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H Sasaki

Publications and source records attributed to H Sasaki.

At least 73 records · Page 4Linked to original sources
PubMed2003

Increased susceptibility to airway responses in CD40-deficient mice.

The interaction between CD40 and its ligand (CD154) is crucial for IL-12 production and effective humoral immunity such as IgE production. Although the interaction seems to play a crucial role in asthmatic inflammation, previous studies investigating the role of the CD40 and CD154 interaction in experimental animal models of asthma are complicated due to multistep reactions in developing asthma. Here, in order to investigate the role of CD40 in the effector phase in the development of airway responses, we used CD40-deficient mice backcrossed with mice transgenic for an ovalbumin (OVA)-specific TCR (TCRtg). Using intranasal OVA administration followed by aerosol inhalation of OVA, greater airway hyperreactivity and eosinophilia in bronchoalveolar lavage fluid (BALF) were observed in CD40-deficient mice backcrossed with TCRtg mice (CD40-/-/ TCRtg mice), compared with control littermates (CD40+/+/ TCRtg mice). CD4+ helper T cell subset analysis of lung draining lymph nodes revealed that the Th1 component was significantly decreased in CD40-/-/ TCRtg mice. Airway hyperreactivity and airway eosinophilia significantly correlated with the predomination of Th2 cells. Cytokine measurements in BALF also showed decreased IL-12 and the predominance of Th2 cells in CD40-/-/ TCRtg mice. These results suggest that CD40 may play a protective role in developing asthma in the phase after establishing specific memory T cells through the regulation of the balance between Th1 and Th2 cells presumably via induction of IL-12.

Animals↗
PubMed2003

Expression of Id2 mRNA in neuroblastoma and normal ganglion.

AIMS: Inhibitors of DNA binding 2 (Id2) has been reported to be overexpressed in neuroblastoma cell lines carrying extra copies of the N-myc gene. It has been suggested that Id2 may be involved in the disturbed regulation of cell cycle by interfering with retinoblastoma protein. METHODS: In this report we assessed Id2 gene expression in 20 neuroblastoma samples and eight normal ganglion tissues using quantitative reverse transcription-PCR (RT-PCR). Id2 expression in resected clinical samples of neuroblastoma needs to be studied. RESULTS: Id2 messenger RNA (mRNA) was expressed in all the neuroblastoma samples. The level of Id2 mRNA expression was not influenced by the patient's age, gender, tumor's clinical stage, DNA ploidy pattern, histological pattern, the level of N-myc mRNA expression and whether the patient was found by mass screening or by symptom. Id2 was also expressed in comparable levels in normal differentiated sympathetic ganglion in adult. CONCLUSION: Our data suggest that Id2's role in the oncogenesis or progression of neuroblastoma is minimal.

DNA-Binding Proteins↗
PubMed2003

The hereditary spinocerebellar ataxias in Japan.

In Japan, multiple system atrophy (MSA) accounts for 40% of all spinocerebellar ataxias (SCAs) and hereditary disorders account for 30%. Among the latter, autosomal dominant disorders are common and recessive ataxias are rare. Although the frequency of SCA genotypes differs between geographic regions throughout Japan, SCA6, SCA3/MJD, and DRPLA are the three major disorders, while SCA7, SCA8, SCA10, SCA12, and SCA17 are infrequent or almost undetected. SCA1 predominantly occurs in the northern part of Japan. Overall, 20-40% of dominant SCAs are due to unknown mutations. From this cluster, pure cerebellar ataxias linked with the SCA4, SCA14, and SCA16 locus have been isolated. Among the recessive SCAs, patients with AVED and EAOH have been detected. However, FRDA associated with GAA repeat expansion in the frataxin gene has not been reported so far.

DNA Repeat Expansion↗
PubMed2003

Hedgehog signaling enhances core-binding factor a1 and receptor activator of nuclear factor-kappaB ligand (RANKL) gene expression in chondrocytes.

Hedgehog signaling is considered to play a crucial role in chondrogenesis by regulation through a network of cytokine actions, which is not fully understood. We examined the effect of hedgehog signaling on the expression of core-binding factor a1 (Cbfa1), a critical transcription factor for the development of bone and cartilage. Primary chondrocytes prepared from the costal cartilage of newborn mice were treated with N-terminal fragment of recombinant murine sonic hedgehog (rmShh-N). Northern blot analysis indicated that Cbfa1 mRNA expression levels in the chondrocyte cultures were elevated by the treatment with rmShh-N. rmShh-N treatment enhanced 1.8 kb Cbfa1 promoter activity in chondrocytes, suggesting the presence of transcriptional control. As Cbfa1-binding site(s) have been located in the promoter of the receptor activator of nuclear factor-kappaB (RANK) ligand (RANKL) gene, we also examined RANKL expression. rmShh-N treatment upregulated RANKL and RANK mRNA expression levels in chondrocytes. Interestingly, RANKL suppressed the hedgehog enhancement of alkaline phosphatase activity in chondrocytes, suggesting the presence of a link between these signaling molecules. We conclude that hedgehog signaling activates Cbfa1 gene expression through its promoter in chondrocytes, and also activates and interacts with RANKL to maintain cartilage development.

Analysis of Variance↗
PubMed2003

[Off-pump coronary artery bypass grafting for octogenarians with acute coronary syndrome].

In recent years, experiences with performing off-pump coronary artery bypass (OPCAB) has increased dramatically. Many early reports suggest that this approach may improve outcome by lowering postoperative complications. The benefit of this procedure to elderly patients seems appealing but is not well studied. We sought to review our experience with OPCAB in octogenarians with acute coronary syndrome (ACS) to better define the potential benefit of this approach in this high-risk group of patients. Until March 2003, OPCAB was performed in 21 octogenarians (10 men and 11 women with mean age of 82.9 +/- 2.8 years) with ACS at the department of cardiovascular surgery of National Kanazawa Hospital. Two had myocardial infarction and 3 unstable angina. Mean left ventricular ejection function was 41.2%. 14 patients had a history of previous cerebral infarction. All procedures were completed without hemodynamic deterioration and conversion to on-pump coronary artery bypass grafting (CABG). There was no operative mortality and no occurrence of major complications such as low output syndrome, re-exploration for bleeding, cerebral infarction, perioperative myocardial infarction, and mediastinitis. And no further deterioration of organ function occurred in patients with preexisting central nervous system dysfunction or kidney. Peak CK-MB concentrations after surgery were within normal limits. This study demonstrates that CABG can be performed safely on high-risk ACS patients 80 years of age and older without the use of cardiopulmonary bypass. OPCAB may be the operation of choice for octogenarians with ACS requiring surgical myocardial revascularization.

Aged↗
PubMed2003

Effects of creatine loading on muscular strength and endurance of female softball players.

AIM: The purpose of this study was to determine the effects of Cr supplementation on muscle strength and endurance of the trained females, the effect of anaerobic exercises performed before the supplementation and disappearance of the effects on the performance. METHODS: Twenty-six collegiate female softball players were divided into the Cr1, 2, Control (Cont.)1 or 2 group, randomly. They performed maximal 2-isometric and 30-isokinetic knee extensions at the angular velocities of 180 degrees and 60 degrees /s. Thereafter, the subjects of the Cr2 and Cont.2 groups performed resistance exercises with 10 RM and cycling with 0.01 kg x kg-1 body weight, alternately during the 1(st) week. During the 2(nd) week, the subjects of the Cr1 and 2 groups ingested 20 g Cr a day for 1 week. Thereafter, the subjects in the Cr2 group continued 3 g Cr ingestion a day for 2 weeks while the Cr1 group ingested the same amount of placebo during the 3(rd) and 4(th) weeks. The subjects of the Cont.1, 2 groups ingested the same amount and taste of placebo during the 1(st) to 4(th) weeks. This study was undergone in double blind fashion. The similar measurements, to which the subjects performed the 1(st) day, were carried out on the final day of the 2(nd), 3(rd) and 4(th) weeks. RESULTS: Though maximal isometric strength did not differ in intra- and intergroups, the isokinetic peak torque in the Cr1 group was significantly decreased in the 4(th) measurement (p<0.01). The mean torque of the 1(st) to 10th knee contractions at 60 inverted exclamation mark /s was significantly decreased from the 2(nd) measurement in the Cont.1, 2 groups, compared with that in the 1(st) measurement (p<0.01). In the Cr groups, the significant decrease was detected from the 3(rd) in the Cr1 and in the 4(th) measurement in the Cr2 group. The mean torque of the latter 20 contractions at 180 inverted exclamation mark /s was significantly increased in the Cr2 group (p<0.001). In the 1(st) measurement, the mean torque in the Cr1 group was significantly higher than that in the Cr2 group (p<0.05). However, the differences between Cr1 and 2 groups were not detected from the 2(nd) measurement. CONCLUSION: Twenty g Cr supplementation a day for a week to the trained females improves not the maximal static strength and dynamic peak torque but the mean strength and endurance of repeated contractions. However, the effects on females are not so great as that ever found in males. The effects are enhanced by anaerobic exercises performed before the supplementation and would disappear in a week if the supplementation were stopped.

Adolescent↗
PubMed2002

Boundary element method-based cortical potential imaging of somatosensory evoked potentials using subjects' magnetic resonance images.

A boundary element method-based cortical potential imaging technique has been developed to directly link the scalp potentials with the cortical potentials with the aid of magnetic resonance images of the subjects. First, computer simulations were conducted to evaluate the new approach in a concentric three-sphere inhomogeneous head model. Second, the corresponding cortical potentials were estimated from the patients' preoperative scalp somatosensory evoked potentials (SEPs) based on the boundary element models constructed from subjects' magnetic resonance images and compared to the postoperative direct cortical potential recordings in the same patients. Simulation results demonstrated that the cortical potentials can be estimated from the scalp potentials using different scalp electrode configurations and are robust against measurement noise. The cortical imaging analysis of the preoperative scalp SEPs recorded from patients using the present approach showed high consistency in spatial pattern with the postoperative direct cortical potential recordings. Quantitative comparison between the estimated and the directly recorded subdural grid potentials resulted in reasonably high correlation coefficients in cases studied. Amplitude difference between the estimated and the recorded potentials was also observed as indexed by the relative error, and the possible underlying reasons are discussed. The present numerical and experimental results validate the boundary element method-based cortical potential imaging approach and demonstrate the feasibility of the new approach in noninvasive high-resolution imaging of brain electric activities from scalp potential measurement and magnetic resonance images.

Algorithms↗
PubMed2002

Sequence analysis of the pro-opiomelanocortin (POMC) gene in obese/diabetic Japanese.

Pro-opiomelanocortin (POMC)-derived peptides play a critical role in body weight regulation in the central nervous system. Mice deficient in POMC developed obesity. We sought mutations in the POMC gene in 50 morbidly obese (body mass index 35-60 kg/m(2)) Japanese subjects with diabetes by direct sequencing. Apart from two silent mutations (C6982T and C7285T), no other mutations were detected. Frequencies of these mutations were not significantly different between 100 obese subjects and 100 controls. Also, the frequencies did not differ in the subjects with or without diabetes. These results suggest that mutations in the POMC gene are unlikely to be a major factor of obesity or diabetes in Japanese subjects.

Body Mass Index↗
PubMed2002

Chemotherapy targeting methylthioadenosine phosphorylase (MTAP) deficiency in adult T cell leukemia (ATL).

Methylthioadenosine phosphorylase (MTAP) is an important enzyme used for the salvage of adenine and methionine. Cells lacking this enzyme are expected to be sensitive to purine synthesis inhibitors and/or methionine starvation. We reported previously that the MTAP gene is deleted in adult T cell leukemia (ATL) cells. In the present study, we expanded our series and used a real-time quantitative PCR assay for accurate diagnosis of the deletion and nine of 65 primary ATL samples (13.8%) were MTAP negative. In spite of this low incidence, ATL cells showed significantly higher sensitivity to L-alanosine, an inhibitor of de novo adenosine monophosphate (AMP) synthesis, than normal lymphocytes, suggesting that the MTAP gene is inactivated not only by deletion but also by other mechanisms. Indeed, a real-time quantitative RT-PCR assay disclosed that primary ATL cells had significantly lower MTAP mRNA expression than normal lymphocytes. Since MTAP-negative ATL cell lines also showed much higher sensitivity to L-alanosine than MTAP-positive ATL cell lines, we used these cell lines to investigate whether it is possible to develop selective therapy targeting MTAP deficiency. A substrate of MTAP, methylthioadenosine (MTA) or its substitutes rescued concanavalin A (Con A)-activated normal lymphocyte proliferation from L-alanosine toxicity. All the compounds except 5'-deoxyadenosine, however, also caused the undesirable rescue of MTAP-negative ATL cell lines. 5'-Deoxyadenosine had the desired ability to rescue hematopoietic progenitor cells without rescuing ATL cell lines. These results support the rationale for a chemotherapy regimen of L-alanosine combined with 5'-deoxyadenosine rescue in MTAP-deficient ATL.

Adenosine Monophosphate↗
PubMed2002

A case of febrile ulceronecrotic Mucha-Habermann disease requiring debridement of necrotic skin and epidermal autograft.

We report a case of febrile ulceronecrotic Mucha-Habermann disease (FUMHD) in a 21-year-old man. This disease is a severe form of pityriasis lichenoides et varioliformis acuta (PLEVA) and is characterized by the sudden onset of diffuse ulcerations associated with high fever and systemic symptoms. It is sometimes lethal especially in elderly patients. In the present case, intense generalized maculopapular erythematous plaques with central necrosis developed progressively in association with a high fever. Initial treatment with systemic betamethasone had been unsuccessful and the skin lesions, which covered about 50% of the body surface, became severely ulcerated. Although the development of new lesions had ceased spontaneously, widespread ulceration of the skin remained. Debridement of the necrotic skin and skin grafting using cultured epidermal autografts and meshed allografts of cadaver skin led to prompt reepithelization.

Adult↗
PubMed2002

Neurochemical regulation of cough response to capsaicin in guinea-pigs.

1. Although monumental efforts have been made to define the action sites of cough, the importance of neurotransmitter systems in the cough reflex has received limited attention. We studied the roles for four major neurotransmitters [acetylcholine, histamine, serotonin (5-hydroxytryptamine, 5-HT) and dopamine] in the modulation of the cough reflex. 2. Atropine (muscarinic cholinergic blocking agent), pyrilamine maleate (PM, histamine H1 blocker), cimetidine (histamine H2 blocker), 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT, specific 5-HT1A receptor agonist) and SCH-23390 (selective dopamine D1 receptor antagonist) were examined on the cough response to inhaled capsaicin in conscious guinea-pigs. 3. All the drugs significantly decreased the number of capsaicin-induced coughs in a dose-dependent manner. To compare the sensitivity of these drugs on cough response, we calculated the effective doses for 50% inhibition of cough (ED50) when the animals were exposed to 3 x 10-4 m capsaicin. The ED50 values were 0.03 microm kg-1 for atropine, 0.2 microm kg-1 for 8-OH-DPAT, 6.2 microm kg-1 for SCH-23390, 8.5 microm kg-1 for PM and 13.9 microm kg-1 for cimetidine. 4. These findings indicated that all these four neurotransmitters may be involved in the regulation of the cough reflex. Multiple changes of these neurotransmitters in disorders of the central nervous system might synergically affect the cough reflex.

Animals↗
PubMed2002

Relationships of the systolic blood pressure response during exercise with insulin resistance, obesity, and endurance fitness in men with type 2 diabetes mellitus.

The purpose of the present study was to investigate the relationships among the resting systolic (SBP) and diastolic blood pressure (DBP) or SBP response during exercise with insulin resistance evaluated by a homeostasis model (HOMA-IR), abdominal fat accumulation (visceral fat area [VFA], subcutaneous fat area [SFA]) by computed tomography (CT), and an estimation of the maximal oxygen uptake (V*O2max) in 63 Japanese middle-aged male patients with type 2 diabetes mellitus (type 2 DM). Body mass index (BMI) and waist-to-hip ratio (WHR) in type 2 DM subjects were significantly higher than in age-matched healthy male control subjects (n = 135) with normal glucose tolerance. Resting SBP (127.7 +/- 16.2 mm Hg v 119.4 +/- 13.0 mm Hg) and DBP (82.2 +/- 11.9mmHg v 76.8 +/- 9.4 mm Hg) levels, and the percentage of hypertension (20.6% v 1.5%) in type 2 DM subjects were significantly higher than in the control subjects (P <.05). According to a multiple regression analysis for resting blood pressure in type 2 DM, VFA was found to be an independent predictor of SBP, while V*O2max and HOMA-IR were independent predictors of DBP. In the controls, however, HOMA-IR was not found to be a significantly independent predictor for either resting SBP or resting DBP. Measurement of the SBP response during graded exercise using a ramp test was performed by an electrical braked cycle ergometer in 54 patients with type 2 DM only. The SBP was measured at 15-second intervals during exercise. The exercise intensity at the double product breaking point (DPBP), which strongly correlated with the exercise intensity at the lactate threshold, was used as an index for the SBP response to standardized exercise intensity. The SBP corresponding to exercise intensity at DPBP (SBP@DPBP) was evaluated as an index of the SBP response to standardized exercise intensity. The change in SBP (deltaSBP = SBP@DPBP - resting SBP) was significantly and positively associated with log area under the curve for glucose (log AUCPG) during a 75-g oral glucose tolerance test (OGTT). In addition, deltaSBP significantly and negatively correlated with the log area under the curve for insulin (log AUCIRI) and log AUCIRI/log AUCPG. Based on these results, insulin resistance was suggested to be independently associated with the resting DBP and SBP response to standardized exercise intensity in type 2 DM patients.

Anthropometry↗
PubMed2002

[Long-term results after femoral vein valve repair for chronic venous insufficiency].

OBJECTIVE: Our long-term results with anterior venous sinus plication (AVSP) for femoral vein reconstruction will be presented. PATIENTS AND METHODS: Between 1986 and 2001 we treated 2 100 patients in our hospital for chronic venous insufficiency. In 3.3 % of the patients (n = 70) an AVSP of the target valve, which is the highest valve of the femoral vein distally of the profundal vein branch was carried out. 50 patients could be followed for 2-15 (average 4.6) years postoperatively by phlebographic control. RESULTS: Four recovery patterns after valve repair were seen on venography. The most typical type was the plicated site stop seen in 22 of 50 patients (44 %). Here the venous reflux was stopped at the plicated site directly. The clinical results were good or excellent for all patients. No patient underwent a second procedure for recurrence of the symptoms. A profundal femoral vein reflux did not negatively influence patient outcome. CONCLUSION: AVSP is an excellent method of valve repair in strictly selected patients with chronic venous insufficiency (= no postthrombotic syndrome, no thrombotic occlusion of the femoral veins). Long-term results up to 15 years were highly satisfactory.

Adult↗