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Biomedical subjects

Takashi Inoue

Publications and source records attributed to Takashi Inoue.

At least 73 records · Page 4Linked to original sources

Myogenic repressor I-mfa interferes with the function of Zic family proteins.

Zinc finger proteins belonging to the Zic family control several developmental processes such as patterning of the axial skeleton. Here we mapped the transcriptional regulatory domains in Zic2 protein and identified a protein which specifically binds to one of them. In the mapping experiments, an amino-terminal region was identified as transcriptional regulatory domains. A search for proteins binding to the amino terminal domain of Zic2 revealed that inhibitor of MyoD family (I-mfa) protein, which has been identified as a repressor of myogenic helix-loop-helix class transcription factors, can physically interact with the amino terminal domain. When Zic1-3 and I-mfa proteins were co-expressed in cultured cells, nuclear import of the Zic proteins was inhibited. Consequently, I-mfa inhibited transcriptional activation by the Zic proteins in cultured cells. These results suggest that the physical and functional interaction between Zic and I-mfa proteins can play a role in the vertebrate development.

3T3 Cells↗

Mouse Zic5 deficiency results in neural tube defects and hypoplasia of cephalic neural crest derivatives.

Zic family genes encode zinc finger proteins, which are homologues of the Drosophila pair-rule gene odd-paired. In the present study, we characterized the fifth member of the mouse Zic family gene, mouse Zic5. Zic5 is located near Zic2, which is responsible for human brain malformation syndrome (holoprosencephaly, or HPE). In embryonic stages, Zic5 was expressed in dorsal part of neural tissues and limbs. Expression of Zic5 overlapped with those of other Zic genes, most closely with Zic2, but was not identical. Targeted disruption of Zic5 resulted in insufficient neural tube closure at the rostral end, similar to that seen in Zic2 mutant mice. In addition, the Zic5-deficient mice exhibited malformation of neural-crest-derived facial bones, especially the mandible, which had not been observed in other Zic family mutants. During the embryonic stages, there were delays in the development of the first branchial arch and extension of the trigeminal and facial nerves. Neural crest marker staining revealed fewer neural crest cells in the dorsal cephalic region of the mutant embryos without significant changes in their migration. When mouse Zic5 was overexpressed in Xenopus embryos, expression of a neural crest marker was enhanced. These findings suggested that Zic5 is involved in the generation of neural crest tissue in mouse development. ZIC5 is also located close to ZIC2 in humans, and deletions of 13q32, where ZIC2 is located, lead to congenital brain and digit malformations known as the "13q32 deletion syndrome". Based on both their similar expression pattern in mouse embryos and the malformations observed in Zic5-deficient mutant mice, human ZIC5 might be involved in the deletion syndrome.

Animals↗

Metformin causes reduction of food intake and body weight gain and improvement of glucose intolerance in combination with dipeptidyl peptidase IV inhibitor in Zucker fa/fa rats.

An incretin hormone, glucagon-like peptide-1 (GLP-1), has been shown to lower plasma glucose via glucose-dependent insulin secretion and to reduce appetite. We previously found that the biguanide metformin, an antidiabetic agent, causes a significant increase of plasma active GLP-1 level in the presence of dipeptidyl peptidase IV (DPPIV) inhibitor in normal rats. This finding suggested that the combination treatment might produce a greater antidiabetic and anorectic effect, based on enhanced GLP-1 action. In this study, we assessed the effects of subchronic treatment with metformin and a DPPIV inhibitor, valine-pyrrolidide (val-pyr), on glycemic control, food intake, and weight gain using Zucker fa/fa rats, a model of obesity and impaired glucose tolerance. The combination treatment caused a significant increase of GLP-1 level in Zucker fa/fa rats. In a subchronic study, val-pyr, metformin, or both compounds were administered orally b.i.d. for 14 days. The combination treatment significantly decreased food intake and body weight gain, although neither metformin nor val-pyr treatment alone had any effect. In an oral glucose tolerance test on day 1, the coadministration caused a greater improvement of glucose tolerance and a prominent increase of plasma active GLP-1 without marked insulin secretion. The 14-day combination treatment produced a potent reduction of fasting blood glucose and plasma insulin levels. These results demonstrate that the combination therapy of metformin with DPPIV inhibitor leads to reduced food intake and body weight gain, most likely through the significant increase of plasma GLP-1 level. The combination therapy seems to be a good candidate for treatment of type 2 diabetes with obesity.

Animals↗

The combination of metformin and a dipeptidyl peptidase IV inhibitor prevents 5-fluorouracil-induced reduction of small intestine weight.

Glucagon-like peptide 2 (GLP-2), which has intestinotrophic effects, is secreted from L-cells in the intestine in response to nutrient ingestion and is degraded by dipeptidyl peptidase IV (DPPIV). In this report, we show that biguanides promote GLP-2 release. Plasma GLP-2 levels were significantly increased by 1.4- to 1.6-fold in fasted F344 rats 1 h after oral meformin (300 mg/kg), phenformin (30 and 100 mg/kg) and buformin (100 mg/kg) treatment. In addition, metformin administration (300 mg/kg, p.o.) significantly elevated plasma GLP-2 in fasted CD-1 mice by about 2.0-fold 1 and 3 h after the treatment. Metformin and/or valine-pyrrolidide, a DPPIV inhibitor, was orally given (300 and 30 mg/kg, respectively, p.o., b.i.d., 3 days) to BALB/c mice treated with 5-fluorouracil (5-FU; 60 mg/kg, s.i.d.), which induces gastrointestinal damage leading to a reduction of small intestine wet weight. Metformin and valine-pyrrolidide co-administration prevented the 5-FU-induced reduction of wet weight of the small intestine, whereas metformin or valine-pyrrolidide alone had no effect. These results suggest that GLP-2 is co-secreted with GLP-1 flollowing biguanide stimulation, and that the combination of metformin with a DPPIV inhibitor might a useful oral treatment for gastrointestinal damage, based on GLP-2 actions.

Animals↗

Use of fractional anisotropy value by diffusion tensor MRI for preoperative diagnosis of astrocytic tumors: case report.

The fractional anisotropy (FA) value calculated by diffusion tensor MRI can indicate the degree of directionality of water diffusion in astrocytic tumors. Here, we report a case of anaplastic astrocytoma in which FA proved invaluable for the preoperative differential diagnosis. A 60-year-old man complained of headache, and underwent routine neuroimaging and DTI. The routine images suggested a low-grade glioma in the left temporal lobe, based on lack of enhancement on MRI with contrast medium and lack of tumor staining on angiograms, whereas FA value was very high. Based on these findings, a preoperative diagnosis of high-grade glioma was suspected. The surgical specimen exhibited the histological features of anaplastic astrocytoma with a high density of spindle shaped cells and low vascularity. In this report, we discuss the relationship between FA and other characteristics of the present tumor, and discuss the utility of FA measurement in astrocytic tumors.

Anisotropy↗

Isolation of ascorbate free radical reductase from rabbit lens soluble fraction.

Ascorbate free radical (AFR) reductase with diaphorase activity was isolated from the rabbit lens soluble fraction to characterise some molecular properties of the enzyme. The isolation was accomplished using gel filtration (Sephadex G-75 superfine or Sephacryl S-200 HR), affinity chromatography (Affi-Gel Blue), native isoelectric focusing and two-dimensional gel electrophoresis. A major soluble AFR reductase was found at an isoelectric point of 8.4 and a molecular weight of 31 kDa, and a few minor enzymes were also detected in the range of pI 7.0-8.6. An unknown N-terminal partial amino acid sequence was determined in one peptide fragment prepared from the major enzyme fraction. From the sequence analysis, it is discussed that the lens soluble AFR reductase may differ from NADH-cytochrome b5 reductase reported to be involved in the membrane-bound AFR reductase activity of mitochondria, microsomes and plasma membrane.

Amino Acid Sequence↗

Effect of defensin peptides on eukaryotic cells: primary epithelial cells, fibroblasts and squamous cell carcinoma cell lines.

BACKGROUND: Although the usefulness of the antimicrobial peptides known as defensins has been suggested against oral and skin infections, possible adverse effects of the defensins on the host should be understood before clinical applications can be contemplated. OBJECTIVE: In the present study, we investigated how alpha-defensin (HNP-1) and beta-defensins (hBD-1, -2, -3) affect cells including primary epithelial cells, fibroblasts and squamous cell carcinoma cell lines, SCC-9 and KB. METHOD: Cell proliferation was assessed by the direct cell counting and XTT assay. RESULTS: We found that alpha-defensin promotes proliferation of the epithelial cells at low concentration but has a cytotoxic effect at high concentration. In contrast, beta-defensins have little effect on these cells at any concentration, suggesting that beta-defensins may have no adverse effects on the host. CONCLUSION: Therefore, in terms of host response beta-defensins may be more suitable antimicrobial agents for clinical applications than alpha-defensins.

Animals↗

Medullary streaks in a patient with atherosclerotic internal carotid artery occlusion: case report.

BACKGROUND: Magnetic resonance imaging (MRI) of a patient with atherosclerotic internal carotid artery (ICA) occlusion demonstrated medullary streaks in the deep white matter, which were previously observed only in moyamoya disease and may indicate decreased cerebral blood flow. Cerebral perfusion and metabolism were evaluated using positron emission tomography (PET). CASE DESCRIPTION: A 46-year-old man presented with right hemiparesis and motor aphasia. Cerebral angiography showed left cervical ICA occlusion. MRI showed medullary streaks in the deep white matter of the left middle cerebral artery (MCA) territory. PET imaging of this region revealed decreased cerebral blood flow and increased oxygen extraction fraction and cerebral blood volume. MRI after superficial temporal artery-MCA anastomosis revealed decreased intensity of the medullary streaks. CONCLUSIONS: Medullary streaks in patients with atherosclerotic ICA occlusion may indicate reduced perfusion pressure and increased risk of recurrent stroke.

Carotid Artery, Internal↗

Three-dimensional anisotropy contrast imaging of gliomatosis cerebri: two case reports.

BACKGROUND: Magnetic resonance imaging (MRI) can provide a preoperative diagnosis of gliomatosis cerebri, but the findings sometimes do not correspond with the clinical symptoms or histologic findings. CASE DESCRIPTION: Three-dimensional anisotropy contrast (3DAC) imaging was used to assess damage to the neuronal fibers in two patients with gliomatosis cerebri who presented with only mental deterioration. Conventional MRI depicted markedly abnormal findings consisting of widespread areas of abnormally high signal intensity in the corpus callosum and in the bilateral white matter in both cases. In contrast, 3-D AC imaging showed no abnormality except for small dark areas in the corpus callosum or white matter. CONCLUSION: 3-D AC imaging provides more accurate information about damage to the neuronal fibers in cases of gliomatosis cerebri than other MRI techniques.

Aged↗

Intracerebral hemorrhage after carotid endarterectomy associated with asymptomatic perioperative cerebral ischemia detected by cerebral perfusion imaging: case report.

BACKGROUND: Risk factors for intracerebral hemorrhage following carotid endarterectomy (CEA) include perioperative cerebral ischemia, postoperative cerebral hyperperfusion, and postoperative anticoagulation therapy, and at least 2 of these risk factors are typically present in the context of intracerebral hemorrhage (ICH). CASE DESCRIPTION: A 75-year-old man with severe bilateral cervical internal carotid artery stenosis and a minor stroke resulting in left motor weakness underwent a right CEA. The operation was uneventful, and the patient did not experience new neurologic deficits upon recovery from anesthesia. Brain single photon emission computed tomography (SPECT) obtained immediately after CEA showed a perfusion defect in the right parietal lobe and absence of cerebral hyperperfusion. A computed tomography (CT) scan showed no new abnormal findings. Aspirin therapy was instituted postoperatively. On the second postoperative day, the patient experienced abrupt worsening of left hemiparesis, and subsequent CT imaging demonstrated a hematoma in the right parietal lobe. Cerebral hyperperfusion was absent on repeat SPECT. CONCLUSION: Perioperative cerebral ischemia can result in intracerebral hemorrhage after CEA even in the absence of cerebral hyperperfusion and/or anticoagulation therapy. Further, cerebral perfusion imaging performed immediately after CEA is a useful modality for the identification of occult cerebral ischemia or hyperperfusion that may lead to intracerebral hemorrhage.

Aged↗

Delayed cerebral hyperperfusion syndrome caused by prolonged impairment of cerebrovascular autoregulation after carotid endarterectomy: case report.

OBJECTIVE AND IMPORTANCE: Cerebral hyperperfusion syndrome is a rare but potentially devastating complication that typically occurs within several days after carotid endarterectomy. CLINICAL PRESENTATION: A 66-year-old man experienced asymptomatic cerebral hyperperfusion as demonstrated by single-photon emission computed tomography (SPECT) during a 2-week period after undergoing right carotid endarterectomy. This phenomenon occurred despite intensive pharmacological control of blood pressure. On the 28th postoperative day, repeat SPECT demonstrated resolution of hyperperfusion, and intensive blood pressure control was discontinued. INTERVENTION: Twelve hours later, the patient experienced left motor seizures with secondary generation. SPECT performed 36 hours after the onset of seizures demonstrated the reappearance of hyperperfusion. Intensive blood pressure control was reinstituted and maintained until the 36th postoperative day. On the next day, SPECT demonstrated resolution of hyperperfusion. CONCLUSION: The present case suggests that cerebral hyperperfusion syndrome may occur at later time points (e.g., 1 mo) after carotid endarterectomy. This delayed hyperperfusion syndrome may be related to prolonged impairment of cerebrovascular autoregulation.

Aged↗

Pretreatment with the free radical scavenger edaravone prevents cerebral hyperperfusion after carotid endarterectomy.

OBJECTIVE: Cerebral hyperperfusion syndrome after carotid endarterectomy (CEA) is a rare but potentially devastating complication. The purpose of the present study, which was not a randomized controlled trial but a case cohort study with historical control, was to determine whether pretreatment with a novel free radical scavenger, edaravone, could prevent occurrence of cerebral hyperperfusion after CEA. METHODS: Fifty patients with ipsilateral internal carotid artery stenosis (>/=70%) underwent CEA with administration of edaravone before internal carotid artery clamping. Preoperative cerebral blood flow and cerebrovascular reactivity (CVR) to acetazolamide were assessed with single-photon emission computed tomography (SPECT). Cerebral blood flow also was measured immediately after CEA and on the 3rd postoperative day. RESULTS: Cerebral hyperperfusion (cerebral blood flow increase >/=100% compared with preoperative values) was revealed by SPECT performed immediately after CEA in only one patient (2%), who also exhibited reduced preoperative CVR. The incidence of post-CEA hyperperfusion as revealed by SPECT in the control group (51 CEA patients without administration of edaravone) was significantly higher (16%) (P = 0.0310, control versus treatment group). In addition, in a subgroup of patients with reduced preoperative CVR, the incidence of post-CEA hyperperfusion as revealed by SPECT in the edaravone group (7%) was significantly lower than that in the control group (67%) (P = 0.0029). Logistic regression analysis demonstrated that reduced preoperative CVR and absence of pretreatment with edaravone were significant independent predictors of post-CEA hyperperfusion as revealed by SPECT. CONCLUSION: Pretreatment with edaravone can prevent occurrence of cerebral hyperperfusion after CEA.

Aged↗

The effect of surface pore size on the differentiation of rat bone marrow cells: morphological observations and expression of bone related protein mRNA.

The purpose of this study was to investigate the behavior of rat bone marrow cells (RBM) growing on surfaces with different pore sizes. RBM behavior on Millipore filters (MF-Millipore membrane filter) made from cellulose mixed esters with 5 different pore surfaces (0.45 microm, 1.2 microm, 3.0 microm, 5.0 microm and 8.0 microm) were compared in terms of morphological changes on the different pore sizes. Furthermore, the expressions of osteopontin and osteocalcin mRNAs were investigated. On the 1.2 microm and 3.0 microm pore surfaces, RBM attached to the substrate well, but cells on the 5.0 microm and 8.0 microm pore surfaces invaded deeply into the pores. Higher levels of both osteopontin and osteocalcin mRNA expression were always observed in cells cultured on the 1.2 microm filter. These results suggest that the 1.2 microm Millipore filter pore size is the most suitable for inducing RBM to differentiate into an osteoblastic phenotype among these surfaces and is probably related to production of the ECM but not to the phenomenon of cell spreading.

Animals↗

Adenomatoid odontogenic tumor arising from the mandibular molar region: a case report and review of the literature.

This case report describes a rare case of an adenomatoid odontogenic tumor (AOT) arising in the mandibular third molar region of a 20-year-old female. The tumor was a well-circumscribed intraosseous lesion with an embedded tooth. Histologically, the induction of extensive globular calcification was evident in addition to the characteristic histological features of AOT. The present case lends support to the categorization of AOT as an odontogenic tumor consisting of a disorderly mixture of odontogenic epithelium and odontogenic ectomesenchyme with calcification.

Adult↗

Canalicular adenoma arising in the upper lip: review of the pathological findings.

This case report describes a rare case of canalicular adenoma arising in the upper lip of a 61-year-old male patient. Macroscopic examination of the tumor revealed a well-defined, smooth, firm, elastic hard, round nodule with a diameter of 1.0 cm. The cut surface was white. Histopathology showed that the tumor was an encapsulated mass with a complex cellular pattern of anastomosing duct-like or trabecular structures lined by a single layer of tall columnar epithelial cells, which were embedded in a loose, fibrous, and highly vascular connective tissue stroma. The tumor cells were immunoreactive to AE1/AE3, CK19 and S-100, were partially positive for CK7, CK8, GFAP and PCNA, but were negative for SMA, CK13, CK14 and vimentin.

Adenoma↗

Acinic cell carcinoma found by recurrence of a mucous cyst in the sublingual gland.

This case report describes an acinic cell carcinoma found by a recurrence of a ranula in the sublingual gland. A 42-year-old male was admitted to the hospital of the Tokyo Dental College with a swelling in his right oral floor but without pain. The lesion was treated by windowing the same day under the diagnosis of a ranula, but the swelling appeared again at the same area eight months after the first operation. A resection was performed, and the specimen was sent to the clinical laboratory for pathological diagnosis. Proliferating serous cells were seen in part of the wall of an exudative mucous cyst. PAS staining was partially positive, and immunohistochemical staining for S-100 protein, lactoferrin, and amylase were also positive in cytoplasmic granules. This report concludes that the pathological diagnosis is beneficial in clarifying the reasons for the recurrence of a benign lesion.

Adult↗

A long-term follow-up study of four cases who underwent curettage and autogenous bone grafting for steroid-related osteonecrosis of the femoral condyle.

We performed curettage followed by autogenous bone grafting in several cases of steroid-related osteonecrosis of the femoral condyle, and reviewed the outcome of this procedure after a mean follow-up of 9.5 years. The number of patients was 4; the mean age at the time of the operation was 30.5 years. The mean Knee Society Objective Score was 52.5 before the operation and had increased to 87.5 at the time of the review. The pre-operative radiographic stages were stage 2 in 2 patients and stage 3 in the other 2 patients. Progression in the disease stage was observed in 3 patients. MRI revealed survival of the grafted bone in only one case, and collapse of the articular surface in all cases. In conclusion, though the clinical results showed improvement, the autogenous bone graft failed to answer the purpose of preventing the progression in disease stage.

Adult↗

Influence of tooth-polishing pastes and sealants on DIAGNOdent values.

OBJECTIVE: The purpose of this study was to investigate the influence of tooth-polishing pastes and sealants on values obtained with a caries diagnostic system based on detection of caries-associated fluorescence (DIAGNOdent, KaVo). METHOD AND MATERIALS: Ten tooth-polishing pastes and four dentifrices were measured alone, and it was shown that products containing pumice gave high DIAGNOdent values. The deepest occlusal pits of 20 extracted sound premolars (12 unsealed teeth, 8 sealed teeth) were measured before polishing, after rotating-brush polishing with pumice-containing tooth-polishing paste, and after final rotating-brush polishing with water in this in vitro study. In the clinical phase, the deepest occlusal pits of 21 molars and 2 premolars that clinically required application of sealant were measured before polishing, after rotating-brush polishing with one of two pumice-containing tooth-polishing pastes, and after sealant application. All measurements were done five times, and the average values were obtained. Data were statistically analyzed using analysis of variance subsequent to Fisher's protected, least significant difference. RESULTS: Clinical study showed that the value after polishing with either of the two polishing pastes was significantly higher than the value before polishing. Both in vitro and clinical studies showed that the value was increased by pumice-containing paste polishing and rotating-brush polishing with water after paste polishing could not recover the value to the level before paste polishing. Sealant treatment in the clinical study significantly decreased DIAGNOdent values, and the values after sealant application were lower than the values before polishing. CONCLUSION: Polishing pastes and sealants used in this study could interfere with DIAGNOdent values.

Analysis of Variance↗