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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
PubMed2003

CrmA gene expression protects mice against concanavalin-A-induced hepatitis by inhibiting IL-18 secretion and hepatocyte apoptosis.

Activated cytotoxic T-cell-mediated hepatocyte apoptosis via Fas/Fas-ligand and perforin/granzyme pathways are believed to involve the model of concanavalin A (ConA)-induced hepatitis. The purpose of the present study is to investigate whether the cytokine response modifier A (crmA) gene effectively inhibits the hepatocyte apoptosis of ConA-induced hepatitis. We examined survival rates, liver pathology, immune histological changes, and cytokine profiles from mice receiving the recombinant adenovirus vectors containing cre and/or crmA genes, transferred to the liver 3 days before ConA injection, and a crmA gene nonexpression control group. Injection of ConA into mice rapidly led to massive hepatocyte apoptosis, and infiltration of leukocytes, especially CD11b(+) inflammatory cells. In contrast, liver damage was dramatically reduced in the mice that expressed the crmA gene. However, infiltration by CD4(+) cells was not affected. The survival of the mice increased significantly to 100% in the treated group versus the control group. Furthermore, we demonstrated that interleukin (IL)-18 plays an important role in ConA-induced hepatitis, and that crmA expression significantly inhibited IL-18 secretion. Our results showed that the crmA gene effectively inhibits apoptosis induced by ConA hepatitis. This indicates a potential therapeutic usage of crmA for protection from cellular damage due to hepatitis.

Adenoviridae↗
PubMed2003

Effects of exercise on platelet and aortic functions in aged rats.

AIM AND METHODS: To assess age- and exercise-related changes in platelet aggregation, we measured the magnitude of platelet aggregation with a four-channel aggregometer, plasma and aortic polyunsaturated fatty acids by gas chromatography and related prostanoids with a reagent kit in young and aged non-exercised and in aged exercised rats. RESULTS: Platelet aggregation in platelet-rich plasma induced by ADP (5 microm) in the primary wave increased with age. In the non-exercised groups, the basal levels of thromboxane B2 in platelet-rich plasma increased in aged rats compared with young rats. In aged exercised rats, the basal levels of 6-keto-prostaglandin F1alpha in platelet-rich plasma were stimulated and those of thromboxane B2 were depressed, compared with non-exercised aged rats. The plasma levels of eicosapentaenoic acid and docosahexaenoic acid increased with age. Only aortic eicosapentaenoic acid in the aged group increased by exercise. In the aged non-exercised and exercised groups, the aortic, but not the plasma, levels of eicosapentaenoic acid correlated inversely with the basal levels of thromboxane B2 in platelet-rich plasma (r = -0.53, P < 0.05) and associated negatively with the magnitudes of platelet aggregation induced by ADP (5 microm) (r = -0.47, P < 0.05). CONCLUSION: These findings suggest that exercise in aged rats increases aortic eicosapentaenoic acid concentrations, which in turn depress the basal levels of thromboxane, B2 in platelet-rich plasma to modulate platelet aggregation.

6-Ketoprostaglandin F1 alpha↗
PubMed2003

Cell signalling and gene expression mediated by RET tyrosine kinase.

Germline mutations of the RET proto-oncogene cause multiple endocrine neoplasia (MEN) 2A or 2B by different mechanisms. As is the case for other receptor tyrosine kinases, mutant RET recruits a variety of signalling molecules via phosphorylated tyrosine residues present in the kinase domain and carboxy-terminal tail. As we previously reported, the signaling via phosphorylated tyrosine 1062 plays a crucial role in the transforming activities of both RET-MEN2A and RET-MEN2B mutant protein. Interestingly, this single tyrosine residue represents a binding site for several signalling molecules including SHC, Enigma, SNT/FRS2, DOK and IRS1 and is responsible for activation of the RAS/ERK, PI3-K/AKT, JNK, p38MAPK and ERK5 signalling pathways. Amongst these, the PI3-K/AKT and JNK pathways appeared to be more strongly activated in the cells expressing RET-MEN2B than in the cells expressing RET-MEN2A, suggesting the possibility that these pathways may be involved in the disease phenotype. In addition, RET is alternatively spliced to produce three isoforms and the splicing site is present just downstream of tyrosine 1062. These isoforms play different roles for the tumour development associated with MEN 2 or the development of the kidney and the enteric nervous system. Moreover, using differential display analysis, we identified several genes whose expression is highly induced by RET-MEN2B mutant proteins. The differential gene expression by RET-MEN2A and RET-MEN2B may also be important for the development of their phenotypes.

Alternative Splicing↗
PubMed2003

Esophageal carcinoma with tracheal stenosis due to tumor invasion and long survival after chemoradiotherapy.

For patients who have esophageal carcinoma with tracheal invasion surgery is usually not indicated because operative complications are considerable and the prognosis is poor. We experienced complete regression of a large esophageal carcinoma with tracheal stenosis due to tumor invasion without tracheo-esophageal fistula. Irradiation of 68 Gy was delivered to a long T field from the neck to the lower thoracic esophagus, and was combined with chemotherapy using cisplatin and 5-fluorouracil. The tumor decreased markedly in size and the tracheal stenosis resolved. The patient has survived for 4 years, although second primary early esophageal carcinoma and hypopharyngeal carcinoma were detected 2 years after his initial chemoradiotherapy. Although the prognosis of advanced esophageal carcinoma with invasion of other organs is usually poor, the effect of chemoradiotherapy can sometimes be dramatic and a good result can be achieved in such patients.

Combined Modality Therapy↗
PubMed2003

Striatal infarcts mimicking frontotemporal dementia: a case report.

We described a patient with bilateral striatal infarcts, in whom stereotyped and disinhibited behaviors were insidiously emerged over 2 years mimicking frontotemporal dementia (FTD). A positron emission tomography with 18-fluorodeoxy glucose showed a hypometabolism in the frontal lobes, basal ganglia, and thalami. The peculiar behavioral alterations remained unchanged for the following 7 years, suggesting that the disease is not degenerative but of vascular origin. A disruption of the fronto-subcortical circuits at the level of the striatum or the anterior thalamic peduncle is attributable to the FTD-like behavioral and cognitive syndrome.

Aged↗
PubMed2003

Tomatoes have natural anti-thrombotic effects.

The prevention of arterial thrombotic diseases has a high priority in developed countries. An inappropriate diet may be an important risk factor for thrombotic events. The daily intake of an anti-thrombotic diet may offer a convenient and effective way of prevention. The aim of the present study was to test tomato extracts for anti-thrombotic effects and to identify those varieties that have such an effect. A shear-induced platelet-function test (haemostatometry) was used to test anti-thrombotic potential in vitro. Extracts from those tomato varieties that showed a significant anti-thrombotic activity in vitro were further assessed in vivo, using a laser-induced thrombosis test in mice. One tomato variety (KG99-4) showed significant anti-thrombotic activity both in vitro and in vivo. KG99-4 inhibited not only platelet-rich thrombus formation but also had a thrombolytic effect. It is concluded that haemostatometry can detect and classify the anti-thrombotic potential of fruits and vegetables and offers a simple way of screening for such effects.

Animals↗
PubMed2003

Dose-response studies on the induction of liver cytochromes P4501A1 and 1B1 by polycyclic aromatic hydrocarbons in arylhydrocarbon-responsive C57BL/6J mice.

1. To determine the biological effects of 23 polycyclic aromatic hydrocarbons (PAHs) and 3,4,3',4'-tetrachlorobiphenyl, the dose-response studies of the induction of CYP1-dependent xenobiotic oxidation activities by these chemicals in liver microsomes of C57BL/6J mice were studied. 2. In arylhydrocarbon-responsive C57BL/6J mice, the liver microsomal xenobiotic oxidation with substrates of 7-ethoxyresorufin, 7-ethoxycoumarin, (+/-)-benzo[a]pyrene-7,8-diol, dibenzo[a, pyrene-11,12-diol and 2-amino-3,5-dimethylimidazo[4,5-f]quinoline increased by increasing the doses of PAHs to mice, particularly when the PAHs that have been reported to be carcinogenic in experimental animals were used. In arylhydrocarbon receptor-knockout mice, there were no increases in liver microsomal 7-ethoxyresorufin O-deethylation activities nor in liver mRNA levels of CYP1A1, 1A2 and 1B1 by these chemicals. 3. Of the chemicals examined, benzo[k]fluoranthene, benzo[b]fluoranthene, benzo[j]-fluoranthene, 3-methylcholanthrene, dibenz[a,h]anthracene, dibenz[a,c]anthracene and 3,4,3',4'-tetrachlorobiphenyl were potent inducers of the induction of liver microsomal 7-ethoxyresorufin O-deethylation in mice. 4. Other PAHs such as 5-methylchrysene, benzo[a]pyrene, dibenzo[a,l]pyrene, dibenz[a,j]acridine, benzo[a]anthracene and 7,12-dimethylbenz[a]anthracene moderately induced 7-ethoxyresorufin O-deethylation activities in mice. PAHs reported to be weak or less carcinogenic in experimental animals did not induce the xenobiotic oxidation activities of CYP1A1 and 1B1 in the mice. 5. The results suggest that induction of liver microsomal CYP1-dependent xenobiotic oxidation activities is a good tool in determining the potencies of carcinogenic PAHs in arylhydrocarbon-responsive C57BL/6J mice.

Animals↗
PubMed2003

Radiation doses to neonates during X ray computed tomography examinations.

As the survival rate of newborns has increased, the number of X ray computed tomography (CT) examinations performed on neonates has been increasing. The exposure doses from CT examinations are known to be higher than those from conventional radiography. Although radiation sensitivity of neonates is higher than that of adults, there are few reports on dose estimates of neonates in CT examinations. Four cylindrical phantoms and one neonatal phantom have been developed to estimate doses to neonates during CT examinations. Using these phantoms and glass dosemeters, absorbed doses were measured. Estimated exposure doses to neonates were higher than those to adults, and our results suggest a need to optimise carefully CT examinations in newborns.

Birth Weight↗
PubMed2003

Aging affects two modes of nanoleakage expression in bonded dentin.

Water sorption into resin-dentin interfaces precedes hydrolytic degradation. We hypothesized that these processes are morphologically manifested by the uptake of ammoniacal silver nitrate, which is thought to trace hydrophilic domains and water-filled channels within matrices. Water sorption is thought to be nonuniform and can be traced by the use of silver nitrate. Human teeth bonded with an experimental filled-adhesive were aged in artificial saliva (experimental) or non-aqueous mineral oil (control). Specimens retrieved for up to a 12-month period were immersed in 50 wt% ammoniacal silver nitrate and examined by transmission electron microscopy for identification of the changes in their silver uptake. Reticular silver deposits initially identified within the bulk of hybrid layers in the experimental group were gradually reduced over time, but were subsequently replaced by similar deposits that were located along the hybrid layer-adhesive interface. Silver uptake in water-binding domains of the adhesive layers increased with aging, resulting in water tree formation. These water-filled channels may act as potential sites for hydrolytic degradation of resin-dentin bonds.

Absorption↗
PubMed2002

The effect of APOE epsilon4 allele on cerebral glucose metabolism in AD is a function of age at onset.

BACKGROUND: Although the APOE epsilon4 allele is a well-known risk factor for developing AD, the impact of the epsilon4 allele on clinical manifestations in patients with AD is still controversial. One possible reason for this controversy is that previous studies did not consider the effect of patient age at symptom onset. OBJECTIVE: To investigate the possible impact of patient age at onset of AD on the effect of APOE genotype on regional cerebral glucose metabolism (rCMRglc). METHODS: The authors compared rCMRglc between probable AD patients (based on criteria of the National Institute of Neurologic Disease and Stroke/AD and Related Disorders Association) with APOE epsilon4/4 and APOE epsilon3/3 alleles in early-onset (< or =65 years old) and late-onset (>65 years old) groups. In each group, the patients with APOE epsilon4/4 and APOE epsilon3/3 alleles were comparable for age at onset, age at examination, sex, disease duration, education level, and severity of dementia. RESULTS: In the early-onset group, the patients with the APOE epsilon4/4 genotype showed a significant decrease of rCMRglc in the medial temporal lobe and a significant increase of rCMRglc in the inferior parietal and posterior temporal cortices as compared with those patients with the APOE epsilon3/3 genotype. In the late-onset group, there were no significant differences in the rCMRglc pattern between the patients with APOE epsilon4/4 and APOE epsilon3/3 alleles. CONCLUSIONS: The current findings indicate that the impact of the APOE epsilon4 genotype on cerebral glucose metabolism of patients with AD may be a function of age at symptom onset.

Age of Onset↗
PubMed2002

Fractured surface characterization: wet versus dry bonding.

OBJECTIVE: Fractographic analysis was conducted to evaluate the resin-dentin bond structures made under wet and dry conditions. METHODS: Resin-dentin bonded specimens were prepared using two adhesive resin systems (Single Bond/SB; 3M and All Bond 2/AB2; Bisco Inc) under wet and dry conditions. The specimens were sectioned perpendicular to the adhesive interface to produce a square bar-shaped specimen (adhesive area: 0.9 mm(2)) by means of a diamond saw. The mean bond tensile test was then conducted at a crosshead speed of 1.0 mm/min. The mean bond strengths were statistically compared with two-way ANOVA and Fisher's PLSD test (p<0.05). Subsequently, the fractured surfaces of all specimens were examined using SEM and the area fractions of failure modes (%) were measured using an image analyzer on SEM microphotographs. RESULTS: No significant differences in tensile-bond strength were observed between SB (60.1+/-16.4MPa) and AB2 (69.8+/-17.4MPa) (p>0.05) under wet conditions. However, the bond strength either of SB or AB2 made under wet conditions was significantly greater than those made under dry conditions (SB: 26.2+/-12.5MPa and AB2: 6.8+/-3.3MPa) (p<0.05). Under fractographic analysis, the major portion at the fractured surface was occupied by the cohesive failure of bonding resin and the resin composite for the wet conditions, and the top of the hybrid layer for the dry conditions in both systems. SIGNIFICANCE: The interaction between the top of the hybrid layer and the bonding resin influenced the bond integrity.

Adhesiveness↗
PubMed2002

Estrogen receptor beta is involved in the anorectic action of estrogen.

OBJECTIVE: Estrogen has been implicated in feeding behavior and adiposity. This study was undertaken to elucidate the mechanism underlying the anti-obesity and anorectic action of estrogen and the role of estrogen receptor (ER) in the central nervous system. METHODS AND RESULTS: Ovariectomy in 8-week-old female Wistar rats induced hyperphagia along with an increase in body weight and abdominal fat accumulation compared to control sham-operated rats. These changes were fully reversed by subcutaneous replacement of estradiol and were abrogated by pair-feeding. Then, the effects of intracerebroventricular infusion of estradiol, alone or in combination with antisense oligodeoxynucleotides (ODN), for ER in ovariectomized rats were examined. The estradiol group showed 10-20% lower daily food intake, and after the 2-week infusion period a 14% reduction in body weight with a similar reduction in abdominal fat compared to the vehicle group. The inhibitory effect of estradiol on food intake and body weight was blocked by co-administration of ER-beta antisense ODN, whereas ER-alpha antisense ODN did not show any influence. CONCLUSION: These results indicate that ER-beta in the central nervous system is involved in the anorectic action of estrogen.

Adipose Tissue↗
PubMed2002

A new model to evaluate the diet-induced prothrombotic state, using He-Ne laser-induced thrombogenesis in the carotid artery of apolipoprotein E-deficient and low-density lipoprotein receptor-deficient mice.

Epidemiological studies suggest the high fat content of the Western diet to be responsible for atherosclerosis and its thrombotic complications. Despite such a prevailing view, few animal experiments have so far succeeded in demonstrating enhanced thrombogenicity due to a high fat diet. Even a high fat and a very high cholesterol (1%) diet has failed to demonstrate an enhanced thrombotic reaction in rodents and rabbits. The aim of the present study was twofold. First, we wanted to establish a new, sensitive and specific thrombosis model in mice, which can then be used to study the effect of diets. Second, we intended to employ such a thrombosis model in investigations into the effect of high or low fat diets on thrombosis. The technique described uses a laser to induce thrombus formation in the exposed carotid artery of apolipoprotein E-deficient and low-density lipoprotein receptor-deficient mice. Thrombus formation was recorded on video, analysed by computer, and the size of thrombus was calculated by image analysis software. Thrombotic status was evaluated by analysing a total of 61 individual images of the thrombotic reaction, which were taken over 600 s. The severity of atherosclerosis was assessed by image analysis of the stained elastic fibers. Two kinds of diets were used: the Western type, high fat diet contained 20% fat (w/w) and 0.05% cholesterol (w/w); the low fat diet contained 7% fat, without cholesterol. These diets were on the basis of AIN93G and were given to mice for 4 or 8 weeks. The high fat diet significantly enhanced both the thrombotic reaction and the development of atherosclerosis as compared with the low fat diet.

Animals↗
PubMed2002

A new method for measuring dynamic change of tracer distribution using dynamic single photon emission tomography with a slip-ring rotational gamma camera.

The clinical applicability of dynamic single photon emission tomograpy (SPET) using a dual-head gamma camera equipped with a slip-ring rotational mechanism, referred to as serial SPET, was examined in the present investigation. Serial SPET enables the production of tomographic images for any arbitrary time frame from an arbitrary range of data to 360 degrees. In a pre-clinical evaluation, a correlation between radioactivity concentration and serial SPET counts was evaluated in a phantom with continuous changes in 99mTc concentration. A differential value was obtained from each pair of SPET images; moreover, moving average approximation processing was investigated with respect to the elimination of noise in the data. In 11 and one patient presenting with cerebrovascular disease and meningioma, respectively, changes in SPET counts were evaluated when 99mTc ethyl cysteinate dimer (99mTc-ECD) was continuously administered at a constant rate in the resting state. Furthermore, in six of 11 subjects with cerebrovascular disease, changes occurring in SPET counts were examined by using acetazolamide loading while continuously administering 99mTc-ECD at a constant rate. Consequently, serial SPET enabled the evaluation of changes in radioactivity concentration over time in both the phantom and preliminary clinical studies. Data analysis by differential processing utilizing moving average approximation processing enabled the detection of minor changes in radioactivity concentration. An increase of 15.1+/-5.4% was observed in SPET counts of the unaffected cerebral hemisphere with acetazolamide loading. The response of the affected hemisphere was less prominent. These findings suggest that serial SPET would be an effective technique for the pharmacokinetic analysis of radiopharmaceuticals.

Acetazolamide↗
PubMed2002

The extent to which resin can infiltrate dentin by acetone-based adhesives.

The combined methodologies of fractography and laser-Raman spectroscopic analysis were used for evaluation of the resin-dentin bonds made with wet and dry bonding. Resin-dentin-bonded beams were produced by means of 2 acetone-based adhesives (One-Step and Prime & Bond NT). The micro-tensile bond test was conducted, and the fractured surfaces of all specimens were examined by SEM and an image analyzer. The amount of resin infiltration within the hybrid layer was quantified by means of a laser-Raman spectroscope. In Raman analysis, the amount of resin impregnation within the hybrid layer of the dry bonding was found to be significantly lower (approximately 50%) than that in the wet one. Under fractographic analysis, a correlation was found between the bond strength and the failure mode. Based on those findings, it was suggested that the integrity between the bonding resin and the top of the hybrid layer played a major role in bond strength.

Acetone↗
PubMed2002

[Surgical treatment for ruptured descending thoracic aortic aneurysm with the left lung hematoma; report of a case].

An 80-year-old female was admitted with sudden onset of back pain and hemoptysis. The diagnosis was ruptured descending aortic aneurysm with the left lung hematoma. Emergency operation was performed. The graft replacement of the ruptured descending thoracic aneurysm and left lower lobectomy was done. She was extubated on the 1st postoperative day. The postoperative course was uneventful without pulmonary and graft complications. We thought that concomitant left lower lobectomy was useful in this patient.

Aged↗