Biomedical subjects

T Kawata

Publications and source records attributed to T Kawata.

At least 91 records · Page 5Linked to original sources

PubMed1999

Congenital osteoclast deficiency in osteopetrotic (op/op) mice is improved by ovariectomy and orchiectomy.

We examined the changes in the appearance of osteoclasts in the femora of ovariectomized (OVX) or orchiectomized (ORX) op/op mice. Osteoclasts on the trabecular bone surface of the OVX or ORX op/op mice significantly increased in number seven or eight times in comparison with sham-operated op/op mice. Furthermore, TRAP-positive cells increased about four times in 100-week-old females and males, compared with sham-operated groups. These results have indicated that a sex hormone reduction due to OVX or ORX induces prominent recruitment of osteoclasts in op/op mice.

Animals↗

PubMed1999

Mechanism in inhibitory effects of vitamin K2 on osteoclastic bone resorption: in vivo study in osteopetrotic (op/op) mice.

Osteoclast deficiency in op/op mice was cured by a single injection of 5 micrograms recombinant human macrophage colony-stimulating factor (M-CSF). On d 5, the osteoclast number reached a maximum value. By d 15, the osteoclast number had decreased to about 70% of the maximum level. Moreover, by d 20, the osteoclast number had decreased to about 30% of its maximum level. On d 5, the osteoclast number of vitamin K2 12 h previously had decreased to about 30% of the M-CSF-only injected mice. Moreover, on d 5, the osteoclast number of the mice receiving a single injection of vitamin K2 24 h previously had decreased to about 15% that of mice injected only with M-CSF. These results indicate that vitamin K2 inhibits in vivo osteoclast formation. On d 20, the osteoclast number of the mice injected with a single dose of vitamin K2 12 or 24 h previously had decreased to 0% compared with those receiving only M-CSF. The present results suggest that the vitamin K2 "causes cell death" to mature osteoclasts and inhibits in vivo osteoclast formation.

Animals↗

PubMed1999

Association between G2-phase block and repair of radiation-induced chromosome fragments in human lymphocytes.

We have studied the induction of chromosomal aberrations in human lymphocytes exposed in G0 to X rays or carbon ions. Aberrations were analyzed in G0, G1, G2 or M phase. Analysis during the interphase was performed by chemically induced premature chromosome condensation, which allows scoring of aberrations in G1, G2 and M phase; fusion-induced premature chromosome condensation was used to analyze the damage in G0 cells after incubation for repair; M-phase cells were obtained by conventional Colcemid block. Aberrations were scored by Giemsa staining or fluorescence in situ hybridization (chromosomes 2 and 4). Similar yields of fragments were observed in G1 and G2 phase, but lower yields were scored in metaphase. The frequency of chromosomal exchanges was similar in G0 (after repair), G2 and M phase for cells exposed to X rays, while a lower frequency of exchanges was observed in M phase when lymphocytes were irradiated with high-LET carbon ions. The results suggest that radiation-induced G2-phase block is associated with unrejoined chromosome fragments induced by radiation exposure during G0.

Adult↗

PubMed1999

[Folic acid].

One-carbon derivatives of tetrahydrofolate, the coenzyme form of the vitamin folic acid, play a key role in DNA synthesis and cell replication, through their involvement in the biosynthesis of purine nucleotides and the amino acids. Although the most conspicuous symptom of folic acid deficiency is pernicius anemia, it has been observed that the lack of folate intake during the pregnancy induce the incidence of neural tube defects such as apina bifida. Recently, it has been reported that clinical progression of coronary heart disease and cerebral peripheral vascular disease occurred at a high rate in hyperhomocysteinemia with low folate content in plasma. Consequently, the nutritional importance of folate has been increasingly recognized.

Female↗

PubMed1999

[Re-coronary artery bypass grafting using a MIDCAB technique in a patient with a patent RITA-LAD graft].

In a patient with a patent RITA-LAD (right internal thoracic artery-left anterior descending artery) graft, re-CABG (re-coronary artery bypass grafting) with re-median sternotomy has been a high risk procedure. A 56-year-old male underwent 4-CABG (RITA-LAD, LITA-Dx, SVG-PL, and SVG-RCA) nine years ago. Coronary angiography showed that the RITA-LAD graft was well patent, but there was 95% stenosis distal to RITA-LAD anastomosis site. We performed re-CABG (right gastroepiploic artery-LAD; RGEA-LAD), using MIDCAB (minimally invasive direct coronary artery bypass) technique with neither re-median sternotomy nor cardiopulmonary bypass. The right gastroepiploic artery was harvested through a small upper median laparotomy and anastomosed to LAD through a small left anterior thoracotomy. The postoperative course was uneventful. This technique seems to be useful for re-revascularization of the LAD in a patient with a patent RITA-LAD graft.

Coronary Artery Bypass↗

PubMed1998

The attenuated effect of ATP-sensitive K+ channel opener pinacidil on renal haemodynamics in spontaneously hypertensive rats.

In hypertension, impairment of hyperpolarization by K+ efflux through ATP-sensitive K+ (K(ATP)) channels may contribute to the elevated renal vascular resistance. To elucidate such a role for K(ATP) channels in the renal vasculature, we used micropuncture techniques to examine the effect of K(ATP) channel opener, pinacidil (0.15 mg/h per kg body wt i.v.), on renal and glomerular haemodynamics in spontaneously hypertensive rats (SHR) and in normotensive controls (Wistar Kyoto, WKY). Since pinacidil reduced blood pressure significantly in both groups, the abdominal aorta was clamped before pinacidil administration to yield a renal perfusion pressure equivalent to that during pinacidil infusion. Pinacidil significantly decreased renal vascular resistance in both groups, but the relative change from baseline value was greater in WKY than in SHR. These effects of pinacidil were abolished by pretreatment with glibenclamide (3 mg/kg body wt i.v.). Proximal tubular stop-flow pressure (Psf), an index of glomerular capillary pressure, was significantly elevated by pinacidil infusion in WKY, a response abolished by pretreatment with glibenclamide, but not in SHR. The tubuloglomerular feedback response of Psf was not affected by pinacidil in either group. These data suggest that the activity of K(ATP) channels in SHR may be attenuated in the renal microvasculature. This may contribute to the elevated vascular tone in the renal preglomerular vasculature in SHR.

Animals↗

PubMed1998

Developmentally and spatially regulated activation of a Dictyostelium STAT protein by a serpentine receptor.

Dd-STAT, the protein that in part controls Dictyostelium stalk cell differentiation, is a structural and functional homolog of metazoan signal transducers and activators of transcription (STATs). Although present during growth and throughout development, Dd-STAT's tyrosine phosphorylation and nuclear localization are developmentally and spatially regulated. Prior to late aggregation, Dd-STAT is not tyrosine phosphorylated and is not selectively localized in the nucleus. During mound formation, the time at which cell-type specific gene expression initiates, Dd-STAT becomes tyrosine phosphorylated and translocates into the nuclei of all cells. The tyrosine phosphorylation and nuclear localization of Dd-STAT are induced very rapidly by extracellular cAMP through the serpentine cAMP receptor cAR1, with Dd-STAT tyrosine phosphorylation being detectable within 10 s of stimulation. This activation is independent of the only known Gbeta subunit, suggesting that it may be G-protein independent. Nuclear enrichment of Dd-STAT is selectively maintained within the sub-population of prestalk cells that form the tip, the organizing center of the slug, but is lost in most of the other cells of the slug. This spatial patterning of Dd-STAT nuclear localization is consistent with its known role as a negative regulator of stalk-cell differentiation.

Amino Acid Sequence↗

PubMed1998

Long-term benefits of internal thoracic artery-coronary artery bypass in Japanese patients.

OBJECTIVES: This study sought to determine the effects of grafting the internal thoracic artery (ITA) to the left anterior descending coronary artery (LAD) on long-term (10-year) survival, the cardiac death-free rate, and on the cardiac event-free rate in Japanese patients. BACKGROUND: The use of ITA grafts has been reported to enhance postoperative survival and to decrease the occurrence of cardiac events in the Western literature. However, the survival benefits in Japanese patients, who may have different prognoses with coronary artery disease and a different fate of a saphenous vein graft, have not yet been determined. SUBJECTS AND METHODS: A total of 954 consecutive patients who underwent coronary artery bypass graft operations (CABG) during the last 12 years at the Nara Medical University were followed and evaluated. Of these, 713 patients underwent ITA-CABG to at least the LAD (ITA group), and 241 patients received a saphenous vein graft (SVG) to the LAD (SVG group). At the time of operation, no significant difference was found between these two groups in age, sex ratio left ventricular ejection fraction, left ventricular end-diastolic pressure, cardiac index, incidence of unstable angina, or in the necessity for an emergency operation. However, those patients who received ITA-CABG had significantly higher incidences of diabetes mellitus, hyperlipidemia, and left main coronary artery disease. RESULTS: The 10-year cumulative graft patency rate for the LAD was 23% higher in the ITA group (90.3%) compared to the SVG group (67.0%), (p < .0001). Despite increased preoperative risk factors, patients in the ITA group showed significant improvements in their 5- and 10-year cumulative survival rates as well as in their cardiac death-free and event-free rates. Furthermore, this study demonstrated that ITA grafts improved the prognoses of patients with diabetes mellitus or left ventricular dysfunction and lowered both the long-term postoperative cardiac-death rate and the cardiac-event rate. CONCLUSIONS: The use of ITA grafts was effective in improving both the postoperative survival and cardiac event-free rates, and should be recommended in patients with diabetes mellitus or left ventricular dysfunction. ITA grafting to the LAD should be a routine operation in almost all categories of such patients.

Aged↗

PubMed1998

Feasibility study of a mechanical suturing device for less invasive mitral operations.

BACKGROUND: Because of smaller incisions and limited exposure, less invasive operations on the mitral valve can be arduous and time-consuming. This study examined the feasibility of a mechanical suturing device to facilitate less invasive mitral replacement. METHODS: Five mongrel dogs underwent limited left thoracotomy. After conventional cardiopulmonary bypass and cardioplegia, the mitral valve was exposed through a left atriotomy. After excision of the anterior leaflet, subannular sutures were placed using a mechanical suturing device. This device simultaneously passes two ends of a pledgeted 2-0 braided suture through the valvular annulus, then mechanically grasps both needles on the atrial aspect. Hence, a mattress suture is accomplished one-handed in a single continuous motion. This procedure was repeated around the entire annulus. A mechanical valve was seated and the sutures were tied and cut. RESULTS: All mechanical valves were implanted successfully. In the 4 animals in which it was attempted, cardiopulmonary bypass was successfully weaned. No evidence of perivalvular leak was observed by echocardiography. CONCLUSIONS: These data establish the feasibility of a mechanical suturing device for operations on the mitral valve. The device is easily mastered, maintains precise spacing between sutures, and permits rapid placement of mattress sutures. We predict widespread application for both less invasive and conventional valve operations.

Animals↗

PubMed1998

Difference in acetylcholine-induced nitric oxide release of arterial and venous grafts in patients after coronary bypass operations.

OBJECTIVES: In vivo investigation of nitric oxide release in coronary bypass grafts has not been reported. We studied acetylcholine-induced nitric oxide release in vivo of coronary bypass grafts and vasomotor responses to acetylcholine of grafted coronary arteries in patients after coronary bypass grafting. METHODS: We examined 24 internal thoracic artery grafts and 16 saphenous vein grafts in 39 patients. The mean ages of the patients were 65 years for the arterial grafts and 68 years for the venous grafts. Nitric oxide was measured as the plasma nitrite level by the Griess reaction. Before and after intragraft acetylcholine infusion (5 microg), blood was sampled from the distal end of the graft, and angiograms were taken and analyzed by cine-densitometry. RESULTS: The plasma nitrite concentration after stimulation with acetylcholine compared with the control value was 134%+/-52% at 4 minutes (p=0.05) and 184%+/-107% at 6 minutes (p=0.01) in the arterial grafts; in the venous grafts these values were 101%+/-24% at 4 minutes (p=0.96) and 108%+/-36% at 6 minutes (p=0.69). Low-dose acetylcholine dilated the coronary arteries supplied by arterial grafts by 6.3%+/-16.6% whereas coronary arteries supplied by venous grafts were reduced by 9.8%+/-11.8% in diameter and the vasoactive responses were different (p=0.01). CONCLUSIONS: In vivo internal thoracic artery grafts had more endothelium-derived nitric oxide release in response to acetylcholine than did saphenous vein grafts after coronary bypass grafting.

Acetylcholine↗

PubMed1998

Biodosimetry of heavy ions by interphase chromosome painting.

We report measurements of chromosomal aberrations in peripheral blood lymphocytes from cancer patients undergoing radiotherapy treatment. Patients with cervix or esophageal cancer were treated with 10 MV X-rays produced at a LINAC accelerator, or high-energy carbon ions produced at the HIMAC accelerator at the National Institute for Radiological Sciences (NIRS) in Chiba. Blood samples were obtained before, during, and after the radiation treatment. Chromosomes were prematurely condensed by incubation in calyculin A. Aberrations in chromosomes 2 and 4 were scored after fluorescence in situ hybridization with whole-chromosome probes. Pre-treatment samples were exposed in vitro to X-rays, individual dose-response curves for the induction of chromosomal aberrations were determined, and used as calibration curves to calculate the effective whole-body dose absorbed during the treatment. This calculated dose, based on the calibration curve relative to the induction of reciprocal exchanges, has a sharp increase after the first few fractions of the treatment, then saturates at high doses. Although carbon ions are 2-3 times more effective than X-rays in tumor sterilization, the effective dose was similar to that of X-ray treatment. However, the frequency of complex-type chromosomal exchanges was much higher for patients treated with carbon ions than X-ray.

Aged↗

PubMed1998

The K(ATP) channel opener nicorandil: effect on renal hemodynamics in spontaneously hypertensive and Wistar Kyoto rats.

Adenosine triphosphate-sensitive K channels (K(ATP)) may subserve vasodilation in the renal microvasculature. Using micropuncture techniques, we examined whether the renal vasomotor action of K(ATP) differs in hypertensive and normotensive animals. Nicorandil (NC), a K(ATP) opener, was given i.v. (1 mg/hr/kg) to spontaneously hypertensive rats (SHR) or Wistar Kyoto rats (WKY). Mean arterial blood pressure decreased in both groups. Renal blood flow was almost unchanged in SHR but increased significantly in WKY. This effect was completely abolished by pretreatment with glibenclamide (GC; 3 mg/kg i.v.). To investigate the effect of NC on the regulatory mechanism of renal microcirculation, we measured proximal tubular stop-flow pressure (SFP) and assessed tubuloglomerular feedback (TGF) by monitoring SFP during loop perfusion with artificial tubular fluid. NC significantly increased SFP in WKY, an effect abolished by pretreatment with GC. In SHR, however, treatment with NC elicited no significant change in SFP. TGF response was not affected by NC treatment in either group. The data suggest that K(ATP) may modulate preglomerular vascular resistance, especially in the larger vascular segments not subject to TGF regulation, and may be attenuated in SHR. This might, at least in part, be attributable to the increased vascular resistance in SHR.

Adenosine Triphosphate↗

PubMed1998

An evaluation of the biomechanical response of the tooth and periodontium to orthodontic forces in adolescent and adult subjects.

This study was designed to quantify the magnitude of tooth mobility in adolescents and adults, and to investigate the differences in the biomechanical response of tooth and periodontium to orthodontic forces. The initial displacement of the maxillary central incisor was measured in 50 adolescent and fifty adult patients and the biomechanical properties of the periodontium were examined using the finite element method (FEM) and supporting experimental data. The magnitude of tooth mobility was significantly greater in the adolescent group than in the adult group. By integrating the differences in tooth mobility in both subject groups with analytical tooth displacements, the Young's modulus of the periodontal ligament (PDL) was demonstrated to be greater in the adults than in the adolescent subjects. The differing biomechanical properties of the PDL in adults were demonstrated to result in almost equivalent or somewhat increased stress levels in the PDL in adult subjects. It is suggested that this might produce a reduction in the biological response of the PDL and thus lead to a delay in tooth movement in adults.

Adolescent↗

PubMed1998

Suppression of murine endotoxin response by E5531, a novel synthetic lipid A antagonist.

As a consequence of blood-borne bacterial sepsis, endotoxin or lipopolysaccharide (LPS) from the cell walls of gram-negative bacteria can trigger an acute inflammatory response, leading to a series of pathological events and often resulting in death. To block this inflammatory response to endotoxin, a novel lipid A analogue, E5531, was designed and synthesized as an LPS antagonist, and its biological properties were examined in vitro and in vivo. In murine peritoneal macrophages, E5531 inhibited the release of tumor necrosis factor alpha (TNF-alpha) by Escherichia coli LPS with a 50% inhibitory concentration (IC50) of 2.2 nM, while E5531 elicited no significant increases in TNF-alpha on its own. In support of a mechanism consistent with antagonism of binding to a cell surface receptor for LPS, E5531 inhibited equilibrium binding of radioiodinated LPS ([125I]2-(r-azidosalicylamido)-1, 3'-dithiopropionate-LPS) to mouse macrophages with an IC50 of 0.50 microM. E5531 inhibited LPS-induced increases in TNF-alpha in vivo when it was coinjected with LPS into C57BL/6 mice primed with Mycobacterium bovis bacillus Calmette-Guérin (BCG). In this model, the efficacy of E5531 was inversely correlated to the LPS challenge dose, consistent with a competitive antagonist-like mechanism of action. Blockade of the inflammatory response by E5531 could further be demonstrated in other in vivo models: E5531 protected BCG-primed mice from LPS-induced lethality in a dose-dependent manner and suppressed LPS-induced hepatic injury in Propionibacterium acnes-primed or galactosamine-sensitized mice. These results argue that the novel synthetic lipid A analogue E5531 can antagonize the action of LPS in in vitro and suppress the pathological effects of LPS in vivo in mice.

Animals↗

PubMed1998

Effects of chronic nitric oxide synthase inhibition on renal function and histology in polycythemic rats.

Augmented endogenous nitric oxide (NO) production may ameliorate derangement of renal functions or glomerular damage in polycythemia. To investigate this possibility, we examined the effect of NO synthase inhibition with N omega-nitro-L-arginine methyl ester (L-NAME; 50 mg/dl in drinking water) on renal functions and histology in heminephrectomized Sprague-Dawley rats treated for 4 weeks with recombinant human erythropoietin (rh-EP; 500 IU/kg on alternate days). L-NAME elevated the blood pressure which was aggravated by concomitant rh-EP and was ameliorated by treatment with a nonpeptide angiotensin type 1 receptor blocker (CV116; 60 mg/kg in chow). The hematocrit level was prominently increased by rh-EP. The glomerular filtration rate was impaired by L-NAME alone, but was maintained by concomitant administration of rh-EP or CV116. Micropuncture experiments revealed that the glomerular capillary pressure was similarly elevated by L-NAME alone or in combination with rh-EP. L-NAME significantly, although not prominently, aggravated glomerular sclerosis observed with rh-EP alone, and concomitant CV116 ameliorated the glomerular damage. These results suggest that, in polycythemia, enhanced NO production buffers the glomerular damage, and the balance between NO and angiotensin II may play an important role in maintaining renal function and glomerular structure.

Angiotensin Receptor Antagonists↗

PubMed1998

Impact of percutaneous transluminal coronary angioplasty on coronary bypass surgery--changes in the patient profile during the past decade.

As percutaneous transluminal coronary angioplasty has become an increasingly common procedure replacing coronary artery bypass grafting (CABG), the clinical profile of the patients referred for CABG has changed markedly. A retrospective study of the changes in the clinical profile and surgical outcome of patients who underwent CABG during the past 10 years was conducted. Between March 1982 and February 1996, 1010 patients underwent isolated CABG at Nara Medical University. The first 100 consecutive patients who underwent CABG in 1984-85 (group 1) were compared with the first 100 consecutive patients who underwent CABG in 1994-95 (group 2). Preoperative risk increased significantly during the decade with respect to patient age (p<0.001), the presence of diabetes mellitus (p=0.048), the number of diseased vessels (p<0.001), left main trunk disease (p=0.008), the presence of aortic or peripheral vascular disease (p=0.032),and the need for emergency surgery (p=0.013). Operative procedures have become more complicated with respect to the number of total and arterial grafts, duration of the aortic cross-clamp and cardiopulmonary bypass. Hospital mortality for elective CABG has not changed (2%) and the overall mortality has not increased significantly (from 2% to 3%) during the decade. In conclusion, although the preoperative risks have increased and more complicated procedures are required, CABG continues to be performed safely with low mortality rates.

Aged↗

PubMed1998

Midpalatal suture of osteopetrotic (op/op) mice exhibits immature fusion.

The midpalatal suture was observed histologically in both toothless osteopetrotic (op/op) and normal (control) mice. The normal mice had a mature sutural structure, which consists of a well-developed cartilage cell zone and palatal bone. In contrast, the thickness of the cartilage cell zone was substantially greater in the op/op mice than that in the controls. Moreover, the cartilage cells in the op/op mice were frequently found in the palatal bone as well as in the sutural space, exhibiting an imperfect fusion. It seems that immature fusion at the sutural interface in the op/op mice is related to a decrease in biting or masticatory force accompanied by the failure of tooth eruption in addition to an essential defect in osteoclast differentiation, which is a congenital symptom in op/op mice.

Animals↗

PubMed1998

Suspension "hypokinesia/hypodynamia" may decrease bone mass by stimulating osteoclast production in ovariectomized mice.

This study was conducted to examine, in detail, the histological changes in the femurs of suspended ovariectomized (OVX) mice to assess the role of mechanical stress on bone remodeling. Suspended-OVX, suspended-sham-ope, nonsuspended-OVX, and nonsuspended-sham-operated mice underwent operations 8 weeks after birth. Immediately after operation, hypokinesia/hypodynamia was created by a suspension harness for one week. Five specimens in each group were sacrificed 9 weeks after birth. The trabecular bone of the femurs in the suspended-OVX mice was removed and replaced extensively by bone marrow. The number of tartrate-resistant acid phosphatase (TRAP)-positive cells was larger in the suspended-OVX mice than in the remaining three groups. No significant differences in the number of TRAP positive cells were found between the suspended-sham-ope, nonsuspended-OVX and nonsuspended-sham-ope mice. The femurs of the OVX mouse with suspension "hypokinesia/hypodynamia" thus exhibits extensive trabecular bone loss in association with an increase of osteoclasts.

Acid Phosphatase↗