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Biomedical subjects

K Takagi

Publications and source records attributed to K Takagi.

At least 19 recordsLinked to original sources
PubMed2006

Expression of the PTH/PTHrP receptor in chondrogenic cells during the repair of full-thickness defects of articular cartilage.

OBJECTIVE: We studied the accumulation of parathyroid hormone (PTH)/PTHrP receptor-positive mesenchymal cells using double immunohistochemistry and examined whether this correlated with the subsequent regeneration of 3-mm-diameter full-thickness defects of articular cartilage. MATERIALS AND METHODS: Cylindrical full-thickness articular cartilage defects (3 mm) were artificially created in the femoral trochlea of male adolescent Japanese white rabbits (n = 210) with a hand-drill. Recombinant human PTH(1-84) was then administered into the defect cavities with an osmotic pump for either 2 or 4 weeks post-injury. Following PTH treatment, the repair processes in the cartilage defects were histologically examined. Double immunostaining analyses for the PTH/PTH-related peptide (PTHrP) receptor and proliferating cell nuclear antigen (PCNA) in the regenerating tissues were then performed. RESULTS: Activation of PTH/PTHrP receptor signaling by hPTH(1-84) results in the inhibition of chondrogenic differentiation in full-thickness articular cartilage defects. At the conclusion of the 2-week PTH treatment, the defect cavities were filled with undifferentiated mesenchymal cells, which were similar to the controls. In addition, almost all of these cells localized at the center of the injuries were both PTH/PTHrP receptor- and PCNA-positive. In contrast, after prolonged PTH treatment for 4 weeks, there was no indication of a cartilaginous repair response and cells that had migrated to the defect cavities were found to have irreversibly lost expression of the PTH/PTHrP receptor. CONCLUSIONS: The chondrogenic capacity of cells that had migrated to the area of these defect cavities is closely associated with their ability to express the PTH/PTHrP receptor. Moreover, these cells maintain their chondrogenic potential within only a limited time-span of 2 weeks.

Animals↗
PubMed2005

Light-scattering study on the shear-orientation coupling of liquids near isotropic-to-nematic phase transition.

Microscopic interaction between the translation and rotation of rodlike molecules yields the shear-orientation coupling in the macroscopic view. The depolarized scattering component arising from orientational fluctuations gives a constant in the strength of the coupling, which is related to the three viscosity parameters introduced by de Gennes. A high-resolution system of light scattering with an improved optical beating method was utilized for measurements in the 4-cyano-4'-alkylbiphenyl nCB series: propyl (3CB), butyl (4CB), pentyl (5CB), hexyl (6CB), heptyl (7CB), and octyl (8CB). All the coupling constants obtained in these samples showed clear dependence on temperature, and their behaviors were interpreted in terms of a critical phenomenon near T*, the virtual isotropic-nematic phase transition point. The values of T* were also given by the light scattering experiment, and the critical exponent of shear-orientation coupling was determined to be 0.31. Furthermore, the characteristic value of the coupling constant was correlated with the aspect ratio of these rodlike molecules, and two clear facts were found: a stronger coupling in longer molecules; and an odd-even effect with respect to the number of C-C bonds in the alkyl chain.

Journal Article↗
PubMed2005

Direct observation of slow molecular relaxation by high-resolution light scattering spectroscopy.

We developed a novel dynamic light scattering system to observe elastic relaxation phenomena with hyper frequency resolution. The principle of the measurement is based on the theory, which describes the dynamic structure factor of fluid under the condition of the frequency dependent compressibility. The dynamic structure factor, which is usually composed of the Brillouin and Rayleigh triplet, is modulated and shows an additional central component that directly reflects the whole aspect of the relaxation. In the experiment, the output from a frequency-doubled cw-YAG laser was incident into the liquid sample and the power spectrum of the light scattered into the backward direction was analyzed by the optical beating spectroscopy technique. The sample is liquid acetic acid that is known to show a strong ultrasonic relaxation around 1 MHz due to the molecular association process. We could find in the observed spectrum, the central component introduced by the phenomenon, whose relaxation frequency and the strength can be obtained from the width and the intensity of the observed central peak, respectively. The results show very good agreement with those previously obtained by the conventional ultrasonic spectroscopy technique.

Journal Article↗
PubMed2004

One day exposure to FGF-2 was sufficient for the regenerative repair of full-thickness defects of articular cartilage in rabbits.

OBJECTIVES: Administration of fibroblast growth factor (FGF)-2 for 2 weeks induces a successful cartilaginous repair response in 5-mm full-thickness articular cartilage defects in rabbits. The purpose of this study was to investigate the effects of a short time exposure to FGF-2 on the repair of the defects. METHODS: Five-mm-diameter cylindrical defects, which do not repair spontaneously, were created in the femoral trochlea of the rabbit knees. The defects were administered sterile saline or FGF-2 (150pg/h) via an osmotic pump for the initial 1 day, 3 days, or 2 weeks, and we assessed the FGF-2 action on the proliferation and migration of mesenchymal cells in the reparative tissue. Using a total of 126 rabbits, we performed three sets of experiments. We also studied the effect of FGF-2 on migration of marrow-derived mesenchymal cells in vitro. RESULTS: FGF-2 treatment for 1 day or 3 days induced the sequential chondrogenic repair responses that led to successful cartilaginous resurfacing of defects within 8 weeks as well as the 2-week treatment did. We confirmed by a radioisotope study that FGF-2 injected was rapidly eliminated from the defects (a residual ratio of 50% within 30min). The effect of FGF-2 on cultured marrow-derived cells suggested that FGF-2 facilitated the mobilization and migration of replicating mesenchymal cells from bone marrow. CONCLUSIONS: Only 1 day exposure to FGF-2 is sufficient for induction of the chondrogenic repair response in 5-mm-diameter full-thickness defects of articular cartilage in rabbits. FGF-2 stimulated the recruitment of mesenchymal cells into the defects, which was a limiting step for the induction of cartilage.

Animals↗
PubMed2004

Antioxidant effect of MCI-186, a new Free-Radical scavenger, on ischemia-reperfusion injury in a rat hindlimb amputation model.

BACKGROUND: A newly synthesized free-radical scavenger, MCI-186 (3-methyl-1-phenyl-2-pyrazolin-5-1), was recently approved in Japan for treating acute brain infarction. The purpose of this study was to investigate whether or not MCI-186 is effective in reducing ischemia-reperfusion injury in the extremities. MATERIALS AND METHODS: Warm ischemia was sustained for 4 hours. The animals were divided into 4 groups: (1) sham group, (2) control group (saline injection), (3) MCI group (MCI-186 injection), and (4) EPC group (EPC-K1 [(l-ascorbic acid 2-[3,4-dihydro-2, 5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1-benzopyran-6-yl hydrogen phosphate] potassium salt], a hydroxyl-radical scavenger, injection). Wet and dry (W/D) weights of the gastrocnemius and tibialis anterior muscles, muscle contractile function, and serum levels of creatine phosphokinase (CPK), lactate dehydrogenase (LDH), glutamic oxaloacetic transminase (GOT), and mitochondrial glutamic oxaloacetic transminase (GOT-m) were measured after 24 h of reperfusion. The cytotoxic aldehydes malondialdehyde and 4-hydroxy-2-nonenal as indices of lipid peroxidation (LPO), and neutrophil-specific enzyme myeloperoxidase (MPO) as an index of neutrophil infiltration, were measured in the gastrocnemius muscle. RESULTS: Contractile functions in the MCI and EPC groups were significantly better than in the control group. In the tibialis anterior muscle, the contractile function was better in the MCI group than in the EPC group. W/D ratios and serum levels of CPK, LDH, GOT, and GOT-m were lower in the sham and MCI groups than in the control group. Levels of LPO and MPO activity were significantly lower in the MCI and EPC groups than in the control group. Histological findings demonstrated that inflammatory tissue reactions rarely occurred in the MCI group. CONCLUSION: MCI-186 is effective in preventing ischemia-reperfusion injury in extremities. MCI-186 seems to have promise as a therapeutic agent, because it prevents ischemia-reperfusion injury even in the tibialis anterior muscle, which contains fast-twitch glycolytic fibers, known to be very susceptible to ischemic insult.

Amputation, Surgical↗
PubMed2004

Single nucleotide polymorphism of the MxA gene promoter influences the response to interferon monotherapy in patients with hepatitis C viral infection.

The biological activity of interferon (IFN) is mediated by the induction of intracellular antiviral proteins, such as 2'-5' oligoadenylate synthetase, dsRNA-activated protein kinase and MxA protein. Among these, MxA protein is assumed to be the most specific surrogate parameter for IFN action. This study was performed to elucidate whether a single nucleotide polymorphism (SNP) (G/T at nt-88) in the promoter region of the MxA gene influences the response to IFN therapy in patients with chronic hepatitis C virus (HCV) infection. Polymorphisms of the MxA gene in 235 HCV patients were determined by polymerase chain reaction-restriction fragment length polymorphism. The frequency of SNP was compared between sustained-responders (n = 78) and nonresponders (n = 157), as determined by biochemical and virological responses to IFN. Multivariate analysis showed that among all patients, HCV genotype, HCV RNA level and the SNP of the MxA gene were independent and significant determinants of the outcome of IFN therapy [odds ratio 3.8 (95% confidence interval 2.0-7.0), P < 0.0001; 0.27 (0.15-0.50), P < 0.0001; 1.8 (1.0-3.4), P = 0.0464, respectively]. Furthermore, among patients with a low viral load (< or =2.0 Meq/mL), MxA-T-positive patients were more likely to show a sustained response compared with MxA-T-negative patients [2.87 (1.3-6.3); 62%vs 36%; P = 0.0075]. Our findings suggested that the SNP of the MxA gene is one of the important host factors that independently influences the response to IFN in patients with chronic HCV infection, especially those with a low viral load.

Adult↗
PubMed2004

Activation of Na+-independent Mg2+ efflux by 20-hydroxyeicosatetraenoic acid in rat renal epithelial cells.

Renal epithelial cells may have Mg(2+) transport pathways that regulate intracellular free Mg(2+) concentration ([Mg(2+)](i)) and reabsorption into the body. In mag-fura 2 fluorescent measurement, extracellular Mg(2+) removal induced a Na(+)-independent [Mg(2+)](i) decrease. The [Mg(2+)](i) decrease was suppressed by methyl arachidonyl fluorophosphonate, a cytosolic and Ca(2+)-independent phospholipase A(2) (iPLA(2)) inhibitor, and bromoenol lactone, an iPLA(2) inhibitor, but it was not suppressed by a secretory phospholipase A(2) inhibitor. On the contrary, the [Mg(2+)](i) decrease was enhanced by the addition of exogenous arachidonic acid (AA). Next, we examined the effect of AA metabolite inhibitors on the [Mg(2+)](i) decrease. 17-octadecynoic acid inhibited the [Mg(2+)](i) decrease, but indomethacin and nordihydroguaiaretic acid did not. In the 17-octadecynoic acid-treated cells, 20-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoic acid (20-HETE) recovered the [Mg(2+)](i) decrease. Nicardipine inhibited both the basal and the 20-HETE-enhanced [Mg(2+)](i) decrease. These results suggest that 20-HETE is a key mediator in the activation of Na(+)-independent Mg(2+) efflux.

Animals↗
PubMed2003

Laser excitation of high-frequency capillary waves.

The laser-induced surface deformation (LISD) technique was applied to generate high-frequency capillary waves on liquid surfaces up to several tens of kHz in a noncontact manner. The dynamic response of the fluid near the surface was theoretically derived under the condition of periodical radiation pressure. The result of the numerical calculation predicts the propagation of induced capillary waves out from the excitation region. The efficiency of the wave generation was experimentally examined by changing the width of the excitation laser beam at the surface. The observed LISD spectra were well reproduced by the theory, showing that the effective frequency band can be extended up to over 100 kHz. The propagation of the optically generated wave was measured with a laser probe sweeping the position of the observation. The spatial profile gives the surface tension and the shear viscosity of the sample liquid. The frequency domain measurement was also carried out and the spectrum obtained at a fixed point agrees with the theory, demonstrating the rapid measurement of frequency-dependent phenomena.

Journal Article↗
PubMed2003

Unrelated donor bone marrow transplantation for acute mixed lineage (myeloid and B-lymphoid lineage) leukemia in an adult with Down syndrome.

This article describes a rare case of bone marrow transplantation (BMT) from an unrelated donor (URD) in an adult Japanese male with Down syndrome (DS) diagnosed as having acute mixed lineage leukemia. Examination of peripheral blood demonstrated WBC 6.2 x 10(9)/l with 45.5% blasts at admission. Leukemic blasts with positive peroxidase stain, but negative periodic acid-Schiff stain comprised 91.6% on bone marrow specimen. Surface marker analysis of these blasts showed the following: CD3(-), CD5(-), CD7(-), CD10(+), CD19(+), CD13(+), CD14(-), CD33(+), CD34(+), CD41a(-), and CD56(-). Based on these data, he was diagnosed as having acute mixed lineage (myeloid and B-lymphoid lineage) leukemia. He achieved complete remission (CR) by lymphoid-oriented chemotherapy performed after ineffective myeloid-oriented therapy. After four courses of consolidation chemotherapy for lymphoid lineage blasts, recurrence due to proliferation of myeloblasts had occurred. Thereafter, a second CR was obtained by low dose cytosine arabinoside (AraC) therapy. As this patient was considered to have a high risk of relapse, we selected allogeneic BMT from URD. Severe stomatitis due to methotrexate (MTX) occurred probably due to altered pharmacokinetics usually observed in DS patients. Though acute graft-versus-host disease (GVHD) of systemic skin (grade II) and pneumonia were observed during neutropenia due to the post-conditioning regimen, he could be discharged from our hospital on the 135th day after BMT. On day 205 post-BMT, however, bronchiolitis obliterans (BO) occurred as a chronic GVHD disorder. Despite therapy with prednisolone and FK506, he died on day 400 post-BMT because of respiratory failure due to BO. In DS patients, superfluous toxicities due to MTX and AraC treatment have been reported, and these toxicities have been considered due to altered pharmacokinetics in patients with DS. This patient could tolerate the transplant conditioning regimen commonly used in patients without DS.

Adult↗
PubMed2003

Compression and stretching of the brachial plexus in thoracic outlet syndrome: correlation between neuroradiographic findings and symptoms and signs produced by provocation manoeuvres.

In order to investigate the mechanism of nerve irritation in thoracic outlet syndrome (TOS), we studied 150 patients who presented with symptoms of neurologic TOS between 1985 and 1999. They first performed various provocative physical manoeuvres and then underwent injection of contrast medium into the supraclavicular part of the brachial plexus. Several of the provocative manoeuvres were then repeated and radiographs were again obtained. Based on the neuroradiographs, we identified three subsets of patients; those with only compression (type 1 TOS, n=27, 18%), those with combined compression and stretching (type 2 TOS, n=111, 74%), and those with only stretching (type 3 TOS, n=12, 8%). We were able to correlate the neuroradiological subsets with symptoms elicited by pre-radiographic provocative manoeuvres; in 92 patients (61%) these were elicited by traction manoeuvres. We conclude that stretching is an important factor of nerve irritation in TOS.

Adolescent↗
PubMed2003

Gastric restitution is inhibited by dexamethasone, which is reversed by hepatocyte growth factor and rebamipide.

BACKGROUND: Glucocorticoids have been shown to induce peptic ulcers, especially when co-administered with NSAIDs. Hepatocyte growth factor (HGF) plays a role in gastric ulcer repair, facilitating the restitution of gastric mucosal epithelial cells. HGF expression is induced by PGs in gastric fibroblasts. We hypothesized that dexamethasone (DEX) may inhibit PG production and HGF expression, thus inhibiting HGF-induced gastric epithelial restitution. AIM: To investigate the effect of DEX on gastric restitution, using cultured gastric cells, the role of HGF in the restitution inhibited by DEX, and the effect of rebamipide on DEX- inhibited restitution. METHODS: Human gastric fibroblasts were prepared from human stomach obtained at surgery; PGE2 and HGF is determined by ELISA; Restitution was assessed by the round wound restitution model, using coculture of gastric fibroblasts and epithelial cells; COX-2 and HGF mRNA were quantified by TaqMan RT-PCR system. RESULTS: 1. DEX inhibited HGF mRNA and COX-2 mRNA. Accordingly, it inhibited PGE2 and HGF release. 2. DEX inhibited the restitution of gastric cells. 3. The inhibition of restitution was reversed by HGF and rebamipide to the same extent. 4. Rebamipide induced PGE2 and HGF. CONCLUSION: DEX inhibits restitution via HGF depletion, and rebamipide reverses the inhibited restitution by HGF induction.

Alanine↗
PubMed2003

RhoA is associated with invasion and lymph node metastasis in upper urinary tract cancer.

OBJECTIVE: To assess the roles of RhoA small GTPase (RhoA) in upper urinary tract cancer by analysing the mRNA and protein levels of RhoA. PATIENTS AND METHODS: The mRNA and protein levels of RhoA in matched sets of tumour, non-tumour and metastatic lymph node tissues of surgical specimens were analysed in 47 consecutive patients with renal pelvic/ureteric cancer, using the polymerase chain reaction after reverse transcription and Western blotting. The relationship between mRNA and protein levels of RhoA in tumour tissues and the clinicopathological features of the patients was also assessed. RESULTS: The mRNA levels of RhoA and RhoA protein were greater in tumour and metastatic lymph node tissues than in non-tumour tissues (all P < 0.001). The expression levels of RhoA mRNA and protein levels in primary tumours was related to poorly differentiated grade (both P < 0.05) and muscle invasion (P < 0.01 and < 0.001, respectively). Kaplan-Meier plots of survival in patients with low or high RhoA showed that high mRNA and protein levels were associated with a shorter disease-free (P < 0.01) and overall survival (P < 0.001). Multivariate analysis using the Cox proportional hazards model showed that a high RhoA protein level was an independent prognostic factor, second to stage, in disease-free and overall survival (both P < 0.05). CONCLUSIONS: These findings suggest that RhoA is involved in the invasion and metastasis of upper urinary tract cancer, indicating that RhoA may be a useful prognostic factor in this disease.

Aged↗
PubMed2003

Serum nitric oxide (NO) levels in systemic sclerosis patients: correlation between NO levels and clinical features.

Vascular damage in systemic sclerosis (SSc) may be a factor in the abnormal regulation of several vasoactive agents. It has been well confirmed that plasma endothelin-1, as a vasoconstrictive factor, is elevated in patients with SSc. However, it is still controversial whether the levels of serum nitric oxide (NO), a strong vasodilator, are increased or decreased in SSc patients compared to healthy donors. In this study, we measured the levels of serum NO metabolites in SSc patients and determined the contribution of the excessive production of NO synthase (NOS)-2 by skin fibroblasts to NO synthesis. Serum NO levels of 45 patients with SSc were significantly higher than those of 20 healthy volunteers. In addition, some clinical features of SSc (the extent of skin fibrosis, short disease duration, and the complication of active fibrosing alveolitis) were all correlated positively with the levels of NO metabolites in SSc patients. To evaluate the levels of NOS-2 produced by skin fibroblasts, skin fibroblast cultures were established from SSc patients and healthy volunteers. Reverse transcription-polymerase chain reaction indicated that NOS-2 mRNA was spontaneously expressed in cultured fibroblasts derived from SSc patients, but not in those derived from healthy normal controls. Immunohistochemical staining also showed that NOS-2 proteins were detected in SSc fibroblasts but not in normal fibroblasts. The production of NO by cultured fibroblasts was visualized directly by a reagent (DAF-2 DA) used for the fluorescent detection of NO. Cultured SSc fibroblasts were capable of NO synthesis in culture media containing L-arginine, whereas normal fibroblasts (with no expression of NOS-2) did not synthesize detectable NO. These observations indicate that NO production is increased markedly in early-stage diffuse cutaneous SSc patients with active fibrosing alveolitis, and that constitutive NOS-2 expression in SSc fibroblasts may contribute to increased NO production.

Adolescent↗
PubMed2002

Leukotriene receptor antagonist, montelukast, can reduce the need for inhaled steroid while maintaining the clinical stability of asthmatic patients.

BACKGROUND: Oral leukotriene receptor antagonists have been shown to have efficacy in chronic asthma. OBJECTIVE: To determine whether the addition of montelukast could lead to a reduction in inhaled corticosteroid dose without a significant decrease in peak expiratory flow rate (PEFR). METHODS: After a 4-week run-in period, 191 moderate-to-severe asthmatic patients whose asthma had been well controlled with daily inhaled corticosteroid therapy (beclometasone dipropionate 800 to 1600 micro g/day), were randomly assigned to one of two treatments - placebo (n = 98) or montelukast 10 mg once daily (n = 93) - for a 24-week, multicentre, double-blind, treatment period. At the beginning of the active treatment period, the daily dose of inhaled corticosteroid was halved in all of the patients. In addition, the inhaled corticosteroid dose was subsequently titrated every 8 weeks, based on PEFR, asthma symptoms and beta-agonist use. RESULTS: After 8 weeks of a 50% reduction in inhaled corticosteroid use, morning PEFR increased by 5.3 +/- 32.3 L/min from baseline in patients receiving montelukast and significantly decreased by 6.9 +/- 29.0 L/min in those receiving placebo (P = 0.035). In addition, evening PEFR significantly decreased by 9.8 +/- 28.5 L/min (P = 0.003) in the placebo group, but was maintained in the montelukast group. In spite of a subsequent 50% reduction in the inhaled corticosteroid dose every 8 weeks, morning and evening PEFRs were maintained over the 24-week treatment period in the montelukast group; PEFR significantly decreased in the placebo group. There was a significant difference between the two groups with regard to morning PEFR, therapy score and asthmatic score at weeks 8, 16 and 24, as well as evening PEFR at week 8. However, the symptom scores were not significantly different between the two groups or within each group. CONCLUSION: These data suggest that montelukast reduces the need for inhaled corticosteroids while maintaining asthma control over a 24-week period. Therefore, montelukast may be useful for long-term treatment in patients with asthma who require high doses of inhaled corticosteroids.

Acetates↗
PubMed2001

Endotoxin impairs biliary transport of sparfloxacin and its glucuronide in rats.

The effect of endotoxin on glucuronidation and hepatobiliary transport of quinolone antimicrobial agents was investigated in rats using sparfloxacin and p-nitrophenyl glucuronide as model drugs. The biliary clearance experiments were performed 24 h after a single intraperitoneal injection of endotoxin (1 mg/kg). Endotoxin significantly delayed the disappearance of sparfloxacin from plasma and increased plasma concentration of its glucuronide after intravenous injection of sparfloxacin (10 mg/kg). Significant decreases in the systemic clearance of sparfloxacin and the biliary clearance of sparfloxacin and the glucuronide were observed. Endotoxin had no effect on in vitro glucuronidation activity using p-nitrophenol as a substrate. When p-nitrophenyl glucuronide (8 mg/kg) was administered in endotoxin-pretreated rats, significant decreases in the systemic clearance, biliary clearance and renal clearance of p-nitrophenyl glucuronide were observed. These findings suggest that endotoxin decreases the biliary excretion of sparfloxacin and its glucuronide probably due to impairment of their hepatobiliary transport systems and renal handling.

Animals↗