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Biomedical subjects

N Hashimoto

Publications and source records attributed to N Hashimoto.

At least 109 records · Page 6Linked to original sources
PubMed1999

Vascular and stromal changes in irradiated and recovering rat thymus.

To analyze the mechanisms responsible for thymocyte proliferation, maturation and migration in the thymus, the rat thymus just after, and recovering from irradiation was studied morphologically. The vascular structures of the rat thymus after a radiation dose of 6 Gy were found to be destroyed on day 3, but had recovered to almost normal by day 7, suggesting that the abrupt recovery of thymus structure after irradiation was due primarily to this change in vascular structure. Furthermore, the epithelial tissues in the thymic cortex appeared to contribute to this abrupt proliferation, and possibly to the abrupt maturation of thymocytes, while medullary epithelial tissues remained sparse and appeared inactive for a relatively long period. These findings are considered important for understanding the interrelationship between thymic epithelial cells and thymocytes with respect to thymocyte proliferation, maturation and migration.

Animals↗
PubMed1999

Dynamic changes of QT dispersion as a predictor of myocardial ischemia on exercise testing in patients with angina pectoris.

The difference between the maximum and minimum QT intervals on the standard 12-lead ECG (QT dispersion) may be a significant predictor of serious arrhythmias. Dynamic changes in QTd were determined during exercise-induced ischemia in 15 patients with effort angina (> or = 75% coronary stenosis) and 10 normal individuals. Treadmill exercise testing was performed according to Bruce's protocol and the rate-corrected QT dispersion (QTcd) was calculated using Bazett's formula. The resting QTcd before exercise was similar in the angina patients and the controls. After the first stage of exercise, QTcd was significantly increased in the angina patients (p = 0.035), while it remained near baseline in the controls. Five minutes after completing exercise, QTcd was significantly greater in the angina patients than in the controls (p = 0.011). Furthermore, QTcd values after the first stage of exercise were significantly correlated with the maximum ST depression observed on completing exercise in the angina patients (r = 0.714, p = 0.0028). Because QTd may represent the heterogeneity of ventricular repolarization, its significant exercise-induced increase in the angina patients suggests that myocardial ischemia caused repolarization disorders. The significant correlation between QTcd values after the first stage of exercise (before significant ST depression) and the maximum ST depression on completing exercise suggests that an increase in QTcd preceding ischemic ST depression may predict myocardial ischemia. In addition, even daily activities not causing significant ST changes may increase QTcd and the risk of serious arrhythmia in angina patients.

Aged↗
PubMed1999

Successful treatment of a patient with febrile, lobular panniculitis (Weber-Christian disease) with oral cyclosporin A: implications for pathogenesis and therapy.

We report a 15-year-old Japanese girl with severe systemic Weber-Christian disease (WCD) who presented with acute onset of high fever associated with tender subcutaneous nodules. Laboratory tests showed an elevated serum concentration of lactate dehydrogenase (LDH), leukopenia, and coagulation abnormalities. The anti-nuclear and anti-DNA antibodies were negative, and the serum pancreatic enzymes and alpha 1-antitrypsin levels were normal. Pulse steroid therapy was not effective, and eventually cerebellar hemorrhage occurred. After initiation of oral cyclosporin A (CyA) therapy, fever came down and her clinical condition improved markedly. Extremely high serum concentrations of interferon-gamma (IFN-gamma) and soluble interleukin-2 receptor (sIL-2R) in this patient returned to normal with CyA therapy. These findings suggest that T-cell immune responses are involved in the pathogenesis of WCD, and that CyA is effective against the disease via suppression of T-cell reactions.

Administration, Oral↗
PubMed1999

Orthostatic hypotension improved after bilateral carotid endarterectomy--case report.

A 60-year-old male with recurrent syncopal attacks presented with orthostatic hypotension on the head-up tilt test. Angiography also showed severe stenosis of the bilateral extracranial carotid arteries. He underwent two-staged bilateral carotid endarterectomy. After the operations, the orthostatic hypotension resolved and the syncopal attacks have disappeared completely. Orthostatic hypotension in this patient was due to vasodepressor-type carotid sinus syndrome caused by compression of the carotid baroreceptors by atherosclerotic plaques.

Carotid Arteries↗
PubMed1999

Moyamoya disease showing atypical angiographic findings--two case reports.

A 7-year-old boy and a 10-year-old girl presented with moyamoya disease showing atypical angiographic findings. In these cases, the internal carotid artery (ICA) had a tapering occlusion just distal to the origin of the ophthalmic artery, whereas the top of the ICA was not occluded and was retrogradely supplied through the posterior communicating artery from the posterior circulation. Surgical treatment resolved the symptoms in both patients. Moyamoya disease may include a number of variant types not showing all the characteristic angiographic findings of moyamoya disease.

Carotid Artery, Internal↗
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↗