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Biomedical subjects

Takashi Ono

Publications and source records attributed to Takashi Ono.

At least 19 recordsLinked to original sources
PubMed2006

Hemostatic action of OC-108, a novel agent for hemorrhoids, is associated with regional blood flow arrest induced by acute inflammation.

Clinically, hemorrhoidal bleeding and prolapse disappeared immediately after injection of the sclerosing agent OC-108 into submucosa of hemorrhoids. The aim of this study was to elucidate the mechanism of action responsible for the immediate hemostatic effect of OC-108 using anesthetized rats. Subcutaneous injection of OC-108 in rats decreased blood flow at the injection site within 5 min. Aluminum potassium sulfate, one of the main ingredients of OC-108, reduced the skin blood flow. However, tannic acid, another main ingredient, did not. By perfusion of OC-108 on the mesenteric surface, microcirculatory blood flow was arrested without remarkable change in blood vessel diameter, accompanied by increased vascular permeability and venous hematocrit. These results indicate that OC-108 induces regional blood flow arrest with rapid onset, this effect being attributed to the action of aluminum potassium sulfate, and that hemoconcentration due to increased vascular permeability (plasma extravasation), an acute inflammatory reaction, is involved in the mechanisms of the immediate hemostatic action of OC-108.

Acute Disease↗
PubMed2006

Tetracycline analogues (doxycycline and COL-3) induce caspase-dependent and -independent apoptosis in human colon cancer cells.

Tetracycline analogues (TCNAs) possess cytotoxic activities as well as matrix metalloproteinase (MMP) inhibitory properties. Previously, we demonstrated that doxycycline (DOXY) could induce apoptosis in human HT29 colon cancer cells. In present study, the molecular apoptotic mechanisms induced by two kinds of TCNAs, designated as DOXY and COL-3 (chemically modified tetracycline-3; 6-demethyl, 6-deoxy, 4-dedimethylamino tetracycline), were evaluated in cultured HT29 cells. Both TCNAs inhibited the proliferation of 6 different colorectal cancer cell lines in a dose-dependent manner. Especially, COL-3 had a stronger effect on cancer cells than DOXY. Apoptotic changes were actually observed by 10 mug/ml COL-3 and 20 mug/ml DOXY in a time-dependent manner. COL-3 produced the increase in cytosolic cytochrome c and the loss of mitochondrial membrane potential after 3 hr treatment, and thereafter activated caspases. In case of DOXY, these changes were observed after 24 hr. Bax translocation was not a prerequisite for cytochrome c releasing in COL-3 treatment. Pretreated pancaspase inhibitor (Z-VAD-FMK) reduced COL-3 and DOXY mediated apoptosis up to 81.3 and 35.3%, as compared with nontreated cells, respectively. These data indicated that TCNAs could induce mitochondria-mediated apoptosis through both caspase-dependent and -independent pathway. In fact, endonuclease G and apoptosis-inducing factor were released into cytosol after the treatment of TCNAs, which indicated that caspase-independent apoptotic pathway is also one of the key mechanisms for the treatment of TCNAs. Taken together, we believe that TCNAs could have strong potentials for clinical application in treating colorectal cancers and improve cancer chemotherapy.

Apoptosis↗
PubMed2006

Changes in nasorespiratory function in association with maxillary distraction osteogenesis in subjects with cleft lip and palate.

OBJECTIVE: The current study aimed to determine how nasorespiratory function changes in association with maxillary distraction osteogenesis (DO). Furthermore, with regard to impaired nasorespiratory function, the possibility of a relationship between the cleft side and laterality and any effect of maxillary distraction osteogenesis was investigated. DESIGN: In this descriptive, prospective clinical report, subjective and objective data regarding nasorespiratory function before and after maxillary distraction osteogenesis were compared. SUBJECTS: Data from 13 subjects with cleft lip and palate were used. Subjects had a severe maxillary deficiency and underwent distraction osteogenesis using a rigid external device system. OUTCOME MEASURES: The subjective measure was the score on a questionnaire regarding nasorespiratory function using a visual analog scale. The objective measure was nasal resistance. RESULTS: The visual analog scale score for two items significantly decreased just after distraction osteogenesis. Nasal resistance also significantly decreased 1 year after distraction osteogenesis. Moreover, nasal resistance on the cleft side was significantly greater than that on the noncleft side just before and 1 year after distraction osteogenesis. There was a significant positive correlation between changes in the visual analog scale score and nasal resistance. CONCLUSIONS: These results suggest that nasorespiratory function changes in association with maxillary distraction osteogenesis in subjects with cleft lip and palate. Moreover, it appears that nasal obstruction on the cleft side does not change in subjects with unilateral cleft lip and palate.

Adolescent↗
PubMed2006

Distinctive cortical articulatory representation in cleft lip and palate: a preliminary functional magnetic resonance imaging study.

OBJECTIVE: To investigate cortical representation of articulation of the bilabial plosive in patients with cleft lip and palate. DESIGN: We examined cortical representation for /pa/-articulation in cleft lip and palate patients using blood oxygenation level-dependent functional magnetic resonance imaging. SUBJECTS: Data from four postsurgical adult cleft lip and palate patients were compared with those from six healthy volunteers. RESULTS: Activation foci were found in the bilateral primary sensorimotor cortex in all cleft lip and palate patients, as in the controls. The sensorimotor cortex ipsilateral to the side of cleft lip and palate showed greater activation in unilateral cleft lip and palate patients, whereas the sensorimotor cortex contralateral to the side on which cheiloplasty had been performed earlier showed greater activation in a bilateral cleft lip and palate patient. CONCLUSIONS: The results suggest that there may be an ipsilateral dominance in cortical representation during bilabial articulation to the side of the cleft in the upper lip.

Adolescent↗
PubMed2005

Sclerosing effect of OC-108, a novel agent for hemorrhoids, is associated with granulomatous inflammation induced by aluminum.

OC-108 is a novel sclerosing agent for hemorrhoids, containing aluminum potassium sulfate (alum) and tannic acid as its main ingredients. In clinical studies, OC-108 injection therapy for severe internal hemorrhoids proved to be highly effective, not only on bleeding but also for prolapse, and the effects were comparable to hemorrhoidectomy. The aim of this study was to elucidate the mode of action by administrating the agent s.c. to mice and rats. In response to OC-108 injection, inflammation with necrosis developed at an early stage followed by granuloma formation with fibrosis at the injection site. Necrotic debris with aluminum was observed in the granuloma for a long period. Alum, as well as OC-108, induced vascular permeability, leukocyte infiltration, and granuloma formation; however, tannic acid did not. On the other hand, tannic acid inhibited leukocyte infiltration induced by alum but did not inhibit granuloma formation. These results indicate that OC-108 causes sclerosis and retraction of hemorrhoids through fibrosis associated with granulomatous chronic inflammation induced by the main active ingredient alum and that the adjunct ingredient tannic acid reduces excessive acute inflammation induced by alum.

Aluminum↗
PubMed2005

Effects of mandibular advancement on brain activation during inspiratory loading in healthy subjects: a functional magnetic resonance imaging study.

Oral appliances have been a popular treatment option for subjects with obstructive sleep apnea. However, little information is available on how brain activation induced by respiratory challenge is modulated by mandibular advancement with these appliances. We hypothesized that the brain activation caused by respiratory stress may be alleviated by mandibular advancement. Respiratory stress was induced in 12 healthy subjects by resistive inspiratory loading. The effects of mandibular advancement during resistive inspiratory loading were assessed subjectively by using a visual analog scale. These effects were also evaluated objectively by using blood oxygenation level-dependent functional magnetic resonance imaging. The score for the visual analog scale significantly decreased with mandibular advancement. Cortical deactivation, in association with mandibular advancement, was localized to several specific regions, including the left cingulate gyrus and the bilateral prefrontal cortexes. These regions are known to be involved in respiratory control. Our results suggest that mandibular advancement with an oral appliance appears to be useful for reducing respiratory stress, based on both subjective and neuronal criteria.

Adult↗
PubMed2005

The representation of the human oral area in the somatosensory cortex: a functional MRI study.

The tactile sensation of the teeth is involved in various oral functions, such as mastication and speech. Using functional magnetic resonance imaging, we investigated the cortical sensory representation of the oral area, including the teeth. First, we identified the somatotopic representation of the lips, teeth and tongue in the postcentral gyrus (GpoC). Tactile stimuli were applied to the lower lip, tongue and teeth. The foci activated by each stimulus were characterized by the center of gravity (COG) of activated areas. Secondly, we examined the rostro-caudal changes in the somatotopic organization in the GPoC in terms of the overlap between each sensory representation. In the rostral portion of the GPoC, the COG of the representation of teeth was located significantly superior to that of the tongue and inferior to that of the lip, consistent with the classical 'sensory homunculus' proposed by Penfield; however, this somatotopic representation became unclear in the middle and caudal portions of the GPoC. The overlap between each representation in the middle and caudal portions of the GPoC was significantly greater than that in the rostral portion of the GPoC. These findings support the theory that the input from oral structures converges hierarchically across the primary somatosensory cortex.

Adult↗
PubMed2005

Overexpression of macrophage migration inhibitory factor induces angiogenesis and deteriorates prognosis after radical resection for hepatocellular carcinoma.

BACKGROUND: Macrophage migration inhibitory factor (MIF) is a pivotal cytokine that regulates inflammatory and immune responses. Recently, many investigators reported that MIF is expressed highly in several tumors, including hepatocellular carcinoma (HCC). However, the role of MIF in tumor angiogenesis and patient prognosis has not been examined in patients with HCC. METHODS: The authors evaluated MIF expression in 56 samples of HCC by Western blot analysis, and the results were correlated with clinicopathologic factors and patient prognosis. MIF localization was determined by immunohistochemical methods, and the results were compared with tumor microvessel density (MVD), as assessed by anti-CD34 antibody. Furthermore, to validate the role of MIF in angiogenesis, both MIF expression during culture of HCC cells (using the Hep3B, HepG2, and Huh7 cell lines) under hypoxic condition and the angiogenic potential of recombinant MIF in an in vitro angiogenic model were examined. RESULTS: Tumors with high MIF expression had high alpha-fetoprotein levels (P = 0.049) and frequent intrahepatic recurrence (P = 0.043). Immunohistochemical MIF scores had a significant correlation with MVD (P = 0.007). Patients who had tumors with high MIF expression levels had a significantly worse (P = 0.025) disease-free survival, and this finding remained significant as an independent prognostic factor in the multivariate analysis. Hep3B cells had high expression of MIF at 6 hours and 12 hours after hypoxic stress and exogenous MIF stimulated endothelial tube formation in in vitro angiogenesis. CONCLUSIONS: The current findings suggest that MIF expression may play a pivotal role in the dismal prognosis of patients with HCC that may be attributable to the modulation of angiogenesis.

Aged↗
PubMed2005

Synovectomy, debridement, and continuous irrigation for infected total knee arthroplasty.

Since 1990, a total of ten joints in nine patients with infected total knee arthroplasty have been treated in our department within 21 days of the onset of infection. Their radiographs showed no evidence of implant loosening or "moth-eaten" appearance. They underwent synovectomy, debridement, and continuous irrigation without implant removal. Continuous irrigation was maintained for 7-29 days. It was possible to retain implants in eight joints of seven patients. Two joints of two patients were removed. Pain disappeared in all eight joints in which the implants were retained. Four patients could walk with one cane; one patient could walk with one crutch. Range of motion in five joints remained over 100 degrees. We recommend synovectomy, debridement, and continuous irrigation to cure an early stage infection of total knee arthroplasty.

Aged↗
PubMed2005

Group X secretory phospholipase A2 can induce arachidonic acid release and eicosanoid production without activation of cytosolic phospholipase A2 alpha.

Group X secretory phospholipase A2 (sPLA2-X) and cytosolic phospholipase A2 alpha (cPLA2alpha) are involved in the release of arachidonic acid (AA) from membrane phospholipids linked to the eicosanoid production in various pathological states. Recent studies have indicated the presence of various types of cross-talk between sPLA2s and cPLA2alpha resulting in effective AA release. Here we examined the dependence of sPLA2-X-induced potent AA release on the cPLA2alpha activation by using specific cPLA2alpha or sPLA2 inhibitors as well as cPLA2alpha-deficient mice. We found that Pyrrophenone, a cPLA2alpha-specific inhibitor, did not suppress the sPLA2-X-induced potent AA release and prostaglandin E2 formation in mouse spleen cells. Furthermore, the amount of AA released by sPLA2-X from spleen cells was not significantly altered by cPLA2alpha deficiency. These results suggest that sPLA2-X induces potent AA release without activation of cPLA2a, which might be relevant to eicosanoid production in some pathological states where cPLA2a is not activated.

Animals↗
PubMed2005

Modulation of masticatory muscle activity by tongue position.

The purpose of this study was to test whether the tongue position affects the electromyographic (EMG) activities of masticatory muscles. We recorded the EMG activities of the masseter and anterior temporalis muscles in 10 skeletal Class I adults. Tongue position was monitored by two pressure transducers embedded in the midpalatal region and the lingual flange of a custom-made acrylic monoblock. We instructed subjects to assume three different tongue positions: rest, superior, and anterior. Friedman's test and Sheffe's F-test were used to statistically examine differences in muscle activities induced by changes in tongue position. Significant differences were found in masseter muscle activity between the rest and anterior positions and in anterior temporalis muscle activity between the rest and both the anterior and the superior tongue positions. We concluded that masticatory muscle activity is affected by tongue position.

Adult↗
PubMed2005

Expression of hypoxia inducible factor-1alpha during liver regeneration induced by partial hepatectomy in rats.

BACKGROUND/AIMS: It has been well established that hypoxia inducible factor-1alpha (HIF-1alpha) transcribes essential factors in cell preservation, including angiogenesis, during hypoxia. However, the transition of HIF-1alpha expression during liver regeneration remains unknown. In this study, a role of HIF-1alpha was experimentally elucidated in relation to sinusoidal endothelial reconstruction during liver regeneration. METHODS: Expression of HIF-1alpha was evaluated in the regenerating liver following 70% hepatectomy in rats. Expressions of nuclear HIF-1alpha, vascular endothelial growth factor (VEGF) and fms-like tyrosine kinase-1 (flt-1) were measured by Western blot and liver blood flow by a laser Doppler. Sinusoidal endothelial cell area (SECA) and HIF-1alpha were localized by immunohistochemistry. HIF-1alpha mRNA was measured by reverse transcription-polymerase chain reaction. RESULT: Liver blood flow and SECA were lowest 36 and 72 h following hepatectomy, respectively. Nuclear HIF-1alpha peaked at 24 h and continuously increased 72-120 h following hepatectomy. This transition was fully supported by histological HIF-1alpha expression and HIF-1alpha mRNA up-regulation. VEGF and flt-1 peaked at 120 and 12 h, respectively. CONCLUSIONS: A significant evaluation in HIF-1alpha expression was revealed in regenerating rat livers. HIF-1alpha expression was preceded by VEGF and flt-1 expression and thus may be related to sinusoidal endothelial reconstruction.

Animals↗
PubMed2005

Dynamic analysis of articulatory movement using magnetic resonance imaging movies: methods and implications in cleft lip and palate.

OBJECTIVES: To visualize articulatory movement using a magnetic resonance imaging (MRI) movie of a subject with cleft lip and palate (clp) and to demonstrate the usefulness of this method for studying oropharyngeal function. MATERIAL AND METHODS: Dynamic changes in oropharyngeal structures were assessed with an MRI movie of a man with cleft lip and palate and in a normal adult male volunteer during the articulation of /pa/, /ta/, and /ka/. RESULTS AND CONCLUSIONS: Different movement patterns were observed during articulation in the subject with CLP compared with the normal volunteer. Posterosuperior movement of the tongue and the anterior movement of the posterior pharyngeal wall were clearly visualized in the subject with CLP. Thus, MRI movies appear to be a promising tool for evaluating speech function in patients with CLP because of their noninvasive and nonradiation nature.

Adult↗
PubMed2005

Evaluation of stomatognathic function in orthodontic treatment.

AIM: To evaluate changes in stomatognathic function related to orthodontic treatment in 4 patients with various types of dysfunction of the stomatognathic system present prior to orthodontic treatment. METHODS: Four patients who visited the Orthodontic Clinic at Tokyo Medical and Dental University Hospital and whose active orthodontic treatment was complete were analyzed both morphologically and functionally. To analyze stomatognathic function, electromyographic activity of the masticatory muscles and mandibular movements was recorded. RESULTS: In all 4 patients, changes in stomatognathic function were observed following improvements in craniofacial structural and interocclusal relationships. Many of these changes consisted of elimination of functional disharmony, although the cause-effect relationship between these functional changes and orthodontic treatment is unclear. CONCLUSION: Functional analysis during orthodontic treatment can provide useful information concerning the relationship between craniofacial structures and stomatognathic function.

Adult↗
PubMed2005

[Changes in shape of upper airway during titrated mandibular advancement: a magnetic resonance imaging study].

OBJECTIVE: To examine adaptive changes in the shape of the upper airway during titrated mandibular advancement. Furthermore, to understand the mechanism of mandible-adjustable therapy to improve the ventilation. METHODS: Fourteen non-apnea participated in the study. A custom-made oral device was used to keep the mandible in titrated advancement at 0% (F0), 50% (F50), 75% (F75), 100% (F100) of the maximum advancement. Magnetic resonance imaging was used to investigate the difference in the shape of upper-airway in these 4 positions. Changes in the anteroposterior direction (AP), lateral direction (Lat) and its ratio (AP/Lat) were calculated, which were transformed into the percentage of the original ones. RESULTS: The dose-dependent decrease of AP/Lat was found when the mandible was advanced (P = 0.0001). Lateral change rate in percentage increased by degrees (P = 0.0023), while the increase of anteroposterior change rate in percentage showed no statistical significance. CONCLUSION: The shape of upper airway tended to be less round. The enlargement of upper airway during titrated mandibular advancement was mainly the result of enlargement in lateral direction.

Asian People↗
PubMed2004

Downregulation of KiSS-1 expression is responsible for tumor invasion and worse prognosis in gastric carcinoma.

KiSS-1 is a promising candidate tumor-suppressor gene and may play a key role in the metastatic cascade. The expression profile and the role of KiSS-1 in cancer progression are largely unknown in most of the cancers, including gastric cancer. In this study, KiSS-1 expression was evaluated by RNase protection assay and localization was done by in situ hybridization in 40 gastric cancers and their adjacent normal gastric mucosa. For comparison with clinicopathologic characteristics and patient prognosis, all patients were divided into 2 groups having high and low KiSS-1 expression by using the median as the cutoff value of KiSS-1 expression as determined by the RNase protection assay. Gastric cancers with low KiSS-1 had frequent venous invasion, distant metastasis and tumor recurrence. Accordingly, patients with low KiSS-1-expressing tumors had a significantly worse overall and disease-free survival. In multivariate analysis, KiSS-1 became the strongest independent prognostic factor among the conventional prognosticators for gastric cancer patients. Collectively, these findings suggest that KiSS-1 may play a crucial role in gastric cancer invasion and could be a useful target for therapeutic intervention.

Adenocarcinoma↗
PubMed2004

Effect of a selective inhibitor of secretory phospholipase A2, S-5920/LY315920Na, on experimental acute pancreatitis in rats.

We investigated the efficacy of a potent inhibitor of secretory phospholipase A2 (sPLA2), S-5920/LY315920Na, in an experimental model of acute pancreatitis in rats. Combined intraductal injection of sodium taurocholate (5 mg/rat) and porcine pancreatic sPLA2-IB (300 microg/rat) caused severe hemorrhagic necrotizing pancreatitis resulting in high mortality, along with rapid increases of catalytic PLA2 and lipase activities in plasma and ascites and with gradual increases of plasma amylase and aspartate aminotransferase levels over 9 h after the pancreatitis. Prophylactic intravenous treatment with S-5920/LY315920Na significantly reduced mortality at 7 days, and strongly abrogated PLA2 activities in both plasma and ascites along with significant reduction of lipase activity, amylase, aspartate aminotransferase, and hemorrhage at 6 h. It also significantly reduced histological damage such as edema and parenchymal and fat necroses of the pancreatic tissue. This sPLA2 inhibitor could become an effective agent for the treatment of severe acute pancreatitis.

Acetates↗