Biomedical subjects

K Tsuchiya

Publications and source records attributed to K Tsuchiya.

At least 163 records · Page 9Linked to original sources

PubMed1999

Over-expression of GAPDH induces apoptosis in COS-7 cells transfected with cloned GAPDH cDNAs.

The cDNAs for glyceraldehyde-3-phosphate dehydrogenase (GAPDH; EC 1.2.1.12) were cloned from cerebellar neurons undergoing age-induced apoptosis and/or healthy cells. COS-7 cells were transfected with the isolated GAPDH cDNAs using to the Lipofectamine method. Assessment of cell death in this paradigm was performed by monitoring the co-transfected luciferase activities and the characterization of cell death was examined by the DNA fragmentation assay and Hoechst dye nuclear staining. These observations show that over-expression of GAPDH occurring from both cDNAs robustly induces apoptotic death in the transfected COS-7 cell cultures. Confocal-immunocytochemical studies using this GAPDH-specific monoclonal antibody revealed that nuclear translocation of overexpressed GAPDH is a primary apoptotic event. Our results directly demonstrate that over-expressed GAPDH functions as a 'killing protein' in apoptosis.

Animals↗

PubMed1999

Cytological, genetic and evolutionary functions of chiasmata based on chiasma graph analysis.

The nature of the chiasma as a cytological parameter for analysing cross-over was reexamined quantitatively by an improved chiasma graph method. It was reconfirmed in Mus platythrix (n =13) that interstitial chiasmata at diakinesis are distributed randomly and almost uniformly along bivalents except for the centromere and telomere regions. The size of these chiasma blank regions was consistently 0.8% of the total length of haploid autosomes in all chromosomes. There was a minimum value of chiasma interference distance between two adjacent chiasmata, which was constantly 1.8% in all chromosomes. The chiasma frequency at diakinesis was 20.1+/-2. 0 by the conventional method including terminal chiasmata. However, the primed in situ labeling technique revealed that terminal chiasmata were mostly telomere-telomere associations. From these data and also from recent molecular data we concluded that the terminal chiasma is cytologically functional for ensuring the normal disjunction of bivalents at anaphase I, but genetically non-functional for shuffling genes. The chiasma frequency excluding terminal chiasmata was 14.6+/-1.8. Reexamination of the chiasma frequency of 106 animal species revealed that the chiasma frequency increased linearly in proportion to the haploid chromosome number in spite of remarkable difference in their genome size. The increase in chiasma frequency would be evolution-adaptive, because gene shuffling is expected to be accelerated in species with high chromosome numbers.

Animals↗

PubMed1999

A synthetic inhibitor of histone deacetylase, MS-27-275, with marked in vivo antitumor activity against human tumors.

Synthetic benzamide derivatives were investigated for their ability to inhibit histone deacetylase (HDA). In this study, one of the most active benzamide derivatives, MS-27-275, was examined with regard to its biological properties and antitumor efficacy. MS-27-275 inhibited partially purified human HDA and caused hyperacetylation of nuclear histones in various tumor cell lines. It behaved in a manner similar to other HDA inhibitors, such as sodium butyrate and trichostatin A; MS-27-275 induced p21(WAF1/CIP1) and gelsolin and changed the cell cycle distribution, decrease of S-phase cells, and increase of G1-phase cells. The in vitro sensitivity spectrum of MS-27-275 against various human tumor cell lines showed a pattern different than that of a commonly used antitumor agent, 5-fluorouracil, and, of interest, the accumulation of p21(WAF1/CIP1) tended to be faster and greater in the cell lines sensitive to MS-27-275. MS-27-275 administered orally strongly inhibited the growth in seven of eight tumor lines implanted into nude mice, although most of these did not respond to 5-fluorouracil. A structurally analogous compound to MS-27-275 without HDA-inhibiting activity showed neither the biological effects in cell culture nor the in vivo therapeutic efficacy. These results suggest that MS-27-275 acts as an antitumor agent through HDA inhibition and may provide a novel chemotherapeutic strategy for cancers insensitive to traditional antitumor agents.

Animals↗

PubMed1999

A novel type of non-coding RNA expressed in the rat brain.

We have characterized a novel type of non-coding RNA which consists of tandem repeats of similar sequences, approximately 0.9 kb in size. This RNA, termed Bsr (brain specific repetitive) RNA, is encoded at a single locus (6 q31-->q32) in the rat genome, where 100 to 150 copies of the 0.9 kb sequences are repeated in tandem. Bsr RNA is preferentially expressed in the rat central nervous system (CNS), especially in phylogenetically old structures, such as the pareo- and archicortex, amygdala, thalamus and hypothalamus. In the developing brains, Bsr RNA is expressed in the subsets of differentiating cells but not in proliferating cells. Despite the finding that Bsr RNA appears to be conserved only among the Rattus species, the specific expression pattern of Bsr RNA suggests that it might have some role in the rat CNS.

Animals↗

PubMed1999

Sporadic amyotrophic lateral sclerosis of long duration mimicking spinal progressive muscular atrophy: a clinicopathological study.

We report an autopsy case of amyotrophic lateral sclerosis (ALS) clinically diagnosed as spinal progressive muscular atrophy (SPMA). The patient was a Japanese woman without hereditary burden. She developed muscle weakness of the distal part of the left lower extremity at age 42, followed by muscle weakness and atrophy of the right lower extremity and upper extremities. At age 57, she needed transient ventilatory support. Slight weakness in the facial muscles and fasciculation of the tongue appeared at age 60. At age 61, she died of sudden respiratory arrest. During the clinical course, neurological examination revealed neither Babinski signs nor hyperreflexia. The neuropathological examination revealed not only neuronal loss with gliosis in the facial nucleus, hypoglossal nucleus, and anterior horns of the spinal cord, but also loss of Betz cells and degeneration of the pyramidal tracts. Based on these clinicopathological findings and review of literature, we conclude that sporadic ALS mimicking SPMA is present.

Amyotrophic Lateral Sclerosis↗

PubMed1999

Argyrophilic glial inclusions in the midbrain of patients with Parkinson's disease and diffuse Lewy body disease are immunopositive for NACP/alpha-synuclein.

Argyrophilic glial inclusions occur in the midbrain of patients with Parkinson's disease (PD) and diffuse Lewy body disease (DLBD). These inclusions are immunohistochemically positive for NACP/alpha-synuclein but negative for tau protein. The results of the present study suggest that a primary degenerative process involves NACP/alpha-synuclein in PD and DLBD and that the process takes place not only in neurons but also in glial cells. Argyrophilic cytoplasmic inclusions, both glial and neuronal, in a variety of degenerative diseases may be grouped into two major categories; one related to aggregates of abnormally phosphorylated tau protein and the other to unusual accumulations of NACP/alpha-synuclein.

Aged↗

PubMed1999

Lymphangioma presenting as a dumbbell tumor in the epidural space of the lumbar spine.

STUDY DESIGN: A case report. OBJECTIVES: To report and discuss a case of lymphangioma presenting as a dumbbell-shaped tumor in the epidural space of the lumbar spine. SUMMARY OF BACKGROUND DATA: Dumbbell tumor of the spine is not uncommon. Although the pathogenesis of such tumors varies widely, lymphangioma has not been reported previously, to these authors' knowledge. METHODS: A 56-year-old woman with pain in the lower back and left leg was examined by plain radiographs and magnetic resonance imaging before surgery. Treatment consisted of the usual technique of surgical resection of the tumor. Histopathologic study of the resected material confirmed the diagnosis. Postoperative follow-up assessment was performed by magnetic resonance imaging. RESULTS: Magnetic resonance imaging demonstrated a dumbbell tumor in the epidural canal area of the lumbar spine. Histopathologic diagnosis of the resected tumor was cavernous lymphangioma. CONCLUSION: To the authors' knowledge, this is the first reported case of lymphangioma presenting as a spinal dumbbell tumor. Further observation is recommended because of the possibility of local recurrence.

Diagnosis, Differential↗

PubMed1999

Requirement of sperm-oocyte plasma membrane fusion for establishment of the plasma membrane block to polyspermy in human pronuclear oocytes.

We investigated whether the incorporation of the sperm membrane into the oolemma contributes to the human plasma membrane block to polyspermy. We used zona pellucida-free oocytes fertilized by intracytoplasmic sperm injection (ICSI) or activated by parthenogenetic activation. Only two of the 35 pronuclear oocytes fertilized by spermatozoa (control) demonstrated one single penetrating spermatozoa. In contrast, the majority of ICSI and parthenogenetically activated pronuclear oocytes were penetrated with an average of three spermatozoa per oocyte. The number of fused and binding spermatozoa of ICSI and parthenogenetically activated oocytes were significantly higher than in control oocytes (3.5+/-0.6 and 4.3+/-0.6 for ICSI; 3.0+/-0.3 and 3.8+/-0.4 for activated and 0.2+/-0.1 and 0.6+/-0.2 for controls, respectively, P < 0.01). Furthermore, the cortical granules were released from the cortex of ICSI and calcium ionophore-puromycin-activated pronuclear oocytes to the same extent as that of pronuclear oocytes fertilized by spermatozoa. These results suggest that the establishment of the plasma membrane block to sperm penetration in the human oocyte may require a fusion process between sperm and oocyte plasma membranes.

Cell Membrane↗

PubMed1999

Postictal blockade of ischemic hippocampal neuronal death in primates using selective cathepsin inhibitors.

This paper is to study the participation of cathepsin in ischemic neuronal death of the monkey hippocampal cornu ammonis (CA) 1 sector and also to clarify whether its selective inhibitor epoxysuccinyl peptides such as CA-074 and E-64c can inhibit the neuronal death or not. In the preceding reports, we demonstrated mu-calpain activation and subsequent rupturing of the lysosomal membrane of postischemic CA1 neurons and also increase of enzyme activity of cathepsins B and L in monkeys undergoing a complete 20-min whole brain ischemia. Here, morphological, immunohistochemical and enzymatical analyses were performed to examine the efficacy of two selective cathepsin inhibitors in the postictal blockade of delayed neuronal death in the monkey hippocampus. Both inhibitors could significantly decrease enzyme activities of cathepsins B and L in all hippocampal sectors. When CA-074 was intravenously administered immediately after the ischemic insult, approximately 67% of CA1 neurons were saved from delayed neuronal death on day 5 after ischemia. In contrast, when E-64c was similarly administered, approximately 84% of CA1 neurons were saved from delayed neuronal death on day 5. The surviving neurons showed mild central chromatolysis and negligible immunoreactivity for cathepsins B and L. These observations indicate that the use of cathepsin inhibitors may become novel strategy for prevention of ischemic delayed neuronal death in the primate hippocampus.

Animals↗

PubMed1999

Saccular descending thoracic aortic aneurysm with dysphagia.

A 76 year old woman had suffered from chest pain, back pain, and dysphagia for 8 months. She was diagnosed as having a thoracic aortic aneurysm by chest X-ray and chest enhanced computed tomography. Simultaneously, severe dysphagia developed. Chest enhanced computed tomography and chest aortic aortography at our hospital demonstrated a saccular descending thoracic aortic aneurysm. Esophagography demonstrated that the esophagus was compressed by the aneurysm; therefore, a graft replacement for the saccular descending thoracic aortic aneurysm was performed on February 17th, 1998. A left sided 6th intercostal approach was made, and graft replacement for the aneurysm using a 22 mm Hemashield prosthetic graft was performed under temporary bypass from the thoracic aorta just distal to the left subclavian artery and to the left femoral artery. The postoperative course was uneventful, the severe dysphagia improved dramatically, but a pleural effusion of 1000 ml collected 3 weeks after the operation. Surgical cases of saccular descending thoracic aortic aneurysm with dysphagia are rare, and with this in mind, we report this case to the the medical literature.

Aged↗

PubMed1999

A new MRI technique for demonstrating the surface of the brain together with the cortical veins.

We assessed combining of surface-anatomy scanning (SAS) MRI and MR venography (MRV). We obtained SAS images with a half-Fourier single-shot fast spin-echo sequence, then MRV of the identical section with a two-dimensional phase-contrast technique. We then added the two sets of images. The combined images, which were obtained within 10 min, provided information about the surface anatomy and cortical veins. This simple technique is useful for demonstrating brain surface structures, especially in patients from whom one plans to excise a lesion.

Adult↗

PubMed1999

MELAS with prominent white matter gliosis and atrophy of the cerebellar granular layer: a clinical, genetic, and pathological study.

This report concerns an autopsy case of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) with unusual neuropathological findings. The patient was a Japanese woman who was 21 years old at the time of death. Her mother is a patient with genetically confirmed MELAS. Her clinical manifestations included convulsions and lactic acidosis in the latter half of the first decade of life, followed by deafness, dementia, muscle weakness in the lower extremities, slight ataxia in the upper and lower extremities, and diabetes mellitus. Muscle biopsy revealed ragged-red fibers, and genetic study showed a point mutation at nucleotide pair 3243 in mitochondrial DNA. She died of lactic acidosis. In the clinical course, she did not develop stroke-like episodes. The neuropathological examination revealed not only minute to small necrotic foci in the cerebral cortex, amygdala, hippocampus, and cerebellum, but also prominent white matter gliosis in the central nervous system and cerebellar cortical degeneration of granular cell type. Our neuropathological findings, including prominent white matter gliosis of the central nervous system and cerebellar cortical degeneration of granular cell type, may indicate morphologically widespread cellular dysfunction, not restricted to either neuronal or vascular derangement, in the brain pathology of MELAS.

Adult↗

PubMed1999

Glial expression of presenilin epitopes in human brain with cerebral infarction and in astrocytoma.

Presenilins, some gene mutations of which are associated with familial Alzheimer's disease (AD), are expressed mainly in neurons in normal brains and brains from patients clinicopathologically diagnosed as AD. They are thought to be related to cell death and survival. We studied the immunolocalization of presenilin to investigate its possible relation to cell death and glial proliferation, using two antibodies against different portions of the presenilin 1 protein, in human brains with cerebral infarction and in astrocytoma, where abundant cell death and glial proliferation are present. Expression of presenilin epitopes was more marked in glial cells than in neurons in and around the ischemic focus, and it was also robust in astrocytoma cells. These findings suggest that presenilins are functioning not only in neurons but also in glial cells in reactive and neoplastic proliferation.

Aged↗

PubMed1999

Sporadic amyotrophic lateral sclerosis with multiple system degeneration: a report of an autopsy case without respirator administration.

This report concerns an autopsy case of amyotrophic lateral sclerosis (ALS) with unusual clinical and neuropathological findings. The patient was a Japanese man without hereditary burden who was 49 years old at the time of death. His clinical manifestation included dysarthria at age 48, followed by dysphagia, atrophy and fasciculation of the tongue, muscle weakness in the four extremities, tremor, rigidity, increased deep tendon reflexes in the upper and lower extremities, and incoordination of the four extremities. He died of respiratory failure 12 months after the disease onset. No respirator administration was performed throughout the clinical course. The neuropathological examination revealed not only degeneration of upper and lower motor neuron systems, including the presence of Bunina bodies and ubiquitin-immunoreactive neuronal inclusions in the lower motor neurons, but also prominent degeneration of the substantia nigra and dentate nucleus with slight neuronal loss in the locus ceruleus and pontine nucleus. To our knowledge, this is the first reported case of sporadic ALS without dementia and respirator support, showing degeneration of the substantia nigra and dentate nucleus. This report may contribute to the resolution of the question concerning the neuropathological heterogeneity of sporadic ALS with respiratory support.

Amyotrophic Lateral Sclerosis↗

PubMed1999

Three-dimensional movement of a liver tumor detected by high-speed magnetic resonance imaging.

OBJECTIVE: Three-dimensional (3D) movement of a spherical liver tumor during respiration was investigated with magnetic resonance imaging (MRI) using a high-speed sequence. METHODS: A marker was placed on the surface of the patient as a reference of distance. Repetition time (TR) was 7.7 ms, echo time (TE) was 4.2 ms, flip angle was 20 degrees, section thickness was 8 mm, and a 256 x 128 matrix was used. The acquisition time was 1.0 s followed by an interval of 0.5 s. The 20 tumor contours extracted during 30 s were superimposed on sagittal and coronal MR images. RESULTS: The maximum value of tumor edge location was 3.9 cm in the cranio-caudal direction, 2.3 cm in the ventro-dorsal direction, and 3.1 cm in the lateral direction. The mean length of tumor displacement observed was 2.1 cm in the cranio-caudal direction, 0.8 cm in the ventro-dorsal and 0.9 cm in the left-right direction, respectively. The locus of the center of the tumor contour in the sagittal cross section was inclined at 23 degrees and in the coronal cross section was inclined at 18 degrees to the cranio-caudal axis of body. CONCLUSION: In conclusion, 3D movement of a spherical liver tumor was detected using rapid MRI sequential examinations. Magnetic resonance imaging has a potential to improve the accuracy of the planning target volume of a liver tumor.

Humans↗

PubMed1999

Effects of the benzodiazepine antagonist flumazenil on conditioned fear stress in rats.

1. The authors investigated the effect of the benzodiazepine receptor antagonist flumazenil on freezing behavior induced by conditioned fear stress and used a time-sampling procedure. 2. Rats were individually subjected to 5 min of inescapable electric footshock in a shock chamber. Twenty-four hours after the footshock, the rats were again placed in the shock chamber and observed for 5 min without shocks: this procedure is termed conditioned fear stress. 3. Subcutaneous administration of flumazenil (10 mg/kg) 30 min before conditioned fear stress reduced conditioned freezing, while flumazenil (1-10 mg/kg) 30 min before footshock did not. This indicates that flumazenil reduced the expression of conditioned fear, suggesting an anxiolytic effect of flumazenil. 4. This effect may be attributable to antagonism by flumazenil to endogenous inverse agonist-like ligands for benzodiazepine receptors. It is suggested that endogenous inverse agonist-like ligands for benzodiazepine receptors are involved in the expression of conditioned fear stress.

Animals↗

PubMed1999

High magnetic field enhances stationary phase-specific transcription activity of Escherichia coli.

When Escherichia coli B was aerobically grown at 37 degrees C under inhomogeneous 5.2-6.1 Tesla (T) magnetic fields in the superconducting magnet biosystem (SBS), the cell number in the stationary phase after the growth had leveled off, was about 3 times higher than that under a geomagnetic field. When the E. coli defective in the rpoS gene which encodes a sigma factor, sigmaS of RNA polymerase and is specifically expressed in the stationary phase was cultivated at 37 degrees C in SBS, such enhancement of cell survival was significantly reduced. The E. coli cells carrying rpoS-lacZ fusion gene or other rpoS dependent genes fused with lacZ were grown, significant increase in the activity of beta-galactosidase was observed in the stationary phase under high magnetic field. These data suggest that enhancement of the transcription activity in stationary phase is involved in the higher survival of the cells under magnetic field.

Bacterial Proteins↗

PubMed1999

Diffusion-weighted MR imaging in multiple sclerosis: comparison with contrast-enhanced study.

OBJECTIVE: To assess the utility of cerebral diffusion-weighted MR imaging in the diagnosis of multiple sclerosis (MS) in comparison with contrast-enhanced T1-weighted imaging. METHODS AND MATERIALS: We reviewed T2-weighted spin-echo (SE), fluid-attenuated inversion-recovery (FLAIR), contrast-enhanced T1-weighted SE and echo-planar diffusion-weighted images (DWIs) obtained in seven patients with definite MS on nine occasions. RESULTS: In total, 94 plaques were demonstrated on T2-weighted SE and/or FLAIR images. A total of 13 of these plaques showed enhancement on contrast-enhanced T1-weighted images and hyperintensity on DWIs, and five non-enhancing plaques showed hyperintensity on DWIs. CONCLUSION: Diffusion-weighted imaging, which provides information based on pathophysiology different from contrast-enhanced imaging, is a potential supplementary technique for characterizing MS plaques.

Adult↗