Search PubMed⌕ Search

Biomedical subjects

K Yamasaki

Publications and source records attributed to K Yamasaki.

At least 19 recordsLinked to original sources
PubMed2006

Pre-B-cell leukemia transcription factor 1 is a major target of promyelocytic leukemia zinc-finger-mediated melanoma cell growth suppression.

Promyelocytic leukemia zinc-finger (PLZF) is a transcriptional repressor and tumor suppressor. PLZF is expressed in melanocytes but not in melanoma cells, and recovery of PLZF expression markedly suppresses melanoma cell growth. Several target genes regulated by PLZF have been identified, but the precise function of PLZF remains uncertain. Here, we searched for candidate target genes of PLZF by DNA microarray analysis. Pre-B-cell leukemia transcription factor 1 (Pbx1) was one of the prominently suppressed genes. Pbx1 was highly expressed in melanoma cells, and its expression was reduced by transduction with the PLZF gene. Moreover, the growth suppression mediated by PLZF was reversed by enforced expression of Pbx1. Knockdown of Pbx1 by specific small interfering RNAs suppressed melanoma cell growth. We also found that Pbx1 binds HoxB7. Reverse transcription-polymerase chain reaction analysis demonstrated that repression of Pbx1 by PLZF reduces the expression of HoxB7 target genes, including tumor-associated neoangiogenesis factors such as basic fibroblast growth factor, angiopoietin-2 and matrix metalloprotease 9. These findings suggest that deregulation of Pbx1 expression owing to loss of PLZF expression contributes to the progression and/or pathogenesis of melanoma.

Angiopoietin-2↗
PubMed2006

[Unusual total anomalous pulmonary venous connection; report of a case].

We report a case of a 7-hour-old infant with total anomalous pulmonary venous connection having abberant origin of the vertical vein. His clinical condition presented hemodynamically severe pulmonary vein obstruction as common pulmonary vein atresia. Without making the definitive diagnosis, he underwent the operation at 11 hours after birth under cardiopulmonary bypass. During the operation, we could not identify the drainage vein. Although we ligated the vessel sized less than 2 mm in diameter draining into superior vena cava which was suspected to be the vertical vein. After the operation pulmonary edema was severe, but his clinical condition improved by using nitric oxide without extracorporeal membrane oxygenation (ECMO) support. Postoperative cardiac catheterization showed normal cardiac function without pulmonary venous obstruction, and moreover identified the drainage vein originated from right upper pulmonary vein. To the best of our knowledge, this is the first case where the vertical vein originated from right upper pulmonary vein. Immediate surgical treatment before the circuratory exacerbation improve the outcome for this congenital anomaly.

Humans↗
PubMed2005

The transport mechanisms of (222)Rn in soil at Tateishi as an anomaly spot in Japan.

The (222)Rn concentration profiles in soil have been measured at an anomaly spot in Tateishi, Japan. In winter, the concentrations were low and showed a negative gradient with depth, but in other seasons, the concentration had both positive and negative gradients with depth, and dramatically changed by time. On the assumption that there was ventilation in deep layers and with driving forces of wind and temperatures, these phenomena were successfully explained. This finding would contribute to a numerical model for (222)Rn transport in soil.

Computer Simulation↗
PubMed2004

Enhancement of nitric oxide and proteoglycan synthesis due to cyclic tensile strain loaded on chondrocytes attached to fibronectin.

OBJECTIVE: Mechanical stress is an essential factor in the pathogenesis of osteoarthrosis. We sought to determine whether the strain-mediated alteration in proteoglycan (PG) synthesis was modulated by nitric oxide (NO) synthesis. METHODS: Cyclic tensile strain was applied to bovine articular chondrocytes. PG and NO synthesis were determined by [35S] sulfate incorporation and chemiluminescence analysis, respectively. To determine the expression of inducible NO synthase (iNOS), quantitative RT-PCR was used. RESULTS: Enhanced PG and NO synthesis were evident when cyclic tensile strain was applied to chondrocytes seeded on fibronectin-coated plates. When NO production was inhibited, PG synthesis was further enhanced. CONCLUSIONS: Cyclic tensile strain loaded on the chondrocytes enhanced NO synthesis and this enhanced NO inhibited PG synthesis.

Animals↗
PubMed2004

Effect of nifedipine on endothelial function in normotensive smokers: potential contribution of increase in circulating hepatocyte growth factor.

Calcium antagonists are reported to have protective effects on the endothelium in vitro and in vivo. Especially, nifedipine, among many calcium antagonists, was shown to improve endothelial dysfunction in patients with hypertension. However, no report has determined whether the improvement of endothelial dysfunction by nifedipine is due to direct effects or indirect effects such as its hypotensive effect. Thus, in this study, we evaluated the direct effects of nifedipine on smoking-induced endothelial dysfunction, since cigarette smoking itself is a major factor in damage of endothelial cells, as well as hypertension. We examined whether nifedipine improves endothelial function in 10 normotensive smokers without any risk factors for atherosclerosis. The subjects were treated with 20 mg nifedipine monotherapy (n = 10) or placebo (n = 10) for 4 weeks. Nifedipine did not affect blood pressure and heart rate of normotensive smokers. We measured forearm blood flow (FBF) by strain-gauge plethysmography after 2 and 4 weeks of treatment. Changes in vasodilator response to reactive hyperaemia were significantly improved in nifedipine-treated subjects (P < 0.05), while there was no significant change in FBP response in control subjects. Response to nitroglycerin was not changed in either group. Moreover, to evaluate the mechanisms of the direct effects of nifedipine on the endothelium, we focused on hepatocyte growth factor (HGF), which is a novel angiogenic growth factor with an antiapoptotic action on endothelial cells. Interestingly, serum HGF concentration in smokers treated with nifedipine was significantly elevated both at 2 and 4 weeks (P < 0.05). Overall, these results demonstrated direct effects of nifedipine in the improvement of endothelial dysfunction in normotensive smokers. The increase in serum HGF concentration by nifedipine might contribute to the improvement of endothelial dysfunction.

Adult↗
PubMed2003

Excitation and decay of the isovector giant monopole resonances via the 208Pb(3He,t p) reaction at 410 MeV.

The excitation and subsequent proton decay of the isovector spin-flip giant monopole resonance (IVSGMR) is studied via the 208Pb(3He,t) reaction at 410 MeV. In the inclusive spectrum (60+/-5)% of the non-energy-weighted sum-rule strength for this 2 variant Planck's over 2h omega resonance was found in the region 29<Ex(208Bi)<51 MeV. The central excitation energy and width of the IVSGMR are 37+/-1 MeV and 14+/-3 MeV, respectively. It is found that the branching ratio for proton decay is (52+/-12)% and that the deep neutron-hole states in 207Pb are strongly fed.

Journal Article↗
PubMed2003

Neurons but not glial cells show reciprocal imprinting of sense and antisense transcripts of Ube3a.

The human UBE3A gene shows brain-specific partial imprinting, and lack of a maternally inherited allele causes Angelman syndrome (AS), which is characterized by neurobehavioral anomalies. In several AS model mice, imprinted Ube3a expression is detected predominantly in the hippocampus, cerebellar Purkinje cells and the olfactory bulb. Therefore, imprinting of mouse Ube3a is thought to be region-specific with different levels of silencing of the paternal Ube3a allele in different brain regions. To determine cell types of imprinted Ube3a expression, we analyzed its imprinting status in embryonic brain cells by using primary cortical cell cultures. RT-PCR and immunofluorescence were performed to determine the allelic expression of the gene. The Ube3a gene encodes two RNA transcripts in the brain, sense and antisense. The sense transcript was expressed maternally in neurons but biallelically in glial cells in the embryonic brain, whereas the antisense transcript was expressed only in neurons and only from the paternal allele. Our data present evidence of brain cell type-specific imprinting, i.e. neuron-specific imprinting of Ube3a in primary brain cell cultures. Reciprocal imprinting of sense and antisense transcripts present only in neurons suggests that the neuron-specific imprinting mechanism is related to the lineage determination of neural stem cells.

Angelman Syndrome↗
PubMed2003

Inhibition of NFkappaB activation using cis-element 'decoy' of NFkappaB binding site reduces neointimal formation in porcine balloon-injured coronary artery model.

Application of DNA technology to regulate the transcription of disease-related genes has important therapeutic potential. The transcription factor NFkappaB plays a pivotal role in the transactivation of inflammatory and adhesion molecule genes, leading to vascular lesion formation. Double-stranded DNA with high affinity for NFkappaB may be introduced as 'decoy' cis elements to bind NFkappaB and block the activation of genes mediating inflammation, resulting in effective drugs for treating intimal hyperplasia. In this study, we tested the feasibility of NFkappaB decoy therapy to treat neointimal formation in a porcine coronary artery balloon injury model as a pre-clinical study. An angioplasty catheter was introduced into the left anterior descending coronary artery of the pig to cause vascular injury. First, we tested the feasibility of transfection of FITC-labeled NFkappaB decoy ODN using a hydrogel balloon catheter. Fluorescence due to NFkappaB decoy ODN could be detected throughout the medial layer. Therefore, we transfected NFkappaB decoy ODN into the balloon-injured LAD using a hydrogel catheter. Histological evaluation demonstrated that the neointimal area in the balloon-injured artery was significantly reduced by NFkappaB decoy ODN as compared to scrambled decoy ODN at 1 week after single transfection, accompanied by a significant reduction in PCNA-positive stained cells (P < 0.01). Interestingly, the reduction of ICAM-positive staining was observed, accompanied by the inhibition of migration of macrophages. Of importance, intravascular ultrasound (IVUS) confirmed that neointimal area in the balloon-injured artery was significantly reduced by NFkappaB decoy ODN at 4 weeks after transfection (P < 0.01). Interestingly, the inhibition of neointimal area was only limited to the lesion transfected with NFkappaB decoy ODN, while other lesions without NFkappaB decoy ODN demonstrated a marked increase in neointimal formation. Here, we report the successful in vivo transfer of NFkappaB decoy ODN using a hydrogel catheter to inhibit vascular lesion formation in balloon-injured porcine coronary artery.

Angioplasty, Balloon, Coronary↗
PubMed2003

Relationship between cognitive function and mastication in elderly females.

In Japan, the elderly population suffering from dementia is rapidly increasing. Several animal studies have indicated a relationship between reduced masticatory function in the elderly subject and cognitive impairment. However, epidemiological studies examining this have been scarce. Using an epidemiological approach, the present study investigated this relationship in 44 females with and 44 without dementia, all aged over 65 years. Age and basic activities of daily living, such as walking, eating, excreting, bathing and dressing, were matched in the two groups. Cognitive impairment of the subjects was measured using the revised Hasegawa Dementia Rating Scale. Masticatory function was assessed in terms of the number of teeth present, maximum bite force, occlusal contact area, and mastication score. The number of teeth present in cognitively normal subjects was significantly higher than in cognitively impaired subjects (P < 0.05). In addition, maximum bite force, occlusal contact area, and mastication scores of cognitively normal subjects were significantly higher than those of cognitively impaired subjects (P < 0.01). These results suggest that masticatory function in the elderly person is associated with cognitive status.

Activities of Daily Living↗
PubMed2003

[Selection of surgical strategy for abdominal aortic aneurysm coexisting with coronary artery disease; one-stage versus two-stage, and off-pump versus on-pump].

BACKGROUND: In patients having a combination of severe coronary artery disease (CAD) and expanding abdominal aortic aneurysm (AAA), one-stage operation of simultaneous coronary artery bypass grafting (CABG) and AAA repair has been recommended. METHODS AND RESULTS: Of 96 patients (94 men, average 65 year) with AAA and CAD, 21 patients underwent one-stage operation of simultaneous CABG and AAA repair (Group A-1: off-pump CABG in 10 and on-pump in 11), and 75 underwent two-stage operation of CABG followed by AAA with an interval of less than 6 months in 23 patients (Group A-2) and more than 6 months in 52 patients (Group B). Baseline characteristics were similar between the one-stage and two-stage groups, and off-pump and on-pump subgroups, except the proportion of single vessel disease. Mean number of distal anastomoses was significantly lower in the off-pump subgroup than in the on-pump subgroup (p = 0.011) and the two-stage group (p = 0.0057). There was 1 hospital death among on-pump patients but none among off-pump patients. Mortality rate was 4.8% in the one-stage group. Two patients (8.7 &) in the two-stage group, who had AAA was 7.0 cm and 7.5 cm diameter, died of AAA rupture prior to repair. The 10-year all death free rates were 44% in Group A (A-1 and A-2), and 86% in Group B (p = 0.0004). CONCLUSIONS: Our data suggest that one-stage operation with off-pump CABG is an attractive option in selected patients with a large AAA (> 7 cm).

Aged↗
PubMed2003

[Off-pump versus standard on-pump reoperative coronary artery bypass grafting].

BACKGROUND: Using standard on-pump procedures, repeat coronary artery bypass grafting (re-CABGs) are associated with a higher morbidity and mortality than first-time CABGs. This retrospective study assessed the clinical outcomes of off-pump re-CABG versus on-pump re-CABG. METHODS: From 1983, 2nd CABG and 3rd CABGs were performed in 162 patients at our institute. The early and late results of 142 patients who received standard on-pump re-CABGs and 20 patients who received off-pump re-CABGs were evaluated. The 2 groups were similar in age, sex, preoperative ejection fraction (EF) and number of coronary lesions. However, mean number of distal anastomoses per patient was significantly higher in on-pump (2.0 +/- 0.8) than in off-pump re-CABG (1.4 +/- 0.6) [p = 0.0009]. RESULTS: Hospital mortality tended to be higher in the on-pump group (5.6%) than in the off-pump group (0%) [p = 0.6]. Morbidity in term of total postoperative complications tended to be higher for on-pump (14.1%) than in off-pump (0%) [p = 0.14]. The 5-year survival rate tended to be higher in the off-pump group (100%) than in the on-pump group (80.8 +/- 3.5%) [p = 0.096]. CONCLUSIONS: In selected patients, off-pump re-CABG can be a reliable and safe option. The mid-term survival and event-free survival rates achievable with the off-pump option are encouraging.

Aged↗
PubMed2002

History of allergic disorders in common neurologic diseases in Japanese patients.

OBJECTIVE: To clarify the association between past and present history of allergic disorders and neurologic diseases. METHODS: The past and present history of common allergic disorders together with family history was prospectively studied in all out-patients at the Department of Neurology at Kyushu University Hospital from March 1998 to February 2000. RESULTS: Among 3113 out-patients, 2152 (69.1%) completed a questionnaire. Myelitis showed a statistically significant increase of concomitant atopic dermatitis (P=0.006) and concomitant and past atopic dermatitis (P=0.014), as compared with neurologically healthy controls. Moreover, patients with lower motoneuron disease (LMND) had a statistically significant increase of past and concomitant asthma (P=0.007). None of the other common neurologic diseases showed any increase of allergic disorders when compared with controls. CONCLUSIONS: The present study supports the significant association between allergic disorders and such spinal cord diseases as myelitis and LMND in Japanese patients.

Adolescent↗
PubMed2002

Molecular strategy using cis-element 'decoy' of E2F binding site inhibits neointimal formation in porcine balloon-injured coronary artery model.

Transcription factor E2F plays a pivotal role in the transactivation of cell cycle regulatory genes, leading to vascular lesion formation. Double-stranded DNA with high affinity for E2F as 'decoy' cis elements may block the activation of genes mediating the cell cycle, resulting in an effective therapeutic agent for treating intimal hyperplasia. In this study, we tested the feasibility of E2F decoy therapy to treat neointimal formation in a porcine coronary artery balloon injury model. An angioplasty catheter was inserted in the left anterior descending coronary artery of pigs to cause vascular injury. Initially, we tested the feasibility of transfection of FITC-labeled E2F decoy ODN using a hydrogel balloon catheter. Fluorescence due to E2F decoy ODN could be detected throughout the medial layer. Therefore, we transfected E2F decoy ODN into the balloon-injured artery using hydrogel catheter. Of importance, intravascular ultrasound (IVUS) and histological evaluation demonstrated that plaque area in the balloon-injured artery was significantly reduced by E2F decoy ODN compared with mismatched decoy ODN at 1 month after a single transfection (P < 0.01). In contrast, luminal and total vessel areas were significantly increased in vessels treated with E2F decoy ODN as compared with mismatched decoy. Endothelial function after angioplasty was not affected by E2F decoy transfection. Finally, we tested the acute toxicity of E2F decoy ODN in monkeys, and no apparent side-effects were detected. Here, we report the successful in vivo transfer of E2F decoy ODN using a hydrogel catheter to inhibit vascular lesion formation in balloon-injured porcine coronary artery without any apparent side-effects.

Angioplasty, Balloon, Coronary↗
PubMed2002

Impaired endothelial dysfunction in diabetes mellitus rats was restored by oral administration of prostaglandin I2 analogue.

We have previously reported that a decrease in hepatocyte growth factor (HGF), which has many protective functions against endothelial damage by high d-glucose, might be a trigger of endothelial injury. However, the regulation of vascular HGF in diabetes mellitus (DM) has not been clarified in vivo, although vascular disease is frequently observed in DM patients. In addition, our previous report revealed that a prostaglandin I(2) (PGI(2)) analogue prevented endothelial cell death through the induction of vascular HGF production in cultured human epithelial cells. Thus, in this study, we examined the effects of a PGI(2) analogue in the regulation of the local HGF system using DM rats. A PGI(2) analogue (beraprost sodium; 300 and 600 micro g/kg per day) or vehicle was administered to 16-week-old DM rats induced by administration of streptozotocin for 28 days. Endothelial function was evaluated by the vasodilator response to acetylcholine, and the expression of vascular HGF mRNA was measured by Northern blotting. Of importance, expression of HGF mRNA was significantly decreased in the blood vessels of DM rats as compared with non-DM (P<0.01). In addition, the in vitro vasodilator response of the abdominal aorta to acetylcholine was markedly impaired in DM rats. Importantly, the vasodilator response was restored by PGI(2) treatment in a dose-dependent manner (P<0.01), whereas N(omega)-nitro-l-arginine methyl ester inhibited the restoration of endothelial function. Of particular interest, vascular HGF mRNA and protein were significantly increased in the blood vessels of DM rats treated with PGI(2) as compared with vehicle. Similarly, an increase in HGF protein was also confirmed by immunohistochemical analysis. In addition, the specific HGF receptor, c-met, was also increased by PGI(2) treatment. Overall, this study demonstrated that treatment with a PGI(2) analogue restored endothelial dysfunction in DM rats, accompanied by the induction of vascular HGF and c-met expression. Increased local vascular HGF production by a PGI(2) analogue may prevent endothelial injury, potentially resulting in the improvement of endothelial dysfunction.

Acetylcholine↗
PubMed2001

Therapeutic angiogenesis induced by human hepatocyte growth factor gene in rat diabetic hind limb ischemia model: molecular mechanisms of delayed angiogenesis in diabetes.

BACKGROUND: Because no study has documented the angiogenic properties of hepatocyte growth factor (HGF) in a diabetes model, we examined the feasibility of gene therapy using HGF to treat peripheral arterial disease in diabetes. METHODS AND RESULTS: Because intramuscular injection of luciferase plasmid by the hemagglutinating virus of Japan (HVJ)-liposome method had much higher efficiency than injection of naked plasmid, we used the HVJ-liposome method to transfect the human HGF gene into the rat diabetic hindlimb model. As expected, transfection of human HGF vector resulted in a significant increase in blood flow as assessed by laser Doppler imaging and capillary density, even in the diabetes model, accompanied by the detection of human HGF protein. Interestingly, the degree of natural recovery of blood flow was significantly greater in nondiabetic rats than in diabetic rats. Thus, in an in vitro culture system, we further studied the molecular mechanisms of how diabetes delayed angiogenesis. Importantly, high-D-glucose treatment of endothelial cells resulted in a significant decrease in matrix metalloproteinase (MMP)-1 protein and ets-1 expression in human aortic endothelial cells. Similarly, high D-glucose significantly decreased mRNA and protein of HGF in endothelial cells. Downregulation of MMP-1 and ets-1 by high D-glucose might be due to a significant decrease in HGF, because HGF stimulated MMP-1 production and activated ets-1. CONCLUSIONS: Overall, intramuscular injection of human HGF plasmid induced therapeutic angiogenesis in a rat diabetic ischemic hindlimb model as a potential therapy for peripheral arterial disease. The delay of angiogenesis in diabetes might be due to downregulation of MMP-1 and ets-1 through a decrease in HGF by high D-glucose.

Animals↗