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Biomedical subjects

T Kawata

Publications and source records attributed to T Kawata.

At least 37 records · Page 2Linked to original sources
PubMed2002

[Off-pump coronary artery bypass grafting for patients with cardiogenic shock due to acute myocardial infarction].

UNLABELLED: Off-pump coronary artery bypass (OPCAB) is less invasive, so we have recently been expanding the indication. We performed OPCAB for 3 patients with cardiogenic shock due to acute myocardial infarction (AMI). PATIENTS: All patients were supported hemodynamically by intra-aortic balloon pumping (IABP) prior to surgery. RESULTS: We performed the revascularization of territories for the left anterior descending artery (LAD) and right coronary artery (RCA) in these high risk patients using OPCAB technique to improve the hemodynamic state. In all patients, IABP was removed within 48 hours after surgery and the postoperative course was uneventful. CONCLUSIONS: It seems that OPCAB is a useful and effective procedure for a selected patient even with cardiogenic shock due to AMI.

Aged↗
PubMed2002

[Modification of repeat lateral minimally invasive direct coronary artery bypass; left axillary artery to circumflex artery bypass].

A 69-year-old man underwent triple coronary artery bypass graftings [LITA (left internal thoracic artery)-LAD (left anterior descending artery), SVG (saphenous vein graft)-PD (postac-descending artery), SVG-PL (postero-lateral artery)] 11 years previously. Recently, angina pectoris occurred due to the graft disease of SVG-PL. A repeat modified lateral minimally invasive direct coronary artery bypass (MIDCAB) [left axillary artery-PL using SVG] was performed. The left axillary artery was chosen as inflow vessel for coronary artery bypass graft because of the difficult descending aorta and patent LITA-LAD. Postoperative course was uneventful. The left axillary artery to circumflex artery bypass could be one of the option of the lateral MIDCAB.

Aged↗
PubMed2001

Sensitized mast cells migrate toward the antigen: a response regulated by p38 mitogen-activated protein kinase and Rho-associated coiled-coil-forming protein kinase.

Although mast cells accumulate within the mucosal epithelial layer of patients with allergic rhinitis and bronchial asthma, the responsible chemotactic factors are undefined. We investigated whether mast cells sensitized with Ag-specific IgE migrate toward the Ag. MC/9 mast cells sensitized with anti-DNP IgE migrated toward DNP-conjugated human serum albumin. This migration was directional, and the degree was stronger than that induced by stem cell factor. IL-3 and stem cell factor-dependent cultured mast cells derived from mouse bone marrow also migrated toward the Ag. Subsequent migration mediated by the Fc(epsilon)RI was significantly inhibited by incubating the cells with Y-27632, a Rho-associated coiled-coil-forming protein kinase inhibitor, or with SB203580, a p38 mitogen-activated protein kinase (MAPK) inhibitor. Both p38 MAPK and MAPK-activated protein kinase (MAPKAPK)2 were activated following Fc(epsilon)RI aggregation, and activation of MAPKAPK2 was almost completely inhibited by 10 microM SB203580. Wortmannin or a low concentration of SB203580 partially inhibited MAPKAPK2, but did not block mast cell migration. In contrast, Y-27632 did not affect the activation of MAPKAPK2. These results indicate that Ag works not only as a stimulant for allergic mediators from IgE-sensitized mast cells, but also as a chemotactic factor for mast cells. Both p38 MAPK activation and Rho-dependent activation of Rho-associated coiled-coil-forming protein kinase may be required for Fc(epsilon)RI-mediated cell migration.

Androstadienes↗
PubMed2001

Atrial natriuretic peptide inhibits tumor necrosis factor-alpha production by interferon-gamma-activated macrophages via suppression of p38 mitogen-activated protein kinase and nuclear factor-kappa B activation.

We investigated whether the atrial natriuretic peptide (ANP) might have an inhibitory effect on inflammatory cells. Treatment of RAW264.7 macrophages with interferon-gamma (IFN- gamma) caused a significant increase in tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) production. Activation of p38 mitogen-activated protein (MAP) kinase was observed 30 to 120 min after IFN-gamma, and transcription factor nuclear factor-kappa B (NF-kappaB) was activated about 7 to 9 times of the basal activity. Human ANP(99-126) and a specific p38 MAP kinase inhibitor SB203580 inhibited the IFN-gamma-induced TNF-alpha production in a dose-dependent manner without affecting NO production. ANP inhibited the IFN-gamma-induced p38 MAP kinase activation, and ANP and SB203580 inhibited NF-kappaB activation. To study the involvement of oxidative stress in this system, the effects of allopurinol and acetovanillone, inhibitors of xanthine oxidase and NADPH oxidase, respectively, were studied. Allopurinol or acetovanillone did not inhibit the IFN-gamma-induced production of TNF-alpha or NO, suggesting little involvement of oxidative stress in this system. This is the first evidence in vitro that ANP has an anti-inflammatory activity on IFN-gamma-activated macrophages by suppressing signal transduction pathway leading to p38 MAP kinase and NF-kappaB activation.

Animals↗
PubMed2001

2-Alkynyl-8-aryl-9-methyladenines as novel adenosine receptor antagonists: their synthesis and structure-activity relationships toward hepatic glucose production induced via agonism of the A(2B) receptor.

Novel adenosine antagonists, 2-alkynyl-8-aryl-9-methyladenine derivatives, were synthesized as candidate hypoglycemic agents. These analogues were evaluated for inhibitory activity on N-ethylcarboxamidoadenosine (NECA)-induced glucose production in primary cultured rat hepatocytes. In general, aromatic moieties at the 8-position and alkynyl groups at the 2-position had significantly increased activity compared to unsubstituted compounds. The preferred substituents at the 8-position of adenine were the 2-furyl and 3-fluorophenyl groups. In modifying the alkynyl side chain, change of the ring size, cleavage of the ring, and removal of the hydroxyl group were well tolerated. The order of the stimulatory effects of adenosine agonists on rat hepatocytes was NECA > CPA > CGS21680, which is consistent with involvement of the A(2B) receptor. In Chinese hamster ovary cells stably transfected with human A(2B) receptor cDNA, one of the compounds potent in hepatocytes, 15o (IC(50) = 0.42 microM), antagonized NECA-induced stimulation of cyclic AMP production (IC(50) = 0.063 microM). This inhibitory effect was much more potent than those of FK453, KF17837, and L249313 which have been reported to be respectively A(1), A(2A), and A(3) selective antagonists. These findings agree very well with the result that, compared to 15o, these selective antagonists for each receptor subtype showed only marginal effects in rat hepatocytes. These results suggest that adenosine agonist-induced glucose production in rat hepatocytes is mediated through the A(2B) receptor. Furthermore, 15o showed hypoglycemic activity in an animal model of noninsulin-dependent diabetes mellitus, the KK-A(y) mice. It is possible that inhibition of hepatic glucose production via the A(2B) receptor could be at least one of the mechanisms by which 15o exerts its in vivo effects. Further elaboration of this group of compounds may afford novel antidiabetic agents.

Adenine↗
PubMed2001

High beta-galactosidase and ganglioside GM1 levels in the human parotid gland.

BACKGROUND: Ganglioside G(M1) is a membrane glycolipid typical of nerve cell membranes, where it partakes in neurotransmitter release and is catabolized by the lysosomal beta-galactosidase (GM1ase) (EC 3.2.1.23). After demonstrating a novel degenerative disease of the parotid gland in mice deficient in GM1ase, mimicking the human storage disease GM(1) gangliosidosis, we studied GM1ase and ganglioside G(M1) content in the human parotid glands. STUDY DESIGN: Levels of GM1ase and ganglioside G(M1) were determined in samples of parotid tissues and neighboring muscle (as a negative control) for 3 subjects. Tissues were also processed for histochemical demonstration of GM1ase. RESULTS: The mean specific activity of GM1ase was more than 6-fold higher in the healthy human parotid tissues (1.4 +/- 0.5 nmol of 4-methylumbelliferone per minute per milligram of protein) relative to the neighboring muscle tissue (0.23 +/- 0.07 nmol of 4-methylumbelliferone per minute per milligram of protein). Activity of GM1ase was histochemically localized mainly to striated duct and acinar cells of the parotid gland. Ganglioside G(M1) content in the parotid gland was on average 30-fold higher relative to muscle. CONCLUSIONS: Our results are consistent with previous findings reported in the mouse and the rabbit, and probably reflect a general property of the mammalian parotid glands. The novel mechanism we previously proposed for the mouse parotid saliva secretion, mimicking neurotransmitter release in ganglioside G(M1)-containing nerve cells, is probably applicable also to the human parotid gland. Similarly, the human parotid gland is probably also severely affected in GM(1) gangliosidosis.

Adult↗
PubMed2001

Reoperative coronary artery bypass grafting using a minimally invasive direct coronary artery bypass procedure.

OBJECTIVE: Reoperative coronary artery bypass grafting with cardiopulmonary bypass tends to cause a higher mortality and morbidity than the primary operation. The purpose of this study was to discuss the effectiveness and safety of a minimally invasive coronary artery bypass procedure for patients who had previously undergone coronary artery bypass surgery. METHODS: We performed redo single coronary artery bypass grafting to the left anterior descending coronary artery in 9 patients and to the right coronary artery in 3 patients using minimally invasive cardiac surgery. The graft to the left anterior descending coronary artery was taken from the left internal thoracic artery in 5 patients, the right gastroepiploic artery in 3 patients, and from the saphenous vein in the other 1 patient. The graft to the right coronary artery was from the right gastroepiploic artery in all 3 patients. RESULTS: All grafts were patent. There was no major postoperative complication and no surgical or hospital death except one late death. CONCLUSIONS: In selected patients, we could safely and completely perform coronary artery bypass re-grafting to the left descending coronary artery or right coronary artery using a minimally invasive operation.

Aged↗
PubMed2001

Influence of oestrogen and androgen on modelling of the mandibular condylar bone in ovariectomized and orchiectomized growing mice.

Oestrogen and androgen exert a substantial influence on bone metabolism, but any differences in their influence on modelling of the condyle, a mandibular growth site, have not been fully clarified. The purpose here was to examine histological and histochemical differences in the condyle of ovariectomized (OVX) or orchiectomized (ORX) mice given injections of oestrogen (E(2), 17 beta-oestradiol) or non-aromatizable androgen (DHT, 5 alpha-dihydrotestosterone). Eight-week-old C57BL/6J mice (n=170) were used: they were divided equally into six experimental groups (OVX, ORX, OVX+E(2), ORX+E(2), OVX+DHT, ORX+DHT), and non-treatment male and female control groups. In each experimental group, five mice were killed 2,4,8 and 12 weeks after OVX and ORX. Oestrogen or androgen were given daily after the surgery by subcutaneous injection of E(2) or DHT. Increases in the number of tartrate-resistant acid phosphatase-positive cells induced in the OVX and ORX mice from 4 to 12 weeks after surgery were obviously suppressed by E(2) and DHT. The trabecular bone volume in the OVX and ORX mice treated with DHT had only increased at 12 weeks after surgery, whereas the E(2) injected mice exhibited a substantial increase from 4 to 12 weeks after surgery. E(2) injected into the OVX and ORX mice increased the trabecular bone volume earlier than did DHT, and both E(2) and DHT suppressed osteoclast differentiation similarly during the same period. These results suggest that metabolic responses of osteoclasts and osteoblasts to E(2) and DHT may be different, producing somewhat different patterns of bone modelling in males and females.

Acid Phosphatase↗
PubMed2001

G2-chromosome aberrations induced by high-LET radiations.

We report measurement of initial G2-chromatid breaks in normal human fibroblasts exposed to various types of high-LET particles. Exponentially growing AG 1522 cells were exposed to gamma rays or heavy ions. Chromosomes were prematurely condensed by calyculin A. Chromatid-type breaks and isochromatid-type breaks were scored separately. The dose response curves for the induction of total chromatid breaks (chromatid-type + isochromatid-type) and chromatid-type breaks were linear for each type of radiation. However, dose response curves for the induction of isochromatid-type breaks were linear for high-LET radiations and linear-quadratic for gamma rays. Relative biological effectiveness (RBE), calculated from total breaks, showed a LET dependent tendency with a peak at 55 keV/micrometer silicon (2.7) or 80 keV/micrometer carbon (2.7) and then decreased with LET (1.5 at 440 keV/micrometer). RBE for chromatid-type break peaked at 55 keV/micrometer (2.4) then decreased rapidly with LET. The RBE of 440 keV/micrometer iron particles was 0.7. The RBE calculated from induction of isochromatid-type breaks was much higher for high-LET radiations. It is concluded that the increased production of isochromatid-type breaks, induced by the densely ionizing track structure, is a signature of high-LET radiation exposure.

Cell Line↗
PubMed2001

2-Alkynyl-8-aryladenines possessing an amide moiety: their synthesis and structure-activity relationships of effects on hepatic glucose production induced via agonism of the A(2B) adenosine receptor.

A series of 2-alkynyl-8-aryladenine derivatives bearing an amide moiety at the 9-position of adenine was synthesized. These analogues were evaluated for inhibitory activity on N-ethylcarboxamidoadenosine (NECA)-induced glucose production in primary cultured rat hepatocytes. The m-primary benzamide derivative 15f was the most potent compound (IC(50)=0.017 microM), being 15-fold more active than the corresponding 9-methyl derivative (1). Compound 15f showed 72- and 5.2-fold selectivity for human A(2B) receptor versus human A(1) and A(2A) receptors, respectively. Structure-activity relationship (SAR) studies of the synthesized compounds indicated that a three-carbon linker, fixed in the form of a benzene ring, between the adenine core and the amide moiety is important for both A(2B) antagonistic activity and selectivity. The IC(50) values in rat hepatocyte glucose assay correlated well with the IC(50) values in cAMP assay using Chinese hamster ovary cells stably transfected with human A(2B) receptors (r(2)=0.94). The A(1) and A(2A) affinities showed no correlation with the potency to inhibit NECA-induced glucose production. These results strongly support our previous conclusion that adenosine agonist-induced hepatic glucose production in rat hepatocytes is mediated through the A(2B) receptor.

Adenine↗
PubMed2001

Vitamin B-12-deficiency affects immunoglobulin production and cytokine levels in mice.

To clarify the role of B-12 in the immunological function, serum C3, IgM, IgG, IgE contents, splenocytes expression of CD4, CD8, and CD4 positive intracellular IFN-gamma and IL-4 were examined in B-12-deficient mice, and the effect of the administration of CH3-B-12 was also studied. Serum C3, IgM and IgG contents were lower in B-12-deficient mice than in the control mice. On the other hand, serum IgE content was significantly higher in B-12-deficient mice, and the value in CH3-B-12 administered mice, administered CH3-B-12 to B-12-deficient mice for 48 h before the end of feeding period, showed a tendency to recovery. CD4+CD8- cells and CD4+CD8-/CD4-CD8+ ratio in splenocytes were significantly higher in B-12-deficient mice than in control mice. CD4+IFN-gamma+ cells was significantly lower in B-12-deficient mice than in control mice, and CD4+IL-4+ was significantly higher in B-12-deficient mice than in control mice. These results suggest that B-12-deficiency causes CD4+CD8-T cells shift from the T helper type 1 to the T helper type 2, which participate in the IgE production and elevates CD4+CD8-/CD4-CD8+ ratio. Thus, B-12 plays a role in maintaining the immune function in mice.

Animals↗
PubMed2001

Breadth of the mandibular condyle affected by disturbances of the sex hormones in ovariectomized and orchiectomized mice.

It is well known that the size of the condyle is different between males and females in humans. It has also been documented that ovariectomy (OVX) and orchiectomy (ORX) influence the remodeling of the condylar head in experimental animals. However, influences of sex hormones on the condyle in terms of its breadth have not been examined. With these considerations, this study was designed to examine the breadth of the mandibular condyle in OVX and ORX mice by histomorphometry 8 weeks after surgery. In the OVX mice, the condylar breadth was significantly larger than in the controls, while no significant differences in the breadth were found between the ORX mice and the controls. The thickness of the condylar cartilage layers exhibited similar findings to the breadth of the condyle. On the contrary, the trabecular bone volume was significantly smaller in the OVX and ORX mice than in the corresponding controls, and the difference was more substantial in female mice than in the males. These findings emphasize that a reduction of sex hormone levels, induced by OVX and ORX, significantly influences condylar morphogenesis.

Journal Article↗
PubMed2001

The expression of osteopontin with condylar remodeling in growing rats.

It is suggested that osteopontin may promote osteoclast binding to resorptive sites by interacting with the alphavbeta3 receptor on osteoclasts. However, the role of osteopontin in functional remodeling of bony structures remains unclear. The present study was conducted to examine the distribution of osteopontin on the condyle and explore the role in condylar remodeling in growing rats using an immunohistochemical method. Twenty Wistar strain male rats aged 7, 14, 28 and 56 days were used. In 7- and 14-day-old rats, no immunoreaction to osteopontin was detected in the cartilage cells. In 28-day-old rats initiating mastication, the thickness of condylar cartilage was decreased abruptly as compared to the younger rats. High immunoreaction to osteopontin was found in the cytoplasm of hypertrophic chondrocytes and on the trabecular bone surfaces of primary spongiosa adjacent to the osteoclasts or chondroclasts. The immunoreactions to osteopontin in the cytoplasm of hypertrophic chondrocytes were less in 56-day-old rats than in 28-day-old rats. It is shown that the alteration in mechanical loading on the mandibular condyle due to functional changes from weaning to mastication correlates with the localization of osteopontin in growing rats. Furthermore, it is suggested that osteopontin may stimulate osteoclastic resorption of calcified matrix by mediating the attachment of osteoclasts and/or chondroclasts during growth-related functional remodeling of the condyle.

Journal Article↗
PubMed2001

Dose--response of initial G2-chromatid breaks induced in normal human fibroblasts by heavy ions.

PURPOSE: To investigate initial chromatid breaks in prematurely condensed G2 chromosomes following exposure to heavy ions of different LET. MATERIAL AND METHODS: Exponentially growing human fibroblast cells AG1522 were irradiated with gamma-rays, energetic carbon (13 keV/ microm, 80 keV/microm), silicon (55 keV/microm) and iron (140 keV/microm, 185keV/microm, 440keV/microm) ions. Chromosomes were prematurely condensed using calyculin-A. Initial chromatid-type and isochromatid breaks in G2 cells were scored. RESULTS: The dose response curves for total chromatid breaks were linear regardless of radiation type. The relative biological effectiveness (RBE) showed a LET-dependent increase, peaking around 2.7 at 55-80keV/microm and decreasing at higher LET. The dose response curves for isochromatid-type breaks were linear for high-LET radiations, but linear-quadratic for gamma-rays and 13 keV/microm carbon ions. The RBE for the induction of isochromatid breaks obtained from linear components increased rapidly between 13keV/microm (about 7) and 80keV/microm carbon (about 71), and decreased gradually until 440 keV/microm iron ions (about 66). CONCLUSIONS: High-LET radiations are more effective at inducing isochromatid breaks, while low-LET radiations are more effective at inducing chromatid-type breaks. The densely ionizing track structures of heavy ions and the proximity of sister chromatids in G2 cells result in an increase in isochromatid breaks.

Azure Stains↗
PubMed2001

High- and low-LET induced chromosome damage in human lymphocytes: a time-course of aberrations in metaphase and interphase.

PURPOSE: To investigate how cell-cycle delays in human peripheral lymphocytes affect the expression of complex chromosome damage in metaphase following high- and low-LET radiation exposure. MATERIALS AND METHODS: Whole blood was irradiated in vitro with a low and a high dose of 1 GeV u(-1) iron particles, 400MeV u(-1) neon particles or y-rays. Lymphocytes were cultured and metaphase cells were collected at different time points after 48-84h in culture. Interphase chromosomes were prematurely condensed using calyculin-A, either 48 or 72 h after exposure to iron particles or gamma-rays. Cells in first division were analysed using a combination of FISH whole-chromosome painting and DAPI/ Hoechst 33258 harlequin staining. RESULTS: There was a delay in expression of chromosome damage in metaphase that was LET- and dose-dependant. This delay was mostly related to the late emergence of complex-type damage into metaphase. Yields of damage in PCC collected 48 h after irradiation with iron particles were similar to values obtained from cells undergoing mitosis after prolonged incubation. CONCLUSION: The yield of high-LET radiation-induced complex chromosome damage could be underestimated when analysing metaphase cells collected at one time point after irradiation. Chemically induced PCC is a more accurate technique since problems with complicated cell-cycle delays are avoided.

Bisbenzimidazole↗
PubMed2001

Effects of vascular endothelial growth factor on osteoclast induction during tooth movement in mice.

UNLABELLED: For orthodontic tooth movement, remodeling of the alveolar bone is maintained by a repeated process of bone resorption and new bone formation, controlled, respectively, by osteoclasts and osteoblasts. Recently, we have found that recombinant human vascular endothelial growth factor (rhVEGF) acts as a macrophage colony-stimulating factor in osteoclast induction in osteopetrotic (op/op) mice. The purpose of this study was to investigate whether rhVEGF stimulates osteoclast differentiation during experimental tooth movement. Purified rhVEGF was injected once into the buccal gingival groove around the incisors. An experimental appliance with a helical loop was bonded onto the upper incisors, and an initial force of 1.0 g was applied for three days. The number of osteoclasts appearing in the periodontal ligament space on the pressure side of the alveolar bone was increased markedly. These results suggest that local administration of rhVEGF enhances the number of osteoclasts, and may increase the rate of orthodontic tooth movement. ABBREVIATIONS: recombinant human vascular endothelial growth factor (rhVEGF), macrophage colony-stimulating factor (M-CSF), osteopetrotic mice (op/op mice),fms-like tyrosine kinase (Flt-1), periodontal ligament (PDL), phosphate-buffered saline (PBS), tartrate-resistant acid phosphatase (TRAP), and analysis of variance (ANOVA).

Acid Phosphatase↗