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Biomedical subjects

T Sugahara

Publications and source records attributed to T Sugahara.

At least 19 recordsLinked to original sources

Hypoxic regulation of stability of connective tissue growth factor/CCN2 mRNA by 3'-untranslated region interacting with a cellular protein in human chondrosarcoma cells.

Connective tissue growth factor (CTGF/CCN2) can be induced by various forms of stress such as exposure to high glucose, mechanical load, or hypoxia. Here, we investigated the molecular mechanism involved in the induction of ctgf/ccn2 by hypoxia in a human chondrosarcoma cell line, HCS-2/8. Hypoxia increased the ctgf/ccn2 mRNA level by altering the 3'-untranslated region (UTR)-mediated mRNA stability without requiring de novo protein synthesis. After a series of extensive analyses, we eventually found that the cis-repressive element of 84 bases within the 3'-UTR specifically bound to a cytoplasmic/nuclear protein. By conducting a UV crosslinking assay, we found the cytoplasmic/nuclear protein to be a 35 kDa molecule that bound to the cis-element in a hypoxia-inducible manner. These results suggest that a cis-element in the 3'-UTR of ctgf/ccn2 mRNA and trans-factor counterpart(s) play an important role in the post-transcriptional regulation by determining the stability of ctgf/ccn2 mRNA.

3' Untranslated Regions↗

Effect of ENU (ethylnitrosourea) mutagenesis in cleft lip and/or palate pathogenesis in mice.

Cleft lip and/or palate (CL/P) are caused by many factors. The aim of this study was to investigate the effects of genetic point mutations in CL/P pathogenesis. ICR and AJ strain mice were used. Ethylnitrosourea (ENU) was injected into 10-week-old male mice (G0) intraperitoneally at a dose of 250 mg/kg. The males were bred with two untreated virgin females of the same strain on day 100 after injection. The uterine contents (G1) of one female were examined on day 18.5 of pregnancy. From the other female, the offspring were delivered naturally, and F3 mice (G3) were also examined in the same way. In ICR strain mice, cleft palate only (CPO) was increased in both the G1 and G3. The frequency was significantly higher in the G3 than the G1 generation. Cleft lip was not observed. In AJ strain mice, CL/P increased in both the G1 and G3. In the G3, the frequency of CPO was increased significantly. Genes related to CPO may be recessive in phenotype. CPO and cleft lip differ from a genetic viewpoint. Point mutations play a significant role in cleft lip and palate.

Animals↗

Expression of osteoclast differentiation factor and osteoclastogenesis inhibitory factor in rat osteoporosis induced by immunosuppressant FK506.

Immunosuppressant drugs are currently required by transplant recipients for the remainder of their lives, despite the many adverse effects associated with these therapies. Acute osteoporosis is one such effect, and a reproducible osteoporosis model has been established through the administration of the immunosuppressant drug FK506 in rats. The cause of this osteoporosis has been shown to be abnormal osteoclast proliferation, altering the process of bone remodeling. However, the reasons why FK506 induces osteoclast proliferation and whether this process is mediated by cytokine changes or an increase in bone resorption factors have been unclear. An investigation was therefore conducted focusing on the recent discoveries of osteoclast differentiation factor (ODF) and osteoclastogenesis inhibitory factor (OCIF). These factors led to elucidation of the osteoclast differentiation-maturation mechanism. An osteoporosis model was produced in rats utilizing intramuscular FK506 injection (1 mg/kg) for 28 consecutive days. Trabecular bone resorption was observed inferior to enchondral ossification in the FK506 group, and tartrate resistant acid phosphatase (TRAP) staining revealed a clear increase in osteoclasts at the site of enchondral ossification, relative to the control group. Real-time PCR and in situ hybridization (ISH) demonstrated minimal differences in OCIF expression between control and the treatment groups. However, Real-time PCR revealed clearly increased ODF expression in the treatment group. ODF expression was also shown to be increased in the treatment group using ISH. This was histologically consistent with a region of osteoclast proliferation inferior to enchondral ossification. The results of this study support the hypothesis that FK506-mediated osteoporosis occurs by action of the drug on osteoclasts, promoting expression of ODF messenger ribonucleic acid (mRNA) and thus prompting osteoclast differentiation and maturation.

Animals↗

Effect of high-level natural radiation on chromosomes of residents in southern China.

To study the effect of low-dose (rate) radiation on human health, we analyzed chromosomes of peripheral lymphocytes of residents in a high background radiation area (HBRA) and compared the results with those obtained from residents in a control area (CA) in Guangdong Province, China. Unstable types of chromosome aberrations (dicentrics and rings) were studied in 22 members of eight families in HBRA and 17 members of five families in CA. Each family consists of three generations. On average 2,600 cells per subject were analyzed. 27 adults and six children in HBRA and 25 adults and eight children in CA were studied with respect to translocations. On average 4,741 cells per subject were examined. We found an increase of the frequency of dicentrics and rings in HBRA, where the natural radiation level is three to five times higher than in the control area. But the increase of translocations in HBRA was within the range of individual variation in the controls.

Adult↗

Pathological change of articular cartilage in the mandibular head treated with immunosuppressant FK 506.

While several reports have documented immunosuppressant-induced osteoporosis, the exact mechanism of the pathological change of the joint remains to be clarified. In the present study, we have demonstrated the pathological change of the articular cartilage in the mandibular head of five Sprague-Dawley rats administered with the immunosuppressant FK 506 for 28 days. Three-dimensional micro-computed tomography of the mandibular heads in treated rats showed a significant decrease in trabecular bone volume compared to control rats. Histological observation revealed atrophic change of the articular cartilage. Immunohistological observation using anti-proliferative cell nuclear antibody (PCNA), type I, II, and type X collagen antibodies showed significantly decreased proliferation and differentiation of chondrocytes in the articular cartilage compared with the control group (p<0.05). Tartrate-resistant acid phosphatase (TRAP) staining revealed no significant difference in the numbers of osteoclasts at the chondro-osseous junction. Thus, FK 506 administration inhibited chondrogenic cell proliferation and differentiation and might cause osteoporotic change of subcartilage trabecular bone that subsequently forms in the mandibular head.

Animals↗

Evaluation of respiratory status and mandibular movement after total temporomandibular joint replacement in patients with rheumatoid arthritis.

We performed total TMJ replacement to improve respiratory status and correct occlusion in six patients with destruction of the temporomandibular joint (TMJ) caused by rheumatoid arthritis. Morphological changes were evaluated on lateral cephalograms before and after surgery. Respiratory function and mandibular movement were assessed with the use of an apnea-monitor and an LED mandibular tracking device, respectively. After surgery, symptoms such as snoring and daytime sleepiness improved, and solid food could be masticated. Postoperative cephalograms showed that both the posterior airway space and ramal height were significantly improved by surgery. Postoperative records of mandibular movement indicated stability of the occlusion and improvement of mandibular movement, as compared with the preoperative records. Mean oxygen saturation significantly improved 1 month after surgery, whereas apnea and apnea-hypopnea indices did not change significantly.

Aged↗

Cerebral gliomas: prospective comparison of multivoxel 2D chemical-shift imaging proton MR spectroscopy, echoplanar perfusion and diffusion-weighted MRI.

Developments in MRI have made it possible to use diffusion-weighted MRI, perfusion MRI and proton MR spectroscopy (MRS) to study lesions in the brain. We evaluated whether these techniques provide useful, complementary information for grading gliomas, in comparison with conventional MRI. We studied 17 patients with histologically verified gliomas, adding multivoxel proton MRS, echoplanar diffusion and perfusion MRI the a routine MRI examination. The maximum relative cerebral blood volume (CBV), minimum apparent diffusion coefficient (ADC) and metabolic peak area ratios in proton MRS were calculated in solid parts of tumours on the same slice from each imaging data set. The mean minimum ADC of the 13 high-grade gliomas (0.92+/-0.27 x 10(-3) mm(2)/s) was lower than that of the four low-grade gliomas (1.28+/-0.15 x 10(-3) mm(2)/s) ( P<0.05). Means of maximum choline (Cho)/N-acetylaspartate (NAA), Cho/creatine (Cr), Cho/Cr in normal brain (Cr-n) and minimum NAA/Cr ratios were 5.90+/-2.62, 4.73+/-2.22, 2.66+/-0.68 and 0.40+/-0.06, respectively, in the high-grade gliomas, and 1.65+/-1.37, 1.84+/-1.20, 1.61+/-1.29 and 1.65+/-1.61, respectively, in the low-grade gliomas. Significant differences were found on spectroscopy between the high- and low-grade gliomas ( P<0.05). Mean maximum relative CBV in the high-grade gliomas (6.10+/-3.98) was higher than in the low-grade gliomas (1.74+/-0.57) ( P<0.05). Echoplanar diffusion, perfusion MRI and multivoxel proton MRS can offer diagnostic information, not available with conventional MRI, in the assessment of glioma grade.

Adolescent↗

MRI of intracranial germ-cell tumours.

Our aim was to review the MRI appearances of primary intracranial germ-cell tumours (GCT). We reviewed the MRI studies of 32 patients: 19 with germinomas, five with teratomas, one with an embryonal carcinoma, five with mixed and two with malignant nongerminomatous GCT. Eleven were in the pineal region, 12 suprasellar, five in the both sites, two in the basal ganglia and two in the corpus callosum. Contrast-enhanced images were available for 27 patients. The solid parts of GCT were nearly isointense with grey matter on both T1- and T2-weighted images. In seven patients with nongerminomatous GCT high-signal components were found on T1-weighted images, representing haemorrhage, high-protein fluid or fat. Cystic components were detected in 17 of 27 patients; eight germinomas and all nine nongerminomatous GCT had cysts. The solid components of germinomas enhanced homogeneously in eight cases and heterogeneously in 10, while all nongerminomatous GCT showed heterogeneous enhancement. MRI features tumours can facilitate correct diagnosis of GCT, including histological subtypes.

Adolescent↗

Immunohistochemical study on expression of alpha-defensin and beta-defensin-2 in human buccal epithelia with candidiasis.

OBJECTIVES AND DESIGN: It has been previously reported that alpha-defensin (HNPs) and beta-defensin-2 (HBD-2) peptides with antifungal and cytotoxic activities can be detected in oral carcinomas and the saliva of patients with oral carcinomas. The present study investigated the presence of HNPs and HBD-2 in oral epithelia with candidiasis. MATERIALS AND METHODS: Tissue sections (4 microm) were prepared from biopsy and surgically removed specimens diagnosed as oral candidiasis (n = 10). The sections were examined immunohistochemically with antibodies directed against HNPs and HBD-2. RESULTS: Tissue sections of oral candidiasis were immunostained with antidefensin antibodies. Neutrophils in the inflamed lamina propria were positively immunostained with anti-HNPs antibody. The cytoplasm of cells in the upper spinous layer, in the lower spinous layer and in the parakeratinized layer of buccal epithelia with candidiasis was immunostained intensely with anti-HBD-2 antibody. In contrast, the expression of HBD-2 in the normal spinous layer was much weaker than that in oral candidiasis. No signals of HNPs were found in normal buccal epithelium. CONCLUSION: Buccal specimens from individuals with oral candidiasis show greater levels of expression of both HNPs and HBD-2. There might be a dual protection manner by defensins against fungal inflammation in infected buccal epithelia locally. Generally, HBD-2 signals have been found everywhere in the buccal epithelium; however, in an infected area, the signal intensity of HBD-2 has increased. HNPs signals have not been found in the normal buccal epithelium; however, HNPs signals have increased when the infection occurred.

Adult↗

Cellular origin of endochondral ossification from grafted periosteum.

Grafted periosteum is known to have potential for heterotopic bone formation by endochondral ossification. Although osteochondrogenic cells have been thought to originate from the osteogenic layer in grafted periosteum, no histological report has yet demonstrated this. The present study was designed to elucidate the origin of chondrogenesis preceding bone formation in grafted periosteum. Periostea harvested from young Japanese white rabbits' tibiae were grafted into suprahyoid muscles and examined radiographically and histologically at postoperative days 1, 7, 9, 14, 21, and 35. Normal periostea and tibial graft site were also examined. Surgical harvesting of the periosteum split and damaged its osteogenic layer but retained the fibrous layer intact. Most of the osteoblasts remained on the tibial bone surface, and only few cells of the osteogenic layer were present in grafted tissue. By the seventh day after grafting, the fibrous layer had thickened. The fibroblastic cells in the fibrous layer had significantly increased in number (P < 0.01) and were positively stained for proliferating cell nuclear antigen. These cells exhibited alkaline phosphatase activity at day 9. The differentiated chondrocytes had formed cartilage at postoperative day 14. Cells in the osteogenic layer appeared necrotic and subsequently disappeared. Following postoperative day 21, cartilage was replaced by trabecular bone. Bone formation was completed by 35 days. An X-ray analysis at this time also revealed new bone formation. These findings indicate that grafted periosteum forms bone by endochondral ossification and that the cells of the fibrous layer play essential roles in chondrogenesis that precedes such bone formation.

Alkaline Phosphatase↗

Comparison between EPI and HASTE for ultra-fast MR imaging of the human brain.

Our purpose was to evaluate and compare the performance of ultra-fast single-shot T2-weighted sequences: echo-planar imaging (EPI) versus half-Fourier single-shot turbo spin-echo (HASTE) and to assess the usefulness of their combined reading. Comparative experiments on a phantom as well as a prospective clinical study in 47 patients were done. Axial images acquired with the following methods were compared: (a) HASTE; (b) segmented HASTE (s-HASTE); (c) single-shot spin-echo EPI (SE-EPI); and (d) gradient-echo EPI (GREEPI). Quantitative and qualitative criteria as well as lesion detectability were analyzed against the "gold standard" fast spin-echo (FSE) sequence. For contrast and contrast-to-noise ratio (CNR) between gray and white matter, GRE-EPI was best. The visibility of small markedly hyperintense lesion was best with HASTE and s-HASTE in the clinical study. Small hyperintense lesions were detected equally well with all four sequences, although all performed significantly worse than FSE. The two HASTE variants were better than the EPIs for the extraaxial lesions. The combination of the GRE-EPI and s-HASTE was judged best, and sometimes superior to the FSE image. HASTE or EPI alone cannot substitute for FSE in the screening evaluation of the brain. However, together, EPI and HASTE could provide comparable diagnostic information to that of FSE because their combination compensates for their individual limitations.

Adolescent↗

Mercaptan-capturing properties of mushrooms.

Mercaptan-capturing properties of 33 kinds of mushrooms were measured. The mushrooms having a high capturing ability toward methyl mercaptan (MeSH) were Agaricus bisporus, A. campestris, Boletus fraternus, B. subvelutipes, Gyrodon lividus, Leccinum scabrum, Suillus grevillei, Morchella esculenta, Russula nigricans, Hypholoma sublateritium, and Lyophyllum sykosporum. These are liable to change their color when injured. The mixture of their acetone powders, which contain polyphenol oxidases, and phenolic compounds such as tyrosine, gamma-L-glutaminyl-4-hydroxybenzene (GHB), DOPA, variegatic acid, grevillin B and C, and pigments, and fluorescent compounds from H. sublateritium also showed high MeSH-capturing properties. 2,5-Bis(methylthio)-DOPA was isolated from the reaction mixture of tyrosine and MeSH with tyrosinase, and the existence of 2- and 5-methylthio-DOPAs was also suggested. Furthermore, acetone powders from fruits and vegetables oxidized the above diphenolic compounds to bind MeSH.

Agaricales↗

Prefabricated bone graft induced from grafted periosteum for the repair of jaw defects: an experimental study in rabbits.

PURPOSE: The purpose of the study was to determine whether a prefabricated graft of new bone induced from periosteum grafted into muscle was an effective material for the repair of jaw defects. MATERIAL AND METHODS: Artificial mandibular jaw defects in young Japanese rabbits were covered either with free grafted periosteum (n = 5) or a prefabricated graft of newly formed bone induced from periosteum, which was first grafted into the floor of the mouth, and placed as a revascularized muscle-pedicled bone flap (n = 5). Bone formation in jaw defects was examined radiographically and histologically 28 days after grafting into defects. RESULTS: Bone formation was confirmed radiographically and histologically in both groups. However, the free grafted periosteum formed thin bone and fibrous tissue existed between the new and the original bone. In contrast, more active bone formation was observed with the prefabricated graft. This grafted new bone developed further and fused to the mandible. Blood vessels surrounding the new bone were observed histologically. CONCLUSION: These experimental findings suggested that prefabricated bone grafts induced from periosteum grafts are potentially useful for correction of jaw defects.

Animals↗

Comparison between the palatal configurations in complete and incomplete unilateral cleft lip and palate infants under 18 months of age.

OBJECTIVE: The purpose of this study was to examine the three-dimensional characteristics of the palatal configurations in incomplete unilateral cleft lip and palate (UCLP) patients and to determine whether there are differences in the effect of early orthopedic treatment between complete and incomplete UCLP patients. DESIGN: Eight infants with incomplete UCLP and 12 infants with complete UCLP, selected at random, wore Hotz plates, and 8 other infants with complete UCLP did not. Palatal impressions were taken of these patients immediately after birth and at 1, 2, 3, 4 (just before cheiloplasty), 6, and 18 months of age (just before palatoplasty). Using our measuring system, the palatal casts were measured and compared three-dimensionally. RESULTS AND CONCLUSIONS: The palate of the incomplete UCLP patients measured immediately after birth, compared with complete UCLP, showed: (1) smaller posterior arch width; (2) sagittal arch length did not differ; (3) incisal point was located more mesially; (4) the gap between the alveolar arch forms of the major and minor segments was smaller; and (5) the curvature of the palatal surface forward the nasal cavity in the minor segment was less. At 18 months of age, the following characteristics could be observed: (1) the difference observed at birth in the posterior arch width between the incomplete and complete UCLP infants vanished; (2) a significant difference in the location of the incisal point was observed only between the incomplete UCLP infants and the complete UCLP infants with a Hotz plate; and (3) the curvature was less in the incomplete UCLP infants than in the complete UCLP infants. Furthermore, the morphological change of the palatal surface was less in the incomplete UCLP infants than in the complete UCLP infants. This suggested that any influence of the Hotz appliance might be less in incomplete UCLP than in complete UCLP.

Age Factors↗

Evaluation of the intracranial dural sinuses with a 3D contrast-enhanced MP-RAGE sequence: prospective comparison with 2D-TOF MR venography and digital subtraction angiography.

BACKGROUND AND PURPOSE: The diagnosis of dural sinus thrombosis is often difficult because of its variable and nonspecific clinical presentation and the overlapping signal intensities of thrombosis and venous flow on conventional MR images and MR venograms. We compared 3D contrast-enhanced magnetization-prepared rapid gradient-echo (MP-RAGE) sequences with 2D time-of-flight (TOF) MR venography, digital subtraction angiography (DSA), and conventional spin-echo (SE) MR imaging for the assessment of normal and abnormal dural sinuses. METHODS: In a phantom study, a plastic tube with pulsating flow was used to simulate the intracranial dural sinus. With 3D MP-RAGE, a variety of flow velocities, contrast material concentrations, and angulations between the phantom flow tube and the plane of acquisition were tested to measure their relationship to signal-to-noise ratio (SNR). In a clinical study, 35 patients, including 18 with suspected dural sinus thrombosis, were studied with both MR imaging and DSA. Receiver operating characteristic (ROC) analysis was performed in a blinded fashion using DSA as the reference standard. RESULTS: With the phantom, the SNR of flow increased with increasing contrast concentration, but was not affected by the angle between the tube and scan slab. There was no relationship between SNR and velocity when the contrast concentration was 1.0 mmol/L or greater. In the clinical study, dural sinus thrombosis as well as the normal anatomy of the dural sinuses were seen better with 3D contrast-enhanced MP-RAGE than with 2D-TOF MR venography. Three-dimensional contrast-enhanced MP-RAGE showed the highest diagnostic confidence on ROC curves in the diagnosis of thrombosis. CONCLUSION: Three-dimensional contrast-enhanced MP-RAGE is superior to 2D-TOF MR venography and conventional SE MR imaging in the depiction of normal venous structures and the diagnosis of dural sinus thrombosis, and is a potential alternative to DSA.

Adult↗