tube-like structures in collagen gel were induced in the presence of HGF alone. In contrast, in HOME cells, t-PA activity and tube-like structures were induced in the presence of TGF-alpha alone, but not in the presence of HGF alone. However, we observed a marked induction of tube formation by HOME cells when both t-PA and HGF were added simultaneously. In the model system for tumor angiogenesis, when HOME cells were co-cultured with a renal cancer cell line, KPK13, tube-like structures were induced in the presence of HGF:KPK13 cells expressed large amounts of t-PA mRNA. Our present study suggested that HGF in concert with active t-PA could be angiogenic in HOME cells.

Cell Line↗

PubMed1994

Relationship between mean arterial pressure and muscle cell pH during forearm ischaemia after sustained handgrip.

Recent evidence suggests that there is a close correlation between the physiological responses to muscle chemoreflex and the decrease in intracellular pH during ischaemia after handgrip. This study evaluated whether the relationship is linear or has an apparent threshold. We measured muscle cellular pH through phosphorous nuclear magnetic resonance spectroscopy (31P-NMR), mean arterial blood pressure (MAP) and heart rate (HR) during ischaemia after sustained handgrip exercise at 50% of maximum voluntary contraction (MVC). Contraction was sustained for 15, 30, 45 and 60 s, followed by 2 min of circulatory arrest, respectively. Muscular pH during the ischaemia decreased linearly with increasing contraction time, from the base-line level of 7.11 +/- 0.03 units (U) to 6.98 +/- 0.03, 6.90 +/- 0.04, 6.72 +/- 0.06 and 6.54 +/- 0.06 U after 15-, 30, 45-, and 60-s contractions, respectively. The MAP was 86 +/- 2 mmHg at rest and did not change during the ischaemia after 15- and 30-s contractions. However, it significantly increased to 95 +/- 2 and 107 +/- 2 mmHg, after 45- and 60-s contractions, respectively. These data indicate that the relationship between MAP and pH is not a single linear relationship, showing one breaking point around the pH of 6.90 units. It suggests that the muscle chemoreflex has a clear threshold around 6.90 units of muscle pH, and below this pH, MAP increased linearly with decreasing muscle cellular pH.

Adolescent↗

PubMed1994

[A case of cardiogenic shock caused by Vibrio parahaemolyticus].

A case of a 53 year old healthy female complaining of diarrhea and abdominal pain after taking raw fish is presented. She immediately went into shock and unconsciousness. Central venous pressure was 8 cmH2O and her ECG showed a first-degree AV block and ST-T changes in almost all leads. After mechanical ventilation and administration of dopamine, dobutamine, cefotiam, ciprofloxacin, she became alert and recovered from her critical condition. V. parahaemolyticus which produces thermostable direct hemolysin (TDH) was cultured from the feces on admission. Kanagawa phenomenon was positive. Arterial blood culture was negative and the titer of serum endotoxin was low. The diagnosis of cardiogenic shock due to exotoxin produced by V. parahaemolyticus was made. Serological examination by ELISA showed elevation of IgG class antibody against TDH and TRH (TDH related hemolysin). And antibody against TDH was normalized after 180 days. By review of literature, there are some case reports of cardiogenic shock complicated with V. parahaemolyticus infection, but few showed elevation of antibody against TDH and TRH in the serum of the survived patient.

Endotoxins↗

PubMed1994

Evidence that FK506 alleviates ischemia/reperfusion injury to the rat liver: in vivo demonstration for suppression of TNF-a production in response to endotoxemia.

The mechanism by which FK506 (FK) prevents hepatic injury induced by ischemia/reperfusion was studied. Adult Sprague-Dawley rats were subjected to 60-min normothermic liver ischemia. Animals were divided into two groups: group I, controls, saline vehicle treatment; group II, FK treatment. FK (1 mg/kg/day, p.o.) was given for 4 consecutive days prior to inducing ischemia. In addition to a survival study, plasma levels of endotoxin and serum activities of tumor necrosis factor-alpha (TNF) and aspartate aminotransferase (AST) were assessed in the blood collected from suprahepatic vena cava. Results showed: (1) FK therapy significantly improved 7-day survival (80.0%) compared with nontreated animals (50.0%, p < 0.05); (2) both TNF and endotoxin were elevated following reperfusion, reaching maximum values at 3 h after reperfusion (217.0 +/- 40.6 and 280.5 +/- 31.4 pg/ml, respectively, in the control; mean +/- SEM), and (3) serum activities of TNF and AST following reperfusion were substantially suppressed with FK treatment, whereas FK did not reduce the rise in endotoxin. These findings suggest that suppression of TNF production in response to endotoxemia might account at least in part for the protective effect of FK against ischemia-induced hepatic injury.

Animals↗

PubMed1994

Changes in plasma catecholamines during fever induced by bacterial endotoxin and interleukin-1 beta.

We have examined whether or not the release of catecholamines into the blood circulation of rabbits during fever is mediated by prostaglandins. The plasma levels of catecholamines (epinephrine and norepinephrine) were measured in 2 ml of blood withdrawn from the marginal ear vein. At an ambient temperature of 21 +/- 1 degree C, intravenous injection of either lipopolysaccharide (LPS, 4 micrograms/kg) or human recombinant interleukin-1 beta (rIL-1 beta, 1 microgram/kg) produced a biphasic fever accompanied by an increase in the plasma level of catecholamines. Pretreatment with intravenous indomethacin (1 mg/kg) markedly suppressed the increase in catecholamines induced by LPS and rIL-1 beta. In contrast, although intracerebroventricular injection of rIL-1 beta (20 ng) produced fever, it did not produce a significant change in plasma catecholamine levels. Similarly, intrahypothalamic injection of prostaglandin E2 (200, 800 ng) induced fever, but did not cause a significant change in catecholamine concentrations. These results suggest that IL-1 acts via prostaglandins on the peripheral tissues to release catecholamines into the circulation.

Animals↗

PubMed1994

[Transjugular intrahepatic portosystemic shunt--early experience in eleven liver cirrhosis patients].

Eleven liver cirrhosis patients with variceal bleeding and/or ascites were treated by transjugular intrahepatic portosystemic shunt. Four of the patients were combined with hepatoma, and 2 had portal thrombosis. Ten of the patients were successfully achieved TIPS, but one patient who had portal thrombosis was failed because of portal vein occlusion; success rate of 90%. An average decrease of 14mmHg in portal vein pressure was measured in the 10 patients. All of the successful patients including 4 with hepatoma were observed the disappeared or diminished varices and ascites without technical complication. Mild encephalopathy was encountered in 2 patients but who responded well to medical therapy. Three dimension MRA before TIPS was helpful for understanding the anatomical relationship between portal vein and hepatic vein. It is concluded that TIPS is an effective and safe treatment, indicating for the patients who have uncontrollable variceal bleeding and/or ascites even with hepatoma.

Adult↗

PubMed1993

Anti-angiogenic activity of arachidonic acid metabolism inhibitors in angiogenesis model systems involving human microvascular endothelial cells and neovascularization in mice.

We have established an in vitro angiogenesis model using human omental microvascular endothelial (HOME) cells, in which epidermal growth factor (EGF) or transforming growth factor-alpha (TGF-alpha) stimulated cell migration and tube formation. In this study, we examined whether alpha-guaiaconic acid (GR-12) and its synthetic 20 derivatives showed inhibition of cell migration and tubular formation of HOME cells. We found that GR-12 inhibits arachidonic acid metabolism, while GR-12 and one derivative, GS-01, inhibit tubular formation of endothelial cells in our model system. Confluent monolayers of HOME cells were damaged with a razor blade and incubated with or without TGF-alpha; HOME cell migration was stimulated about 1.5-fold over control values in the presence of TGF-alpha. Treatment of HOME cells with GR-12 or GS-01 inhibited both spontaneous and TGF-alpha-stimulated migration. GR-12 or GS-01 inhibited TGF-alpha-induced HOME-cell tube formation in type-1 collagen gels. We examined whether these compounds could modulate tubular formation of HOME cells induced by human cancer cells. Enhanced tube formation of HOME cells by co-cultured esophageal cancer cells was almost completely inhibited by co-administration of GR-12 or GS-01. Both compounds also inhibited formation of tubular networks of HOME cells on Matrigels. We also examined anti-angiogenic activity of these compounds in an in vivo model system of tumor angiogenesis in mice. In this system, GS-01 inhibited development of capillary networks at a rate comparable to that of a well-known anti-angiogenic compound, fumagillin, but GR-12 did not. The inhibitor of arachidonic acid metabolism is thus expected to modulate tumor angiogenesis.

Animals↗

PubMed1993

[Percutaneous arterial prostheses of femoro-femoral bypass: using a new method of Modified Seldinger technique].

An experimental study of percutaneous arterial prostheses of femoro-femoral bypass was performed in 3 dogs using Modified Seldinger technique. Modified Seldinger technique with an arc needle was a newly designed method to penetrate the arterial wall due to introduce a bypass graft into the artery percutaneously. In all dogs, the bypass graft was successfully placed and proved to be effective in excellent blood flow. No significant complication was encountered. It is concluded that this method is feasible in the dog model.

Animals↗

PubMed1993

Organum vasculosum laminae terminalis (OVLT) is a brain site to produce interleukin-1 beta during fever.

The present study was carried out to determine whether interleukin-1 (IL-1) production occurs in the rabbit organum vasculosum laminae terminalis (OVLT) during fever induced by endotoxin. The intravenous (i.v.) injection of endotoxin (4 micrograms/kg) caused significant fever in rabbits. Through the use of in situ hybridization and immunohistochemical techniques, the synthesis of IL-1 was observed in the OVLT during the fever. The present results support the hypothesis that IL-1 is produced in the brain during fever.

Animals↗

PubMed1993

Irsogladine is a potent inhibitor of angiogenesis.

We describe a novel inhibitor of angiogenesis, Irsogladine, an anti-ulcer drug. Irsogladine inhibited plasminogen activator synthesis of, and tube formation by, human microvascular endothelial cells in type 1 collagen gel treated with an angiogenic growth factor, EGF. Furthermore, Irsogladine administered orally significantly inhibited in vivo angiogenesis in mice. Irsogladine may be useful in the treatment of diseases associated with angiogenesis.

Animals↗

PubMed1993

Organum vasculosum laminae terminalis (OVLT) in rabbit and rat: topographic studies.

The microcirculation and fine structure of the rabbit and rat organum vasculosum laminae terminalis (OVLT) were examined by light microscopy and scanning and transmission electron microscopy. In both animals, the microcirculation is composed of a superficial and a deep vascular bed but the system is more complex and extensive in the rabbit. This was particularly true of the deep vascular bed. In the rabbit, the deep bed is composed of fenestrated capillaries, which are arranged in glomerular tufts surrounded by very wide perivascular spaces (PVS). In contrast, the deep vascular bed of the rat OVLT usually consists of only one or two small vessels. These are either fenestrated and surrounded by a PVS or lined by continuous endothelium with only a few fenestrae and without a dilated PVS. A corresponding difference was seen in the contours of the ventricular surface. It is much more irregular in the rabbit than in the rat and numerous bulges reflect the underlying vascular tufts and pockets of PVS in the rabbit. Supraependymal cells are present in both species and two sizes of them occur in the rabbit. The results demonstrate that the microcirculation of the OVLT is more elaborate and more highly developed in the rabbit than in the rat. We suggest that this might result in a different neurohemal microenvironment and, ultimately, in functional differences.

Animals↗

PubMed1993

Indispensable role of tissue-type plasminogen activator in growth factor-dependent tube formation of human microvascular endothelial cells in vitro.

Epidermal growth factor (EGF) stimulates the migration and proliferation of, and tissue-type plasminogen activator (tPA) synthesis in, human omental microvascular endothelial (HOME) cells in culture, as well as inducing the formation by these cells. In the present study, we examined the effects of various growth factors, i.e., transforming growth factor-alpha (TGF-alpha), insulin-like growth factor 1 (IGF-1), and hepatocyte growth factor (HGF) on HOME cells, and compared their effects with that of EGF. IGF-1 stimulated the proliferation and migration of these cells at a level comparable to EGF. EGF and TGF-alpha induced expression of tPA in HOME cells, while IGF-1 and HGF did not. EGF and TGF-alpha induced tube formation by HOME cells in type I collagen gel, while IGF-1 and HGF did not. The stimulatory effect of EGF on tube formation in the gel was blocked by anti-tPA antibody and by a serine protease inhibitor, aprotinin. When exogenous tPA and IGF-1 or HGF were added simultaneously to the culture, a marked induction of tube formation in the gel was observed. Exogenously added tPA alone, however, had no such inducible effect on tube formation. These results indicated an indispensable role of tPA in growth factor-dependent tube formation by HOME cells. Two subsets of growth factors appeared to modulate angiogenesis: One with fully active angiogenic activity which could induce PA (this included EGF and TGF-alpha), and the other, which could not induce PA and was not angiogenic, but could promote angiogenesis in the presence of PA. This subset included IGF-1 and HGF.

Cell Division↗

PubMed1993

Morphological change and destabilization of beta-actin mRNA by tumor necrosis factor in human microvascular endothelial cells.

Tumor necrosis factor-alpha (TNF-alpha) produced morphological changes from a cobblestone-like shape into a spindle shape in human omental microvascular endothelial (HOME) cells and also a drastic rearrangement of actin filaments. Expression of beta-actin gene was diminished in HOME cells treated with TNF-alpha for 24 h. Northern blot analysis of the beta-actin gene demonstrated that the cellular level of beta-actin mRNA was decreased at 6-12 h after exposure to TNF-alpha. However, there appeared to be no changes in cellular mRNA levels of beta-tubulin, fibronectin, laminin B1, laminin B2, and laminin binding protein genes after treatment with TNF-alpha. Nuclear run-on assays showed increased transcription of the low-density lipoprotein receptor gene, but not of the beta-actin gene. These data suggested that the TNF-alpha-induced inhibition of beta-actin gene expression was not due to altered transcription activity. The degradation rates of beta-actin, plasminogen activator inhibitor-1, and epidermal growth factor receptor mRNAs were examined in the presence of actinomycin D. beta-Actin mRNA was found to be specifically destabilized in TNF-alpha-treated HOME cells, while other mRNA species were not. Coadministration of cycloheximide blocked the TNF-alpha-induced degradation of beta-actin mRNA. The TNF-alpha-induced destabilization of beta-actin mRNA and rearrangement of actin filaments are discussed in relation to the morphological changes in human microvascular endothelial cells.

Actin Cytoskeleton↗

PubMed1993

Augmentation of hepatocyte proliferation by immunosuppressant pretherapy is associated with up-regulation of malondialdehyde production.

We studied the relationship between augmentation of liver regeneration with immunosuppressants and malondialdehyde (MDA, an end-product of lipid peroxides) production. MDA was determined using the thiobarbituric acid reaction. Rats underwent a 4-day treatment of FK506 (FK, 1 mg/kg per day), cyclosporine (Cs, 10 mg/kg) or azathioprine (AZA, 1 mg/kg) by gavage prior to 70% hepatectomy. They were then divided into four groups: (1) controls (vehicle-treated); (2) FK; (3) Cs; (4) AZA. MDA levels, uptake of BrdU (5-bromo-2-deoxyuridine) in the liver and serum biochemistry were investigated 24 h after hepatectomy. Immunosuppressant pretherapy significantly stimulated BrdU uptake by hepatocytes, in association with increased MDA production, while there were no differences in serum liver injury parameters among the groups given or not given immunosuppressants. The implications of the rising MDA values during liver regeneration are discussed with respect to immunosuppression and a measure of lipid peroxidation. Additional study indicated that one immunodepressant pretreatment (24 h prior to hepatectomy) was effective for up-regulation of liver regeneration.

Animals↗

PubMed1993

Effects of electrical stimulation or local anesthesia of the rabbit's hypothalamus on the acute phase response.

The effects of electrical stimulation of the rostral hypothalamic region on the acute phase response (APR) were examined in rabbits. As indicators of APR, we measured changes in the plasma concentrations of iron, zinc, copper, and fibrinogen and changes in the red and white blood cell counts. Electrical stimulation of the rostral hypothalamic region near the preoptic and anterior hypothalamic region did not induce any aspect of the APR. However, stimulation near the anteroventral portion of the third ventricle (AV3V) induced responses that were, in part, opposite to those observed in the APR: an increase in the plasma concentration of zinc and a decrease in the circulating leukocyte count. Microinjections of procaine into the brain regions near the AV3V did not induce any changes in the plasma levels of trace metals and fibrinogen but increased the circulating leukocyte count. These results suggest that nonspecific stimulation or inhibition of the rostral hypothalamic region does not induce APR.

Acute-Phase Reaction↗