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S Takai

Publications and source records attributed to S Takai.

At least 91 records · Page 5Linked to original sources
PubMed1999

A method of tracking donor cells after simulated autologous transplantation: a study using synovial cells of transgenic rats.

A transgenic rat was used as a transplantation donor to simulate autologous transplantation. The sex-matched transplantation between a female transgenic and a wild-type rat can theoretically be regarded as an autologous transplantation due to the genetic agreement of these rats except for the non-protein-producing transgenes. Transgene-containing synovial cells were tracked in the joint using this autologous transplantation model. The transgenes in the donor synovial cells were detected using in situ hybridization (ISH), while mitotic activities were simultaneously examined by immunodetection of 5-bromo-2'-deoxyuridine (BrdU). A defect was generated in the knee joint capsule of a Fischer 344 (wild-type) rat. The synovium of a transgenic rat was sutured to the defect of the wild-type rat in group 1 and was allowed to free float in the joint in group 2. A large number of BrdU-labeled, transgene-containing synovial cells were detected in both groups at 3 days. The number of these cells then decreased, but they could still be identified even at 4 weeks after autologous transplantation. These results indicated that transplanted synovial cells were viable in the joint for at least 4 weeks. Furthermore, the transgenic rat was shown to be an effective animal model for distinguishing the extrinsic from the intrinsic cells in the cellular intermixed tissues in vivo. The combined method of ISH for detecting transgene-containing cells and the immunohistochemistry of BrdU for detecting proliferating cells was also shown to be effective for tracking the viability of extrinsic cells after autologous transplantation.

Animals↗
PubMed1999

Effects of daphnodorin A, daphnodorin B and daphnodorin C on human chymase-dependent angiotensin II formation.

We investigated whether daphnodorin A, daphnodorin B and daphnodorin C inhibited human chymase-dependent angiotensin II-forming activity. Although the structures of these compounds are very similar, daphnodorin A completely inhibited angiotensin II formation generated by chymase, while daphnodorin B partially inhibited and daphnodorin C did not. On the other hand, these daphnodorins did not affect angiotensin converting enzyme-dependent angiotensin II formation. Furthermore, these daphnodorins did not inhibit purified human tryptase, which, like chymase, is contained in mast cells. Therefore, daphnodorin A, but not daphnodorin B and daphnodorin C, may specifically inhibit the chymase-dependent angiotensin II formation, and such differences between inhibitory effects of these compounds to human chymase may be useful for the development of human chymase inhibitor.

Adult↗
PubMed1999

Suppression of parathyroid hormone-related protein messenger RNA expression by medroxyprogesterone acetate in breast cancer tissues.

The level of parathyroid hormone-related protein (PTHrP) expressed in breast cancer tissue is closely related to the incidence of bone metastasis. We examined the PTHrP mRNA expression in breast cancer tissues by coamplification polymerase chain reaction (PCR) in mole ratio to internal standard beta-actin mRNA. The PTHrP expression was higher in premenopausal patients than in postmenopausal patients (P < 0.05). More pronounced difference by menopause found in estrogen receptor (ER) positive groups (P < 0.001) indicated that the PTHrP expression in breast cancer tissue is hormonally regulated and might be altered by endocrine agents. To clarify the changes of PTHrP expression by endocrine therapy of breast cancer, we measured PTHrP expression in the breast cancer tissue incubated for 24 h with 1 x 10(-8) M of estradiol (E2), 1 x 10(-6) M of tamoxifen (TAM) and 1 x 10(-5) M of medroxyprogesterone acetate (MPA). The PTHrP expression was decreased significantly by MPA (P < 0.005), while E2 and TAM did not change the PTHrP expression. Progesterone receptor (PgR) mRNA expression was also examined to confirm that the breast cancer tissue responds to E2 and TAM. The results were well compatible with the better therapeutic effect of MPA reported for the treatment of breast cancer with bone metastases. As a potential candidate for the receptor that mediates the suppressive effect of MPA, androgen receptor (AR) is suggested most probable. Present results also demonstrated that the clinical response of individual tumors is closely associated with the early in vitro changes of gene expression detected in the cancer specimen.

Antineoplastic Agents, Hormonal↗
PubMed1999

Anti-atherosclerotic effects of an angiotensin converting enzyme inhibitor and an angiotensin II antagonist in Cynomolgus monkeys fed a high-cholesterol diet.

1. We investigated the relationship between angiotensin II formation and the development of atherosclerotic lesions in the aorta of monkeys (Macaca fascicularis) fed a high-cholesterol (4% cholesterol and 6% corn oil) diet for 6 months, and studied the effects of an angiotensin converting enzyme (ACE) inhibitor, trandolapril (10 mg kg-1 per day, p.o.), and an angiotensin II type 1 receptor antagonist, 2-butyl-4-(methylthio)-1-[[2'[[[(propylamino)carbonyl]amino]sulfonyl] (1,1'-biphenyl)-4-yl]methyl]-1H-imidazole-5-carboxylate (HR 720; 20 mg kg-1 per day, p.o.). 2. The level of low-density lipoprotein was significantly increased by the cholesterol diet, whereas that of high-density lipoprotein was significantly decreased. The relative areas of the atherosclerotic lesions in the thoracic aorta in the normal and cholesterol-diet groups were 1.3+/-0.3 and 64+/-10%, respectively. 3. Plasma renin and ACE activities showed no differences between the normal and cholesterol-diet groups. ACE activity and the concentration of angiotensin II were significantly increased in the aorta of the cholesterol-fed monkeys. 4. Trandolapril and HR 720 decreased significantly the area of the atherosclerotic lesions in the thoracic aorta of cholesterol-fed monkeys, but not the mean blood pressure and the levels of low-density and high-density lipoproteins. 5. In plasma and aorta, trandolapril, but not HR 720, decreased significantly the ACE activities in the cholesterol-fed monkeys, while both of these drugs decreased significantly the angiotensin II levels. 6. In conclusion, blockade of angiotensin II function in vascular tissues by trandolapril or HR 720 may play an important role in preventing the development of atherosclerotic lesions.

Angiotensin II↗
PubMed1999

Effect of an angiotensin II receptor antagonist, candesartan cilexetil, on canine intima hyperplasia after balloon injury.

The roles of angiotensin (Ang) II as produced by two different enzymes, angiotensin-converting enzyme (ACE) and chymase, were investigated in a canine experimental model where intima hyperplasia was induced by balloon catheterization in the common carotid and femoral arteries. The animals received oral candesartan cilexetil (3 mg/kg) or enalapril (10 mg/kg) twice a day for 5 weeks. After 1 week of active drug therapy, the common carotid and femoral arteries were unilaterally injured by balloon catheterization. In the common carotid arteries, both ACE and chymase activities were increased by the injury, with the increase in chymase activities being greater than that in ACE activities. In the femoral arteries, ACE, but not chymase, activities were significantly increased by the injury. Both candesartan cilexetil and enalapril reduced blood pressure almost equally. Enalapril increased plasma renin activity more strongly than did candesartan cilexetil, and significantly decreased vascular and plasma ACE activities. Candesartan cilexetil significantly suppressed the formation of intima hyperplasia in both the carotid and femoral arteries, while enalapril significantly suppressed intima hyperplasia in the femoral, but not in the carotid arteries. These results indicate that local Ang II production by ACE and chymase is involved in the hyperplasia seen in injured intima, and the difference in the inhibitory action of candesartan and enalapril reflects the extent of contribution of each enzyme. The effect of the ACE inhibitor, enalapril, depended on the activity of ACE, whereas that of the Ang II receptor antagonist, candesartan, was independent of ACE activity.

Angiotensin Receptor Antagonists↗
PubMed1999

Tumour necrosis factor and interferon-gamma are required in host resistance against virulent Rhodococcus equi infection in mice: cytokine production depends on the virulence levels of R. equi.

Rhodococcus equi is a facultative intracellular bacterial pathogen that causes pneumonia in foals and immunosuppressed humans. There are at least three virulence levels of R. equi and these pathogenicities are associated, in mice, with the presence of virulence plasmids. This study focused on cytokine secretion, in mice, in the course of a primary infection with sublethal doses of R. equi strains of different virulence levels (virulent, intermediately virulent and avirulent). Tumour necrosis factor (TNF) and interferon-gamma (IFN-gamma), but not interleukin-4 (IL-4) and interleukin-10 (IL-10), were induced endogenously in mice in relation to the multiplication and clearance of virulent and intermediately virulent strains of R. equi. These cytokines were not detected in mice infected with avirulent R. equi. Deaths occurred among mice treated with monoclonal antibodies (mAbs) against either TNF or IFN-gamma prior to sublethal dose infection with virulent and intermediately virulent strains of R. equi, but not with avirulent R. equi. These results suggested that cytokine production depended largely on the virulence levels of R. equi: TNF and IFN-gamma were required early during infection with virulent R. equi to limit replication and clearance of bacteria within the organs, but they were not necessary for limiting infection with avirulent R. equi.

Actinomycetales Infections↗
PubMed1999

Effect of prophylactic administration of hyperimmune plasma to prevent Rhodococcus equi infection on foals from endemically affected farms.

The effect on foals of prophylactic administration of hyperimmune plasma to prevent R. equi infection was investigated on three farms at which R. equi infection was endemic. Sixteen foals between 10 and 39 days of age were intravenously given 1-21 of hyperimmune plasma. ELISA antibody titres against R. equi were significantly increased and maintained at high levels for over 30 days in most of the recipient foals. The prevalence of R. equi infection was 6.3% (1/16) in the foals that received the immune plasma, and 26.3% (5/19) in the control foals not given the immune plasma on the three farms. For 2 years before and after this field trial on the three farms, 18 of 64 foals (28.1%) showed clinical signs of respiratory tract infection and four of them died of R. equi pneumonia. Heavy contamination of horses and their environment with virulent R. equi was detected by colony blotting, and plasmid profiles also suggested that foals on the three farms were constantly exposed to virulent R. equi. The results of this field trial support previous observations by some researchers that the administration of hyperimmune plasma to foals in the early days of life promotes prevention of R. equi infection on endemic farms; however, the mechanism of hyperimmune plasma protection remains unclear.

Actinomycetales Infections↗
PubMed1999

Evaluation of new monoclonal anti-MyoD1 and anti-myogenin antibodies for the diagnosis of rhabdomyosarcoma.

New monoclonal anti-MyoD1 and anti-myogenin antibodies were evaluated immunohistochemically to determine whether they are useful in discriminating rhabdomyosarcoma (RMS) from other soft tissue tumors in routinely processed sections. Neither MyoD1 nor myogenin was expressed in normal, mature striated muscle. In RMS, nuclear expression of MyoD1 and myogenin was found in 82 and 80% of non-overlapping cases, respectively. MyoD1 was generally expressed in small, primitive tumor cells, and larger cells exhibiting morphological evidence of skeletal muscle differentiation failed to express positive nuclear immunostaining. Positive nuclear staining for myogenin was stronger than that for MyoD1 in cases with abundant differentiated tumor cells, but was less prominent in cases in which small, primitive tumor cells predominated. No leiomyosarcomas, Ewing's sarcomas/peripheral primitive neuroectodermal tumors or other soft tissue tumors exhibited nuclear expression of MyoD1 or myogenin. In conclusion, both anti-MyoD1 and anti-myogenin antibodies are useful for diagnosing RMS and for discriminating RMS from other soft tissue tumors.

Actins↗
PubMed1999

Ex vivo liver perfusion with arterial blood from a pig with ischemic liver failure.

To simplify liver support using an ex vivo perfused liver, an isolated pig liver was perfused with arterial blood from the recipient pig while monitoring the metabolic capacity of the ex vivo perfused liver. It was possible to perfuse the isolated liver for more than 24 h using arterial blood from a pig with ischemic liver failure. The viability of the isolated liver during support from the liver failure pig was well maintained as evidenced by the high adenylate energy charge (0.815) and a constant ketone body ratio (KBR) of over 1.0 sampled from the hepatic vein. Oxygen consumption (mean, 29.0 microl/min/g of liver) and bile production (mean, 24.2 microl/h/g of liver) were significantly higher in the isolated liver connected to the liver failure pig than in the organ connected to the pig without liver failure (15.5 microl/min/g and 7.3 microl/h/g, respectively). These findings suggest that this liver support system has sufficient metabolic capacity to support a failed liver. Further studies may provide the experimental basis necessary for the clinical application of this device in treatment of patients with acute liver failure.

Animals↗
PubMed1999

Effects of a new 12-lipoxygenase inhibitor, daphnodorin A, on angiotensin II-induced vascular contraction in hamster.

We studied whether lipoxygenase inhibition suppressed angiotensin II-induced vascular contraction. In the present study, we used a new 12-lipoxygenase inhibitor, daphnodorin A, and an analogue of daphnodorin A, daphnodorin B, which has no inhibitory effects on 12-lipoxygenase. Daphnodorin A at 30 microM and 100 microM significantly suppressed the contractile responses induced by angiotensin 11 (3 x 10(-8) M) in isolated hamster aorta, while daphnodorin B up to 100 microM did not affect the responses. These results suggest that daphnodorin A, but not daphnodorin B, may suppress angiotensin II-induced vascular contractile responses through the inhibition of 12-lipoxygenase.

Angiotensin II↗
PubMed1999

Live virulent Rhodococcus equi, rather than killed or avirulent, elicits protective immunity to R. equi infection in mice.

Mice inoculated intravenously with a sublethal dose of live virulent Rhodococcus equi ATCC 33701 that contained an 85-kb virulence plasmid were immune to a lethal intravenous challenge of ATCC 33701. This immunity depended upon the dose of immunization and developed rapidly: mice primed with 10(5) live ATCC 33701 eliminated the challenged bacteria more rapidly than mice primed with doses ranging from 10(2) to 10(4) bacteria, and mice given 10(5) live ATCC 33701 intravenously withstood the lethal challenge as early as 5 days after the initial inoculation. However, this protective immunity did not develop in mice immunized with doses of heat-killed ATCC 33701 ranging from 10(6) to 10(8), or in mice immunized with doses of live ATCC 33701P-, a plasmid-cured derivative (avirulent), in doses ranging from 10(5) to 10(7). These mice had positive antibody titers against R. equi at the challenge (14 days after priming). Adoptive transfer of resistance to virulent R equi was obtained with spleen cells from mice immunized with live ATCC 33701, but not monoclonal antibody to 15- to 17-kDa virulence-associated antigens. These results revealed that live ATCC 33701P-, a plasmid-cured derivative of virulent R equi, could not elicit protective immunity, and are consistent with previous observations that protective immunity was induced by live virulent, but not killed organisms.

Animals↗
PubMed1999

Restriction fragment length polymorphisms of virulence plasmids in Rhodococcus equi.

Virulent Rhodococcus equi, which is a well-known cause of pyogranulomatous pneumonia in foals, possesses a large plasmid encoding virulence-associated 15- to 17-kDa antigens. Foal and soil isolates from five countries-Argentina, Australia, Canada, France, and Japan-were investigated for the presence of 15- to 17-kDa antigens by colony blotting, using the monoclonal antibody 10G5, and the gene coding for 15- to 17-kDa antigens by PCR. Plasmid DNAs extracted from positive isolates were digested with restriction endonucleases BamHI, EcoRI, EcoT22I, and HindIII, and the digestion patterns that resulted divided the plasmids of virulent isolates into five closely related types. Three of the five types had already been reported in Canadian and Japanese isolates, and the two new types had been found in French and Japanese isolates. Therefore, we tentatively designated these five types 85-kb type I (pREAT701), 85-kb type II (a new type), 87-kb type I (EcoRI and BamHI type 2 [V. M. Nicholson and J. F. Prescott, J. Clin. Microbiol. 35:738-740, 1997]), 87-kb type II (a new type), and 90-kb (pREL1) plasmids. The 85-kb type I plasmid was found in isolates from Argentina, Australia, Canada, and France. Plasmid 87-kb type I was isolated in specimens from Argentina, Canada, and France. The 85-kb type II plasmid appeared in isolates from France. On the other hand, plasmids 87-kb type II and 90-kb were found only in isolates from Japan. These results revealed geographic differences in the distribution of the virulence plasmids found in the five countries and suggested that the restriction fragment length polymorphism of virulence plasmids might be useful to elucidate the molecular epidemiology of virulent R. equi in the world.

Plasmids↗
PubMed1999

Angiotensin II type 2 receptor overexpression activates the vascular kinin system and causes vasodilation.

Angiotensin II (Ang II) is a potent vasopressor peptide that interacts with 2 major receptor isoforms - AT1 and AT2. Although blood pressure is increased in AT2 knockout mice, the underlying mechanisms remain undefined because of the low levels of expression of AT2 in the vasculature. Here we overexpressed AT2 in vascular smooth muscle (VSM) cells in transgenic (TG) mice. Aortic AT1 was not affected by overexpression of AT2. Chronic infusion of Ang II into AT2-TG mice completely abolished the AT1-mediated pressor effect, which was blocked by inhibitors of bradykinin type 2 receptor (icatibant) and nitric oxide (NO) synthase (L-NAME). Aortic explants from TG mice showed greatly increased cGMP production and diminished Ang II-induced vascular constriction. Removal of endothelium or treatment with icatibant and L-NAME abolished these AT2-mediated effects. AT2 blocked the amiloride-sensitive Na(+)/H(+) exchanger, promoting intracellular acidosis in VSM cells and activating kininogenases. The resulting enhancement of aortic kinin formation in TG mice was not affected by removal of endothelium. Our results suggest that AT2 in aortic VSM cells stimulates the production of bradykinin, which stimulates the NO/cGMP system in a paracrine manner to promote vasodilation. Selective stimulation of AT2 in the presence of AT1 antagonists is predicted to have a beneficial clinical effect in controlling blood pressure.

Actins↗
PubMed1999

[Pathophysiological roles of chymase and effects of chymase inhibitor].

Human chymase forms angiotenin (ANG) I to ANG II, whereas the roles of ANG II generated by chymase and the effects of chymase inhibitors have been unclear. On the other hand, rat chymase could not convert ANG I to ANG II. In isolated rat arteries, the ANG I-induced vascular contraction was completely suppressed by angiotensin-converting enzyme (ACE) inhibitor only. However, 30% of ANG I-induced vascular contraction in isolated human arteries was suppressed by an ACE inhibitor, but the remainder was blocked by chymostatin. In hamster hypertensive models, ANG II formation by ACE, but not by chymase, in vascular tissues plays an important role in maintaining hypertension. ANG II formation also induces vascular remodeling such as neointima formation. After balloon injury of vessels in dog, chymase and ACE activities were significantly increased in the injured vessels. In this model, an ANG II receptor antagonist was effective in preventing neointimal formation after balloon injury of vessels in dog, but an ACE inhibitor was ineffective. In dog grafted veins, the activities of chymase and ACEmin the grafted vein were significantly increased 15- and 2-fold, respectively, compared with those in the symmetrical veins. The intimal area of the grafted vein was reduced by a chymase inhibitor. Therefore, chymase-dependent ANG II formation plays an important role in the proliferative response, and chymase inhibitors may appear useful for preventing vascular proliferation.

Angiotensin I↗
PubMed1999

Inhibition of the angiotensin II Type 1 receptor by TCV-116: quantitation by in vitro autoradiography.

Inhibition of angiotensin (Ang) II type 1 (AT1) receptors in various target tissues of adult Sprague-Dawley rats was studied after single oral administration of TCV-116. The effects of TCV-116 on Ang II-receptor binding were assessed by quantitative in vitro autoradiography using 125I-[Sar1,Ile8]Ang II as a ligand. Four hours after the administration of TCV-116 (1 mg/kg), Ang II-receptor binding was markedly inhibited in the kidney (20% of control), adrenal cortex (27%), thoracic aorta (57%), heart (55%) and testis (76%) where AT1 receptors predominate. In the brain, orally administered TCV-116 produced a significant inhibition of binding both to the circumventricular organs (38%), which are devoid of the blood-brain barrier (BBB), and to the discrete regions within the BBB such as the paraventricular hypothalamic nucleus (48%), nucleus of the solitary tract (60%). Twenty-four hours after the administration, Ang II-receptor binding had partly recovered to approximately 50-85% of control levels. In contrast, throughout the experimental period, Ang II-receptor binding was little affected in sites where Ang II type 2 (AT2) receptors predominate such as the adrenal medulla and the nucleus of the inferior olive. These data indicate that orally administered TCV-116 specifically binds to AT1 receptors both in peripheral tissues and the central nervous system.

Administration, Oral↗
PubMed1999

Angiotensin II type 1 receptor antagonist, TCV-116, prevents neointima formation in injured arteries in the dog.

We investigated the effect of an angiotensin (Ang) II antagonist, (+/-)-1-(cyclohexyloxycarbonyloxy)-ethyl 2-ethoxy- 1- [[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]- 1H-benzimidazole-7-carboxylate (TCV-116), on neointima formation in dog artery injured by a balloon catheter. Dogs were orally treated with 10 mg/kg TCV-116 or placebo twice a day for 5 weeks. After treatment with these drugs for 1 week, the right carotid artery was injured by a balloon catheter. The left carotid artery was regarded as the control. In the group treated with placebo, neointima formation in the injured arteries was observed. The activities of angiotensin converting enzyme (ACE) and chymase in the injured carotid arteries were increased 2.56- and 3.26-fold compared with those in the non-injured arteries, respectively. The neointimal area in dogs treated with placebo and TCV-116 were 0.51 +/-0.07 and 0.21 +/-0.07 mm2, respectively, and this difference was significant. In conclusion, an Ang II antagonist, TCV-116, prevented neointima formation by blocking the action of Ang II generated by both ACE and chymase in the injured arteries.

Angiotensin Receptor Antagonists↗
PubMed1999

Effects of a lipoxygenase inhibitor, panaxynol, on vascular contraction induced by angiotensin II.

We investigated whether a lipoxygenase inhibitor, panaxynol, affected the vascular contraction induced by angiotensin (Ang) II and the mean arterial pressure in spontaneously hypertensive rats (SHR). Panaxynol suppressed dose-dependently the contractile responses induced by 30 nM Ang II in isolated intact and endothelial cell-denuded aorta in the hamster. IC50 values in the intact and endothelial cell-denuded aorta were 23 and 20 microM, respectively. In SHR, the mean arterial pressure after injection of 30 and 60 mg/kg panaxynol was reduced, and the maximum hypotensive values were 23 and 48 mmHg, respectively. Thus, lipoxygenase products may affect the renin-angiotensin system.

Alkynes↗