Biomedical subjects

N Kawahara

Publications and source records attributed to N Kawahara.

At least 19 recordsLinked to original sources

PubMed2006

Radiation myelopathy after radioactive iodine therapy for spine metastasis.

A case of radiation myelopathy after radioactive iodine therapy is reported. This is the first report to describe radiation myelopathy after I-131 therapy. A 62-year-old female with spinal metastasis of T10 received I-131 therapy. She presented with radiation myelopathy 34 months after the irradiation. We need to recognize the possibility of this serious complication even in the case of I-131 therapy. There is a risk of radiation myelopathy even after I-131 therapy, especially in cases with spinal cord compression such as this.

Female↗

PubMed2004

Potent protecting effects of Catuaba (Anemopaegma mirandum) extracts against hydroperoxide-induced cytotoxicity.

Ishigami et al. (Ishigami et al., 1998) reported that squalene monohydroperoxide (SQOOH) induced skin damage in hairless mice. Kohno and Takahashi (Kohno and Takahashi, 1993) reported that SQOOH induced cytotoxicity against Chinese hamster lung fibroblasts. We have already evaluated the efficacy of extracts obtained from Brazilian herbal medicines in protecting the normal human epidermis keratinocytes [NHEK(B)] against the cytotoxicity caused by SQOOH. The EtOAc extract was separated by silica-gel column chromatography into eight fractions. Fractions (Fr) 1,3 and 5 significantly protected rat basophilic leukemia (RBL-2H3) cells from the release of beta-hexosaminidase due to SQOOH. Additionally, Fr5-1 was most effective in a Gunze three-dimensional cultured human skin model (Vitrolife-skin) against the cytotoxicity due to SQOOH and the release of interleukin (IL)-2 and IL-4. The mixture of cinchonains Ia and Ib and the mixture of cinchonains IIa and IIb were isolated from Fr3 and Fr5-1, respectively. The results suggest that the addition of SQOOH caused the reduction in cell viability and the release of beta-hexosaminidase and cytokines as chemical mediators. The extract of Catuaba (Anemopaegma mirandum) prevented these toxic effects with the main active agents suggested to be cinchonains IIa and IIb.

Animals↗

PubMed2004

Expression of Tie-1 and 2 receptors, and angiopoietin-1, 2 and 4 in gastric carcinoma; immunohistochemical analyses and correlation with clinicopathological factors.

AIMS: There is strong evidence that tyrosine kinases are involved in the regulation of tumour progression, cellular growth and differentiation. Recently, many kinds of tyrosine kinase receptors have been reported, and among them Tie-1 and 2 constitute a major class. Angiopoietin (Ang)-1 is known as a ligand of the Tie-2 tyrosine kinase receptor. The aim of this study was to determine the expression profile of Tie-1 and 2 and Ang-1, 2 and 4 in gastric adenocarcinoma. METHODS AND RESULTS: Eighty-nine cases of surgically resected human gastric adenocarcinoma were studied by immunohistochemistry. Of these, 60 (67.4%), 61 (68.5%), 69 (77.5%), 75 (84.3%), and 47 cases (52.8%) showed positive staining in the cytoplasm of carcinoma cells for the Tie-1 and 2 and Ang-1, 2 and 4 proteins, respectively. The expression of Ties and Angs was significantly correlated with several type of histological differentiation and several clinicopathological factors. CONCLUSIONS: Ties and Angs were highly expressed in human gastric adenocarcinoma cells. These findings suggest that the Tie-Ang receptor-ligand complex is one of the factors involved in the cellular differentiation and progression of human gastric adenocarcinoma.

Adenocarcinoma↗

PubMed2003

Intradural spinal seeding of a clival chordoma.

BACKGROUND: Following recent progress in radiological and surgical techniques for treating skull base tumours, more attention should be paid to the relatively rare phenomenon of intradural spinal seeding in cases of clival chordoma. CASE PRESENTATION: A 53-year-old man harboured intradural spinal seeding from a clival chordoma 11 years after his initial surgical treatment. He had undergone skull base surgery five times with extra- and intradural approaches, and adjuvant radiotherapy. His complaints of lumbago, paraparesis, and sensory disturbance of the lower left extremity prompted us to carry out imaging studies of the spinal cord, which revealed multiple intradural, extramedullary mass lesions at the thoracic and lumbosacral spinal level. The tumours were histopathologically diagnosed as spinal seeding of the clival chordoma with high proliferative potential (Ki-67 labelling index of 8.4%). INTERPRETATION: As long-term local control of skull base chordoma appears to be improving by the introduction of skull base surgical techniques and adjuvant radiotherapy, spinal intradural seeding might emerge as a potential complication. Close observation and timely imaging studies for spinal seeding of skull base chordoma would be required in long-term postoperative follow-ups, particularly for those patients with highly proliferative tumours.

Chordoma↗

PubMed2003

Bone development in neurofibromatosis 1.

Bony abnormalities are common findings in cases of neurofibromatosis 1. We might hypothesize that neurofibromin, the protein encoded by the neurofibromatosis 1 gene, plays important roles in bone development. Loss of function of oligodendrocyte-myelin glycoprotein gene and increased activity of ras p21 might increase the level of c-fos proto-oncogene in bones with formation of fibrous dysplasia-like tissue. Also, increased ras p21 might disturb collagen I synthesis by osteoblasts. Moreover, increased ras activity might increase the mitogenic signals to the nucleus through mitogen-activated protein kinase (MAPK) and disturb the level of the transcription factor core-binding factor alpha(1) (Cbfa1). Abnormal fibrous tissue and neurofibromas formed at the site of pseudarthrosis might represent abnormal response of periosteal fibroblasts for injury, an effect simulating the response of skin fibroblasts in neurofibromatosis 1 to injury.

Animals↗

PubMed2002

Hypophosphatemic osteomalacia in neurofibromatosis 1: hypotheses for pathogenesis and higher incidence of spinal deformity.

Osteomalacia is rarely encountered in association with neurofibromatosis 1, characterized by phosphate loss in the urine and its pathogenesis is still unknown. Incidence of spinal deformities in cases of neurofibromatosis 1 associated with osteomalacia seems to be high. Spinal deformities are unlikely to be due to osteomalacia itself. Melatonin deficiency was proposed to be present in cases of neurofibromatosis 1 and to be an operating factor in progression of spinal deformities. We might hypothesize that putative melatonin deficiency in cases of neurofibromatosis 1 might play a role in the pathogenesis of hyperphosphaturea by decreasing sodium-phosphate cotransport, increasing the level of cAMP, the un-antagonized effect of dopamine on phosphate reabsorption and increasing glucocorticoid levels. Parathyroid overactivity that may occur secondary to osteomalacia might have synergistic effects with dopamine and further exaggerate phosphate loss in urine. On the other hand, excess corticosteroid secretion would decrease nocturnal melatonin level. Moreover, in the presence of hypophosphatemia, hypercortisolism might further inhibit melatonin secretion that might lead to progression of spinal deformities in these cases.

Hypophosphatemia, Familial↗

PubMed2001

Structures of mutagens produced by the co-mutagen norharman with o- and m-toluidine isomers.

Norharman, abundantly present in cigarette smoke and cooked foods, is not mutagenic to Salmonella typhimurium strains. However, norharman shows mutagenicity to S. typhimurium TA98 and YG1024 in the presence of S9 mix when coexisting with aromatic amines, including aniline, o- and m-toluidines. We previously reported that the mutagenicity from norharman and aniline in the presence of S9 mix was due to the formation of a mutagenic compound, 9-(4'-aminophenyl)-9H-pyrido[3,4-b]indole (aminophenylnorharman). In the present study, we analyzed the mutagens produced by norharman with o- or m-toluidine in the presence of S9 mix. When norharman and o-toluidine were reacted at 37 degrees C for 20 min, two mutagenic compounds, which were mutagenic with and without S9 mix, respectively, were produced, and these were isolated by HPLC. The former mutagen was deduced to be 9-(4'-amino-3'-methylphenyl)-9H-pyrido[3,4-b]indole (amino-3'-methylphenylnorharman) on the basis of various spectral data, and this new heterocyclic amine was confirmed by its chemical synthesis. The latter mutagen was identified to be the hydroxyamino derivative. Amino-3'-methylphenylnorharman induced 41,000 revertants of TA98, and 698,000 revertants of YG1024 per microg with S9 mix. Formation of the same DNA adducts was observed in YG1024 when amino-3'-methylphenylnorharman or a mixture of norharman plus o-toluidine was incubated with S9 mix. These observations suggest that norharman reacts with o-toluidine in the presence of S9 mix to produce amino-3'-methylphenylnorharman, and this compound is metabolically activated to yield its hydroxyamino derivative. After activation by O-acetyltransferase, it might bind to DNA and exert mutagenicity in S. typhimurium TA98 and YG1024. When norharman and m-toluidine were reacted in the presence of S9 mix, 9-(4'-amino-2'-methylphenyl)-9H-pyrido[3,4-b]indole (amino-2'-methylphenylnorharman) was identified as a mutagen. Thus, the mutagenicity of norharman with m-toluidine may follow a mechanism similar to that with o-toluidine.

Animals↗

PubMed2001

Phenanthroindolizidine alkaloids as cytotoxic substances in a Danaid butterfly, Ideopsis similis, against human cancer cells.

We previously reported the presence of cytotoxic substances in extracts of the Danaid butterfly, Ideopsis similis. In the present study, we isolated cytotoxic substances against a human gastric cancer cell line, TMK-1, in I. similis pupae, with an activity similar to that of the adult butterfly. The basic fraction, prepared from a methanol extract, accounted for 83% of the cytotoxic activity. Two major cytotoxic substances were purified by HPLC, and one was determined to be a new phenanthroindolizidine alkaloid, trans-(+)-3,14alpha-dihydroxy-6,7-dimethoxyphenanthroindolizidine (1), and the other a known compound, trans-(+)-3,14alpha-dihydroxy-4,6,7-trimethoxyphenanthroindolizidine (2). The IC(50) values for TMK-1 cells were 0.5 ng/mL and 0.7 ng/mL, respectively. These two compounds showed similar cytotoxic potential with four other cancer cell lines including cervical, lung, and colon carcinomas and leukemia. Quantitative analyses indicated the presence of each of the two phenanthroindolizidine alkaloids at levels of 11-74 microg in each larva, pupa, or adult of I. similis. However, 1 was not detected in the leaves of Tylophora tanakae, a host plant for larvae of I. similis, and the level of 2 (2 microg per gram of leaves) was far less than that in the larvae. Since the leaves of T. tanakae are known to contain various phenanthroindolizidines, compounds 1 and 2 are presumably metabolically converted from such alkaloids in larvae of I. similis.

Alkaloids↗

PubMed2001

A new ray-tracing program RIGTRACE for X-ray optical systems.

A new ray-tracing simulation program, RIGTRACE, has been developed specifically for the X-ray optics range. It traces consecutively each ray, following its path from the source to the observation plane, and treats diffraction by a monochromator crystal by adopting the Darwin-Prins theory so that it may be seen how rays of slightly different energies and incident angles reach the plane. It is also possible to treat the case of the laboratory system, in which the optical elements are disposed close to each other. Examples of the application are provided.

Journal Article↗

PubMed2001

Closing-opening wedge osteotomy to correct angular kyphotic deformity by a single posterior approach.

STUDY DESIGN: Seven patients with angular kyphotic deformity of the thoracic or thoracolumbar spine were treated by closing-opening wedge osteotomy using a single posterior approach. OBJECTIVES: To examine the safety and efficacy of closing-opening wedge osteotomy for angular kyphosis. SUMMARY OF BACKGROUND DATA: Correction osteotomy of severe kyphosis is a challenging operation. A two-stage operation has been commonly used: anterior release and decompression followed by posterior correction and fusion. METHODS: Seven patients with angular kyphosis were treated. The apex level of kyphosis was T5 in one patient, T11 in one, and T12 in five. There was old fracture in five patients, congenital deformity in one, and neurofibromatosis in one. The first 30-35 degrees of kyphosis are corrected using the closing wedge technique with the hinge of the anterior longitudinal ligament after veretebrectomy and circumspinal decompression of the spinal cord. Then the hinge is moved posteriorly to the spinal cord and the remainder of the requisit angle of osteotomy is corrected using the opening-wedge technique (closing-opening wedge osteotomy). Spinal curvature is stabilized using posterior instrumentation and graft. RESULTS: Localized kyphosis was reduced from an average of 67 degrees to 18 degrees at 2.2 to 7.5 years' follow-up. Sagittal alignment from T1 to the sacrum became more physiologic than before. There were no neurologic complications. Bony fusion was achieved in all patients, and there was no correction loss. CONCLUSIONS: Satisfactory correction is safely performed by closing-opening wedge osteotomy with a direct visualization of the circumferentially decompressed spinal cord. Although the performance is technically laborious, it offers good correction without jeopardizing the integrity of the spinal cord.

Adult↗

PubMed2001

Surgical strategy for spinal metastases.

STUDY DESIGN: A new surgical strategy for treatment of patients with spinal metastases was designed, and 61 patients were treated based on this strategy. OBJECTIVES: To propose a new surgical strategy for the treatment of patients with spinal metastases. SUMMARY OF BACKGROUND DATA: A preoperative score composed of six parameters has been proposed by Tokuhashi et al for the prognostic assessment of patients with metastases to the spine. Their scoring system was designed for deciding between excisional or palliative procedures. Recently, aggressive surgery, such as total en bloc spondylectomy for spinal metastases, has been advocated for selected patients. Surgical strategies should include various treatments ranging from wide or marginal excision to palliative treatment with hospice care. METHODS: Sixty-seven patients with spinal metastases who had been treated from 1987-1991 were reviewed, and prognostic factors were evaluated retrospectively (phase 1). A new scoring system for spinal metastases that was designed based on these data consists of three prognostic factors: 1) grade of malignancy (slow growth, 1 point; moderate growth, 2 points; rapid growth, 4 points), 2) visceral metastases (no metastasis, 0 points; treatable, 2 points: untreatable, 4 points), and 3) bone metastases (solitary or isolated, 1 point; multiple, 2 points). These three factors were added together to give a prognostic score between 2-10. The treatment goal for each patient was set according to this prognostic score. The strategy for each patient was decided along with the treatment goal: a prognostic score of 2-3 points suggested a wide or marginal excision for long-term local control; 4-5 points indicated marginal or intralesional excision for middle-term local control; 6-7 points justified palliative surgery for short-term palliation; and 8-10 points indicated nonoperative supportive care. Sixty-one patients were treated prospectively according to this surgical strategy between 1993-1996 (phase 2). The extent of the spinal metastases was stratified using the surgical classification of spinal tumors, and technically appropriate and feasible surgery was performed, such as en bloc spondylectomy, piecemeal thorough excision, curettage, or palliative surgery. RESULTS: The mean survival time of the 28 patients treated with wide or marginal excision was 38.2 months (26 had successful local control). The mean survival time of the 13 patients treated with intralesional excision was 21.5 months (nine had successful local control). The mean survival time of the 11 patients treated with palliative surgery and stabilization was 10.1 months (eight had successful local control). The mean survival time of the patients with terminal care was 5.3 months. CONCLUSIONS: A new surgical strategy for spinal metastases based on the prognostic scoring system is proposed. This strategy provides appropriate guidelines for treatment in all patients with spinal metastases.

Adult↗

PubMed2001

Incidence of von Hippel-Lindau disease in hemangioblastoma patients: the University of Tokyo Hospital experience from 1954-1998.

BACKGROUND: Incidence of von Hippel-Lindau disease among hemangioblastomas is important clinical information affecting the management of hemangioblastomas. Studies from Western countries reported 36-40% for the incidence, but no report has been made on the Japanese population. METHOD: To investigate the incidence in Japan, we retrospectively analyzed all hemangioblastoma patients treated at The University of Tokyo Hospital from 1954 to 1998. By reviewing medical records and imaging studies, von Hippel-Lindau disease was diagnosed clinically following the currently suggested diagnostic criteria. FINDINGS: There were 82 hemangioblastoma patients recorded during the period, and 14 cases (17%) were compatible with von Hippel-Lindau disease. However, when the incidence was calculated for each of the three 15-year periods, which are 1954-1968 (first), 1969-1984 (second), and 1985-1998 (third), the number increased dramatically in the later periods: 2 of 33 (6%) during the first, 4 of 26 (15%) during the second, and 8 of 22 (36%) during the third period. Such increase occurred after the introduction of whole body CT to our institution in 1981, suggesting that improvement of imaging techniques contributed to the sensitivity of diagnosis. In addition, one recent patient with multiple hemangioblastomas was found to harbor germline mutation of the VHL, thereby being diagnosed as von Hippel-Lindau disease on the basis of molecular genetics. INTERPRETATION: The 40% incidence of von Hippel-Lindau disease in hemangioblastomas suggests that extensive screening for von Hippel-Lindau disease associated neoplasms, and probably molecular genetic examination, is indicated for all patients with hemangioblastomas, which should aim for earlier diagnosis and better management of this devastating hereditary disease.

Adolescent↗

PubMed2001

Anterior lumbar interbody fusion using two standard cylindrical threaded cages, a single mega-cage, or dual nested cages: a biomechanical comparison.

Our purpose was: (1) to compare the biomechanical properties of an interbody reconstruction using two standard threaded cages (18-mm diameter), a reconstruction using a single mega-cage (24-mm diameter), and a reconstruction using dual nested cages (22-mm diameter); and (2) to quantify the surface area of the cancellous bone bed exposed by reaming for the cages. Each motion segment was tested according to a nondestructive biomechanical loading sequence (compression, flexion, extension, lateral bending, axial torsion). Load was applied first to the intact motion segment and again after the insertion of cages, and stiffness values were calculated at each step. After the testing, each specimen was bisected through the disc and the surface area of the vascular bed was calculated. Comparison of the biomechanical properties of the three reconstructions showed that the dual nested cages produced the stiffest reconstruction. However, when the standard cages were compared with the nested cages, there was no significant difference, and compared with the mega-cage, the only difference was in flexion. The surface area of cancellous bone exposed by reaming for each of the three reconstructions showed the greatest value with the dual nested cages. These findings, together with the improved safety afforded by the nested or mega-cage, suggest that they are appropriate alternatives to the standard dual threaded cage reconstruction.

Aged↗

PubMed2001

The association of neurofibromatosis 1 and spinal deformity with primary hyperparathyroidism and osteomalacia: might melatonin have a role?

A 35-year-old woman with neurofibromatosis 1 and thoracic kyphoscoliosis had incomplete paraplegia. She had a history of hyperparathyroidism due to a parathyroid adenoma which had been excised 4 years previously. Plain radiographs of the spine revealed kyphoscoliosis from the third to sixth thoracic vertebrae. Kyphosis and scoliosis angles were 86 degrees and 28 degrees, respectively. Radiographs of the skull and hands showed radiological changes suggestive of hyperparathyroidism. Laboratory tests showed low-normal serum calcium, hypophosphatemia, elevated serum alkaline phosphatase, and low serum 25-hydroxyvitamin D. Retrospective review of the patient's laboratory data showed that she had osteomalacia at the time of diagnosis of primary hyperparathyroidism. The patient had been treated by anterior and posterior decompression and fusion with posterior instrumentation through a single posterior approach. The postoperative kyphosis and scoliosis angles were 30 degrees and 12 degrees, respectively. Neurological recovery and spinal fusion had been achieved. Osteomalacia responded well to vitamin D therapy. This is the first case of coexisting neurofibromatosis 1, primary hyperparathyroidism due to parathyroid adenoma and osteomalacia to be reported in the literature. The osteomalacia in this patient could be related to primary hyperparathyroidism, and not to neurofibromatosis 1. A drop in melatonin level after parathyroidectomy may have been the cause of spinal curvature progression in this patient.

Adenoma↗

PubMed2001

Tumor growth potential after tumoral and instrumental contamination: an in-vivo comparative study of T-saw, Gigli saw, and scalpel.

In the field of spinal tumors, intralesional tumor cutting is sometimes inevitable. The purpose of this study was to compare the potential for tumor growth after intralesional cutting by T-saw, Gigli saw, and scalpel. Tumors, prepared by the subcutaneous injection of human HT 1080 fibrosarcoma cells in nude mice, were harvested and cut with a T-saw, Gigli saw, or scalpel. A 3-cm wound was created in the skin on the back in another group of nude mice. The cut surface of the tumor was rubbed for 10 s against the subcutaneous tissue in this second group of nude mice. In the same manner, the instrument used for tumor cutting was rubbed against the subcutaneous tissue in the 3-cm wound in the back of a third group of nude mice for 10 s. Other instruments used for tumor cutting were immediately washed in culture medium, and the total number of tumor cells was counted. Tumor blocks and single-cell suspensions prepared from tumor tissues of the same weight were inoculated and injected into a fourth group of nude mice. The incidence of tumor growth after the rubbing of the subcutaneous tissue with the tumor surface cut with a T-saw, Gigli saw, and scalpel was 16.7%, 50.0%, and 33.3%, respectively. The corresponding figures after the rubbing of the subcutaneous tissue with a T-saw, Gigli saw, and scalpel was 16.7%, 33.3%, and 33.3%, respectively. The mean numbers of tumor cells attached to the T-saw, Gigli saw, and scalpel were 1.88 x 105, 5.02 x 105, and 4.92 x 105, respectively. Finally, the incidence of tumor growth after the inoculation of tumor blocks and single-cell suspensions was 100% and 77.8%, respectively. These findings show that tumor recurrence is less likely after intralesional tumor cutting with a T-saw than after such cutting with a Gigli saw or scalpel.

Animals↗

PubMed2001

Bacopaside I and II: two pseudojujubogenin glycosides from Bacopa monniera.

Two saponins, designated as bacopaside I and II, have been isolated from Bacopa monniera Wettst. and their structures have been elucidated as 3-O-alpha-L-arabinofuranosyl-(1-->2)-[6-O-sulphonyl-beta-D-glucopyranosyl-(1-->3)]-alpha-L-arabinopyranosyl pseudojujubogenin (1) and 3-O-alpha-L-arabinofuranosyl-(1-->2)-[beta-D-glucopyranosyl (1-->3)]-beta-D-glucopyranosyl pseudojujubogenin (2) mainly on the basis of 2D NMR and other spectral analyses.

Bufanolides↗

PubMed2001

Aetiology of spinal deformities in neurofibromatosis 1: new hypotheses.

Neurofibromatosis 1 is a common heritable disorder. The gene causing neurofibromatosis 1 had been recognized and the protein encoded by this gene, neurofibromin, was supposed to play a role in development of various tissues. Neurofibromin was found to have GTP-ase (GAP) domain against small p21 ras. IQGAP1 is another human ras-specific GAP that was found to have calmodulin-binding motifs. Spinal deformities in cases of neurofibromatosis 1 are generally classified into dystrophic and non-dystrophic. Aetiologies of both types are still unknown. We hypothesize that muscle pathology could be the initiating factor for non-dystrophic curves due to neurofibromin deficiency and/or increase of the level of IQGAP. Dystrophic curves might begin as a developmental error due to neurofibromin deficiency in bone. Melatonin deficiency, increased serotonin level with disturbed melatonin-serotonin interactions and calmodulin antagonism by increased IQGAP1 may be responsible for progression of both types of spinal deformities in neurofibromatosis 1.

Calmodulin↗

PubMed2001

Total en bloc spondylectomy.

We have developed a surgical technique of total en bloc spondylectomy (TES) through a posterior approach applied to solitary metastatic vertebral tumors. Our TES is a radical en bloc resection of a whole vertebra in two parts with an oncological wide margin to obtain local curability. It consists of two steps: (1) en bloc laminectomy and setting of posterior spinal instrumentation for stabilization and (2) en bloc corpectomy and replacement by a vertebral prosthesis. We have performed this procedure in 72 patients with malignant vertebral tumors. Three of these 72 patients had local recurrence. TES is the most radical method for malignant spinal tumors.

Humans↗