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Biomedical subjects

Y Asakura

Publications and source records attributed to Y Asakura.

At least 37 records · Page 2Linked to original sources

Repeat intervention for in-stent restenosis: re-expansion of the initial stent is a predictor of recurrence of restenosis.

BACKGROUND: In-stent restenosis has become a significant clinical problem as use of stents has increased. The optimal strategy for dealing with in-stent restenosis needs to be evaluated. OBJECTIVE: To compare the acute and late results of interventions for in-stent restenosis according to the device used, and to analyze the clinical and procedural variables of the lesions treated and identify the determinants of recurrence of restenosis and target lesion revascularization (TLR). METHODS: Procedural and late outcomes for 58 lesions in 50 patients who underwent repeat intervention for in-stent restenosis were analyzed. The results of interventions according to the device employed were compared. The predictors of recurrence of restenosis and TLR within 6 months were analyzed. The ratio of balloon diameter in repeat intervention to minimal lumen diameter after initial stenting (MLD0) was used as an index of re-expansion of stents. Serial intravascular ultrasound imaging was performed before and after repeat intervention for 33 lesions, and re-expansion of the initial stent was evaluated. RESULTS: Repeat intervention was successful in treating all lesions. Angiographic follow-up was possible for 49 lesions (84%). The overall incidences of recurrence of restenosis and TLR were 40.1 and 27.6%, respectively. Despite the immediate results having been good, the late results of stenting for in-stent restenosis were not favorable. Diffuse-type in-stent restenosis, early in-stent restenosis, and balloon diameter:MLD0 ratio > 1.25 are independent predictors of poor late results. Intravascular ultrasound findings have shown that expansion of the initial stent leads to recurrence of restenosis and TLR. CONCLUSIONS: Re-expansion of the initial stent can cause further vascular injury and there is a risk of recurrence of restenosis. Alternative therapeutic strategies that work without dilating the initial stent may be necessary for treating lesions with high risk of recurrence of restenosis.

Aged↗

Three novel PHEX gene mutations in Japanese patients with X-linked hypophosphatemic rickets.

X-linked hypophosphatemic rickets (XLH) is an X-linked dominant disorder characterized by renal phosphate wasting, abnormal vitamin D metabolism, and defects of bone mineralization. The phosphate-regulating gene on the X-chromosome (PHEX) that is defective in XLH has been cloned, and its location identified at Xp22.1. It has been recognized to be homologous to certain endopeptidases. So far, a variety of PHEX mutations have been identified mainly in European and North American patients with XLH. To analyze the molecular basis of four unrelated Japanese families with XLH, we determined the nucleotide sequence of the PHEX gene of affected members. We detected a new nonsense mutation (R198X) in exon 5, a new 3 nucleotides insertion mutation in exon 12 and a new missense mutation (L160R) in exon 5 as well as a previously reported nonsense mutation in exon 8 (R291X). These results suggest that: 1) PHEX gene mutations are responsible for XLH in Japanese patients, and 2) PHEX gene mutations are heterogeneous in the Japanese population similarly to other ethnic populations.

Adult↗

Determining appropriate small vessels for stenting by intravascular ultrasound.

To re-evaluate outcomes of stenting in small vessels, we studied 176 patients successfully treated with several types of stent by way of intravascular ultrasound (IVUS) and quantitative coronary angiography (QCA). These lesions were divided into 3 subgroups according to reference diameter (RD) by QCA, and vessel diameter (VD) by IVUS (group I: pre-RD 2.5 mm; group II: pre-RD < 2.5 mm and pre-VD 4.0 mm; group III: pre-RD < 2.5 mm and pre-VD < 4.0 mm). Post-procedure percent diameter stenosis (4 +/- 3%), post-procedure percent plaque area (42 +/- 3%), and loss index (39 +/- 11%) in group II were not significantly different from those in group I (7 +/- 2%, 37 +/- 2%, 45 +/- 5%, respectively). The rates of restenosis and target lesion revascularization in group II (24.0% and 16.0%, respectively) were not different from those in group I (25.9% and 21. 2%, respectively), and were significantly favorable compared to group III (66.7% and 39.4%, respectively; p < 0.05). By the use of IVUS, we not only identified those vessels which would normally go unstented when only using QCA, but also documented excellent long-term outcome in these patients.

Aged↗

Evaluation of scaffolding effects of five different types of stents by intravascular ultrasound analysis.

The acute elastic recoil of 5 types of stents immediately after deployment by intravascular ultrasound and quantitative coronary angiography measurements was analyzed. Successfully implanted stents were: Palmaz-Schatz in 104 lesions, Gianturco-Roubin in 65, Wiktor in 45, gfx in 22, and Multi-Link stents in 22. Before and after stenting, the cross section of the smallest luminal area and vessel area was measured with intravascular ultrasound. The postdilatation balloon area was calculated by quantitative coronary angiography. Percent recoil was calculated as: [1-(preluminal area)/balloon area)] x 100. The ratio of balloon area-to-vessel area was also compared. Although preluminal areas in Gianturco-Roubin and Palmaz-Schatz stents were similar (2.4 +/- 0.1 vs 2.5 +/- 0.1 mm2, p = NS), postluminal area in the Gianturco-Roubin was significantly smaller than the area in the Palmaz-Schatz (6.3 +/- 0.2 vs 8.3 +/- 0.3 mm2, p <0.05). Although both the balloon area/vessel area (0.68 +/- 0.05, 0.80 +/- 0.08 vs 0.83 +/- 0.02, p <0.05) and the preluminal area (2.1 +/- 0.4, 1.6 +/- 0.2 vs 2.5 +/- 0.1 mm2, p <0.05) were smaller in gfx and Multi-Link than in the Palmaz-Schatz, postluminal area was comparable to the area in the Palmaz-Schatz (7.8 +/- 0.4, 7.4 +/- 0.4 vs 8.3 +/- 0.3 mm2, p = NS). Percent recoil in the Gianturco-Roubin was poorest among these 5 groups. More favorable initial gain can be obtained with Palmaz-Schatz, Wiktor, gfx, and Multi-Link stents than with the Gianturco-Roubin stent.

Aged↗

Eicosapentaenoic acid inhibits vasopressin-activated Ca2+ influx and cell proliferation in rat aortic smooth muscle cell lines.

The purpose of this study was to clarify how eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, modulates the vascular action of vasopressin in rat aortic smooth muscle cell lines. The effects of EPA on Ca2+ mobilization and DNA synthesis elicited by vasopressin were investigated and compared to those of Ca2+ channel blocking agents, by means of Ca2+ measurements and the incorporation of [3H]thymidine. Patch-clamp techniques were also employed. Vasopressin (100 nM) elicited an initial peak of intracellular Ca2+ ([Ca2+]i), followed by a sustained phase due to Ca2+ entry. Nifedipine or nicardipine (1 microM), a potent L-type Ca2+ channel blocker, partly inhibited the sustained phase, but La3+ completely abolished it. EPA (10 microM) also inhibited it even in the presence of nicardipine. Under voltage-clamp conditions with CsCl-internal solution, depolarizing pulses positive to -30 mV from a holding potential of -40 mV elicited a slow inward current. The inward current was blocked by La3+, nicardipine, and nifedipine (1 microM), suggesting that the inward current mainly consisted of the voltage-dependent L-type Ca2+ channel (ICa.L). EPA (1-30 microM) also inhibited ICa.L in a concentration-dependent manner. The inhibitory effect of EPA was observed at concentrations higher than 1 microM, and its half-maximal inhibitory concentration (IC50) was 7.6 microM. Vasopressin induced a long-lasting inward current at a holding potential of -40 mV. The vasopressin-induced current was considered as a non-selective cation current (Icat) with a reversal potential of approximately +0 mV. Both nifedipine and nicardipine (10 microM) failed to inhibit it significantly, but La3+ completely abolished Icat. EPA also inhibited vasopressin-induced Icat in a concentration-dependent manner; its IC50 value was 5.9 microM. Vasopressin (100 nM) stimulated [3H]thymidine incorporation. Exclusion of extracellular Ca2+ with EGTA or La3+ markedly inhibited it. EPA (3-30 microM) also inhibited the incorporation induced by vasopressin, while nifedipine and nicardipine (1 microM) only partly inhibited it. These results suggested that EPA, unlike nifedipine and nicardipine, inhibited vasopressin-induced Ca2+-entry and proliferation in rat vascular smooth muscle cells, where the inhibitory effects of EPA on Icat as well as ICa.L might be involved. Thus, EPA would exert hypotensive and antiatherosclerotic effects.

Animals↗

Induction of mucosal IgA by a novel jet delivery technique for HIV-1 DNA.

Novel ways of delivering plasmid DNA to elicit humoral IgA, IgG and cell-mediated immune responses in mice were investigated. Intraoral administration of DNA in the cheek, using a jet immunization technique, elicited the highest IgA mucosal responses. Intranasal immunization gave strong mucosal IgA responses and persistent systemic IgG. Immunoglobulin isotype analysis revealed an IgG1 profile for intramuscular tongue and gene gun immunizations and an IgG2a profile following oral jet injection and intranasal application. The route of delivery was of importance for the characteristics and quality of the mucosal immune response following DNA immunization. For DNA vaccine delivery, the intraoral jet injection technique has the advantages of being a simple and rapid way of administering the DNA in solution and of provoking specific mucosal IgA when administered in the mucosal associated lymphoid tissue.

Administration, Intranasal↗

Gonadoblastoma, mixed germ cell tumor, and Y chromosomal genotype: molecular analysis in four patients.

This study reports on Y chromosomal genotypes of three patients with gonadoblastoma and one patient with gonadoblastoma and mixed germ cell tumor. Molecular analysis for 35 Y chromosomal loci was performed for DNA samples taken from peripheral leukocytes and lymphoblastoid cell lines, showing that the four patients shared the region between DYS267 at interval 4A and DYF50S1 at interval 6D, with the exception of the region around DYS202 at interval 5K. In the patient with gonadoblastoma and mixed germ cell tumor, Y chromosomal material was preserved in the gonadoblastoma but was lost from the mixed germ cell tumor. The results, in conjunction with previous reports, suggest that GBY (gonadoblastoma locus on the Y chromosome) may be located to a roughly 5-Mb pericentromeric region between DYS267 at interval 4A and DYS270 at interval 5A. The presence of Y chromosomal material in gonadoblastoma is consistent with GBY being involved in the development of gonadoblastoma, and the absence of Y chromosomal material in mixed germ cell tumor would be explained as a consequence of Y chromosomal loss from rapidly proliferating gonadal cancer cells.

Adolescent↗

Successful stenting on tortuous coronary artery with accordion phenomenon: strategy--a case report.

Guidewire manipulation through tortuosities is difficult. Straightening a tortuous coronary artery by using a stiff guidewire has been recognized to induce vessel wall shortening referred to as an "accordion phenomenon." With inappropriate identification as dissection or thrombus formation, the risk of performing unnecessary dilation at the pseudo-narrowing site exists. The authors describe here two cases showing the accordion phenomenon induced by a stiff guidewire during successful stenting at a tortuous right coronary artery. In another case, the authors experienced an "accordion phenomenon" at the proximal edge of the Palmaz-Schatz stent implanted in a tortuous right coronary artery. The stent edge was better positioned at the straight portion than at the contour portion in a tortuous coronary artery.

Aortic Dissection↗

A male patient presenting with major clinical symptoms of glucocorticoid deficiency and skeletal dysplasia, showing a steroid pattern compatible with 17alpha-hydroxylase/17,20-lyase deficiency, but without obvious CYP17 gene mutations.

We report the case of a 17-year-old boy with delayed puberty, who presented a complexity of clinical problems. An analysis of steroid hormones led to a diagnosis of 17alpha-hydroxylase/17,20-lyase deficiency (17OHD). Unlike typical cases of 17OHD, however, the patient had pubertal development without medical intervention. In addition, he never exhibited the symptoms of mineralocorticoid excess, showing instead the symptoms of glucocorticoid deficiency, including fatigability, emaciation, and weight-loss induced by minor infection. He also had dysmorphic features, which comprised marfanoid habitus, arachnodactyly and putative craniosynostosis. The combination of these malformations substantially resembled that of Shprintzen-Goldberg syndrome. Direct sequencing of the CYPl7 gene did not reveal any significant aberrations in the exons or exon-intron boundaries. We speculate that the association of partial combined 17OHD with the Shprintzen-Goldberg phenotype in the present patient may result from an aberration of a hitherto unknown gene that controls both steroid hormone synthesis and skeletal development.

Adolescent↗

DNA-plasmids of HIV-1 induce systemic and mucosal immune responses.

DNA-based immunization has been shown to induce protective immunity against several microbial pathogens including HIV-1. Several routes of DNA vaccination have been exploited. However, the properties of the immune responses seem to differ with the different routes used for DNA delivery, ultimately affecting the outcome of experimental challenge. We measured the primary immune response following one vaccination. This report presents differences associated with three different DNA delivery routes: intramuscular injection, intranasal application, and gene-gun based immunization. Induction of systemic humoral immune responses was achieved most efficiently by either intranasal or gene-gun mediated immunization, followed by intramuscular injection. Mucosal IgA was reproducibly induced by intranasal instillation of the DNA, and found in lung washings, faeces, and vaginal washings. Cytotoxic T cells were not induced by a single immunization, but were observed after three immunizations using intramuscular injections.

AIDS Vaccines↗

Angioplasty/bypass combination therapy in an 89-year-old man with left main trunk disease.

We report a case of an 89-year-old man presenting with unstable angina and left main trunk disease. Minimally invasive direct coronary artery bypass grafting supplemented by catheter intervention was successfully performed. In view of the increasing elderly population, angioplasty/bypass combination therapy may be an important alternative for elderly coronary artery disease patients.

Aged↗

Association between preinfarction angina and a lower risk of right ventricular infarction.

BACKGROUND: Right ventricular infarction occurs in conjunction with inferior myocardial infarction caused by proximal occlusion of the right coronary artery. However, right ventricular infarction occurs infrequently, and the reasons for this are uncertain. METHODS: We retrospectively assessed the association between preinfarction angina and right ventricular infarction, as well as the short-term outcome, in 113 patients with a first acute inferior myocardial infarction caused by right-coronary-artery occlusion. The association between the timing of angina during the week before infarction and the clinical outcome was also assessed. RESULTS: The absence of preinfarction angina predicted the development of right ventricular infarction (odds ratio, 6.3; 95 percent confidence interval, 2.7 to 15.1; P<0.001), complete atrioventricular block (odds ratio, 3.6; 95 percent confidence interval, 1.4 to 10.3; P=0.01), and combined hypotension and shock (odds ratio, 12.4; 95 percent confidence interval, 4.5 to 40.6; P<0.001). Angina 24 to 72 hours before infarction was most strongly associated with reductions in the rates of right ventricular infarction (adjusted odds ratio, 0.2; 95 percent confidence interval, 0 to 0.8; P=0.02) and combined hypotension and shock (adjusted odds ratio, 0.1; 95 percent confidence interval, 0 to 0.5; P=0.02). CONCLUSIONS: Preinfarction angina was an independent predictor of the absence of right ventricular infarction in patients with acute inferior myocardial infarction. The patients with preinfarction angina also had better short-term outcomes than those without preinfarction angina.

Angina Pectoris↗

Successful predilation of a resistant, heavily calcified lesion with cutting balloon for coronary stenting: a case report.

A 65-year-old man with a restenotic lesion of the mid LAD was scheduled for Wiktor stent placement. The IVUS revealed circumferential severe calcification. Two conventional, non-compliant angioplasty balloons inflated to high pressures failed to achieved sufficient dilatation and both ruptured. At this point, we selected high pressure inflation of the Cutting Balloon. The Cutting Balloon achieved adequate dilation for stenting and proved to be useful in predilating a circumferential, heavily calcified lesion.

Aged↗

Lipoprotein disorder in brain infarction and hemorrhage.

The cholesterol, triglyceride, and apolipoprotein B content of very low-, intermediate-, low-, and high-density lipoprotein fractions (separated by ultracentrifugation) and plasma were measured in healthy controls and patients with atherothrombotic infarction (26), lacunar infarction (26), and brain hemorrhage (14). In both atherothrombotic and lacunar infarction, increased plasma and low-density lipoprotein apolipoprotein B and a decreased low-density lipoprotein cholesterol/apolipoprotein B ratio were noted. In brain hemorrhage patients, a decreased ratio was also observed. These findings suggest that increased small dense low-density lipoprotein is a characteristic risk factor for atherothrombotic and lacunar infarction.

Adult↗

Influence of cellular incorporation of n-3 eicosapentaenoic acid on intracellular Ca2+ concentration and membrane potential in vascular smooth muscle cells.

Long-term treatment with n-3 eicosapentaenoic acid (EPA) has been shown to exert hypotensive effects and have beneficial effects on atherosclerosis. To elucidate one of the underlying mechanisms of these effects, intracellular calcium concentration [Ca2+]i, and resting membrane potential were measured in rat vascular smooth muscle cells (A7r5 cell) treated with EPA, using Ca2+-sensitive dye fura-2 AM and the patch clamp technique. The alterations in fatty acid compositions of phospholipids and cell migration after treatment with EPA (30 microM) for 6 h-7 days were also examined. After treating cells with EPA, the EPA and DPA (docosapentaenoic acid) content of the phospholipid fraction (mol.%) increased in a time-dependent manner. Alternatively, arachidonic acid (AA) decreased, and then the ratio of EPA and AA (EPA/AA) increased significantly. The resting [Ca2+]i decreased from 170 +/- 46 nM (n = 16) in control cells to 123 +/- 29 nM (n = 16) in cells treated with EPA (30 microM) for 7 days. Vasopressin (100 nM), endothelin-1 (100 nM) and platelet-derived growth factor (PDGF 5 ng/ml) evoked an initial peak of [Ca2+]i, followed by a smaller sustained rise of [Ca2+]i in the presence of extracellular Ca2+. In EPA-treated cells, both the peak and the sustained rise of [Ca2+]i induced by these agonists decreased in comparison to the control cells. EPA treatment also decreased the transient [Ca2+]i rise evoked by these agonists in the absence of extracellular Ca2+. Under the current clamp condition, resting membrane potential was significantly higher in EPA-treated cells (-49.8 +/- 10.4 mV, n = 41) than in control cells (-44.6 +/- 7.4 mV, n = 41, P < 0.05), and the input resistance of the cell was lower in EPA-treated cells, while cell size and capacitance were not statistically different. In addition, long-term treatment with EPA for 7 days significantly inhibited PDGF-induced cell migration. These results suggest that cellular incorporation of n-3 eicosapentaenoic acid attenuates intracellular mechanisms related to changes of [Ca2+]i and affects membrane potential, thereby inhibiting migration of vascular smooth muscle cells. These actions of EPA may contribute to its vasorelaxant and antiatherosclerotic effects.

Animals↗

C-reactive protein as a predictor of infarct expansion and cardiac rupture after a first Q-wave acute myocardial infarction.

BACKGROUND: Pump failure after acute myocardial infarction (AMI) can be predicted by several indices that estimate infarct size. However, there are few indices that predict infarct expansion and cardiac rupture. We focused on the prognostic significance of serum C-reactive protein (CRP) after AMI. METHODS AND RESULTS: Serum CRP levels were measured every 24 hours in 220 patients with a first Q-wave AMI. In-hospital complications, predischarge left ventriculographic findings, and long-term prognosis were assessed in relation to peak CRP levels. Peak levels of both CRP and creatine kinase (CK) were higher in patients with pump failure than in those without pump failure. In patients with cardiac rupture, peak CRP levels were higher than in those without rupture (P=.001); peak CK levels were not predictive. Higher CRP levels were found in patients with left ventricular aneurysm (P=.001 versus those without), aggravated heart failure (P=.03 versus those without), and cardiac death (P<.0001 versus survivors) during the first year after AMI. Multivariate analysis confirmed that an elevation of the peak CRP level > or = 20 mg/dL was an independent predictor of cardiac rupture (relative risk, 4.72; P=.004), left ventricular aneurysmal formation (relative risk, 2.11; P=.03), and 1-year cardiac death (relative risk, 3.44; P<.0001). CONCLUSIONS: Cardiac rupture, left ventricular aneurysmal formation, and 1-year cardiac death were associated with an elevation of serum CRP early after AMI, suggesting that elevation of CRP levels after AMI may predict infarct expansion.

Adult↗

IL-2-induced IL-5 synthesis, but not proliferation, of human CD4+ T cells is suppressed by FK506.

Regulation of T cell IL-5 synthesis was investigated using human Th cell clones. Immunosuppressant FK506 suppressed IL-5 synthesis of T cells activated through TCR in a dose-dependent manner. IL-5 gene transcription and protein synthesis were also induced in the same T cell clones upon stimulation with IL-2 and were suppressed by FK506 in a dose response similar to that induced by TCR stimulation. In contrast to TCR stimulation, neither activating protein-1, nuclear factor-AT (NF-AT), nor NF-kappaB binding activity was significantly up-regulated by IL-2 stimulation. Human IL-5 promoter/enhancer-luciferase gene construct transfected to T cell clones was transcribed upon either TCR or IL-2 stimulation and was clearly down-regulated by FK506, indicating that the approximately 500-bp human IL-5 gene segment located 5' upstream of the coding region contained FK506-sensitive enhancer elements. Our present findings clearly indicate that FK506-sensitive signaling molecules are involved in T cell IL-5 production induced by both TCR and IL-2 stimulation and suggest that IL-2 receptor signal leading to IL-5 gene transcription is transduced by a unique FK506-sensitive pathway other than the Ca2+-dependent signal transduction pathway, such as the calcineurin-NF-AT system.

CD4-Positive T-Lymphocytes↗

Two distinct pathways of interleukin-5 synthesis in allergen-specific human T-cell clones are suppressed by glucocorticoids.

Glucocorticoids (GC) have long been used as the most effective agents for the treatment of allergic diseases accompanied by eosinophilia such as chronic asthma and atopic dermatitis. The development of chronic eosinophilic inflammation is dependent on interleukin-5 (IL-5), a selective eosinophil-activating factor, produced by helper T cells. To delineate the regulatory mechanisms of human IL-5 synthesis, we established allergen-specific CD4+ T-cell clones from asthmatic patients. GC efficiently suppressed IL-5 synthesis of T-cell clones activated via either T-cell receptor (TCR) or IL-2 receptor (IL-2R). Induction of IL-5 mRNA upon TCR and IL-2R stimulation was totally inhibited by dexamethasone. Human IL-5 promoter/enhancer-luciferase gene construct transfected to T-cell clones was transcribed on either TCR or IL-2R stimulation and was clearly downregulated by dexamethasone, indicating that the approximately 500-bp human IL-5 gene segment located 5' upstream of the coding region contains activation-inducible enhancer elements responsible for the regulation by GC. Electrophoretic mobility shift assay analysis suggested that AP-1 and NF-kappaB are among the possible targets of GC actions on TCR-stimulated T cells. NF-AT and NF-kappaB were not significantly induced by IL-2 stimulation. Our results showing that GC suppressed IL-5 production by human CD4+ T cells activated by two distinct stimuli, TCR and IL-2R stimulation, underscore the efficacy of GC in the treatment of allergic diseases via suppression of T-cell IL-5 synthesis.

Allergens↗