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Biomedical subjects

H Kurata

Publications and source records attributed to H Kurata.

At least 55 records · Page 3Linked to original sources
PubMed2000

Two-phase partition method for simulating a biological system at an extremely high speed.

To accelerate the calculation speed for simulating a biological system, we proposed a novel simulation method, the two-phase partition method, which calculated molecular processes at a higher speed than any other proposed method. This method divides a biological system, which can be described by chemical reaction equations, into two-phases: the binding and reaction phases. We demonstrated the capability of the two-phase partition method to simulate a complex biological system at an extremely high speed and clarified the accuracy of the simulation. The two-phase partition method is very useful for simulating complex interactions among proteins and DNAs.

Ammonia↗
PubMed1999

Idiopathic spinal cord herniation. Report of two cases and review of the literature.

The authors describe two occurrences of idiopathic spinal cord herniation, an entity that has been reported previously in only 11 cases. The patients described in this report presented in midlife with Brown-Sequard syndrome. Computerized tomography myelography and magnetic resonance (MR) imaging showed ventral displacement of the spinal cord with no apparent dorsal mass. Intraspinal cerebrospinal fluid (CSF) flow studies in which phase-contrast pulse sequence cine MR imaging was used displayed a normal pattern dorsal to the spinal cord. Percutaneous intrathecal endoscopic observation did not disclose dorsal intradural cysts, but ventral adhesions were seen between the spinal cord and the dura. Microsurgical intradural exploration revealed ventrolateral herniation of the cord and a ventral root through a dural defect into an epidural arachnoid cyst. The adhesions were released, the cord was repositioned intradurally, and the dural defect was patched. The patients showed gradual improvement postsurgery, as did most of the patients in the previously reported cases. The CSF flow and endoscopic studies were found to be particularly informative, and dural patching with surgical membrane is recommended.

Journal Article↗
PubMed1999

Formation of cell junctions between grafted and host cardiomyocytes at the border zone of rat myocardial infarction.

BACKGROUND: Cardiomyocyte transplantation is an innovative strategy for the treatment of heart failure after myocardial infarction. Cell junctions show diverse temporal polarization toward intercalated disks during postnatal development and exhibit altered distribution in diseased hearts. To elucidate the formation of cell junctions between grafted and host cardiomyocytes at the border zone of myocardial infarction, the 3D distribution of cell junctions was examined using immunohistochemistry and confocal microscopy. METHODS AND RESULTS: Neonatal cardiomyocytes obtained from 3-day-old rats by collagenase digestion and Percoll density centrifugation were injected into the border zones of infarction sites 10 days after coronary ligation in adult rats. At 4 to 14 days after transplantation, hearts were harvested and processed by immunohistochemistry. Antibodies against connexin43, desmoplakin, and cadherin were used to analyze the distribution of gap junctions, desmosomes, and adherens junctions, respectively. Grafted cardiomyocytes were identified by immunohistochemistry for alpha-smooth muscle actin. Grafted cardiomyocytes tended to align parallel to the host cardiomyocytes. Connexin43, desmoplakin, and cadherin were localized between grafted cardiomyocytes themselves and between grafted and host cardiomyocytes. Semiquantitative analysis revealed that all junctions showed increasing polarization to longitudinal cell termini, especially at the border of grafted and host cardiomyocytes, as time advanced from 4 to 7 days after transplantation. CONCLUSIONS: These findings indicate that grafted cardiomyocytes foster electrical pathways with host counterparts through the gap junction and suggest that the environment in infarcted hearts could influence the localization of gap junctions, desmosomes, and adherens junctions.

Animals↗
PubMed1999

Combined NK1 and NK2 tachykinin receptor antagonists: synthesis and structure-activity relationships of novel oxazolidine analogues.

We report herein the synthesis and structure-activity relationships of a series of novel oxazolidine analogues with regards to NK1 and NK2 tachykinin receptor binding affinity. Among this series of oxazolidine analogues, some compounds exhibited excellent high binding affinities for both NK1 and NK2 receptors. In addition, we describe the inhibitory effect in vivo on SP-induced airway vascular hyperpermeability and NKA-induced bronchoconstriction in guinea pigs.

Animals↗
PubMed1999

Recombinant adenovirus vectors for cytokine gene therapy in mice.

BACKGROUND: Adenoviruses have several specific features useful for gene therapy. They infect various lineages of cells irrespective of cell cycle status. However, the exact mechanism of their infection and in vivo kinetics as a gene expression vector have not been elucidated. OBJECTIVE: Using adenovirus vectors expressing marker genes, we examined the infectivity of these vectors (including cellular and tissue tropism), the duration and intensity of transgene expression, and the side effects. METHODS: Various cells were infected with adenovirus expressing LacZ gene at various doses, and beta-galactosidase activity was measured and compared in relation with dose, time course, and cellular vitronectin receptor. Mice were injected with adenoviruses expressing LacZ, luciferase and GM-CSF, and in vivo gene expression was examined. RESULTS: Adenovirus infection induced viral dose-dependent transgene expression that persisted for 2 weeks. Adherent cells were infected much more efficiently than nonadherent cells, probably because the former expressed much higher levels of the vitronectin receptor, one of the main receptors for adenovirus. Studies performed in mice with luciferase-expressing adenovirus revealed that the liver was the main target organ after intravenous injection and showed that the intravenous route was superior to other routes with regard to transgene expression. After intravenous injection of adenovirus expressing human GM-CSF, there was a transient and dose-dependent increase in the serum level of this cytokine. Administration of adenovirus expressing mouse GM-CSF enhanced hematopoiesis in the spleen and bone marrow. CONCLUSION: These results indicated that adenoviruses can be used for in vivo cytokine gene therapy but suggested the necessity of taking into consideration the route of administration, the duration of transgene expression, the toxic dose, and host immune reactions.

Adenoviridae↗
PubMed1999

Ectopic expression of activated Stat6 induces the expression of Th2-specific cytokines and transcription factors in developing Th1 cells.

Stat6 is critical for IL-4-mediated Th2 cell development, but its molecular mechanism remains unclear. Here we constructed Stat6:ER, a Stat6-estrogen receptor fusion protein that can be activated by 4-hydroxy-tamoxifen, independently of IL-4 and endogenous Stat6. Retrovirus-mediated introduction of Stat6:ER into developing Th1 cells induced Th2-specific cytokines and suppressed IFNgamma production in a 4-HT-dependent manner and in the absence of IL-4. It also induced GATA-3 and c-maf expression and downregulated IL-12Rbeta2 chain expression. Its decreased ability to induce the Th2 phenotype with progressing Th1 cell commitment correlated with a decreased induction of GATA-3 and c-maf. This study indicates that Stat6 functions upstream of GATA-3 and c-Maf to induce Th2 development.

Animals↗
PubMed1999

Detection of antifungal activity in Anemarrhena asphodeloides by sensitive BCT method and isolation of its active compound.

Antifungal activity was detected from Anemarrhena asphodeloides by the Bio-Cell Tracer (BCT) method. An active fraction was separated by silica gel column chromatography and reverse-phase HPLC. The molecular weight was determined by GC-MS, and the molecular structure was analyzed by IR, (1)H NMR, and (13)C NMR. The isolated compound was found to be identical to nyasol, (Z)-1, 3-bis(4-hydroxyphenyl)-1,4-pentadiene, which formerly appeared in the literature without any remark on the antifungal activity. This compound showed antimicrobial activity against 38 strains of fungi and five strains of bacteria. The minimum inhibitory concentration (MIC) ranged from 12.5 to 200 microg mL(-)(1), except for two strains based on the broth dilution method.

Antifungal Agents↗
PubMed1999

Mechanism of preventive effect of HMG-CoA reductase inhibitor on diabetic nephropathy.

BACKGROUND: Previously, we have found that pravastatin prevents diabetic nephropathy in streptozotocin-induced diabetic rats independently of serum lipid levels. The aim of this study was to clarify the impact of pravastatin on the mesangial cells exposed to high glucose. METHODS: Rat mesangial cells were cultured in DMEM containing low glucose (5 mM glucose), high glucose (25 mM glucose) and 25 mM glucose with 500 microM pravastatin for 48 hours, respectively. After harvesting, we examined membrane-associated Ras with immunoblot analysis, activity of mitogen-activated protein kinase (MAPK) in the cytosol fraction with in-gel kinase assay and expressions of TGF-beta mRNA with Northern blot analysis. RESULTS: Membrane-associated Ras, activity of MAP kinase, and expression of transforming growth factor-beta (TGF-beta) mRNA were increased in the mesangial cells cultured exposed to high glucose compared to low glucose. Pravastatin suppressed all these changes in membrane-associated Ras, MAP kinase and TGF-beta mRNA in high glucose. CONCLUSIONS: This study suggests that pravastatin suppresses the activity of Ras-MAP kinase cascade and induction of TGF-beta in the mesangial cells that have been exposed to high glucose.

Animals↗
PubMed1999

Endoscopy of spinal cord and posterior fossa by a lumbar percutaneous approach: endoscopic anatomy in cadavers.

Endoscopy has a long history and is used extensively today following recent technical improvements. Endoscopy has been used in neurosurgery to examine ventricles, cisterns, and intra-arteries. In this study, we evaluated the possibility of endoscopic examination and treatment in the narrow confines of the subarachnoid space of the spine and the posterior fossa. Endoscopes with external diameters of 0.5, 1.4, and 2.2 mm were used. While the first two endoscopes had rigid tips, the 2.2-mm endoscope had a directable tip. Each endoscope was inserted percutaneously in the lumbar region in five cadavers and was advanced cranially into the posterior fossa under endoscopic monitoring. Arteries, veins and nerve roots upon the surface of the spinal cord could be distinguished readily with all endoscopes. All endoscopes could be inserted under direct observation, avoiding these vessels and nerve roots. Further rostral advancement of the endoscope permitted visualization of the upper spinal cord, cisterna magna at the foramen magnum, and the fourth ventricle. The lower aspect of the cerebellum, the foramen of Magendie, and the cerebral aqueduct could be observed from below. When the endoscope was advanced ventrolaterally, the vertebral artery and lower cranial nerves were observed. From this preliminary cadaver study, endoscopy via lumbar puncture appeared useful for inspection of structures surrounding the spinal cord and posterior fossa, and for some simple treatments.

Cadaver↗
PubMed1999

Endoscopy of the spinal cord: cadaveric study and clinical experience.

Recent improvements in instruments permit endoscopic examination of previously inaccessible sites. We report on the clinical use of a small-diameter endoscope to examine the spinal subarachnoid space, cord surface and syrinx cavities. Prior to clinical application, three types of endoscopes with external diameters of 0.5, 1.4 or 2.2 mm were inserted percutaneously in the lumbar region of five cadavers for preclinical evaluation of the procedure and the three endoscopes. The observations permitted us to perform spinal endoscopy preoperatively or intraoperatively using the 0.5-mm instrument in seven patients with spinal cord lesions between 1995 and 1997. The patients included two with spinal cord herniation through a dural defect, two with syringomyelia, one with spinal arachnoid cyst, one with spinal epidural cyst and one undergoing lumboperitoneal shunt for hydrocephalus. In patients in whom an endoscope was used preoperatively, the endoscope provided morphological information useful in preoperative diagnosis and planning surgical strategy. When the endoscope was used intraoperatively, areas outside the field of vision of a microscope could be examined, and physiological evaluation could include visualizing improved cord perfusion from the spinal subarachnoid space after surgery. Endoscopes could be safely inserted and approached to the lesions under direct vision while avoiding blood vessels and nerve roots on the spinal cord surface. No changes in symptoms or complications occurred in association with endoscopy. Using a small-diameter endoscope, the contents of the spinal subarachnoid space could be examined. Further improvements to increase possible endoscopic manipulation and enhance safety may extend the possibilities for endoscopic examination and permit endoscopic treatment.

Adult↗
PubMed1999

Failure of high-dose chemotherapy with peripheral blood stem cell support for refractory placental site trophoblastic tumor.

Placental site trophoblastic tumor (PSTT) is a rare form of gestational trophoblastic disease. The metastatic and refractory cases have a very poor prognosis. To our knowledge, this is the first report of the application of high-dose chemotherapy with autologous peripheral blood stem cell transplantation (PBSCT) for the treatment of refractory metastatic PSTT. A 36-year-old woman had a metastatic PSTT refractory to several lines of chemotherapy. She was treated with high dose of carboplatin and etoposide with autologous PBSCT. She showed only a temporary response to high-dose chemotherapy with PBSCT support and died of disease.

Adult↗
PubMed1999

Effect of cerebrospinal fluid shunting on experimental syringomyelia: magnetic resonance imaging and histological findings.

The histological changes associated with syringomyelia after reduction of the syrinx size were investigated after cerebrospinal fluid shunting in experimental syringomyelia in the rabbit. Five weeks after syringomyelia was induced by the injection of kaolin into the cisterna magna in Japanese white rabbits, ventriculosubgaleal shunting or syringoepidural shunting were performed. After 1 week magnetic resonance (MR) imaging and histological examination were then carried out. Five of 11 shunted animals showed postoperative reduction of syrinx size on MR imaging. Grossly, some specimens showed cavity collapse and parenchymal healing, and others showed a small residual syrinx in the dorsal horn. The most dramatic histological changes occurred in the gray matter. Specimens with syrinx collapse showed rarefaction and tearing of the gray matter, with mild glial reaction. The edematous gray matter showed both degeneration and regeneration, with neuronal processes surrounded by edema fluid. Reactive astrocytes were observed mainly at the margin of the residual syrinx. Some astrocytic processes invested the extraaxonal space and gray matter lacked supportive tissue. Greater reduction of the syrinx after shunting operation was correlated with more regeneration and less degeneration, and the white matter was edematous and histological changes were milder. Syrinx shrinkage occurred after shunting in this experimental model of syringomyelia. The selective vulnerability of gray matter even after shunting may explain discrepancies between imaging findings and clinical features in this disease. The study supports the potential benefit from early treatment, considering the associated morphological findings of regeneration.

Animals↗
PubMed1999

Interleukin-4 adenoviral gene therapy reduces production of inflammatory cytokines and prostaglandin E2 by rheumatoid arthritis synovium ex vivo.

BACKGROUND: The rheumatoid arthritis (RA) joint is characterized by an inflammatory synovial pannus which mediates tissue destruction. Interleukin (IL)-4 reduces the production of many proinflammatory cytokines, particularly by activated macrophages. Therefore, we examined the ability of adenovirally delivered IL-4 for the treatment of human RA to reduce the secretion of proinflammatory molecules. METHODS: Adenoviral vectors encoding the genes for human IL-4 (AxCAIL-4) and bacterial beta-galactosidase (AxCAlacZ) were generated and examined for appropriate production and biological activity. RA synovial tissue (ST) explants or fibroblasts were infected with AxCAIL-4 or a beta-galactosidase producing vector, as a control, and conditioned medium (CM) was collected for ELISA analysis. RESULTS: AxCAIL-4 decreased the production of the inflammatory cytokines IL-1 beta and tumor necrosis factor-alpha in RA ST explant CM. IL-8 levels were significantly reduced by 71%, 88%, and 82% at 24, 48, and 72 hours, respectively, in RA ST explant CM. In the same CM, monocyte chemotactic protein-1 (MCP-1) levels decreased 60% at 48 hours. In contrast, RA synovial fibroblast CM levels of MCP-1 were increased by AxCAIL-4. Epithelial neutrophil activating peptide-78 levels produced by RA ST explants were significantly decreased by AxCAIL-4 by 88%, 92%, and 93% at 24, 48, and 72 hours, respectively. Growth related gene product-alpha levels were likewise decreased in RA ST explant CM. In ST explants as well as RA synovial fibroblasts, IL-4 treatment decreased prostaglandin E2 (PGE2) production. CONCLUSIONS: Increased expression of IL-4 via gene therapy may decrease RA-associated inflammation by reducing proinflammatory cytokines and PGE2.

Adenoviridae↗
PubMed1999

[Regrowth of bullae around the staple-line is one of the causes of postoperative recurrence in thoracoscopic surgery for spontaneous pneumothorax].

Since August 1994, we have performed 65 thoracoscopic surgeries for spontaneous pneumothorax. Our operative method is partial resection of the lung with bullae using endoscopic autosuture. Three patients underwent reoperation because of persistent air leakage in one case and postoperative recurrences in two cases. In addition, we performed a second operation in one case that had undergone thoracoscopic surgery for spontaneous pneumothorax in another hospital. At the second operation, regrowth of bullae was found at the edge of staple-line in three of the 4 cases, and in one of these cases, such regrown bullae seemed to be a cause of recurrence of pneumothorax. The regrowth of the bullae was caused by incomplete resection at the initial surgery in one case. Such incomplete resection and oversight were not noticed in the review of the videotape of the initial surgeries in two cases. Reinforcement of the staple-line is necessary for prevention of recurrence of pneumothorax.

Adolescent↗
PubMed1999

[The family of HDL receptor].

Several HDL binding proteins have recently cloned and their roles in HDL metabolism have been gradually elucidated. HBP (vigilin), which lacks a transmembrane domain, is responsive to cell cholesterol levels, however, its physiological roles remain unknown. SR-B1, a member of the class B scavenger receptor, has been reported to bind with not only oxidized LDL but also HDL. The level of SR-B1 expression correlates with both the selective cholesterol transfer into cells and cholesterol efflux from cells. These data suggest that SR-B1 plays important roles in steroid hormone production. HB2 shows high sequence homology with ALCAM (activated leukocyte-cell adhesion molecule). When overexpressed with HB2, HDL binding is increased in the cells. After PMA-induced differentiation of monocytes into macrophages, HB2 mRNA is elevated, which correlates with increased binding of HDL, but is down-regulated by cholesterol loading of macrophages. However, physiological role of HB2 also remains unknown.

Animals↗
PubMed1998

Combined transpetrosal and fronto-orbito-zygomatic approach to a giant skull based meningioma: a case report.

BACKGROUND: Recently, various surgical approaches to skull base lesions have been developed. Skillful use of the combination of two standard approaches make possible the removal of large brain lesions, which conventionally had been considered inoperative. In this study, we present a case of a giant meningioma located in the cerebellopontine angle and middle cranial fossa. A near total resection was achieved using a combined transpetrosal and fronto-orbito-zygomatic approach. CASE REPORT: A 15-year-old boy presented with a meningioma that caused a left hearing loss, dysarthria, and cerebellar ataxia. Preoperative magnetic resonance imaging revealed a giant meningioma located in the right cerebellopontine angle, middle fossa, and cavernous sinus. The patient underwent a near total resection of the tumor through a combined transpetrosal and fronto-orbito-zygomatic approach. He experienced a marked improvement postoperatively and entered high school the following year. CONCLUSIONS: An approach from several angles was necessary for the giant skull based tumor presented here. A combination approach was selected for obtaining a wide operative field with minimal brain compression during resection of neoplasm. According to the individual features of each case, selection of the operative approach, decisions regarding the extent of excision, and postoperative treatment regimens should be adequately planned in the preoperative period.

Adolescent↗
PubMed1998

Large and invasive silent corticotroph-cell adenoma with elevated serum ACTH: a case report.

BACKGROUND: A silent corticotroph-cell adenoma (SCCA) is defined as evidence of immunoreactive ACTH in tumor cells of a pituitary adenoma that is not associated with symptoms of Cushing's disease. Most previous reports have discussed the etiology of this unique entity; however, the precise mechanisms of its "silence" are not clear yet. We discuss the pitfalls of endocrinological diagnosis and surgical management of SCCA. METHODS: A 63-year-old man, without the symptoms of Cushing's disease, demonstrated elevated serum levels of ACTH, but normal levels of cortisol. ACTH was measured by newly developed immunoradiometric assays (RMA), which are more specific for biologically active ACTH than conventional radioimmunoassay (RIA). The tumor was more than 3 cm in diameter and invaded both the cavernous sinus and the sphenoid sinus. RESULTS: Two different types of IRMAs revealed elevated serum ACTH levels. The tumor was removed successfully by staged operations. The high levels of serum ACTH were normalized after the second operation. CONCLUSION: The cause of the silence of SCCA is not clear yet. The elevated serum ACTH levels in the present case were not attributable to "Big ACTH." We suggest one possibility: the cause of the silence might be a minor variant of ACTH, detected by IRMA, leading to less biological activity of ACTH. This type of adenoma is invasive in nature and can potentially grow large because it is free of endocrinological symptoms. We emphasize the appropriate surgical strategy to normalize the serum levels of ACTH in case of SCCA.

Adenoma↗