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Biomedical subjects

M Hashimoto

Publications and source records attributed to M Hashimoto.

At least 55 records · Page 3Linked to original sources
PubMed1998

Beneficial effects of FK409, a novel nitric oxide donor, on reperfusion injury of rat liver.

BACKGROUND: Nitric oxide (NO) seems to play an important role in modulating tissue injury during reperfusion of the liver. In this study, we have evaluated and compared the effects of FK409 (FK), a potent spontaneous NO releaser, and L-arginine in ischemia-reperfusion injury of the rat liver. METHODS: Male Sprague-Dawley rats underwent 90 min of hepatic ischemia followed by reperfusion. FK or L-arginine was used (intravenously) in two different doses for each drug (group I, 3.2 mg/kg FK; group II, 1.6 mg/kg FK; group IV, 100 mg/kg L-arginine; and group V, 300 mg/kg L-arginine). Saline was used in control animals (group III). Hepatic enzyme status, microcirculation, serum nitrite (NO2-) and nitrate (NO3-) and tissue injury score were evaluated at predetermined times. RESULTS: Serum NO2-/NO3- was elevated immediately by FK treatment dose-dependently but not by L-arginine. However, L-arginine caused late (6-24 hr) elevation of the NO metabolites dose-dependently. The elevation of serum aspartate aminotransferase and alanine aminotransferase was suppressed and hepatic microcirculation was improved in the FK-treated groups dose-dependently. L-Arginine also improved the microcirculation, but hepatic enzymes at 24 hr of reperfusion were significantly higher in group V than in the control group. These findings were well reflected by the extent of tissue injury in respective groups. CONCLUSION: FK treatment in the immediate reperfusion period improves hepatic microcirculation and confers a significant protective effect on hepatic ischemia-reperfusion injury in the rat.

Animals↗
PubMed1998

Stimulation of the neostriatum induces jaw-opener muscle activity, but not jaw-closer muscle activity: an electromyographic study in the rat.

Microstimulation was carried out at 36 sites in the dorsal striatum in lightly anesthetized rats. Only at two sites, microstimulation of 40 microA induced a considerable EMG activity in the jaw-opener (anterior digastric muscle). No activity was evoked in the jaw-closers (masseter and temporalis muscles). The effective sites were confirmed to be localized in a small central region of the striatum at a level corresponding to the caudal end of the anterior commissure. The effect was ascribed to excitation of a small cluster of striatal neurons, rather than to antidromic activation of cerebral cortical neurons through their axons within the striatum. (1) The effect was abolished after destruction of neurons in the striatal region by injecting kainic acid. (2) The effect was not influenced by ablation of the neocortex. (3) Microinjection of kainic acid into the striatal region also induced the similar muscle activity in the jaw-opener, but not in the jaw-closers.

Animals↗
PubMed1998

Cytokine-induced expression of parathyroid hormone-related peptide in cultured human vascular endothelial cells.

Parathyroid hormone-related peptide (PTHrP) is a potent vasodilatory peptide whose expression has been demonstrated in various tissues. The present study was undertaken to examine the regulation of PTHrP expression in cultured endothelial cells derived from human umbilical vein. Immunoradiometric assay revealed that the amount of PTHrP in the conditioned medium was increased by both tumor necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta) in both a time- and a dose-dependent manner. The induction of PTHrP mRNA was also observed, with a peak after 2 hours of incubation with both TNF-alpha and IL-1beta. Angiotensin II, endothelin-1, and arginine vasopressin had no affect on PTHrP production. Our results suggest that PTHrP produced in vascular endothelial cells in response to cytokines may modulate vascular function as a local factor.

Cells, Cultured↗
PubMed1998

Human recombinant NACP/alpha-synuclein is aggregated and fibrillated in vitro: relevance for Lewy body disease.

The precursor of non-amyloid beta protein component of Alzheimer's disease amyloid (NACP/alpha-synuclein) is aggregated and fibrillated under certain conditions, i.e., increasing time lag, high temperature and low pH. These in vitro aggregates form Thioflavine-S-positive filamentous structures, reminiscent of amyloid-like fibrils. Since some Lewy bodies in Parkinson's disease display Thioflavine-S reactivity, our results may suggest that amyloidogenic properties of NACP/alpha-synuclein may play a crucial role in pathogenesis of disorders with Lewy bodies such as Parkinson's disease.

Benzothiazoles↗
PubMed1998

Expression of peroxisome proliferator-activated receptor gamma (PPARgamma) in rat aortic smooth muscle cells.

Peroxisome proliferator-activated receptor gamma (PPARgamma), a member of nuclear receptors, is expressed at a high level in adipose tissue and plays an important role in adipocyte differentiation. In the present study, we identified the expression of PPARgamma in rat aortic smooth muscle cells (RASMC) using reverse transcription-polymerase chain reaction and gel mobility shift assay. In addition, to investigate whether PPARgamma in RASMC is functional or not, we examined the effect of two specific ligands for PPARgamma, a thiazolidinedione anti-diabetic agent, troglitazone, and 15-deoxy-Delta12,14-prostaglandin J2, on the transcriptional activity of PPAR responsive element (PPRE). A significant increase in the activity of PPRE by addition of these ligands was found. These results suggest that in RASMC, target genes for PPARgamma may be activated by specific ligands for PPARgamma through PPRE in their promoters. In conclusion, PPARgamma is expressed and functional in vascular smooth muscle cells.

Animals↗
PubMed1998

Rapid fragmentation of vimentin in human skin fibroblasts exposed to tamoxifen: a possible involvement of caspase-3.

Tamoxifen (TAM), an anti-estrogen compound, is widely used for chemotherapy of breast cancer, although the molecular mechanisms underlying TAM cytotoxicity are obscure. Here, we show that TAM dramatically caused degradation of vimentin (VIM) in human skin fibroblasts, in a time and dose dependent manner. Addition of caspase-3 inhibitor, Z-DEVD-FMK, inhibited formation of some fragments of VIM, and caspase-3 was proteolytically activated by TAM treatment. Expression of functional estrogen receptors were negative in these cells, and neither transcription nor protein synthesis was required for TAM-induced degradation of VIM. Moreover, quinestrol, an ethinyl estradiol derivative, weakly degraded VIM, whereas neither estradiols nor estriol had any effects. Taken together, TAM may induce fragmentation of VIM associated with an activation of caspase-3, which may be attributed to non-genomic actions of TAM.

Antineoplastic Agents, Hormonal↗
PubMed1998

Electrical stimulation of the lower midbrain around retrorubral field decreases temperatures of brown fat and rectum in anesthetized Wistar rats.

To investigate a neuronal mechanism controlling heat production of brown adipose tissue (BAT), ventral regions of the lower midbrain was stimulated by rectangular electric current (0.1 ms, 1 mA, 5-50 Hz) while recording temperatures of the interscapular BAT (IBAT), rectum and arterial blood pressure in urethane-anesthetized Wistar rats at room temperature of 24-26 degrees C. Unilateral stimulation (10 Hz) for 5 min to the midbrain around the retrorubral field decreased temperatures of IBAT (0.33 +/- 0.03 degrees C, n = 33) and rectum (0.10 +/- 0.01 degrees C). The response was reversed when procaine (10%, 800 nl) was injected into the same locus. The results support the hypothesis that a tonic inhibitory mechanism for metabolic heat production locates around the retrorubral field.

Adipose Tissue, Brown↗
PubMed1998

Effect of continuous infusion of vasopressin on glomerular growth response in spontaneously hypertensive rats.

Vasopressin (VP) is thought to play an important role in the pressor and proliferative responses of renal glomeruli. We have utilized the spontaneously hypertensive rat (SHR) model to determine if glomerular proliferation is induced by chronic infusion of exogenous VP. SHR were continuously infused with 0.1 ng/kg/min VP (H-VP group), 1.0 ng/kg/min (H-VP group), or vehicle alone (control group) for fifteen days using osmotic minipumps, and the histological alterations and level of expression of platelet-derived growth factor B-chain (PDGF-B) and transforming growth factor (TGF)-beta1 mRNA were determined. We observed no significant differences in systolic blood pressure, heart rate, serum electrolytes, protein and creatinine among the three groups of rats, but urine volume was found to be significantly decreased, and urine osmolality significantly increased, in the H-VP group. Kidney weight was significantly higher in the H-VP and L-VP groups than in the control group, and glomerular diameter was higher in the H-VP group. When we measured mesangial injury score and cellularity in the glomeruli of these animals, we observed VP dose-dependent proliferative changes. In the immunofluorescence study, although we did not find an obvious difference in depositions of collagen types III, IV and VI, alpha-smooth muscle actin and PDGF-B among the groups, the collagen type I and TGF-beta1 increased in several glomeruli in the H-VP group. Reverse transcription polymerase chain reaction (RT-PCR) revealed no significant differences in the glomerular levels of PDGF-B mRNA among the three groups of rats, but the level of expression of TGF-beta1 mRNA was significantly higher in the L-VP and H-VP groups than in the control group. These findings suggest that VP may contribute to glomerular proliferation, and that VP may exert its effects in part through the induction of TGF-beta1 expression. These results also raise the possibility that blockade of VP receptors may be useful in the treatment of some forms of glomerular disease.

Animals↗
PubMed1998

Influence of docosahexaenoic acid on cerebral lipid peroxide level in aged rats with and without hypercholesterolemia.

Female Wistar rats, 100 weeks old, were divided into four groups: one group was fed a high-cholesterol diet, one received a non-cholesterol diet, and the others were fed either a non- or a high-cholesterol diet plus docosahexaenoic acid. The level of lipid peroxide (LPO) in brain tissue was measured with a LPO assay kit. Fatty acid concentrations were analyzed by gas chromatography. Brain LPO in the aged and hypercholesterolemic rats fed docosahexaenoic acid decreased in the cerebrum but not in the brain stem or cerebellum. In the cerebrum, LPO showed a decrease, with an increase in the ratio of docosahexaenoic acid to arachidonic acid. The cerebrum, unlike the other areas of the brain, was more sensitive to docosahexaenoic acid as the concentrations of LPO decreased.

Aging↗
PubMed1998

Ergonovine-induced alterations in coronary flow velocity preceding onset of occlusive spasm in patients without significant coronary artery stenoses.

This study examined serial changes in coronary flow velocity to elucidate the dynamic change of coronary circulation during coronary spasm. Twenty patients with variant angina and 27 control patients were studied. Coronary flow velocity was monitored using a Doppler guidewire following intracoronary ergonovine administration. In the control group, diastolic flow velocity either did not change or increased slightly in response to ergonovine. However, in patients with variant angina, 2 patterns of flow velocity alterations were observed. In the first pattern, flow initially increased and then suddenly decreased (16 of 20 patients). In the second pattern, flow gradually decreased (3 of 20 patients). In the remaining patient, the coronary flow alteration could not be detected because of branch spasm. When abnormally high flow velocity was defined as a 100% increase in flow after ergonovine administration within 1 minute, and abnormally low flow velocity was defined as a 50% decrease in flow to diagnose variant angina, sensitivities of 35%, 75%, and 85% were noted if flow was measured 1.0, 2.0, and 3.0 minutes after ergonovine administration, respectively. These abnormal flow velocities were observed before ischemic ST changes appeared. In conclusion, in patients with variant angina, characteristic serial changes in coronary flow velocity occur before occlusive spasm. Variant angina may be diagnosed earlier by monitoring flow velocity rather than by monitoring for ischemic electrocardiographic changes.

Aged↗
PubMed1998

Functional expression of a mammalian odorant receptor.

Candidate mammalian odorant receptors were first cloned some 6 years ago. The physiological function of these receptors in initiating transduction in olfactory receptor neurons remains to be established. Here, a recombinant adenovirus was used to drive expression of a particular receptor gene in an increased number of sensory neurons in the rat olfactory epithelium. Electrophysiological recording showed that increased expression of a single gene led to greater sensitivity to a small subset of odorants.

Adenoviridae↗
PubMed1998

Cognitive loss in dementia with Lewy bodies and Alzheimer disease.

BACKGROUND: Dementia with Lewy bodies (DLB) is emerging as a common cause of degenerative dementia. Some preliminary evidence exists that the pattern of cognitive impairment in DLB is different from that in Alzheimer disease (AD). OBJECTIVE: To delineate features of cognitive impairment of DLB on standardized neuropsychological tests. METHODS: We performed neuropsychological assessments of 26 patients with probable DLB (based on criteria of the consortium on DLB international workshop) and of 52 patients with probable AD (based on criteria of the National Institute of Neurological and Communicative Disorders and Stroke [now the National Institute of Neurological Disorders and Stroke])-Alzheimer's Disease and Related Disorders Association) who were matched to the patients with DLB 2:1 by age, sex, education, and Mini-Mental State Examination score. RESULTS: Compared with the group with probable AD, the group with probable DLB scored significantly lower on the picture arrangement, block design, object assembly, and digit symbol substitution subtests of the Wechsler Adult Intelligence Scale-Revised and on the Raven Colored Progressive Matrices test and significantly higher on the Mini-Mental State Examination locational orientation subtest and the Alzheimer's Disease Assessment Scale word recall subtest. A discriminant analysis revealed that the word recall score on the Alzheimer's Disease Assessment Scale and the block design score on the Wechsler Adult Intelligence Scale-Revised were the best discriminant factors. CONCLUSIONS: The disproportionately severe visuoperceptual, visuoconstructive, and visuospatial dysfunction and the disproportionately mild memory impairment in DLB compared with AD, which likely reflect the distribution of the pathologic changes in DLB, can help to differentiate DLB from AD.

Aged↗
PubMed1998

Emergence and takeover of YMDD motif mutant hepatitis B virus during long-term lamivudine therapy and re-takeover by wild type after cessation of therapy.

Treatment of hepatitis B virus (HBV) with lamivudine is effective in suppressing virus replication and results in reduced inflammatory activity. However, the emergence of lamivudine-resistant mutant virus, with amino acid substitution in the YMDD motif of DNA polymerase, has been reported. We report the emergence and takeover of YMDD mutant and re-takeover by wild type during and after long-term lamivudine therapy. YMDD mutants were detected in five patients who showed DNA breakthrough (HBV DNA becoming detectable after a period of DNA negativity), which occurred after 9 to 14 months of lamivudine therapy. Four of five mutants had amino acid sequence YIDD, and the remaining mutant had YVDD. Patients with high HBV-DNA titer and/or hepatitis B e antigen tended to develop breakthrough (P = .038). Using a sensitive and specific polymerase chain reaction (PCR)-based method developed in this study, the emergence of YMDD mutants was detected 1 to 4 months before DNA breakthrough, but not detected in any of the pretreatment sera. The mutants were predominant at breakthrough, but were replaced by wild-type virus 3 to 4 months after cessation of therapy in the two patients who discontinued therapy. One of these patients had a relapse of hepatitis. Mutant continued to replicate in the remaining three patients who continued to receive treatment, and relapse occurred in only one of these patients. Our results suggest that the replication of YMDD mutant viruses is less than wild type and is re-overtaken by wild type after cessation of therapy. Re-administration of lamivudine, possibly combined with other antiviral therapy, might be useful in some patients experiencing hepatitis with lamivudine-resistant variants.

Adult↗
PubMed1998

Spontaneous activity of preoptic neurons in slice preparations of the hypothalamus of European hamsters (Cricetus cricetus) and Wistar rats under different states of hypothermia.

Hypothermia was induced in European hamsters (hibernators) and Wistar rats (nonhibernators), and changes in the firing rate and spike duration of extracellularly recorded action potentials were investigated in hypothalamic slices in vitro. At slice temperatures close to normal body temperature (37 +/- 3 degreesC), 32 and 57% of spontaneously active neurons in the medial preoptic area were classified as warm-sensitive in rats and hamsters, respectively. With decreasing slice temperature, the number of active neurons decreased progressively without a significant difference between rats and hamsters. At a slice temperature of 10 degreesC, 57% of all hypothalamic neurons in rats and 42% in hamsters were still spontaneously active. The average temperature at which activity ceased completely when the temperature was decreased further (the cut-off temperature) was 7.9 +/- 0.3 degreesC (n = 14) in rats but was significantly lower at 4.9 +/- 0.4 degreesC (n = 8) in hamsters (P < 0.001). Firing rates and temperature coefficients did not differ in their temperature dependence between rats and hamsters. Action potential duration increased with decreasing slice temperature in both species, but the increase in duration was significantly greater in rats.

Action Potentials↗
PubMed1998

A novel strategy for introducing exogenous bcl-2 into neuronal cells: the Cre/loxP system-mediated activation of bcl-2 for preventing programmed cell death using recombinant adenoviruses.

We have established a novel strategy for introducing exogenous Bcl-2 into neuronal cells that is mediated by Cre/loxP recombination using recombinant adenoviral vectors. An on/off-switching cassette for Bcl-2 (CALNLbcl-2) was designed to express Bcl-2 by recombinase Cre-mediated excisional deletion of a spacer DNA flanked by a pair of loxP sites. Exogenous Bcl-2 was clearly induced in PC12 cell lines carrying CALNLbcl-2 after infection with recombinant adenovirus producing recombinase Cre (AxCANCre). Dual infection with both AxCANCre and a recombinant adenovirus bearing CALNLbcl-2 showed efficient delivery of exogenous Bcl-2 into a hybrid motoneuronal cell line and primary chicken spinal motoneurons. The delivery of foreign Bcl-2 promoted survival of motoneurons in medium either containing or lacking trophic support. Thus, this strategy for delivery of exogenous Bcl-2 will be useful for studying neuronal death as well as for introducing foreign genes into postmitotic neurons under the control of recombinase Cre.

Adenoviridae↗
PubMed1998

[A case of adenocarcinoma of the thymus].

We report an adenocarcinoma of the thymus in a 39-year-old male. The patient presented with chest pain, and the chest X-ray film and chest CT showed an abnormal mass in the mediastinum. A preoperative clinical diagnosis of invasive thymoma was suspected. The tumor was resected along with the pleura and pericardium. The pathological findings were compatible with those of adenocarcinoma of the thymus. Despite a thorough examination, no primary tumor could be found. An adenocarcinoma of the thymus is rare and to the authors knowledge there are few previous reports in the literature.

Adenocarcinoma↗
PubMed1998

Spondyloepiphyseal dysplasia with accumulation of glycoprotein in the chondrocytes: spondyloepiphyseal dysplasia, Stanescu type.

OBJECTIVE: To clarify the phenotype in a bone dysplasia termed "spondyloepiphyseal dysplasia with accumulation of glycoprotein in the chondrocytes" by Stanescu et al. DESIGN AND PATIENTS: Subjects comprised two definitive cases of one family and one probable case of another family. Histologic examination in one patient warranted the diagnosis of the first family, whereas the diagnosis of the second family was based solely on clinical and radiologic grounds. RESULTS: Pedigrees revealed an autosomal dominant mode of transmission. All three patients shared painful large joints with joint restriction, progressive contracture with osseous expansion of the finger joints, and normal height despite the presence of a short trunk. Moderate platyspondyly, hypoplastic ilia, epiphyseal flattening with metaphyseal splaying of the tubular bones, and most characteristically, broad, elongated femoral necks with striking coxa valga were identical in all patients, but the patient of the second family showed severe brachydactyly unlike the other two patients. Histologic examination revealed PAS-positive, amylase-resistant intracytoplasmic inclusion bodies in the chondrocytes, corresponding to dilated rough endoplasmic reticulum filled with moderately electron-dense materials found by electron microscopy. CONCLUSION: The manifestations of our patients are sufficiently characteristic to constitute a distinct entity.

Adolescent↗