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Biomedical subjects

Y Muragaki

Publications and source records attributed to Y Muragaki.

At least 19 recordsLinked to original sources

Direct maxacalcitol injection into hyperplastic parathyroids improves skeletal changes in secondary hyperparathyroidism.

Direct maxacalcitol (OCT) injection into a parathyroid gland (PTG) ameliorates several important etiologic factors of resistance to medical treatments for secondary hyperparathyroidism (s-HPT): the upregulations of vitamin D receptor (VDR) and Ca-sensing receptor (CaSR) in PTGs and the regression of PTG hyperplasia by the induction of apoptosis. In this study, we evaluated the bone histomorphology on the basis of maintaining these effects in advanced s-HPT. Five/six nephrectomized Sprague-Dawley rats were fed a high-phosphorus and low-calcium diet for 8 weeks. These rats were divided into four treatment groups: (1) basic uremic (at the baseline), (2) direct OCT single injection into PTGs (DI-OCT) followed by OCT intravenous administration for 4 weeks (IV-OCT), (3) direct vehicle injection and IV-OCT, and (4) no treatment for an additional 4 weeks. The effects of these treatments on serum intact-parathyroid hormone (PTH) level, PTG weight, VDR and CaSR expression levels in PTGs, and bone histomorphometric parameters were investigated. In the DI-OCT+IV-OCT group, the significant decrease in serum intact-PTH level was maintained by the following IV-OCT. A significant decrease in PTG weight and the upregulations of VDR and CaSR expression levels in PTGs were also observed. Bone histomorphometric analysis showed significant improvements in osteitis fibrosa in both cancellous and cortical bones. However, these findings were not observed in the other groups. These results suggest that osteitis fibrosa caused by advanced s-HPT can be successfully reversed by a control of PTH at an appropriate level through the improvement of PTG hyperplasia as induced by DI-OCT+IV-OCT.

Animals↗

Usefulness of intraoperative magnetic resonance imaging for glioma surgery.

BACKGROUND: Radical resection of gliomas can increase patient's survival. There is known concern, however, that aggressive tumour removal can result in neurological morbidity. The objective of the present study was to evaluate the usefulness of low magnetic field strength (0.3 Tesla) open intraoperative magnetic resonance imaging (iMRI) for complete resection of glioma with emphasis on functional outcome. METHODS: From 2000 to 2004, 96 patients with intracranial gliomas underwent tumour resection with the use of iMRI in Tokyo Women's Medical University. There were 50 men and 46 women; mean age was 39 years. Tumour volume varied from 1.2 ml to 198 ml (median: 36.5 mL). Resection rate and postoperative neurological status were compared between control group (46 cases, operated on during the initial period after installation of iMRI), and study group (50 most recent cases, in whom surgery was done using established treatment algorithm and improved image quality). FINDINGS: Overall, mean resection rate was 93%, and medial residual tumour volume was 0.17 ml. Total tumour removal was achieved in 44 cases (46%). Compared to control group, resection rate in the study group was significantly higher (91%, vs. 95%; P < 0.05), whereas residual tumour volume was significantly smaller (1.7 mL vs. 0.025 mL; P < 0.001). Nine patients in the control group (20%) and 24 in the study group (48%) experienced temporary postoperative neurological deterioration (P < 0.01), however, the rate of permanent morbidity evaluated 3 months after surgery did not differ significantly between the groups investigated (13% vs. 14%). CONCLUSIONS: Use of iMRI during surgery for intracranial gliomas permits to attain aggressive tumour resection with good functional outcome. Nevertheless, surgical experience with the iMRI system, establishment of treatment algorithm, and improvement of image quality are of paramount importance for optimal results.

Adult↗

Differentiation of the radiation-induced necrosis and tumor recurrence after gamma knife radiosurgery for brain metastases: importance of multi-voxel proton MRS.

Comparative analysis of the diagnostic accuracy of FDG PET, single-voxel, and multi-voxel proton MRS for differentiation between radiation-induced necrosis and tumor recurrence was done in 9 patients with brain metastases treated by gamma knife radiosurgery. In all cases enlargement of the lesion and increase of the perilesional edema were demonstrated by MRI on average 10.6+/-2.6 months after initial treatment. Radiation-induced necrosis was identified in 5 patients (histologically in 2, clinically in 3). In one of these a false positive result of FDG PET was observed, whereas data of proton MRS were always correct. The diagnosis of tumor recurrence was established in 4 patients (histologically in 3, clinically in 1). Among these both FDG PET and single-voxel proton MRS showed false negative results (each method twice), whereas multi-voxel proton MRS always permitted us to establish the correct diagnosis. The present study demonstrates the higher diagnostic accuracy of multi-voxel proton MRS, in comparison with single-voxel proton MRS and FDG PET, for the differentiation of the radiation-induced necrosis and tumor recurrence. Its use is especially important in mixed lesions with co-existence of both post-irradiation changes and viable neoplasm. Monitoring of the treatment response by serial multi-voxel proton MRS seems to be reasonable during follow-up of patients with brain metastases after radiosurgery.

Abnormalities, Radiation-Induced↗

Malignant progression of benign brain tumors after gamma knife radiosurgery: is it really caused by irradiation?

Malignant transformation of benign neoplasm after radiosurgery is usually diagnosed based on the initial presence of benign tumor, its exposure to ionizing radiation, elapsed time from radiation exposure to malignant progression, and different histological characteristics or growth rate of the regrowing tumor comparing with those originally treated. Three presented cases fulfilled these diagnostic criteria; however, it seems that progression of the tumors (schwannoma, meningioma, chordoma) resulted from the natural course of the disease, rather than represented side effects of gamma knife radiosurgery. Evaluation of the proliferative potential of the benign neoplasm before radiosurgical treatment either directly, if tumor sampling is available, or indirectly, by calculation of the tumor growth rate and/or analysis of the data of the metabolic imaging (PET, MRS) is important for identification of "aggressive" subtypes, precise prediction of prognosis, and confirmation of the radiation-induced malignant transformation in cases of tumor regrowth.

Adult↗

Keloid-derived fibroblasts show increased secretion of factors involved in collagen turnover and depend on matrix metalloproteinase for migration.

BACKGROUND: A keloid is a specific skin lesion that expands beyond the boundaries of the original injury as it heals. Histologically, it is characterized by the excessive accumulation of collagen. However, the reasons for the expansion and the invasive nature of keloids remain unknown. OBJECTIVES: We evaluated collagen degradation and migration by cultured keloid fibroblasts based on the assumption that these variables were of functional relevance to the expanding and invasive nature of keloid lesions. METHODS: Collagen production was investigated by the detection of type 1 collagen (procollagen type 1C peptide: P1P). Matrix metalloproteinase (MMP)-1 (interstitial collagenase) and MMP-2 (gelatinase-A), were investigated as elements of the collagen degradation system. Enzyme immunoassays were performed to measure the production of P1P, MMP-1, MMP-2, and tissue inhibitor of metalloproteinase (TIMP)-1. To assess the production of MMP-2 its gelatinolytic activity was measured by zymography using gelatin-containing gels. The participation of transforming growth factor-beta1 (TGF-beta1) in the production and degradation of collagen was also investigated. Finally, the migratory activity of keloid fibroblasts was evaluated using a colony dispersion assay. RESULTS: The production of type 1 collagen, MMP-1, MMP-2, and TIMP-1 by keloid fibroblasts was 3-fold, 6-fold, 2.4-fold, and 2-fold greater than that of normal dermal fibroblasts, respectively. Production of P1P was increased when TGF-beta1 was added to cultures of keloid fibroblasts, while it was decreased when anti-TGF-beta1 antibody was added to the cultures. In contrast, the production of MMP-1 was decreased by the addition of TGF-beta1 to cultured keloid fibroblasts, while it was increased when anti-TGF-beta1 antibody was added to the cultures. The production of MMP-2 increased after treatment with TGF-beta1, but did not change significantly when anti-TGF-beta1 antibody was added to the cultures. Production of TIMP-1 did not change significantly when either TGF-beta1 or anti-TGF-beta1 antibody was added to the cultures. Keloid fibroblasts showed a 2.5-fold increase of migratory activity compared with normal dermal fibroblasts, while the migratory activity of these fibroblasts was reduced to the control level by treatment with a broad-spectrum MMP inhibitor (GM 6001). CONCLUSIONS: Cultured keloid fibroblasts showed increased production of collagen and MMPs, and TGF-beta1 played a role in this regulation of production. In addition, increased production of MMPs had a role in the high migratory activity of cultured keloid fibroblasts.

Cell Movement↗

Minimally invasive management of the third ventricle glioma in a patient without hydrocephalus: neurofiberscopic biopsy followed by gamma knife radiosurgery.

There is usually concern that ventricular enlargement is necessary for safe neuroendoscopic procedures. However, newly developed models of neurofiberscopes with a small outer diameter can be effectively used even in patients without ventriculomegaly. We present the case of a successful neurofiberscopic biopsy of a third ventricle anaplastic astrocytoma in a previously shunted patient without hydrocephalus. Subsequent gamma knife radiosurgery led to complete disappearance of the tumor. It seems that presence of collapsed ventricles, and even symptoms consistent with the slit ventricle syndrome, should not be considered as contraindications for neurofiberscopic surgery when brain compliance is sufficiently preserved. The latter should be considered as the key point of safe endoscopic manipulations. The combination of the neuroendoscopy and stereotactic radiosurgery provides wide possibilities for minimally invasive management of selected intracranial tumors.

Adolescent↗

New possibilities for stereotaxis. Information-guided stereotaxis.

Information-guided stereotaxis, assisted by visualization of medical information, will become the next generation of neurosurgical systems. We performed 76 open MRI surgeries at Tokyo Women's Medical University between March 3, 2000 and April 12, 2001. Of them, comparisons of pre- and post-operative MR images for malignant gliomas in 21 cases revealed an average resection rate of 90.3% (the maximum 100%, the minimum 55%). In this article we describe real time updated navigation, augmented reality navigation, three-dimensional navigation, chemical navigation, information-guided navigation system (High definition visual Computer Aided Surgery System: HivisCAS), and open MRI-guided surgery that we are developing.

Humans↗

Overexpression of type IV collagen in chorionic villi in hydatidiform mole.

To investigate the characteristic structure of hydatidiform mole, type IV collagen expression was determined in human villous tissues obtained from normal pregnancies (n = 17) and complete hydatidiform moles (n = 10). Indirect immunofluorescent staining was performed to detect type IV collagen with specific monoclonal antibody, and Northern blot analysis was performed to assess expression of messenger ribonucleic acid for the alpha1(IV) chain. In addition, serum levels of type I, III, and IV collagen were measured by RIA. Immunohistochemical staining for type IV collagen revealed stronger staining of the trophoblastic basement membrane in hydatidiform mole than in normal pregnancy. Northern blot analysis revealed that the villous expression of messenger ribonucleic acid for the alpha1(IV) chain was significantly increased in hydatidiform moles compared with normal pregnancy (P < 0.01). Although there were no differences in the serum type I and III collagen levels between hydatidiform mole and normal pregnancy, the type IV collagen level was significantly higher in patients with hydatidiform mole than in normal pregnancy (P < 0.05). These results suggest that type IV collagen might play an important role in determining the pathophysiology and structure of hydatidiform mole.

Adult↗

Decreased type III and V collagen expression in chorionic villi of hydatidiform mole.

To investigate the characteristic structure of hydatidiform mole, various types of collagen expression were determined in human villous tissues obtained from normal pregnancies (n = 17) and complete hydatidiform moles (n = 10). Indirect immunofluorescent staining was performed to detect type I, III, and VI collagen with specific monoclonal antibodies. Collagens were also extracted from the villous tissues obtained from normal pregnancy and hydatidiform mole by the salt precipitation method. Immunohistochemical staining for type I, III, and VI collagen revealed weak staining of the villous stroma in hydatidiform mole compared with that in normal pregnancy. Both the ratios of type III to type I collagen and the ratios of type V to type I collagen in the villous tissues were significantly decreased (P < 0.05) in molar pregnancy compared with those in normal pregnancy. These results suggest that alterations in the distribution and composition of collagen might play an important role in determining the pathophysiology and structure of hydatidiform mole.

Adult↗

Type VI collagen expression during growth of human ovarian follicles.

OBJECTIVE: To identify type VI collagen expression in human ovarian follicles during follicular growth. DESIGN: In vitro experiment. SETTING: Department of Obstetrics and Gynecology, Wakayama Medical College, Japan. PATIENT(S): Regularly cycling women who underwent adnexectomy. INTERVENTION(S): Immunohistochemistry and in situ hybridization for human type VI collagen. MAIN OUTCOME MEASURE(S): Expression of type VI collagen. RESULT(S): Expression of type VI collagen was observed in the theca cell layers during folliculogenesis, whereas no expression of type VI collagen was observed in the granulosa cell layers at the mRNA and protein levels. As the follicles grew, immunostaining for type VI collagen became intense in the theca cell layers, especially the theca externa. In preovulatory follicles, however, weak, fragmented, or discontinuous immunostaining of the theca cell layers was observed. This fragmented or discontinuous immunostaining was evident predominantly in the apical area of preovulatory follicles rather than in the basal area. CONCLUSION(S): Type VI collagen is present in the theca cell layers of follicles during folliculogenesis and plays an important role in interactions between the theca cells and extracellular matrix. These interactions may lead to changes in the shape, proliferation, migration, or differentiation of follicular cells during follicular development, maturation, and ovulation.

Adult↗

[Clinical evaluation of intraoperative radiotherapy using photon radiosurgery system for brain tumors].

The photon radiosurgery system is a miniature X-ray generator that can be placed stereotactically and intraoperatively into intracranial tumors to deliver a single fraction of high-dose interstitial irradiation. This battery-powered device produces low energy X-ray photons in a spherical and symmetrical pattern at the probe tip. Dose rates of up to 200 cGy/Mim are possible, allowing for the administration of 15 Gy to a lesion 3 cm in diameter in less than 1 hr. Background exposure is minimal, and no special shielding of the patient or health care personnel is required. Thirty-nine patients with brain tumor were treated in this method. There were no adverse effects. During the follow-up period of 1-30 months, 3 cases with 5 metastatic brain tumors died about 8 months after this treatment. Five recurrent cases of 21 malignant gliomas died about 4 months after treatment. Interstitial radiotherapy using photon the radiosurgery system promises to be a useful treatment for brain tumors.

Aged↗

Synpolydactyly phenotypes correlate with size of expansions in HOXD13 polyalanine tract.

Synpolydactyly (SPD) is a dominantly inherited congenital limb malformation. Typical cases have 3/4 finger and 4/5 toe syndactyly, with a duplicated digit in the syndactylous web, but incomplete penetrance and variable expressivity are common. The condition has recently been shown to be caused by expansions of an imperfect trinucleotide repeat sequence encoding a 15-residue polyalanine tract in HOXD13. We have studied 16 new and 4 previously published SPD families, with between 7 and 14 extra residues in the tract, to analyze the molecular basis for the observed variation in phenotype. Although there is no evidence of change in expansion size within families, even over six generations, there is a highly significant increase in the penetrance and severity of phenotype with increasing expansion size, affecting both hands (P = 0.012) and feet (P < 0. 00005). Affected individuals from a family with a 14-alanine expansion, the largest so far reported, all have a strikingly similar and unusually severe limb phenotype, involving the first digits and distal carpals. Affected males from this family also have hypospadias, not previously described in SPD, but consistent with HOXD13 expression in the developing genital tubercle. The remarkable correlation between phenotype and expansion size suggests that expansion of the tract leads to a specific gain of function in the mutant HOXD13 protein, and has interesting implications for the role of polyalanine tracts in the control of transcription.

Base Sequence↗

Nerve growth factor induces apoptosis in human medulloblastoma cell lines that express TrkA receptors.

Neurotrophins act through their cognate receptors to promote the differentiation and/or survival of neuronal progenitor cells, immature neurons, and other cells. Here, we examined the effects of nerve growth factor (NGF) and its cognate receptor (Trk or TrkA) on the survival of a common childhood brain tumor, i.e., medulloblastoma, a tumor that resembles CNS neuroepithelial progenitor cells. To do this, we engineered two human medulloblastoma cell lines (i.e., D283MED and DAOY cells) to express human TrkA using a retroviral expression vector. Surprisingly, NGF-treated medulloblastoma cells expressing the TrkA receptor (D283trk and DAOYtrk cells) grown in the presence or absence of serum underwent massive apoptosis, but similar treatment did not induce apoptosis in wild-type uninfected cells, cells expressing an empty vector, or cells expressing the TrkC receptor. Furthermore, D283MED cells engineered to express the human p75 NGF receptor (D283p75) also did not undergo apoptosis. Significantly, NGF-induced apoptosis in D283trk and DAOYtrk cells can be inhibited by anti-NGF antibodies and by K-252a, an inhibitor of TrkA tyrosine phosphorylation and mimicked by high concentrations of NT3. Because NGF treatment primarily eliminated D283trk cells from the S phase of the cell cycle, this form of NGF-mediated apoptosis is cell cycle-dependent. These findings suggest that a NGF/TrkA signal transduction pathway could activate apoptotic cell death programs in CNS neuroepithelial progenitor cells and in childhood brain tumors.

3T3 Cells↗

Increased laminin-1 expression in hydatidiform mole.

To investigate the aetiology of hydatidiform mole, laminin-1 expression was determined in human villous tissues obtained from normal pregnancies (n = 17) and complete hydatidiform moles (n = 10). Indirect immunofluorescent staining was performed to detect laminin-1, and Northern blot analysis was performed to assess expression of laminin mRNA. Serum concentrations of laminin P-1 were also measured. Immunohistochemical analysis revealed stronger staining of the trophoblastic basement membrane in hydatidiform mole than in normal pregnancy. Northern blot analysis revealed that villous expression of laminin mRNA was significantly increased in hydatidiform mole compared with normal pregnancy (P < 0.05). The serum laminin P-1 concentration was also significantly higher in those patients with hydatidiform mole than in normal pregnancy (P < 0.05). These results suggest that laminin-1 might play an important role in determining the pathophysiology and structure of hydatidiform mole. In addition, measurement of serum laminin P-1 in combination with human chorionic gonadotrophin might be useful in the diagnosis of hydatidiform mole, to evaluate the prognosis, and to detect the presence of metastatic or recurrent disease.

Adult↗

Volumegraph (overlaid three-dimensional image-guided navigation). Clinical application of augmented reality in neurosurgery.

OBJECTIVE: We have developed an overlaid three-dimensional image (Volumegraph)-guided navigation system that allows navigation during operative procedures. The three-dimensional image is superimposed on the patient's head and body via a semi-transparent mirror. The Volumegraph can display three-dimensional images in the air by a light beam which is based on CT/MRI. METHOD: The system consists of a Volumegraph (thin plate of three-dimensional recorded medium), a Volumegraphscope and an original designed triangular-shaped marker system for registration. The three-dimensional data obtained from CT and MRI before the operation were processed by a computer. Such image data are applied for preoperative investigation to recognize the three-dimensional structure of organs and tumor. These reconstructed three-dimensional images were superimposed and registered at the patient's head according to a fiducial marker (registration). Then the operator can operate with this three-dimensional-image-guided navigation system. RESULTS: Based on clinical application in 7 cases, the system was found to be advantageous because the surgical procedures could be navigated easily by augmented reality in the surgical field. Invisible parts of the surgical field were supplemented with the overlaid three-dimensional images (Volumegraph) as if it were the virtual operative field. At another time, spatial positioning and overlaid visualization by the Volumegraph was useful for identifying anatomical structures and functional location in the image. CONCLUSION: This preliminary study of overlaid three-dimensional-image-guided navigation demonstrated its clinical usefulness. The application of augmented reality in the surgical field makes it possible to do a neurosurgical intervention easily and accurately.

Brain Neoplasms↗