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Biomedical subjects

S Ichikawa

Publications and source records attributed to S Ichikawa.

At least 19 recordsLinked to original sources
PubMed2006

Elevated arterial stiffness in postmenopausal women with osteoporosis.

OBJECTIVES: Osteoporosis and increased pulse wave velocity (PWV) are cardiovascular risk factors. We investigated the relationship between PWV and bone mass in the lumbar spine in postmenopausal women. METHODS: We studied the PWV in 95 women; 38 postmenopausal women with normal spinal bone mineral density (BMD), 32 osteopenic postmenopausal women, and 25 osteoporotic postmenopausal women. The brachial-ankle PWV (baPWV) was measured using an automated device. The BMD of the lumbar spine (L2-L4) was measured using dual-energy X-ray absorptiometry. RESULTS: After adjusting for age and years since menopause, women with osteoporosis had a significantly higher baPWV than those with normal BMD (1500 +/- 220 cm/s versus 1340 +/- 215 cm/s; P < 0.05), but no significant differences in baPWV were seen between the osteoporotic and osteopenic groups or between the osteopenic and normal BMD groups. In univariate regression analysis, the baPWV was significantly negatively correlated with BMD (r = -0.450, P < 0.01), and significantly positively correlated with age (r = 0.601, P < 0.01), years since menopause (r = 0.577, P < 0.01), systolic blood pressure (r = 0.295, P < 0.01), and diastolic blood pressure (r = 0.264, P < 0.05), but was not with other variables. In multivariate regression analysis, the baPWV was significantly correlated with BMD (P < 0.05), but not with other variables. CONCLUSIONS: Postmenopausal women with osteoporosis may have elevated arterial stiffness, suggesting that osteoporotic postmenopausal women may have a higher risk of cardiovascular disease.

Absorptiometry, Photon↗
PubMed2006

Effects of torasemide on cardiac sympathetic nerve activity and left ventricular remodelling in patients with congestive heart failure.

OBJECTIVE: To determine the effect of torasemide, a loop diuretic with antialdosteronergic properties, compared with furosemide on cardiac sympathetic nerve activity in patients with congestive heart failure (CHF). METHODS: 40 patients with non-ischaemic CHF (left ventricular ejection fraction (LVEF) < 45%) were randomly assigned to torasemide (4-8 mg/day; n = 20) or furosemide (20-40 mg/day; n = 20). All patients were also treated with angiotensin-converting enzyme inhibitor. The delayed heart to mediastinum count (H/M) ratio, delayed total defect score (TDS) and washout rate were determined from iodine-123 meta-iodobenzylguanidine measured before and 6 months after treatment. Left ventricular end diastolic volume (LVEDV), left ventricular end systolic volume (LVESV) and LVEF were also determined by echocardiography. RESULTS: After treatment, in patients receiving torasemide, TDS decreased from 44 (8) to 36 (8) (p < 0.001), H/M ratio increased from 1.61 (0.19) to 1.77 (0.24) (p < 0.001), and washout rate decreased from 52 (12)% to 41 (14)% (p = 0.001). In addition, LVEDV decreased from 173 (22) ml to 147 (30) ml (p < 0.001) and LVESV decreased from 117 (19) ml to 95(24) ml (p < 0.001). Although LVEF tended to increase, the change was not significant (from 31 (7)% to 34 (7)%, NS). Conversely, these parameters did not change significantly in patients receiving furosemide. Moreover, percentage change of TDS was significantly correlated with percentage change of LVEDV (r = 0.473, p < 0.05) and of LVESV (r = 0.579, p < 0.01) after torasemide treatment. CONCLUSION: These findings indicate that torasemide treatment can ameliorate cardiac sympathetic nerve activity and left ventricular remodelling in patients with CHF.

Aged↗
PubMed2006

Polymorphisms in the bone morphogenetic protein 2 (BMP2) gene do not affect bone mineral density in white men or women.

INTRODUCTION: Peak bone mineral density (BMD) achieved during adulthood is a major determinant of osteoporotic fracture in later life. Although environmental factors affect peak BMD, it is a highly heritable trait. Recently, bone morphogenetic protein 2 (BMP2) was reported as a susceptibility gene for osteoporotic fractures and low BMD in Icelandic and Danish populations. METHODS: To determine whether polymorphisms in the BMP2 gene contribute to BMD variation in our population of healthy American whites, we tested seven single nucleotide polymorphisms (SNPs), four of which were associated with osteoporotic phenotypes in the previous study. BMD at the femoral neck and lumbar spine (L2-L4) were measured by dual energy X-ray absorptiometry (DXA) in 411 men (age 18-61) and 1,291 pre-menopausal women (age 20-50). SNP genotypes/haplotypes were tested for population-based association with BMD using analysis of variance. RESULTS: None of the polymorphisms tested reached statistical significance (all p values >0.05) for BMD at the femoral neck or lumbar spine in either gender. Two of the SNP haplotypes spanning the entire BMP2 gene were marginally associated with BMD in men (p values=0.019-0.043). However, these haplotypes would account for only a small, if any, portion of BMD variation and would not be significant after adjustment for multiple comparisons. CONCLUSIONS: These results demonstrate that genetic variations in BMP2 do not substantially contribute to BMD variation in our population of healthy American whites.

Absorptiometry, Photon↗
PubMed2005

Comparative effects of valsartan and enalapril on cardiac sympathetic nerve activity and plasma brain natriuretic peptide in patients with congestive heart failure.

OBJECTIVE: To evaluate the effects of valsartan on cardiac sympathetic nerve activity, plasma brain natriuretic peptide (BNP) concentration, cardiac function, and symptoms in patients with congestive heart failure (CHF) by comparison with those of enalapril. METHODS: 50 patients with CHF (left ventricular ejection fraction (LVEF) < 40%) were randomly assigned to valsartan (80 mg/day; n = 25) or enalapril (5 mg/day; n = 25). All patients were also treated with a loop diuretic. The delayed heart to mediastinum count (H/M) ratio, delayed total defect score (TDS), and washout rate were determined from (123)I-meta-iodobenzylguanidine (MIBG) images. Plasma BNP concentrations were measured before and after six months of treatment. The left ventricular end diastolic volume (LVEDV) and LVEF were also determined by echocardiography. RESULTS: In patients receiving valsartan, TDS decreased from a mean (SD) of 43 (8) to 39 (10) (p < 0.01), H/M ratio increased from 1.70 (0.17) to 1.78 (0.22) (p < 0.05), washout rate decreased from 46 (11)% to 41 (10)% (p < 0.05), and plasma BNP concentration decreased from 237 (180) pg/ml to 143 (93) pg/ml (p < 0.05). In addition, LVEDV decreased from 172 (42) ml to 151 (45) ml (p < 0.05) and LVEF increased from 31 (7)% to 39 (10)% (p < 0.001). However, these parameters did not change significantly in patients receiving enalapril. CONCLUSION: Plasma BNP concentration and (123)I-MIBG scintigraphic and echocardiographic parameters improved significantly after six months of treatment with valsartan. These findings indicate that valsartan can improve cardiac sympathetic nerve activity and left ventricular performance in patients with CHF.

3-Iodobenzylguanidine↗
PubMed2005

Coffee and risk of death from hepatocellular carcinoma in a large cohort study in Japan.

We examined the relation between coffee drinking and hepatocellular carcinoma (HCC) mortality in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study). In total, 110,688 cohort members (46,399 male and 64,289 female subjects) aged 40-79 years were grouped by coffee intake into three categories: one or more cups per day, less than one cup per day and non-coffee drinkers. Cox proportional hazards model by SAS was used to obtain hazard ratio of HCC mortality for each coffee consumption categories. The hazard ratios were adjusted for age, gender, educational status, history of diabetes and liver diseases, smoking habits and alcohol. The hazard ratio of death due to HCC for drinkers of one and more cups of coffee per day, compared with non-coffee drinkers, was 0.50 (95% confidence interval 0.31-0.79), and the ratio for drinkers of less than one cup per day was 0.83 (95% confidence interval 0.54-1.25). Our data confirmed an inverse association between coffee consumption and HCC mortality.

Adult↗
PubMed2005

Experimental identification of spin-parities and single-particle configurations in 257No and its alpha-decay daughter 253Fm.

alpha-gamma and alpha-electron coincidence spectroscopy for a short-lived heavy actinide nucleus (257)No (T(1/2) = 24.5 s) has been performed using a gas-jet transport system and an on-line isotope separator. Spin-parities of excited states in (253)Fm fed by the alpha decay of (257)No have been identified on the basis of the measured internal conversion coefficients. The nu3/2(+)[622] configuration has been assigned to the ground state of (257)No as well as to the 124.1 keV level in (253)Fm. It was found that the ground-state configuration of (257)No is different from that of lighter N = 155 isotones.

Journal Article↗
PubMed2005

Conjugated estrogen plus medroxyprogesterone does not impair blood rheological properties in hypertensive postmenopausal women.

OBJECTIVES: Hypertension and estrogens are both prothrombotic. We used the microchannel method to investigate whether hormone replacement therapy (HRT) with conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA) affects blood flow through the microchannels in hypertensive postmenopausal women being treated with antihypertensive drugs and in normotensive postmenopausal women. METHODS: Sixty-two consecutive postmenopausal women were randomly assigned to a hypertensive HRT group (n=16), hypertensive control group (n=15), normotensive HRT group (n=16) and normotensive control group (n=15). Each HRT group received CEE 0.625 mg plus MPA 2.5 mg daily orally for 12 months. Both hypertensive groups were being treated with antihypertensive drugs before the study. Microvascular blood flow was assessed on the basis of blood passage time, the time required for 100 microl of whole blood to pass through a cylinder, was determined before and 12 months after the start of HRT by the microchannel method (micro channel array flow analyzer). RESULTS: CEE plus MPA therapy did not change blood passage time in any of the groups. Microscopic observation showed that the whole blood passed smoothly through the microchannels in every group. CONCLUSIONS: CEE plus MPA therapy may not impair blood flow through the microchannels in hypertensive postmenopausal women receiving antihypertensive drugs or in normotensive postmenopausal women. However, administration of CEE plus MPA to postmenopausal women with hypertension warrants caution against the occurrence of thromboembolic events.

Aged↗
PubMed2004

Comparison of the fine-scale genetic structure of three dipterocarp species.

We investigated the fine-scale genetic structure of three tropical-rainforest trees, Hopea dryobalanoides, Shorea parvifolia and S. acuminata (Dipterocarpaceae), in Peninsular Malaysia, all of which cooccurred within a 6-ha plot in Pasoh Forest Reserve. A significant genetic structure was found in H. dryobalanoides, weaker (but still significant) genetic structure in S. parvifolia and nonsignificant structure in S. acuminata. Seeds of all three species are wind dispersed, and their flowers are thought to be insect pollinated. The most obvious difference among these species is their height: S. parvifolia and S. acuminata are canopy species, whereas H. dryobalanoides is a subcanopy species. Clear differences were also found among these species in their range of seed dispersal, which depends on the height of the release point; so taller trees disperse their seed more extensively. The estimates of seed dispersal area were consistent with the degree of genetic structure found in the three species. Therefore, tree height probably had a strong influence on the fine-scale genetic structure of the three species.

DNA, Plant↗
PubMed2004

Current status on the development of a totally implantable biventricular assist device: the Baylor Gyro BVAD.

OBJECTIVE: The Baylor Gyro BVAD is under development with the final goal of establishing a totally implantable biventricular assist system (BVAD). The aim of this study was to evaluate the safety, reliability, and effectiveness of the device in a long-term in vivo model. METHODS: The BVAD was implanted into eight calves for longer than 4 weeks in a biventricular bypass fashion, with the native heart remaining. Pump performance was assessed with the system's digital data acquisition unit. Postoperatively, anticoagulation was maintained with i.v. heparin perfusion (ACT< or = 250 sec) gradually replaced by coumadin. Treadmill exercise tests were performed daily following a 10-day reconvalescence period after surgery. RESULTS: The animals were kept alive for 37-90 days. The pumps yielded average flows of 5.3 +/- 1.1 l/min and 4.9 +/- 0.7 l/min for the LVAD and RVAD, respectively. Power consumption was 8.2 +/- 2.7 W and 9.6 +/- 4.7 W at 1935 +/- 123 rpm and 2015 +/- 365 rpm, respectively. All cases exhibited low hemolysis; renal and liver function were kept normal throughout the experiments. The animals demonstrated no thromboembolic neurological symptoms and tolerated moderate treadmill exercise. CONCLUSION: The Baylor Gyro BVAD demonstrated effective and reliable in vivo performance with acceptable biocompatibility. Based on these studies, we conclude that the system will be suitable as a long-term totally implantable BVAD for uses intended for longer than two years.

Animals↗
PubMed2003

Effects of hormone replacement therapy on weight, abdominal fat distribution, and lipid levels in Japanese postmenopausal women.

OBJECTIVE: To investigate the effects of hormone replacement therapy (HRT) on weight, abdominal fat distribution, and fasting lipid levels in Japanese postmenopausal women (PMW). DESIGN: Prospective, 12-month-controlled clinical comparison of women with and without HRT. SUBJECTS: In all, 35 PMW with HRT (conjugated estrogens, 0.625 mg daily; medroxyprogesterone acetate, 2.5 mg daily; HRT group) and 26 PMW without HRT (control group). MEASUREMENTS: Weight, abdominal fat distribution by computed tomographic measurements, lipid profiles, and sex hormones were determined at baseline and after 12 months of treatment or observation. RESULTS: Weight did not change in any group. Visceral abdominal fat increased in controls, but not in the HRT group. Total and low-density lipoprotein cholesterol decreased, and triglyceride (TG) and high-density lipoprotein cholesterol increased in the HRT group; these did not change in the control group. When we divided women into those with android and gynoid types of abdominal fat distribution. Subjects with an android distribution showed reduced visceral fat with HRT, which also decreased the proportion of patients maintaining an android distribution. HRT did not alter abdominal fat distribution in subjects with a gynoid distribution. HRT increased serum TG in the android and the gynoid subgroups. CONCLUSION: Improved distribution of abdominal fat and fasting lipid levels except for TG may represent beneficial effects of HRT with respect to cardiovascular disease, but caution is warranted concerning TG elevation from HRT performed in PMW.

Abdomen↗
PubMed2003

Low-dose dobutamine stress 99mTc tetrofosmin quantitative gated SPECT performed during the acute phase of myocardial infarction predicts subsequent myocardial viability and detects stunned myocardium.

This study evaluated the ability of low-dose dobutamine stress 99mTc tetrofosmin (DSTF) quantitative gated single photon emission computed tomography (QGS) performed during the acute phase of myocardial infarction to predict subsequent myocardial viability and detect stunned myocardium. Twenty-four patients suffering their first acute myocardial infarction (AMI) underwent coronary angioplasty after coronary angiography (CAG) immediately following admission. Follow-up CAG and left ventriculography (LVG) were performed 10 days and 6 months later. All patients underwent DSTF QGS to measure left ventricular ejection fraction (LVEF) at rest and during dobutamine infusion (10 microg.kg(-1).min(-1)) 14 days after angioplasty. No patient suffered coronary restenosis. After 6 months, the LVEF measured by LVG improved >5% in 12 patients (group A), and did not improve in the remaining 12 patients (group B). The culprit coronary artery, the peak serum creatine phosphokinase concentration, the recanalization time, and the LVEF during the acute phase were similar in the two groups. However, the increase in the LVEF was greater in group A than in group B during dobutamine infusion (deltaLVEF) as measured by DSTF QGS (11.2+/-3.8% vs 2.9+/-4.7%, P <0.001). If a cut-off value of 6.5% for the deltaLVEF was used to predict the improvement in LVEF during the chronic phase, then the sensitivity of this test was 83.3% and its specificity was 83.3%. It is concluded that DSTF QGS during AMI can be used to predict myocardial viability and detect stunned myocardium.

Acute Disease↗
PubMed2002

[Multivessel off-pump coronary aortic bypass grafting with an impaired and severely dilated left ventricle using the Starfish heart positioner].

Off-pump coronary artery bypass grafting (OPCAB) is gaining acceptance and is now more widely used for coronary revascularization worldwide. Accessing the vessels, particularly on the lateral and inferior walls of the heart, can sometimes be challenging while the heart is beating, especially in hearts with an impaired and severely dilated left ventricle. The Starfish heart positioner was designed to achieve optimal exposure of the lateral and inferior walls of the heart with minimal hemodynamic compromise. This device was used in a patient with a severely impaired and dilated left ventricle to successfully position the heart for quadruple bypass grafting using all in situ arterial grafts, such as bilateral international thoracic arteries (ITAs) and the right gastroepiploic artery. The degree of hematoma caused by the pressure of the suction cup of this device was minimal. This case report suggests that the use of Starfish heart positioner will facilitate and expand the ability of surgeons to easily and consistently perform OPCAB.

Coronary Artery Bypass↗
PubMed2001

Enzymes inside lipid vesicles: preparation, reactivity and applications.

There are a number of methods that can be used for the preparation of enzyme-containing lipid vesicles (liposomes) which are lipid dispersions that contain water-soluble enzymes in the trapped aqueous space. This has been shown by many investigations carried out with a variety of enzymes. A review of these studies is given and some of the main results are summarized. With respect to the vesicle-forming amphiphiles used, most preparations are based on phosphatidylcholine, either the natural mixtures obtained from soybean or egg yolk, or chemically defined compounds, such as DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) or POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine). Charged enzyme-containing lipid vesicles are often prepared by adding a certain amount of a negatively charged amphiphile (typically dicetylphosphate) or a positively charged lipid (usually stearylamine). The presence of charges in the vesicle membrane may lead to an adsorption of the enzyme onto the interior or exterior site of the vesicle bilayers. If (i) the high enzyme encapsulation efficiencies; (ii) avoidance of the use of organic solvents during the entrapment procedure; (iii) relatively monodisperse spherical vesicles of about 100 nm diameter; and (iv) a high degree of unilamellarity are required, then the use of the so-called 'dehydration-rehydration method', followed by the 'extrusion technique' has shown to be superior over other procedures. In addition to many investigations in the field of cheese production--there are several studies on the (potential) medical and biomedical applications of enzyme-containing lipid vesicles (e.g. in the enzyme-replacement therapy or for immunoassays)--including a few in vivo studies. In many cases, the enzyme molecules are expected to be released from the vesicles at the target site, and the vesicles in these cases serve as the carrier system. For (potential) medical applications as enzyme carriers in the blood circulation, the preparation of sterically stabilized lipid vesicles has proven to be advantageous. Regarding the use of enzyme-containing vesicles as submicrometer-sized nanoreactors, substrates are added to the bulk phase. Upon permeation across the vesicle bilayer(s), the trapped enzymes inside the vesicles catalyze the conversion of the substrate molecules into products. Using physical (e.g. microwave irradiation) or chemical methods (e.g. addition of micelle-forming amphiphiles at sublytic concentration), the bilayer permeability can be controlled to a certain extent. A detailed molecular understanding of these (usually) submicrometer-sized bioreactor systems is still not there. There are only a few approaches towards a deeper understanding and modeling of the catalytic activity of the entrapped enzyme molecules upon externally added substrates. Using micrometer-sized vesicles (so-called 'giant vesicles') as simple models for the lipidic matrix of biological cells, enzyme molecules can be microinjected inside individual target vesicles, and the corresponding enzymatic reaction can be monitored by fluorescence microscopy using appropriate fluorogenic substrate molecules.

Animals↗
PubMed2001

Structure and ligand recognition of the PB1 domain: a novel protein module binding to the PC motif.

PB1 domains are novel protein modules capable of binding to target proteins that contain PC motifs. We report here the NMR structure and ligand-binding site of the PB1 domain of the cell polarity establishment protein, Bem1p. In addition, we identify the topology of the PC motif-containing region of Cdc24p by NMR, another cell polarity establishment protein that interacts with Bem1p. The PC motif-containing region is a structural domain offering a scaffold to the PC motif. The chemical shift perturbation experiment and the mutagenesis study show that the PC motif is a major structural element that binds to the PB1 domain. A structural database search reveals close similarity between the Bem1p PB1 domain and the c-Raf1 Ras-binding domain. However, these domains are functionally distinct from each other.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Developmental patterns of ceramide glucosyltransferase (GlcT-1) expression in the mouse: in situ hybridization using DIG-labeled RNA probes.

Glycosphingolipids (GSLs) play significant roles in a variety of cell membrane events, including cellular interactions, signaling, and trafficking. Ceramide glucosyltransferase (glucosylceramide synthase, GlcT-1, EC 2.4.1.80) catalyzes the initial step in GSL synthesis, the transfer of glucose from UDP-glucose to ceramide. The reaction product of glucosylceramide serves as a core structure for over 400 species of GSLs. The enzyme is a key regulatory factor controlling intracellular levels of ceramide and GSLs. Appearance and differential distribution of GlcT-1 mRNA during mice postimplantation embryogenesis [embryonic (E) days; E9, E11, E13, E15] were investigated by in situ hybridization with digoxigenin-labeled RNA probes, coupled with alkaline phosphatase detection. On E9, tissues of the mesencephalon, myelecephalon, diencephalons, and telencephalon expressed GlcT-1. On E11, it was expressed to a detectable extent in various tissues including mesencephalon, myelecephalon, diencephalon, telencephalon, nose, lung, liver, vertebra, tail, spinal cord, and tongue. The expression patterns of E13 were similar to those of E11, except that the heart and stomach became positive. On E15, a specific signal for GlcT-1 was detected in all organs of the embryo. These results provide the first evidence that GlcT-1 is differentially expressed during postimplantation embryogenesis.

Animals↗
PubMed2001

beta-estradiol 3-benzoate affects spermatogenesis in the adult mouse.

beta-estradiol 3-benzoate (E(2)B) (10, 16, 20, 40, 80 and 160 microg/kg body weight) was administered daily to experimental groups of adult mice for the following periods; 2, 3 days, 1, 2, 4, and 8 weeks. Morphological changes in the testes were observed by both light and electron microscopy. Exfoliation of the germ cells was observed in the lumen of the seminiferous tubule. The spermatogenic cycle, especially stage XII, was disordered. Spermatids older than step 6 were severely affected. Detected abnormalities in the spermatids were deformation of the nucleus and acrosome. Partial deletion in the Sertoli-spermatid ectoplasmic specialization was also observed. Germ cells younger than step 7 spermatids were not affected morphologically. These abnormalities were not detected in the mice treated with the chemical at less than 16 microg/kg body weight. It is concluded that the chemical seems to affect round spermatids metabolically, but the morphological effect can be detected only from the spermatids older than step 6. The effects of the chemical on adult mice were reversible.

Animals↗
PubMed2001

Total synthesis of fostriecin (CI-920).

The first total synthesis of the potent antitumor agent fostriecin (CI-920) is described, confirming the relative and absolute stereochemistry assignments. Fostriecin is a unique phosphate monoester which exhibits weak topoisomerase II inhibition (IC(50) = 40 microM) and more potent and selective protein phosphatase 2A and 4 (PP2A and PP4) inhibition (IC(50) = 40-3 nM and 1.5 nM), resulting in mitotic entry checkpoint inhibition. Phase I clinical trials with fostriecin, which were the first to explore the potential of this novel mechanism of action, were halted even before therapeutic concentrations were reached or dose-limiting toxicity established due to problems of drug stability observed during storage of naturally derived material. The synthesis of fostriecin detailed herein is the first stage of efforts that may serve to address these limitations to the clinical examination of this or related promising new antitumor agents.

Alkenes↗