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M Akagi

Publications and source records attributed to M Akagi.

At least 19 recordsLinked to original sources
PubMed2006

Possible involvement of the oxidized low-density lipoprotein/lectin-like oxidized low-density lipoprotein receptor-1 system in pathogenesis and progression of human osteoarthritis.

OBJECTIVE: Using human cartilage samples and cultured chondrocytes, to assess the possible involvement of oxidized low-density lipoprotein (ox-LDL) and lectin-like ox-LDL receptor-1 (LOX-1) in pathogenesis and progression of osteoarthritis (OA). METHODS: Thirty-two cartilage samples were obtained from 16 patients with knee OA, and 12 Control samples from six with femoral neck fracture. LOX-1 mRNA expressions in 12 OA and six Control samples were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemistry for ox-LDL and LOX-1 was performed in all samples. The histological OA grade was assessed with the modified Mankin score. The relative percentage of the ox-LDL and LOX-1 immunopositive chondrocytes was calculated in all samples. The effects of ox-LDL on cell viability in cultured human chondrocytes were investigated by the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay and on proteoglycan synthesis by monitoring [35S] sulfate incorporation. RESULTS: There was a statistically significant difference between mean LOX-1/GAPDH (LOX-1/human glyceraldehyde-3-phosphate dehydrogenase) ratio of OA samples and that of Control samples (40.6%+/-10.3 and 11.9%+/-2.8, respectively, P<0.0001). The mean percentage of ox-LDL-positive cells was 23.0+/-15.7% in OA and 4.3+/-3.7% in Control cells (P=0.0002). The mean percentage of LOX-1-positive cells was 51.7+/-29.5% in OA and 10.0+/-8.1% in Control cells (P<0.0001). Both the ox-LDL immunoreactivity and the LOX-1 immunoreactivity were significantly correlated with the modified Mankin scores (R2=0.67 and 0.48, respectively; P<0.0001 for each). ox-LDL significantly reduced the human chondrocyte viability and proteoglycan synthesis, and pretreatment with anti-human LOX-1 monoclonal antibody reversed these effects. CONCLUSION: The ox-LDL/LOX-1 system may be involved in human OA.

Aged↗
PubMed2004

ZD6126 inhibits orthotopic growth and peritoneal carcinomatosis in a mouse model of human gastric cancer.

The purpose of this study was to examine the effects of ZD6126, a novel vascular-targeting agent, on tumour growth and angiogenesis in an orthotopic model of gastric cancer. TMK-1 human gastric adenocarcinoma cells were injected into the gastric wall of nude mice. After the tumours were established (day 14), therapy was initiated. Mice (n=11-12/group) received (a). vehicle, (b). ZD6126 at 100 mg x kg day(-1) i.p. one time per week or (c) ZD6126 at 100 mg x kg day(-1) i.p. five times per week. Tumour mass, volume and the presence or absence of peritoneal carcinomatosis were determined at sacrifice on day 38. Tumours from each group were stained for markers of blood vessels, proliferation and apoptosis. To further define the time frame of the vascular-targeting effects of chronic therapy with ZD6126, TMK-1 cells were again injected into the gastric wall of mice in a second experiment. On day 14, a single i.p. injection of ZD6126 100 mg x kg(-1) mouse(-1) or vehicle was delivered. Groups of three mice each were killed and the tumours harvested at days 1, 3 and 5 post-ZD6126 injection. Tumours were processed and stained for endothelial and tumour cell apoptosis and proliferation. No overt toxicity was observed with ZD6126 therapy. ZD6126 led to a marked inhibition of tumour growth (82% decrease vs control (P<0.001)). ZD6126 also led to a significant decrease in the incidence of peritoneal carcinomatosis (10 out of 12 controls, vs one out of 12 ZD6126) (P<0.01). Histological analysis of tumours revealed large regions of central necrosis in the treated group, as well as a dramatic increase in tumour cell apoptosis (7.4-fold increase (P<0.001)), consistent with the vascular-targeting activity of ZD6126. Mice treated with ZD6126 demonstrated a 59% decrease in PCNA-positive cells (P< 0.02), indicating reduced tumour cell proliferation. In addition, tumours treated with ZD6126 exhibited a 40% decrease in microvessel density (P<0.05). Results from mice treated with a single injection of ZD6126 demonstrated the acute effects this agent has on the tumour vasculature. The ratio of endothelial cell apoptosis to endothelial cell proliferation was increased within 24 h of a single injection. In conclusion, ZD6126 significantly inhibited tumour growth and metastasis in an orthotopic model of human gastric adenocarcinoma, without detectable problematic adverse effects. These data suggest that ZD6126 may be worthy of investigation in the treatment of primary gastric adenocarcinoma.

Adenocarcinoma↗
PubMed2003

Induction of neuropilin-1 and vascular endothelial growth factor by epidermal growth factor in human gastric cancer cells.

The epidermal growth factor receptor (EGF-R) pathway plays a pivotal role in the progression of human gastric cancer. The angiogenic factor vascular endothelial growth factor (VEGF) has been shown to be induced by EGF in various cancer cell lines. Neuropilin-1 (NRP-1) acts as a coreceptor for VEGF-165 and increases its affinity for VEGF receptor 2 (VEGFR-2) in endothelial cells. Furthermore, NRP-1 has been found to be expressed by tumour cells and has been shown to enhance tumour angiogenesis and growth in preclinical models. We examined the expression of NRP-1 mRNA and EGF-R protein in seven human gastric cancer cell lines. NRP-1 expression was expressed in five of seven cell lines, and EGF-R expression closely mirrored NRP-1 expression. Moreover, in EGF-R-positive NCI-N87 and ST-2 cells, EGF induced both NRP-1 and VEGF mRNA expression. C225, a monoclonal antibody to EGF-R, blocked EGF-induced NRP-1 and VEGF expression in NCI-N87 cells in a dose-dependent manner. The treatment of NCI-N87 cells with EGF resulted in increases in phosphorylation of Erk1/2, Akt, and P38. Blockade of the Erk, phosphatidylinositol-3 kinase/Akt, or P38 pathways in this cell line prevented EGF induction of NRP-1 and VEGF. These results suggest that regulation of NRP-1 expression in human gastric cancer is intimately associated with the EGF/EGF-R system. Activation of EGF-R might contribute to gastric cancer angiogenesis by a mechanism that involves upregulation of VEGF and NRP-1 expression via multiple signalling pathways.

Base Sequence↗
PubMed2002

Effects of combination anti-vascular endothelial growth factor receptor and anti-epidermal growth factor receptor therapies on the growth of gastric cancer in a nude mouse model.

We hypothesised that the combination of anti-angiogenic and anti-epidermal growth factor (EFG)-receptor (R) therapies would more effectively inhibit gastric cancer growth than single-agent therapy. TMK-1 gastric cancer cells were injected into the gastric wall of nude mice to generate tumours. After 4 days, mice were randomly assigned to the following groups: control, DC101 ([vascular endothelial growth factor (VEGF)-receptor (R)-2 antibody], C225 (EGF-R antibody), or a combination of DC101 and C225. The combination therapy significantly inhibited gastric tumour growth compared with the control group, whereas the decrease in tumour growth in mice treated with DC101 or C225 alone did not reach statistical significance. All mice administered DC101 demonstrated decreased tumour vascularity and increased endothelial cell apoptosis. C225 alone did not affect angiogenesis, but inhibited tumour cell proliferation. The combination therapy led to a further decrease in tumour cell proliferation. The combination of anti-VEGF-R and anti-EGF-R therapies was effective in inhibiting gastric cancer growth. These findings support the hypothesis that inhibiting multiple biological pathways that mediate tumour growth may be an effective therapeutic strategy.

Animals↗
PubMed2002

Functional analysis of the effect of the posterior stabilising cam in two total knee replacements. A comparison of the Insall/Burstein and Bisurface prostheses.

The Bisurface knee prosthesis (BP) has a posterior stabilising cam (ball-and-socket joint) in the mid-posterior region of the femorotibial joint in an attempt to improve the range of movement. Based on an in vitro weight-bearing study contact areas of the Insall/Burstein 2 (IB2) and the BP knee were compared using pressure-sensitive films. The stability afforded by the cam was evaluated by means of dislocation distances in the vertical and horizontal planes. Significant adverse anterior translation in mid-flexion was not observed with the BP knee since the cam was effective above 60 degrees of flexion. At flexion of 60 degrees or more, the total contact areas were larger, as the cam represented a weight-bearing surface. The dislocation distances for the BP knee compared favourably with those for the IB2 knee. We conclude that the cam of the BP knee allows good movement, stability and wear.

Arthroplasty, Replacement, Knee↗
PubMed2001

Effects of A-P translation and rotation on the wear of UHMWPE in a total knee joint simulator.

We developed a three-channel total knee joint simulator and studied the effect of tibial anterior-posterior translation and internal/external rotation on the wear of polyethylene tibial inserts in total knee replacements (Anatomic Graduated Component knees). The wear rate was the lowest in experiment (Exp.) 1, without translation and rotation [1.74 mg/million (mg/Mc) cycles]. In Exp. 2, with +/-5 degrees tibial rotation added, the wear rate increased to 10.6 mg/Mc. In Exp. 3, with rotation and -12 mm tibial translation added, the wear rate was 15.1 mg/Mc, whereas in Exp. 4, with rotation and +12 mm tibial translation, the wear rate was 18.7 mg/Mc. Internal/external rotation and anterior-posterior translation added a 6- to 11-fold increase in the wear rates of tibial knee inserts. The shapes of the tibial wear tracks were rectangular and the area of the track increased when rotation and translation were added.

Biomechanical Phenomena↗
PubMed2001

Mutational analysis of MECP2 in Japanese patients with atypical Rett syndrome.

Rett syndrome (RTT) is one of the most common neurodevelopmental disorders in females. Recently, this disease was found to be linked with mutations in the methyl-CpG-binding protein 2 gene (MECP2) and various mutations have been reported. To explore the spectrum of phenotypes resulting from MECP2 mutations, we searched for mutations in the MECP2 of 20 Japanese patients who had more than five of the criteria necessary for RTT diagnosis proposed in 1988 (The Rett Syndrome Diagnostic Criteria Work Group, Ann Neurol 23 (1988) 425) and compared the phenotype between patients with and without mutation by giving a score to each diagnostic criterion. We found four missense mutations (T158M, R133C, Y120D, and R306C), two nonsense mutations (R168X and R270X), one frameshift (726delAAAG) mutation, and one polymorphism (A201V) in ten patients (50%). This included two novel mutations (726delAAAG and Y120D). All mutations were found in the highly conserved methyl-binding and transcription repression domains. Comparison of the mean total diagnostic criterion score of the groups with and without mutation did not reveal any statistically significantly difference (P=0.28). The only difference between the groups, which was of borderline significance (P=0.051), was the sum of the scores for diagnostic criteria 2 (apparently normal psychomotor development through the first 6 months) and 5 (loss of acquired purposeful hand skills between the ages of 6 and 30 months). From these results, it is suggested that the clinical phenotype of RTT is variable and it is important to investigate the MECP2 genotype for patients having more than five criteria and not only in those who exhibit all RTT diagnostic criteria. The diagnosis of RTT is clinically difficult before 3 years of age, especially in atypical cases, but molecular analysis of the MECP2 will assist diagnosis in some patients.

Adolescent↗
PubMed2001

Bridging a peripheral nerve defect using collagen filaments.

We describe bridging a peripheral nerve defect using collagen filaments instead of a tube. Cords of collagen filaments were grafted to bridge 20-mm defects of rat sciatic nerves. Nerve autografts were grafted as the control. The mean number and the mean fiber diameter of regenerated myelinated axons were approximately 4,800 and 3.3 microm, respectively, in the distal end of the nerve autograft and approximately 5,500 and 2.3 microm, respectively, in the distal end of the collagen-filaments nerve guide 8 weeks after surgery. The mean number and the mean fiber diameter of regenerated myelinated axons were approximately 6,900 and 3.1 microm, respectively, in the distal end of the nerve autograft and approximately 6,300 and 3.3 microm, respectively, in the distal end of the collagen-filaments nerve guide 25 weeks after surgery. Histologic studies suggested that the collagen filaments guided regenerating axons effectively. This new procedure offers a possible solution for the need to sacrifice a healthy nerve and for the shortage of graft material available for the repair of severed nerves.

Animals↗
PubMed2001

A new variant neuropathic type of Gaucher's disease characterized by hydrocephalus, corneal opacities, deformed toes, and fibrous thickening of spleen and liver capsules.

We report a new variant type of Gaucher's disease characterized by hydrocephalus, corneal opacities, deformed toes, gastroesophageal reflux, and fibrous thickening of splenic and hepatic capsules. This patient had 1 D409H allele. He differed from other reported cases with a 1342G to C (D409H) homozygous mutation (onset at 4 months, no cardiac involvement until the age of 12 years, and massive hepatosplenomegaly with fibrous thickening of spleen and liver capsules). Enzyme replacement therapy was given for 4 years, resulting in an improvement of visceral and hematologic abnormalities but no neurologic improvement.

Biopsy↗
PubMed2001

Antiallergic effect of ardisiaquinone A, a potent 5-lipoxygenase inhibitor.

The antiallergic effects of ardisiaquinone A, a potent 5-lipoxygenase inhibitor, were examined. Pretreatment with ardisiaquinone A (0.1-10 microM) significantly inhibited compound 48/80-induced production of cysteinyl-leukotrienes (cys-LTs; LTC4, LTD4 and LTE4) in rat peritoneal mast cells, but not histamine release. The IC50 value was 5.56 microM. Pre-administration with ardisiaquinone A (0.1-1 mg/kg, s.c.) dose-dependently inhibited rat homologous passive cutaneous anaphylaxis (PCA) and the maximal inhibitory ratio was 22.3 +/- 3.9% at the dose of 1 mg/kg. Ardisiaquinone A (1-5 mg/kg, s.c.) dose-dependently prevented the allergen-induced increase of tracheal pressure in ovalbumin-sensitized guinea pigs, especially during the late phase. In conclusion, the findings of this study show that 5-lipoxygenase inhibitor ardisiaquinone A partially attenuates the allergen-induced increases of vascular permeability and tracheal pressure via the inhibition of cys-LTs production in mast cells.

Animals↗
PubMed2001

Characterization of DNA, RNA and DNA/RNA duplexes containing an L-nucleotide.

In order to investigate the duplex structure of DNA and RNA containing an L-nucleotide residue, we carried out the UV-melting and CD experiments. Although the introduction of an L-nucleotide into DNA/DNA, DNA/RNA and RNA/RNA duplexes reduced their Tm values, the typical two-state transitions were observed for all of the duplexes. The incorporation of an L-nucleotide into the RNA strand caused more remarkable decreases of the Tm value than that into the DNA strand. The CD spectra of the DNA/DNA and RNA/RNA duplexes containing an L-nucleotide are similar to those of unmodified duplexes. On the other hand, the spectra of the heterochiral DNA/RNA hybrid duplexes are significantly different from those of the homochiral DNA/RNA hybrid duplexes, which are generally thought to adopt the A-form.

Base Sequence↗
PubMed2001

Relationship between frontal knee alignment and reference axes in the distal femur.

The two transepicondylar axes (the clinical and surgical epicondylar axes), the posterior condylar axis, and the anteroposterior axis were constructed using computed tomography scans in 111 (66 patients) knees with symptomatic arthritis. The relationships between angles made by these reference axes and two angles indicating frontal knee alignment (the tibiofemoral valgus angle and the femoral valgus angle) were investigated. In Y of the knees, the surgical epicondylar axis could not be constructed because the sulcus of the medial epicondyle was not recognizable. The condylar twist angle was almost constant and averaged 6 degrees when the femoral valgus angle was 9 degrees or less, but increased gradually when the angle was greater than 9 degrees. The difference between the condylar twist angle and the posterior condylar angle was constantly 3 degrees. The anteroposterior axis was almost at right angles to the clinical epicondylar axis, and the relationship between these axes was constant, independent of the femoral valgus angle. With 3 degrees to 6 degrees external rotation relative to the posterior condylar axis, the femoral component could be set parallel to the transepicondylar axis in common varus or neutral knees. In cases with a larger femoral valgus angle, the anteroposterior axis would be a more reliable reference axis. Preoperative computed tomography scans are recommended for patients with knees with severe valgus deformity or severe hypertrophic osteoarthritis.

Aged↗
PubMed2001

In vivo three-dimensional knee kinematics using a biplanar image-matching technique.

A biplanar image-matching technique was developed and applied to a study of normal knee kinematics in vivo under weightbearing conditions. Three-dimensional knee models of six volunteers were constructed using computed tomography. Projection images of the models were fitted onto anteroposterior and lateral radiographs of the knees at hyperextension and every 15 degrees from 0 degrees to 120 degrees flexion. Knee motion was reconstructed on the computer. The femur showed a medial pivoting motion relative to the tibia during knee flexion, and the average range of external rotation associated with flexion was 29.1 degrees . The center of the medial femoral condyle translated 3.8 mm anteriorly, whereas the center of the lateral femoral condyle translated 17.8 mm posteriorly. This rotational motion, with a medially offset center, could be interpreted as a screw home motion of the knee around the tibial knee axis and a posterior femoral rollback in the sagittal plane. However, the motion of the contact point differed from that of the center of the femoral condyle when the knee flexion angle was less than 30 degrees. Within this range, medial and lateral contact points translated posteriorly, and a posterior femoral rollback occurred. This biplanar image-matching technique is useful for investigating knee kinematics in vivo.

Adult↗
PubMed2001

Roles of superoxide dismutase in rat mast cell granules.

BACKGROUND: It has been suggested that in the granules of rat mast cells there is some kind of superoxide dismutase (SOD), but details of this SOD in mast cells remain unclear. In the present study, we studied the mode of existence of SOD in mast cells and its releasing mechanism from the granules. In addition, we discussed the physiological role of SOD in allergic events. METHODS: Purified rat mast cells were disrupted with a sonic disrupter and granules (sample I) were separated from supernatant (sample II) by centrifugation. The granules were treated with 1 mM Ca(2+), and the supernatant (sample III) was separated from the pellet (sample IV). Sample III was applied to a heparin column and the eluate was used as sample V. SOD activity was measured in these samples. RESULTS: SOD existed in mast cell granules as a heparin-binding and an inactive form. However, when granules were released and exposed to high Ca(2+) concentration, SOD was discharged from heparin and shifted to the active form. The expression of macrophage inflammatory protein-1 alpha mRNA was enhanced when hydrogen peroxide (H(2)O(2)) or sample III with the xanthine-xanthine oxidase system were added to the culture media. CONCLUSIONS: These findings suggest that in stimulated rat mast cells, the released SOD may transform the generated superoxide anion into H(2)O(2), and the generated H(2)O(2) may enhance the expression of chemokine mRNA in the mast cells.

Animals↗
PubMed2001

Inhibitory effect of egualen sodium: a new stable derivative of azulene on histamine release from mast cell-like cells in the stomach.

We studied the inhibitory effect of egualen sodium (ES) (sodium 3-ethyl-7-isopropyl-1-azulenesulfonate 1/3 hydrate, KT1-32), a new derivative and more stable compound than azulene, on histamine release from the mucosal histaminocytes and elucidated the mechanism for this action. ES prevented the histamine release from isolated mast cell-like cells of the guinea pig stomach induced by A23187 in a dose-dependent fashion. ES dose-dependently inhibited the histamine release from lung pieces of sensitized guinea pigs induced by an antigen-antibody reaction. ES also inhibited histamine release from rat peritoneal mast cells induced by compound 48/80 or antigen-antibody reaction. ES exhibited the membrane stabilizing activity on DPPC liposomes. These findings suggest that ES may prevent histamine release from histaminocytes induced by various stimuli and the stabilizing action of the cell membrane may be responsible for the inhibition of histamine release.

Androstanes↗
PubMed2001

[Fucosidosis].

Explore the source record for details and available documents.

Fucosidosis↗
PubMed2000

Antibody response to toxic shock syndrome toxin-1 of Staphylococcus aureus in dairy cows.

Antibody response to toxic shock syndrome toxin-1 (TSST-1) of Staphylococcus aureus in dairy cows was examined by enzyme linked immunosorbent assay (ELISA). Serum antibody to TSST-1 was not detected in 39 (76.5%) of 51 calves, which were 1-6 months of age. In contrast, TSST-1 antibody was demonstrated in 1728 (72.6%) of 2380 lactating cows housed on 36 dairy farms. The ELISA values of antibody ranged from 0.2 to 3.0 OD and presented a distribution with the peak at 1.6 OD. The mean ELISA value differed between farms, and it increased slightly along with parturient history. Somatic cell counts of milk from 174 lactating cows was compared with TSST-1 antibody and tst1,000,000 cells per ml. The mean ELISA values in milk were lower than those of sera, but they rose as somatic cells increased. The tst gene of S. aureus detected in 76.0-86.2% of the milk samples containing somatic cells > 500,000 cells per ml, a level which indicates mastitis. The data suggests that many lactating cows may be infected by TSST-1- producing S. aureus.

Animals↗