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N Hashimoto

Publications and source records attributed to N Hashimoto.

At least 181 records · Page 10Linked to original sources
PubMed1999

[A case of systemic lupus erythematosus associated with thrombotic thrombocytopenic purpura manifestating homonymous hemianopsia].

We report on a 35-year-old Japanese woman with systemic lupus erythematosus (SLE) in whom homonymous hemianopsia developed. In August 1987, SLE was diagnosed. In November 1987, the patient was admitted to our hospital because of severe thrombotic thrombocytopenic purpura; however, clinical symptoms improved after treatment with vincristine. In 1992, severe lupus nephritis developed but improved after steroid therapy. In February 1994, diplopia developed owing to inflammatory invasion of the orbit by acute maxillary sinusitis. Humphrey Field Analyzer perimetry revealed a homonymous quadrantic hemianopic scotoma in the lower left side. Magnetic resonance imaging of the brain revealed a small infarct lesion in the posterior pole of the upper calcarine cortex. This lesion was thought to be responsible for homonymous hemianopsia. However, the lesion was not visualized with computed tomography. Our experience in the present case suggests that magnetic resonance imaging is more useful than computed tomography for identifying lesion causing visual field disorders in SLE.

Adult↗
PubMed1999

Modification of beta 2-microglobulin with D-glucose or 3-deoxyglucosone inhibits A beta 2M amyloid fibril extension in vitro.

beta 2-microglobulin (beta 2M) is a major constituent of amyloid fibrils (fA beta 2M) deposited in patients with A beta 2M amyloidosis. Recently, advanced glycation end products (AGE) of beta 2M and fA beta 2M have been suggested to play an important role in the pathogenesis of A beta 2M amyloidosis. We first characterized the states of AGE modification of fA beta 2M. Western blot analysis with a monoclonal anti-AGE antibody showed that purified fA beta 2M was naturally modified with AGE. Immunohistochemical studies of amyloid-deposited tissue have revealed a patchy distribution of the AGE-modified area in the amyloid deposits. Then we modified beta 2-m either with D-glucose or with 3-deoxyglucosone (3-DG) and investigated the effect of these modification on fA beta 2M extension in vitro, using the recently established first-order kinetic model of fA beta 2M extension in vitro. Western blot analysis and enzyme linked immunosorbent assay with a monoclonal anti-AGE antibody showed that these sugar-modified beta 2M contained AGE. During the incubation of fA beta 2M with native beta 2-m at 37 degrees C, the fluorescence of thioflavin T increased without a lag phase and proceeded to equilibrium. On the contrary, only a slight increase in fluorescence was observed during the incubation of fA beta 2M with sugar-modified beta 2M. Moreover, sugar-modified beta 2M exhibited a dose-dependent inhibitory effect on the extension reaction of fA beta 2M with native beta 2M. These results may suggest that in some in vivo situations, the modification of beta 2-m with AGE could play an inhibitory role for the formation of fA beta 2M.

Amyloid↗
PubMed1999

Skull bone regeneration in primates in response to basic fibroblast growth factor.

OBJECT: The feasibility of using a biodegradable hydrogel incorporating basic fibroblast growth factor (bFGF) to induce bone regeneration at the site of a skull defect in monkeys was investigated. METHODS: Basic fibroblast growth factor was incorporated into a bioabsorbable hydrogel, which was prepared through glutaraldehyde crosslinking of gelatin. Following treatment of monkey skull defects measuring 6 mm in diameter (six defects/experimental group) with gelatin hydrogel incorporating bFGF, skull bone regeneration was evaluated using soft x-ray studies, dual x-ray absorptometry, and histological examinations. The water content of the hydrogels varied according to the glutaraldehyde concentration in the hydrogel preparation. Gelatin hydrogels incorporating 100 microg of bFGF significantly promoted bone regeneration and the skull defect was completely closed 21 weeks after implantation. This is in marked contrast with the effect of the same dose of bFGF in solution form. Bone mineral density (BMD) measured at the sites of skull defect was enhanced by the bFGF-incorporating hydrogels. The BMD enhancement was more prominent at lower water contents of hydrogel. Empty gelatin hydrogels neither induced nor interfered with skull bone regeneration. CONCLUSIONS: The findings of this study indicate that bFGF coupled with bioabsorbable hydrogel is a very promising tool to assist in the regrowth of bone at the site of a skull defect, which clinically has been recognized as almost impossible.

Absorptiometry, Photon↗
PubMed1999

Decreased tissue distribution of L-carnitine in juvenile visceral steatosis mice.

We kinetically analyzed the disposition of L-carnitine of juvenile visceral steatosis (JVS) mice compared with that of normal mice to elucidate the mechanism of the systemic L-carnitine deficiency of JVS mice. There were significant differences in the plasma concentration-time course of total radioactive carnitine (L-[3H]carnitine, [acetyl-3H]carnitine, and other [acyl-3H]carnitines) between normal and JVS mice after a single i.v. or p.o. administration of L-[3H]carnitine (250 ng/kg). The oral bioavailability of L-[3H]carnitine in JVS mice (0.341) was about half of that in normal mice (0.675). The cumulative urinary excretion of total radioactive carnitine in JVS mice was about 10-fold more than that in normal mice, and the total clearance of unchanged L-[3H]carnitine for JVS mice (6.70 ml/min) was significantly higher than that for normal mice (2.45 ml/min). The distribution volume at the steady state of unchanged L-[3H]carnitine in JVS mice (1.10 liters/kg) was significantly smaller than that in normal mice (8.16 liters/kg). At 4 h after an i.v. administration, the apparent tissue-to-plasma concentration ratios of unchanged L-[3H]carnitine for various tissues of JVS mice, except for brain, were about one half to one 20th of those in normal mice. In conclusion, this in vivo disposition kinetic study of L-carnitine supports the previous in vitro finding that the L-carnitine transporter is absent or functionally deficient in JVS mice because the renal reabsorption, the intestinal absorption, and the apparent tissue-to-plasma concentration ratios in JVS mice are significantly lower than those in normal mice. The JVS mouse should be a useful experimental model for studying carnitine deficiency diseases.

Animals↗
PubMed1999

[Relationship between identified patient (IP) with alcoholic problems and familial factors: in reference to family function, co-dependence, family group and self-help group participation].

In 1994, a survey was conducted to 105 wives of alcoholics (identified patient: IP) about levels of their family adaptability, cohesion, co-dependence, family group and self-help group participation. In 1995, a follow-up survey was conducted to the same wives. 87 wives responded to the follow-up questionnaire. 17 responses were excluded due to too many missing responses. Statistical analyses were therefore conducted to the remaining 70 subjects. The following results were found. 1) Balanced as opposed to extreme levels of cohesion were associated with abstinence. 2) Family system changes on cohesion and/or adaptability dimensions were associated with abstinence. 3) Wife's over-involvement with drinking husband somewhat appeared to be related to continuation of drinking. As for participation in family group or self-help groups, there was no significant difference between abstinence and drinking groups.

Alcoholics Anonymous↗
PubMed1999

Intraoperative extracorporeal autogenous irradiated bone grafts in tumor surgery.

There are several procedures for reconstruction of bony defects after resection of malignant musculoskeletal tumors. The clinical results of intraoperative extracorporeal autogenous irradiated bone grafts in 20 patients with musculoskeletal tumors are discussed. The authors' method of treatment consists of: (1) wide en bloc resection of the tumor with involved bone; (2) curettage of the tumor from the resected bone; (3) extracorporeal irradiation with 50 Gy as a bolus single dose to the isolated bone; and (4) reimplantation of the irradiated bone into the host with fixation devices. Twelve bone sarcomas and eight soft tissue sarcomas with bone involvement were treated surgically with this reconstruction method after wide resection of the tumors. The irradiated bone was used as an intercalary graft in seven cases, as an osteoarticular graft in 11 cases, and as a hemicortical graft in two cases. The theoretical advantages of this method are certain sterilization of tumor cells with radiation, easy availability and good adaptation of size and shape, no risk of disease transmission, preservation of bone stock and ligamentous tissue, and no immunologic reaction. Radiologically, bony union occurred in 23 of 29 (79%) osteotomy sites. The overall radiographic evaluation rating was 74% and the functional rating was 73% according to the International Society of Limb Salvage rating system. Nonunion (20%) and infection (15%) were the two major complications. Preservation of the tendon insertions and ligamentous structures of the irradiated bone seemed to restore excellent joint function. No local recurrence was detected from the irradiated bones during the mean followup of 45 months. These results indicate intraoperative extracorporeal irradiated bone graft can be a widely applicable method for reconstruction in tumor surgery.

Adolescent↗
PubMed1998

High-affinity arginine transport of bovine aortic endothelial cells is impaired by lysophosphatidylcholine.

The mechanisms of endothelial dysfunction characterized by the impaired nitric oxide (NO) release have not yet been clarified. Because the phenomenon is mimicked in vitro by the application of oxidized LDL and its major lipid constituent, lysophosphatidylcholine (LPC), we analyzed their effects on the arginine-NO system, especially on the arginine transport system. LPC inhibited NO release induced by ADP in cultured bovine aortic endothelial cells. The inhibition was attenuated by the excess amount of extracellular arginine. LPC was found to inhibit the arginine transport in bovine aortic endothelial cells, which is mediated by high- and low-affinity components. LPC predominantly impaired the high-affinity component. In the presence of a high concentration of arginine, LPC showed apparently no inhibition of arginine transport, because the low-affinity transporter compensated for the activity. Taken together, the impairment of the high-affinity transport system might account for the inhibition of NO release by LPC. LPC also inhibited arginine transport in the intima of intact bovine aorta. Furthermore, LPC inhibited the activity of the high-affinity arginine transporter in endothelial cells, in the cationic amino acid transporter-1 expressed in COS-7 cells. The activity of cationic amino acid transporter-1 might be important for the prevention of endothelial dysfunction.

Adenosine Diphosphate↗
PubMed1998

Cortactin associates with the cell-cell junction protein ZO-1 in both Drosophila and mouse.

Cortactin is an actin filament-binding protein localizing at cortical regions of cells and a prominent substrate for Src family protein-tyrosine kinases in response to multiple extracellular stimuli. Human cortactin has been identified as a protein product of a putative oncogene, EMS1. In this report, we describe the identification of a Drosophila homolog of cortactin as a molecule that interacts with Drosophila ZO-1 using yeast two-hybrid screening. Drosophila cortactin is a 559-amino acid protein highly expressed in embryos, larvae, and pupae but relatively underexpressed in adult flies. Deletion and substitution mutant analyses revealed that the SH3 domain of Drosophila cortactin binds to a PXXP motif in the proline-rich domain of Drosophila ZO-1. Colocalization of these proteins at cell-cell junction sites was evident under a confocal laser-scanning microscope. In vivo association was confirmed by coimmunoprecipitation of cortactin and ZO-1 from Drosophila embryo lysates. We also demonstrate an association for each of the murine homologs by immunoprecipitation analyses of mouse tissue lysates. Our previous work has demonstrated the involvement of ZO-1 in a signaling pathway that regulates expression of the emc gene in Drosophila. The potential roles of the cortactin.ZO-1 complex in cell adhesion and cell signaling are discussed.

Amino Acid Sequence↗
PubMed1998

An early stage mechanism of the age-associated mitochondrial dysfunction in the brain of SAMP8 mice; an age-associated neurodegeneration animal model.

In order to characterize the early stage of mitochondrial dysfunction, we investigated the redox state and oxidative phosphorylation of the brain mitochondria from 2-month-old Senescence-accelerated mouse (SAM)P8 and SAMR1 mice; SAMP8 mice exhibit various signs of age-associated neurodegeneration and rapid mitochondrial dysfunction, although SAMR1 mice do not. The redox state was estimated as the reduction rate of Cu-pyruvaldehyde-bis (N4-methylthiosemicarbazone) (Cu-PTSM), the reduction of which is closely related to the electron leakage from the mitochondrial electron transport system in the brain, using electron spin resonance spectrometry (ESRS). The oxidative phosphorylation was measured polarographically. The SAMP8 mouse brain mitochondria demonstrated higher redox state and a higher activity of mitochondrial respiration with lower respiration control ratio than the mitochondria of SAMR1 mouse brains. This indicates that an inefficient hyperactive state can exist in the mitochondrial electron transport system before the age-associated mitochondrial dysfunction develops.

Aging↗
PubMed1998

Expression and distribution of redox regulatory protein, thioredoxin during transient focal brain ischemia in the rat.

We assayed redox regulatory protein, thioredoxin (TRX) and TRX mRNA in the rat brain after transient and permanent middle cerebral artery (MCA) occlusion. The immunoreactivity for TRX and TRX mRNA disappeared after MCA occlusion in the ischemic core regions. On the other hand, in the perifocal ischemic regions, TRX immunoreactivity and TRX mRNA was enhanced. In addition, in transient MCA occlusion, TRX induction was stronger in the hippocampus and more widespread in the contralateral cortex than in permanent occlusion. Moreover, the induced TRX was translocated into the cellular nucleus after ischemia and ischemia-reperfusion. These results suggest that TRX induction was accompanied with reactive oxygen intermediates (ROI) overproduction and may play an important role not only in scavenging ROI but also in signal transduction during ischemia.

Animals↗
PubMed1998

Loss of material from chromosome arm 1p during malignant progression of meningioma revealed by fluorescent in situ hybridization.

BACKGROUND: Atypical and anaplastic meningiomas tend to recur and to invade adjacent brain, bone, and skin. They also can metastasize to extracranial organs such as the lung, liver, or bone, causing death. Recent reports have indicated that allelic deletion of chromosome 1p is associated with malignant progression of meningiomas. METHODS: Cytogenetic analysis of 37 meningiomas was performed using double-target fluorescent in situ hybridization (FISH) and focusing on chromosome arm 1p. The meningioma series included 17 benign meningiomas, 11 atypical meningiomas, and 9 anaplastic meningiomas. FISH was performed with pericentromeric (1q12) and subtelomeric (1p36) DNA probes to cell nuclei prepared from surgically extirpated tumor samples. RESULTS: A high incidence of deletion of at least part of 1p was observed in 60.0% of atypical and 85.7% of anaplastic meningiomas. Furthermore, statistically significant differences were found with respect to these data between benign versus atypical/anaplastic meningiomas. In four cases both primary and recurrent tumors from the same patient also were investigated for allelic status. CONCLUSIONS: The results of the current study support the existence of tumor suppressor gene(s) on 1p associated with malignant progression of meningioma, and suggest that detection of the allelic status of chromosome 1p by FISH may assist physicians in predicting the clinical prognosis of patients affected by this type of brain tumor.

Adult↗
PubMed1998

Molecular cloning of rat Pax4: identification of four isoforms in rat insulinoma cells.

Molecular cloning of rat Pax4 cDNA from a rat insulinoma cell line, RINm5F, library by PCR-based cloning strategy revealed four isoforms of the protein. Analysis of tissue distribution using Northern blotting and RT-PCR showed specific expression of Pax4 mRNA in pancreatic islets and RIN cells. RT-PCR confirmed that the mRNAs of four isoforms are expressed in RIN cells. These Pax4 variants may regulate the transcriptional activity of Pax4 during the development of pancreatic islets.

Amino Acid Sequence↗
PubMed1998

Male-to-female sex reversal in M33 mutant mice.

Polycomb genes in Drosophila maintain the repressed state of homeotic and other developmentally regulated genes by mediating changes in higher-order chromatin structure. M33, a mouse homologue of Polycomb, was isolated by means of the structural similarity of its chromodomain. The fifth exon of M33 contains a region of homology shared by Drosophila and Xenopus. In Drosophila, its deletion results in the loss of Polycomb function. Here we have disrupted M33 in mice by inserting a poly(A) capture-type neo(r) targeting vector into its fifth exon. More than half of the resultant M33cterm/M33cterm mutant mice died before weaning, and survivors showed male-to-female sex reversal. Formation of genital ridges was retarded in both XX and XY M33cterm/M33cterm embryos. Gonadal growth defects appeared near the time of expression of the Y-chromosome-specific Sry gene, suggesting that M33 deficiency may cause sex reversal by interfering with steps upstream of Sry. M33cterm/M33cterm mice may be a valuable model in which to test opposing views regarding sex determination.

Animals↗
PubMed1998

Induction of the N-methyl-D-aspartate receptor subunit 1 in the immortalized neuronal progenitor cell line HC2S2 during differentiation into neurons.

Conditionally immortalized neuronal progenitor cell line HC2S2 differentiates into mature neurons after suppression of the v-myc expression with tetracycline. Reverse transcription-polymerase chain reaction analyses were used to measure expression levels of N-metyl-D-aspartate receptor subunit 1 (NMDAR1) mRNAs encoding splice variants (NMDAR1a, -exon 5; NMDAR1b, +exon 5) in HC2S2 cells during the differentiation. Differential induction of NMDAR1a and NMDAR1b mRNAs was observed during the differentiation. Very low expression of NMDAR1 was observed in undifferentiated HC2S2 cells. NMDAR1a mRNA was induced coincidentally with the emergence of neurites, whereas NMDAR1b mRNA was induced at the time of network formation. Immunohistochemistry also demonstrated induction of NMDAR1 immunoreactivity in differentiated HC2S2 cells. In addition, expression of NMDAR2 mRNA and immunoreactivity was observed in undifferentiated and differentiated HC2S2 cells, suggesting that functional NMDA receptors are present in differentiated HC2S2 cells. While exposure to NMDA resulted in almost no cell death in undifferentiated HC2S2 cells, NMDA induced cell death in differentiated HC2S2 cells in a dose-dependent fashion. These findings suggest that the expression of NMDAR1 mRNA may be regulated by myc or its counterpart during neuronal terminal differentiation and that the splicing choice between NMDAR1a and NMDAR1b may vary according to the formation of neuronal network.

Animals↗
PubMed1998

Gene-dose effect on carnitine transport activity in embryonic fibroblasts of JVS mice as a model of human carnitine transporter deficiency.

Recently, the marked decline in renal carnitine reabsorption has been thought to account fotr the systemic carnitine deficiency in juvenile visceral steatosis (JVS) mice. We have conducted a kinetic analysis using embryonic fibroblasts derived from normal, heterozygous, and homozygous jvs mice and found that the high-affinity carnitine transporter (Km = 5.5 microM), which shows Na+ and temperature dependency and stereospecificity, is defective in homozygous jvs mice. Moreover, a gene dose-dependent decrease of carnitine transport activity, which was due to a decrease in the number of the transporter molecules, was found in heterozygous jvs mice. Similar phenomena have been observed in human primary carnitine deficiency. Therefore, JVS mice may be useful for understanding this extremely rare human hereditary disorder.

Animals↗