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Biomedical subjects

M Hashimoto

Publications and source records attributed to M Hashimoto.

At least 19 recordsLinked to original sources
PubMed2006

Comparative studies of AJG049, a novel Ca2+ channel antagonist, on voltage-dependent L-type Ca2+ currents in intestinal and vascular smooth muscle.

BACKGROUND AND PURPOSE: Antagonists of Ca2+ channels reduce contraction of intestinal smooth muscle but also affect vascular smooth muscle. We have therefore examined the effects of AJG049, a newly synthesized antagonist for regulation of gut motility, on voltage-dependent L-type Ca2+ channels, in vascular and intestinal smooth muscle, comparing AJG049 with two other Ca2+ channel antagonists, verapamil and diltiazem. EXPERIMENTAL APPROACH: Affinities of AJG049 for various types of voltage-dependent Ca2+ channels were examined by binding studies. Effects of AJG049 on voltage-dependent inward Ca2+ (or Ba2+) currents (ICa or IBa) in dispersed smooth muscle cells from guinea-pig ileum, colon and mesenteric artery were measured using conventional whole-cell configurations. KEY RESULTS: In binding studies, AJG049 showed a high affinity for the diltiazem-binding site of L-type Ca2+ channels. In whole-cell configuration, AJG049 suppressed ICa in ileal myocytes, with concentration-, voltage-and use-dependencies. AJG049 shifted the steady-state inactivation curve of ICa to the left. The order of potency to inhibit ICa in ileal myocytes was AJG049>verapamil>diltiazem. AJG049 also suppressed IBa in guinea-pig mesenteric arterial myocytes, showing concentration- and voltage-dependencies and the potency order for this action was also AJG049>verapamil>diltiazem. For the relative ratio of Ki values between ileal and mesenteric arterial myocytes, the order was AJG049>diltiazem>>verapamil. CONCLUSIONS AND IMPLICATIONS: These results show that AJG049 inhibits L-type Ca2+ channels mainly through the diltiazem-binding site(s). From our results, AJG049 showed a little selectivity for these Ca2+ channels in intestinal smooth muscle.

Animals↗
PubMed2006

Actions anchored by concepts: defective action comprehension in semantic dementia.

OBJECTIVE: To study the ability of patients with semantic dementia to understand actions, in order to examine the contribution of semantic memory to action comprehension. METHODS: The ability to comprehend symbolic and instrumental actions was assessed in 6 patients with semantic dementia and 10 healthy controls. The patients were also given the imitation test of meaningful and meaningless actions. RESULTS: In all patients with semantic dementia, comprehension of both symbolic and instrumental actions was defective. The comprehension of symbolic actions was more impaired than that of instrumental actions. Their ability to imitate other's actions was well preserved. CONCLUSION: This study showed that comprehension of action was impaired in semantic dementia, suggesting that semantic memory has an important role in comprehension of human action.

Aged↗
PubMed2006

Photoemission from buried interfaces in SrTiO3/LaTiO3 superlattices.

We have measured photoemission spectra of SrTiO3/LaTiO3 superlattices with a topmost SrTiO3 layer of variable thickness. A finite coherent spectral weight with a clear Fermi cutoff was observed at chemically abrupt SrTiO3/LaTiO3 interfaces, indicating that an "electronic reconstruction" occurs at the interface between the Mott insulator LaTiO3 and the band insulator SrTiO3. For SrTiO3/LaTiO3 interfaces annealed at high temperatures (approximately 1000 degrees C), which leads to Sr/La atomic interdiffusion and hence to the formation of La(1-x)Sr(x)TiO3-like material, the intensity of the incoherent part was found to be dramatically reduced whereas the coherent part with a sharp Fermi cutoff was enhanced due to the spread of charge. These important experimental features are well reproduced by layer dynamical-mean-field-theory calculation.

Journal Article↗
PubMed2006

Reduced tau expression in gastric cancer can identify candidates for successful Paclitaxel treatment.

A recent study disclosed that breast cancer cases with low 'tau' expression can predict susceptibility to Paclitaxel administration. In the current study, the clinical significance of tau expression in gastric cancer cases was established by identifying candidates with Paclitaxel administration. Tissue specimens from 20 cases of in-operable or noncuratively resected gastric cancer were examined. Subsequent to the administration of 80 mg m(-2) of Paclitaxel in six 3-h intravenous infusions, the clinical effectiveness of Paclitaxel was evaluated by the size of metastatic lesions with computed tomography. The status of the tau expression was determined by immunohistochemistry. Based on a previously reported classification scheme, six were classified as tau-negative expression (0, 1+) cases and 14 were classified as tau-positive expression (2+, 3+) cases. All six (100%) cases of tau-negative expression showed a favourable response (partial response or minor response) to Paclitaxel administration. However, 12 (86%) of the 14 cases of tau-positive expression showed progressive disease (n = 11) or no change (n = 1) after Paclitaxel administration. The serum carcinoembryonic antigen values of the six cases of tau-negative expression were markedly decreased in comparison to the 14 tau-positive cases. These data indicate that tau-negative expression can be used to select gastric cancer patients, which will favourably respond to Paclitaxel treatment.

Adenocarcinoma↗
PubMed2006

Creation of tumorigenic human endometrial epithelial cells with intact chromosomes by introducing defined genetic elements.

Several genetic mutations have been identified in human endometrial cancers, but the specific combinations of mutations required to form endometrial cancer cells remain unknown. In the present study, we established an in vitro model of endometrial carcinogenesis, in which defined genetic elements were introduced into endometrial epithelial cells to create transformed endometrial cells at different stages. Introduction of the human papillomavirus type 16 E6/E7 gene and the human telomerase reverse transcriptase (hTERT) gene into human primary endometrial epithelial cells was sufficient to generate immortalized cells. Introduction of hTERT in early passages stabilized telomeres and created immortalized cells with normal karyotype, whereas introduction of hTERT in later passages generated immortalized cells but with widespread chromosome abnormalities. However, neither of those two immortalized cell lines exhibited tumorigenic phenotypes. Tumorigenic endometrial epithelial cells with invasive capacity were created by introducing a mutant K-ras allele into immortalized cells, keeping their chromosomes intact. Inhibiting the PTEN gene and activating Akt pathways did not create tumorigenic phenotypes, although the latter conferred anchorage-independent growth capacity. These findings suggest that neoplastic transformation of human endometrial cells can occur in the absence of widespread chromosomal abnormality, and that the combination of Rb inactivation, telomerase activation and altered K-ras signaling is sufficient for in vitro neoplastic transformation. The present experimental model can help clarify the genetic requirements for endometrial carcinogenesis, and it is useful for testing and developing specific inhibitors of specific oncogenic pathways.

Animals↗
PubMed2006

Docosahexaenoic acid promotes neurogenesis in vitro and in vivo.

Docosahexaenoic acid (22:6n-3), one of the main structural lipids in the mammalian brain, plays crucial roles in the development and function of brain neurons. We examined the effect of docosahexaenoic acid on neuronal differentiation of neural stem cells in vitro and in vivo. Neural stem cells obtained from 15.5-day-old rat embryos were propagated as neurospheres and cultured under differential conditions with or without docosahexaenoic acid for 4 and 7 days. Docosahexaenoic acid significantly increased the number of Tuj1-positive neurons compared with the control on both culture days, and the newborn neurons in the docosahexaenoic acid group were morphologically more mature than in the control. Docosahexaenoic acid significantly decreased the incorporation ratio of 5-bromo-2'-deoxyuridine, the mitotic division marker, during the first 24 h period; it also significantly decreased the number of pyknotic cells on day 7. Thus, docosahexaenoic acid promotes the differentiation of neural stem cells into neurons by promoting cell cycle exit and suppressing cell death. Furthermore, dietary administration of docosahexaenoic acid significantly increased the number of 5-bromo-2'-deoxyuridine(+)/NeuN(+) newborn neurons in the granule cell layer of the dentate gyrus in adult rats. These results demonstrate that docosahexaenoic acid effectively promotes neurogenesis both in vitro and in vivo, suggesting that it has the new property of modulating hippocampal function regulated by neurogenesis.

Animals↗
PubMed2006

Distinct telomere length regulation in premalignant cervical and endometrial lesions: implications for the roles of telomeres in uterine carcinogenesis.

Mouse models show that progressive shortening of telomeres with ageing causes chromosomal instability, which can lead to the initiation of cancer. However, it is unclear what roles telomere shortening plays in human carcinogenesis. The present study has investigated the involvement of telomere dynamics in uterine carcinogenesis. Using telomere-FISH (telo-FISH) assays, telomere lengths in premalignant and malignant cervical and endometrial lesions were measured and compared with chromosomal arm loss or gain. Telo-FISH signals were visualized with Cy3-labelled telomere-specific probes and presented as telomere intensity (TI). Early-stage cervical intraepithelial neoplasias (CINs), especially CIN2, had significantly shorter telomeres than corresponding normal squamous epithelia (p = 0.019), together with increased rates of chromosomal arm loss/gain (p < 0.001). Cervical cancers had relatively short telomeres, but they also showed greater heterogeneity than other sampled tissues, including those with long telomeres. In contrast, there was no significant difference between the telomere length of normal endometrium and of endometrial hyperplasia and endometrial cancer. There was no significant difference in the rate of chromosomal arm loss/gain between normal endometrium and endometrial hyperplasia. These findings suggest that progressive shortening of telomeres occurs in CIN, in association with chromosomal instability, which may play critical roles in cervical carcinogenesis. In contrast, endometrial hyperplasias have relatively stable telomeres without widespread chromosome alteration, implying that endometrial carcinogenesis involves mechanisms distinct from those of cervical carcinogenesis, possibly including microsatellite instability.

Animals↗
PubMed2006

Air trapping on computed tomography images of healthy individuals: effects of respiration and body mass index.

AIM: To evaluate the relationships of changes in the lung area during respiration and of individual body mass index (BMI) to air trapping on expiratory computed tomography (CT) in young non-smoking adults of either gender. METHODS: The volunteers were 10 women and 10 men (mean age 25.7 years) who were healthy lifelong non-smokers. We obtained both end-inspiratory and end-expiratory CT images at three levels: the upper, middle and lower lung. The ratio of cross-sectional lung area upon expiration to cross-sectional lung area upon inspiration (lung area ratio) was determined for each lung at each of the three levels. In cases showing air trapping, we calculated the percentage of area of air in relation to the total lung area in each section. BMI was calculated for each participant. RESULTS: Air trapping was present in dependent areas of the lungs of 6 women and 5 men. The mean percentage of area of air trapped was statistically greater for men (9.8+/-9.2%) than for women (4.9+/-5.2%). The mean lung area ratio was 0.52+/-0 14 among volunteers with air trapping (66 sections) and 0.69+/-0.12 among those without air trapping (54 sections) (p < 0.001). At each lung level, the mean lung area ratio was greater in individuals with air trapping than in those without. Mean BMI was also greater in these people (p = 0.009). CONCLUSION: Change in the respiratory lung area and BMI contribute to development of air trapping.

Adult↗
PubMed2006

Troglitazone inhibits cell growth and induces apoptosis of B-cell acute lymphoblastic leukemia cells with t(14;18).

Peroxisome proliferator-activated receptor-gamma (PPARgamma), a member of the nuclear receptor superfamily, has been detected in several human leukemia cells. Recent studies reported that PPARgamma ligands inhibit cell proliferation and induce apoptosis in both normal and malignant B-lineage cells. We investigated the expression of PPARgamma and the effects of PPARgamma ligands on UTree-O2, Bay91 and 380, three B-cell acute lymphoblastic leukemia (B-ALL) cell lines with t(14;18), which show a poor prognosis, accompanying c-myc abnormality. Western blot analysis identified expression of PPARgamma protein and real-time PCR that of PPARgamma mRNA on the three cell lines. Troglitazone (TGZ), a synthetic PPARgamma ligand, inhibited cell growth in these cell lines in a dose-dependent manner, which was associated with G(1) cell cycle arrest and apoptosis. We also found this effect PPARgamma independent since PPARgamma antagonists failed to reverse this effect. We assessed the expression of c-myc, an apoptosis-regulatory gene, since c-myc abnormality was detected in most B-ALL cells with t(14;18). TGZ was found to dose-dependently downregulate the expression of c-myc mRNA and c-myc protein in the three cell lines. These results suggest that TGZ inhibits cell growth via induction of G(1) cell cycle arrest and apoptosis in these cell lines and that TGZ-induced apoptosis, at least in part, may be related to the downregulation of c-myc expression. Moreover, the downregulation of c-myc expression by TGZ may depend on a PPARgamma-independent mechanism. Further studies indicate that PPARgamma ligands may serve as a therapeutic agent in B-ALL with t(14;18).

Adolescent↗
PubMed2006

Contraction stress in dentin adhesives bonded to dentin.

Adhesives cured under constrained conditions develop contraction stresses. We hypothesized that, with dentin as a bonding substrate, the stress would reach a maximum, followed by a continuous decline. Stress development was determined with a tensilometer for two total-etch systems and two systems with self-etching primers. The adhesives were placed in a thin layer between a glass plate and a flat dentin surface pretreated with phosphoric acid or self-etching primer. After an initial maximum shortly after light-curing, the stress decreased dramatically for the total-etch systems (70%) and, to a lesser extent, for the adhesives with self-etching primers (30%). The greater stress decrease for the total-etch systems was ascribed to water and/or solvents released into the adhesives from the fully opened dentinal tubules by the pulling/sucking action of the contraction stress. This happened less with the adhesives with self-etching primers, where the tubules remained mainly closed.

Analysis of Variance↗
PubMed2006

[Aortic valve replacement in elderly patients with small aortic annulus; is the indexed effective orifice area important?].

We sought to determine whether the small indexed effective orifice area (EOAI) increased mortality and morbidity after aortic valve replacement (AVR) in patients over 75 years of age. From May 1999 to July 2005, 77 patients underwent isolated AVR for aortic stenosis. They were divided into 3 groups (S-EOAI : EOAI < or = 0.7 cm2/m2, M-EOAI : 0.7 cm2/m2 <EOAI < or = 0.85 cm2/ m2, L-EOAI : 0.85cm2/m2 <EOAI) for evaluation. We examined the body surface area (BSA), EOAI, and the left ventricular (LV) mass index (LVMI). We found that patients with S-EOAI had less symptomatic improvement (p <0.05, vs L-EOAI) and LV mass regression (p< 0.01, vs L-EOAI). But, their average New York Heart Association (NYHA) class was improved significantly (2.3 +/- 0.8 vs 1.8 +/- 0.7 : preoperative vs postoperative, p=0.001). Furthermore, severe patient-prosthesis mismatch (PPM) had no significant negative impacts on the freedom of valve-related complications (75.1% : S-EOAI group vs 92.0% : L-EOAI group) and the 5-year survival (84.9% : S-EOAI group vs 87.8% : L-EOAI group). In elderly patients, the average NYHA class was 1.9 +/- 0.6 postoperatively (p<0.0001 vs preoperative) and the LVMI showed significant regression (p<0.0001) despite an average EOAI of 0.73 +/- 0.13 cm2/m2. It is important to consider whether the benefits of avoiding PPM overcome the drawbacks of other complicated techniques. In this study, we found that moderate PPM (0.7 cm2/m2 < or = EOAI) is acceptable to elderly patients.

Aged↗
PubMed2006

[Successful removal of aberrant needles in the pericardium and lung].

A 28-year-old woman who had been diagnosed as schizophrenia was admitted to our hospital, complaining of chest pain. Her chest X-ray demonstrated 9 foreign bodies in the pericardium, lung and others. Her chest computed tomography (CT) confirmed needle-like shadows in the pericardium and lung. They were diagnosed as aberrant needles, and surgically removed. The intrapulmonary aberrant needle was removed with video-assisted thoracoscopic surgery. Aberrant needle in pericardium or lung should be removed surgically, because it is very dangerous. Intraoperative chest X-ray is always necessary before closing the wound to avoid leaving the residual fragments.

Adult↗
PubMed2006

[Lung cancer associated with bulla found during an operation of pneumothorax; report of a case].

A 50-year-old man was admitted to our hospital because of dyspnea. His chest X-ray and computed tomography (CT) showed right pneumothorax and multiple bullae. His pneumothorax was drained with a chest tube, however, because of a persistent air leak, bullectomy was performed 18 days after the occurrence of pneumothorax. Intraoperatively, we found a palpable tumor in the bulla approximately 10 mm in diameter and resected it with the bullae. Histologically, the tumor was diagnosed as a large cell carcinoma.

Blister↗
PubMed2005

Overeruption without root exposure of third molars and periodontal health in the mandible.

Bone formation is seen around the third molar even when the tooth is exposed to the oral environment due to overeruption. To determine if overeruption of the third molar with or without root exposure is related to the status of the exposure of other teeth in the mandible, using orthopantomographs, 424 third molars were studied in 371 patients who were over 41 years of age. The rate of overeruption and root exposure in third molars was measured, and its relationship to the number of teeth lost and the rate of root exposure in other teeth in the mandible was analyzed. Tooth loss in the group of third molars with overeruption without root exposure was greater than in that without overeruption or root exposure in men, whereas the relationship was not seen in women. We found that root exposures of other teeth in the group of third molars with overeruption without root exposure were significantly smaller than in those with root exposure in both genders. Third molars with overeruption without root exposure, in which bone formation was easy to observe for radiographic diagnosis, were correlated with periodontal health in the mandible, suggesting a component of precision determination for predicting resistance to periodontitis.

Adult↗
PubMed2005

Sympathetic alpha-adrenergic regulation of blood flow and volume in hamsters arousing from hibernation.

Mammals arousing from hibernation display pronounced regional heterothermy, where the thoracic and head regions warm faster than the abdominal and hindlimb regions. We used laser-Doppler flowmetry to measure peripheral hind foot blood flow during hibernation and arousal and gamma imaging of technetium-labeled albumin to measure whole blood volume distribution in hamsters arousing from hibernation. It was discovered that the hibernating hamster responds to physical but not to sound or hypercapnic stimulation with rapid, 73% reduction of hind foot blood flow. Hind foot blood flow vasoconstriction was maintained from the onset of arousal until late in arousal when rectal temperature was rapidly increased. alpha-Adrenergic blockade early in arousal increased hind foot blood flow by 700%, suggesting that vasoconstriction was mediated by activation of sympathetic tone. Gamma imaging revealed that, by the early phase of arousal from hibernation, the blood volume of the body below the liver is greatly reduced, whereas blood volumes of the thorax and head are much greater than corresponding volumes in anesthetized hamsters. As arousal progresses and cardiac activity increases and regional heterothermy develops, this regional blood volume distribution is largely maintained; however, blood volume slowly decreases in the thoracic region and slowly increases in the shoulder and head regions. The rapid increase in rectal temperature, characteristic of mid- to late- arousal phases, is probably mediated, in part, by reduction of adrenergic tone on abdominal and hindlimb vasculature. Warm blood then moves into the hind body, produces an increase in temperature, blood flow, and blood volume in the hind body and compensatory reductions of blood volume in the neck, head, and thoracic regions.

Animals↗
PubMed2005

Portal flow into the liver through veins at the site of biliary-enteric anastomosis.

The aim of this study was to establish the role played by jejunal veins in hepatopetal flow after biliary-enteric anastomosis and to evaluate the helical CT features of hepatopetal flow through the anastomosis. We retrospectively analyzed helical CT images of the liver in 31 patients with biliary-enteric anastomosis who underwent hepatic angiography with (n=13) or without (n=18) CT arterial portography within 2 weeks of the CT examination during the last 4 years. Arterial portography showed hepatopetal flow through small vessels located (communicating veins) between the elevated jejunal veins and the intrahepatic portal branches in two (9%) of 22 patients with a normal portal system. Helical CT showed focal parenchymal enhancement around the anastomosis in these two patients. All nine patients with extrahepatic portal vein occlusion (100%) had hepatopetal flow through the anastomosis, and four of the nine had decreased portal flow. CT revealed small communicating veins in two of these four patients. In five patients with normal portal perfusion despite extrahepatic portal vein occlusion, CT detected dilated communicating veins and elevated jejunal veins. The presence of communicating veins and/or focal parenchymal enhancement around the anastomosis indicates hepatopetal flow through the elevated jejunal veins.

Adult↗
PubMed2005

Changes in the properties of mouse tongue muscle fibres before and after weaning.

The purpose of this study was to clarify any changes in muscle fibre properties in different regions of murine tongue during development, and to assess the effects of functional changes including weaning on these muscle fibres. The tongue was divided into upper and lower regions at the lateral margin, and the expression of myosin heavy chain (MHC) isoforms at different ages was investigated. Expression of genes encoding MHC proteins was quantified at the transcription level by quantitative reverse transcriptase polymerase chain reaction, and the protein expression of MHC isoforms was assessed by immunostaining. No difference was found in isoform expression between the upper and lower regions of the tongue before weaning. However, the expression of MHC-2b increased markedly in both regions after weaning, while that of MHC-2a decreased. At the age of 16 weeks, the expression of MHC-2b in the lower region was greater than that in the upper region. These findings show that during weaning, when there is a shift from sucking behaviour to mastication, the expression of MHC-2b increases along with an increase in the speed and strength of muscle contraction. Also, contraction force becomes stronger in the lower region of the tongue than the upper region at the age of 16 weeks.

Animals↗