Biomedical subjects

T Kaji

Publications and source records attributed to T Kaji.

At least 55 records · Page 3Linked to original sources

PubMed1998

Repair of wounded monolayers of cultured vascular endothelial cells after simultaneous exposure to lead and zinc.

We investigated the interaction between lead and zinc on the repair of wounded monolayers of cultured bovine aortic endothelial cells. A half area of the monolayers was wounded and then incubated in the presence of lead (5.0 and 10 microM) and/or zinc (10 microM). It was morphologically observed that the appearance of the cells in the wounded area was strongly decreased by lead alone but considerably increased by zinc alone. The repair of wounded area after simultaneous exposure to lead and zinc showed that lead inhibits not only spontaneous but also zinc-promoted repair of endothelial cell layers without a change of the leakage of lactate dehydrogenase. Interaction between lead and zinc on the DNA synthesis of growing endothelial cells was similar to that on the repair, suggesting that the repair reflected the proliferation. In growing endothelial cells, the intracellular accumulation of lead was significantly increased by zinc; that of zinc was unaffected by lead; and that of metallothionein was slightly increased by zinc and lead but the effect of zinc was suppressed in the presence of lead. Although zinc significantly decreased the intracellular accumulation of radioactive calcium, lead increased it in the presence or absence of zinc. It was therefore concluded that lead inhibits not only spontaneous but also zinc-promoted repair of the damaged endothelial cell layers through an inhibition of the proliferation mediated by the calcium-mediated signalling pathways and/or a disturbance of intracellular calcium homeostasis.

Animals↗

PubMed1998

Promotion of cultured vascular smooth muscle cell proliferation by low levels of cadmium.

Cadmium is a toxic heavy metal which has been shown to be a possible risk factor of atherosclerosis in epidemiological and experimental studies. Since intimal hyperplasia in vascular tissue is an important component of atherosclerosis, we examined the effect of cadmium on the proliferation of vascular smooth muscle cells cultured in a serum-free medium. It was found that cadmium at 100 nM or less can increase the incorporation of [3H]thymidine into the acid-insoluble fraction of growing bovine and rabbit aortic smooth muscle cells but not of growing bovine aortic endothelial cells. Although vascular smooth muscle cells are sensitive to cadmium cytotoxicity, no increase in the leakage of lactate dehydrogenase from the cells was caused by the metal at 200 nM or less in bovine aortic smooth muscle cells. Intracellular accumulation of radioactive calcium in bovine aortic smooth muscle cells was significantly increased by cadmium. It was therefore suggested that low levels of cadmium may promote the proliferation of vascular smooth muscle cells through intracellular calcium-dependent signalling pathway. The present study supports the hypothesis that cadmium can be a risk factor of atherosclerosis through dysfunction of vascular smooth muscle cells as well as vascular endothelial cells under certain conditions.

Animals↗

PubMed1997

Thrombin reduces large heparan sulfate proteoglycan molecules in cultured vascular endothelial cell layers through inhibition of core protein synthesis.

We investigated the alteration of heparan sulfate proteoglycans induced by thrombin in cultured vascular endothelial cells. Heparan sulfate proteoglycans, which were metabolically labeled with [3H] glucosamine and [35S] sulfate, were isolated by DEAE-Sephacel ion-exchange chromatography and characterized by molecular sieve gel filtration. Core proteins were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of [35S] amino acids-labeled heparan sulfate proteoglycans after digestion with hepartinase. It was revealed that the high molecular weight subclass of heparan sulfate proteoglycans in the cell layer was markedly decreased by thrombin without changes of the hydrodynamic size of the molecules and the molecular weight of heparan sulfate chains. In addition, thrombin decreased the amount of large heparan sulfate proteoglycan core protein with a molecular weight of approximately 400 kDa, probably perlecan core, in the cell layer and the conditioned medium. The present data suggest that thrombin-induced decrease in the amount of heparan sulfate in vascular endothelial cell layer includes a reduction of the number of large heparan sulfate proteoglycan perlecan molecules through a suppression of the core protein synthesis.

Animals↗

PubMed1997

Tolerance to cadmium cytotoxicity is induced by zinc through non-metallothionein mechanisms as well as metallothionein induction in cultured cells.

To investigate the relationship between metallothionein induction and zinc-induced tolerance to cadmium cytotoxicity at the cell level, Chang liver cells were pretreated with a wide range of concentrations of zinc sulfate and challenged with toxic levels of cadmium after removal of zinc. It was found that zinc-pretreated cells were significantly resistant even when the extracellular level of zinc was low and metallothionein was not induced by the metal. Pretreatment with zinc resulted in a lesser accumulation of cadmium and metallothionein after challenge with cadmium. In porcine kidney LLC-PK1 cells and bovine aortic smooth muscle cells pretreated with low levels of zinc, the intracellular accumulation of cadmium was significantly less and cadmium-induced decrease in intracellular zinc was significantly prevented without a change of metallothionein content; as the result, the toxic effect of cadmium was significantly diminished. It was therefore concluded that a tolerance to cadmium cytotoxicity is induced by zinc via non-metallothionein mechanisms such as decreasing intracellular cadmium as well as metallothionein induction at the cell level. The non-metallothionein mechanism was postulated to be particularly importatnt when the extracellular concentration of zinc is under the threshold for metallothionein induction.

Analysis of Variance↗

PubMed1997

Lead-induced alteration of heparan sulfate proteoglycans in cultured vascular endothelial cells.

We investigated the alterations of heparan sulfate proteoglycans produced by vascular endothelial cells after exposure to lead. Bovine aortic endothelial cells were cultured and metabolically labeled with [3H]glucosamine and [35S]sulfate in the presence of lead chloride at 10 microM. Radiolabeled HSPGs were separated by ion-exchange chromatography and either their hydrodynamic size or the length of heparan sulfate chains were characterized by gel filtration. It was found that lead markedly suppresses the incorporation of the radioactive precursors into HSPGs in the cell layer; the incorporation into chondroitin/dermatan sulfate proteoglycans was decreased by the metal only slightly. The suppression by lead occurred in the low molecular weight subclass of HSPGs rather than the high molecular weight subclass. However, the length of heparan sulfate chains was not changed by the metal. A sodium dodecyl sulfate-polyacrylamide gel electrophoresis of [35S]methionine-labeled proteoglycans after heparitinase digestion showed that there were slightly more HSPG core proteins without a change of the size in lead-treated cell layer. It was, therefore, suggested that vascular endothelial cell layer after exposure to lead has more HSPG core proteins with fewer heparan sulfate chains without a change in length.

Animals↗

PubMed1997

Lead perturbs the regulation of spontaneous release of tissue plasminogen activator and plasminogen activator inhibitor-1 from vascular smooth muscle cells and fibroblasts in culture.

To evaluate the toxicity of lead on the blood fibrinolytic system during hemostasis, human aortic smooth muscle cells and human fetal lung fibroblasts were cultured in the presence of lead chloride. Tissue plasminogen activator antigen (t-PA:Ag) and plasminogen activator inhibitor-1 antigen (PAI-1:Ag) released were determined by enzyme immunoassay. It was found that lead decreased the release of both t-PA:Ag and PAI-1:Ag from vascular smooth muscle cells. On the other hand, in fibroblasts, the release of t-PA:Ag was markedly decreased whereas that of PAI-1:Ag was markedly increased by the metal. Fibrin zymography showed that lead reduced the plasminogen activator activity in the conditioned medium of both cell types. However, lead did not cause a nonspecific cell damage and an alteration of protein synthesis when evaluated by lactate dehydrogenase leakage and [14C]leucine incorporation, respectively. Lead accumulated within either vascular smooth muscle cells or fibroblasts in a dose-dependent manner; intracellular accumulation of calcium could be increased by lead. However, the effects of lead on the release of t-PA:Ag and PAI-1:Ag were different from those of calcium ionophore A23187. It was therefore suggested that regulation of spontaneous release of fibrinolytic proteins from subendothelial cells is disturbed by lead through intracellular calcium-independent pathway.

Aorta↗

PubMed1997

Inhibitory effect of lead on the repair of wounded monolayers of cultured vascular endothelial cells.

We investigated the effect of lead nitrate (0.5-5.0 microM) on the repair of wounded monolayer of cultured bovine aortic endothelial cells. It was morphologically found that lead decreases the appearance of the cells in the wounded area in a concentration-dependent manner without degenerative changes after a 48-h incubation. Although mercury weakly inhibited the repair with nonspecific cell damage, the other cations including bismuth, cobalt, manganese and nickel failed to affect the repair. The inhibition of endothelial repair caused by lead was observed even when stimulated by exogenous either basic or fibroblast growth factor. These results indicated that inhibition of the repair process of damaged endothelial cell layer is a component of lead-induced vascular lesions such as atherosclerosis.

Animals↗

PubMed1997

Scanning electron microscope examination of pancreatic ducts in stroke-prone spontaneously hypertensive rats (SHRSP).

CONCLUSION: Ischemic injury to the pancreatic ductal cells causes stasis of pancreatic juice, which in turn induces chronic pancreatitis. BACKGROUND: The pathogenesis of chronic ischemic pancreatitis is still unclear. METHODS: In 12-, 24-, and 36-wk-old male stroke-prone spontaneously hypertensive rats (SHRSP), which have sclerotic arterioles with a marked narrowing lumen in the pancreas, pancreatic tissue was examined using light and scanning electron microscopy. Corrosion casts of pancreatic ducts and blood vessels were examined using scanning electron microscopy. RESULTS: Ductular proliferation, tortuous ductal channels, crater-like depressions of ductal inner surfaces, and long cilia of ductal cells were found to be sporadically distributed throughout the pancreatic tissue. Similar pancreatic abnormalities had been found in previous studies using WBN/Kob rats that exhibited pancreatic juice stasis. A few interlobular ducts in the pancreatic tissue of the SHRSP had an inner surface that was gyrus-like in appearance, a feature not found in WBN/Kob rats.

Aging↗

PubMed1997

Atypical MRI features of Wilson's disease: high signal in globus pallidus on T1-weighted images.

Most reports of MRI in Wilson's disease have been of abnormal low-signal lesions on T1-weighted images and high signal intensity on T2-weighted images. In contrast, we report three patients who had high-signal lesions in the globus pallidus on T1-weighted images, a finding seen in patients with portal-systemic encephalopathy. The possible causes include the paramagnetic effect of copper or iron and accumulation of Alzheimer type II glial cells.

Adult↗

PubMed1997

Basic fibroblast growth factor-induced glycosaminoglycan production in cultured vascular endothelial cells results from enhanced protein synthesis mediated by the lipoxygenase pathway.

To investigate the intracellular regulation of glycosaminoglycan (GAG) production induced by basic fibroblast growth factor (bFGF), bovine aortic endothelial cells were cultured with recombinant human bFGF in the presence of [3H]glucosamine or [35S]sulfate. It was shown that bFGF-induced incorporation of the radioactive precursors into GAGs was diminished by lipoxygenase inhibitors, nordihydroguaiaretic acid (NDGA) and esculetin, but not by a cyclooxygenase inhibitor indomethacin. A protein synthesis inhibitor cycloheximide also diminished the enhancement of the [3H]glucosamine incorporation by bFGF. On the other hand, the incorporation of [14C]leucine into the acid-insoluble fraction was strongly inhibited by NDGA but not by indomethacin in the presence or absence of bFGF. It was also shown that bFGF significantly increased the incorporation of [14C]xylose into GAGs. The present data suggested that bFGF may increase the number of GAG chains as a result of enhanced protein synthesis including xylosyl transferase through the lipoxygenase pathway of arachidonic acid metabolism in vascular endothelial cell layer.

Animals↗

PubMed1997

Yolk sac tumor of the ovary in a conjoined twin.

A 5-year-old conjoined twin girl had a yolk sac tumor of the right ovary. She was admitted to our hospital because of abdominal distension. Comprehensive clinical and radiological investigations revealed a tumor of the right ovary. She underwent right salpingo-oophorectomy. The diagnosis was yolk sac tumor (stage I A), and postoperative chemotherapy (vincristine, actinomycine-D, cyclophosphamide) according to the UK-CCSG was provided. The postoperative course was uneventful with no evidence of recurrence 3 years after surgery. Her twin sister had no tumor. This is the first reported of yolk sac tumor of the ovary in a conjoined twin.

Child, Preschool↗

PubMed1997

Helicobacter pylori infection accelerates gene expression of glicentin in the gastric mucosa. Its association with intestinal metaplasia of the stomach.

BACKGROUND: Glicentin is an intestinal polypeptide hormone which seems to promote intestinal metaplasia (IM) in the gastric mucosa. The aim of this study was to clarify whether Helicobacter pylori infection accelerates glicentin gene expression. METHOD: Glicentin mRNA was investigated by reverse-transcription polymerase chain reaction using gastric biopsies from 47 patients examined endoscopically and denying IM. RESULTS: IM was observed in 18 (38.3%) cases histologically, but not in the other 29 (62.7%). Glicentin mRNA was significantly correlated with histological IM (P < 0.01) and was positively correlated with H. pylori infection (P < 0.05). CONCLUSION: Our results indicate that H. pylori infection is associated with the induction of glicentin in the gastric mucosa, thus supporting the hypothesis that H. pylori infection accelerates IM of the stomach.

Adult↗

PubMed1997

[A case of primary orbital chondrosarcoma].

The case of a twenty-year-old male with orbital chondrosarcoma is reported. He visited National Defense Medical College Hospital because of reduced vision in the right eye since two months previously. His corrected visual acuity was 8/20 in the right eye and 20/20 in the left eye. Fifteen degrees lateral displacement of the right globe and limitation of right ocular movement were recognized. Right fundus examination revealed optic disc edema and protuberant nasal fundus. Orbital computed tomography (CT) demonstrated a high density area between the inner part of the right orbit and the ethmoid sinus. Magnetic resonance imaging (MRI) showed a smoothly outlined and low intensity (T1) space occupying lesion. This lesion was irregularly enhanced by gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA). This orbital tumor was removed by an anterior approach. Histopathological examination revealed well-differentiated chondrosarcoma (grade 1) as determined by small prominent chondromatous cell projection into the collagen fibrous stroma, and existence of binucleate cells in the hypercellular region. After the operation the disc edema disappeared and his corrected right visual acuity improved to 20/20.

Adult↗

PubMed1997

[Dural arteriovenous fistula presenting as acute-onset dementia: a case report].

We report here a unique case of acute-onset dementia caused by a posterior fossa dural arteriovenous fistula (AVF), which was successfully treated by surgical resection of the isolated transverse-sigmoid sinus combined with endovascular procedures. A 70-year-old female was admitted to our hospital with acute-onset dementia and pulsatile tinnitus on the left side. CT scan revealed a low-density area in the parieto-temporal region. Cerebral angiography revealed a dural AVF of the transverse-sigmoid sinus with retrograde drainage into cerebral cortical veins. After transarterial endovascular embolization of the dural AVF, a xenon-CT scan revealed increased cerebral blood flow. Four months postoperatively, however, she was admitted to our hospital again with seizure and aphasia due to recanalizaion of the dural AVF. After trans-arterial embolization, transvenous embolization was attempted, but was unsuccessful due to inaccessibility of the isolated sinus segment. Since this patient could not be cured by endovascular embolization, an open surgical resection of the isolated sinus segment was performed. Following this, CT scans revealed that the low density area present on the first admission had disappeared. The patient's dementia resolved postoperatively. We discuss the pathophysiological mechanism by which venous ischemia due to dural AVF can cause reversible dementia.

Acute Disease↗

PubMed1997

Zinc potentiates the stimulation by basic and acidic fibroblast growth factors on the proliferation of cultured vascular smooth muscle cells.

We investigated the effect of zinc sulfate on the proliferation of cultured bovine aortic smooth muscle cells stimulated with or without growth factors. Zinc had no effect on the incorporation of [3H]thymidine into the acid-insoluble fraction of the cells stimulated with or without platelet-derived growth factor or transforming growth factor beta 1. However, it was shown that stimulation of the [3H]thymidine incorporation by either basic or acidic fibroblast growth factor was significantly potentiated by zinc. Other cations including copper, manganese and nickel did not exhibit such an activity. The present data suggest that zinc is a particular heavy metal which potentiates vascular smooth muscle cell proliferation stimulated by basic and acidic fibroblast growth factors as well as thrombospondin. Zinc may be involved in the intimal hyperplasia of atherosclerosis.

Animals↗

PubMed1996

Sensitive response of cultured vascular smooth-muscle cells to cadmium cytotoxicity: comparison with cultured vascular endothelial cells and kidney epithelial LLC-PK1 cells.

Response to cadmium cytotoxicity of cultured bovine aortic smooth-muscle cells was compared with that of cultured bovine aortic endothelial cells and porcine kidney epithelial LLC-PK1 cells. The cell damage was evaluated by morphology and the lactate dehydrogenase leakage assay. It was found that vascular smooth-muscle cells are markedly sensitive to cadmium cytotoxicity. The accumulation of intracellular cadmium was much higher but that of metallothionein was much less in vascular smooth-muscle cells than in LLC-PK1 cells; vascular endothelial cells were in between vascular smooth-muscle cells and LLC-PK1 cells. The content of reduced glutathione was slightly increased by cadmium in all three cell types. The present data suggest that a much lower inducibility of metallothionein with a high accumulation of intracellular cadmium in vascular smooth-muscle cells resulted in a marked sensitivity of the cells to cadmium cytotoxicity. Vascular smooth-muscle cells may be one of the critical target of cadmium toxicity.

Animals↗

PubMed1996

Phorbol 12-myristate 13-acetate stimulates the release of glycosaminoglycans from cultured vascular endothelial cells: possible involvement of protein kinase C activation.

We investigated the release of glycosaminoglycans (GAGs) labeled with [3H]glucosamine and [35S]sulfate into the medium from cultured bovine aortic endothelial cells stimulated by phorbol 12-myristate 13-acetate (PMA) which is an activator of protein kinase C (PKC). The GAG release was significantly accelerated by PMA without an increase in the leakage of lactate dehydrogenase but was unchanged by 4 alpha-phorbol 12,13-didecanoate which lacks the ability of PKC activation. The acceleration of GAG release by PMA was strongly suppressed by a PKC inhibitor H-7 but not by HA 1004 which is an inactive analogue of H-7. Characterization of GAGs released into the medium revealed that PMA increased both heparan sulfate and the other GAGs in a similar degree. Although the release of GAGs stimulated by thrombin was also suppressed by another PKC inhibitor staurosporine, stimulation by plasmin was unaffected by the inhibitor. The present data suggest that protein kinase C mediates the release of endothelial cell GAGs including anticoagulant heparan sulfate and the stimulation of the release by thrombin includes this mechanism.

Animals↗

PubMed1996

Cyclic AMP-dependent pathway that mediates suppressive regulation of glycosaminoglycan production in cultured vascular endothelial cells.

We investigated the effect of agents which increase the intracellular level of cyclic AMP (cAMP) on the production of glycosaminoglycans (GAGs) by cultured bovine aortic endothelial cells. It was found that the incorporation of [3H] glucosamine into GAGs was significantly decreased by forskolin, 8-bromo cAMP, 3-isobutyl-1- methylxanthine and prostaglandin E1. The leakage of lactate dehydrogenase into the medium, a marker of nonspecific cell damage, were not changed by forskolin. Forskolin-induced decrease in the [3H]glucosamine incorporation occurred in both heparan sulfate and the other GAGs. The [3H]glucosamine incorporation into GAGs was suppressed by forskolin also in human aortic and human umbilical vein endothelial cells, bovine aortic smooth muscle cells, porcine kidney epithelial LLC-PK1 cells and human fetal lung fibroblastic IMR-90 cells. In conclusion, it was suggested that intracellular cAMP mediates the suppressive regulation of GAG production in vascular endothelial cells; as a result, the cell surface heparan sulfate was reduced. The cAMP-dependent pathway appears to be important as an intracellular mechanism by which endothelial production of anticoagulant heparan sulfate is regulated.

1-Methyl-3-isobutylxanthine↗