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Biomedical subjects

Akira Yamada

Publications and source records attributed to Akira Yamada.

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

Induction of cellular and humoral immune responses to tumor cells and peptides in HLA-A24 positive hormone-refractory prostate cancer patients by peptide vaccination.

BACKGROUND: To assess the safety and immune response of a peptide-based immunotherapy for patients with hormone-refractory prostate cancer, a phase I clinical trial was conducted. METHODS: This study first investigated whether cytotoxic T-lymphocyte (CTL) precursors reacting to peptide with vaccine candidates (14 peptides for HLA-A24 positive patients) were detectable in the pre-vaccination peripheral blood mononuclear cells (PBMCs) of ten patients with hormone-refractory prostate cancer. Patients were then vaccinated subcutaneously with only those peptides to which pre-vaccination PBMCs reacted (CTL precursor-oriented peptide vaccine) for up to four kinds of peptides. RESULTS: Overall vaccinations were generally well tolerated, but most patients (nine of ten) developed grade 1 local redness and swelling at the injection site. Increased CTL response to both peptides and cancer cells were observed in four of ten patients. Anti-peptide IgG antibodies were also detected in post-vaccination sera of seven of ten patients. One patient achieved a partial response with an 89% decrease in PSA. Stable disease was demonstrated in five of ten patients (50%) for the median duration of 2 months (range, 2-5 months). There were no objective responses of measurable lesions. CONCLUSIONS: Increase in cellular and humoral immune responses, and decrease in PSA level in some patients support further development of peptide-based immunotherapy for hormone refractory prostate cancer.

Adenocarcinoma↗
PubMed2003

Direct coating of gold nanoparticles with silica by a seeded polymerization technique.

Gold nanoparticles prepared through a conventional citrate-reduction method were directly coated with silica by means of a seeded polymerization technique based on the Stöber method. The method required no surface modification. The addition of tetraethylorthosilicate and water prior to ammonia was found to be critical to obtain a proper coating. The silica shell thickness was varied from 30 to 90 nm for TEOS concentrations of 0.0005-0.02 M at 10.9 M of water and 0.4 M of ammonia. The optical spectra of the core-shell gold-silica composite particles agreed with predictions of Mie theory.

Journal Article↗
PubMed2003

Myocardial velocity gradient as a noninvasively determined index of left ventricular diastolic dysfunction in patients with hypertrophic cardiomyopathy.

OBJECTIVES: We investigated the utility of the peak negative myocardial velocity gradient (MVG) derived from tissue Doppler imaging (TDI) for evaluation of diastolic dysfunction in patients with hypertrophic cardiomyopathy (HCM). BACKGROUND: Hypertrophic cardiomyopathy is characterized by impaired diastolic function with abnormal stiffness and prolonged relaxation. However, it remains difficult to evaluate these defects noninvasively. METHODS: Both TDI and conventional echocardiography were performed in 36 patients with HCM and in 47 control subjects. Left ventricular (LV) pressure was measured simultaneously in all HCM patients and in 26 controls. RESULTS: The peak negative MVG occurred soon after the isovolumic relaxation period during the initial phase of rapid filling (auxotonic relaxation). It was significantly smaller in HCM patients than in control subjects (2.32 +/- 0.52/s vs. 4.82 +/- 1.15/s, p < 0.0001); the cutoff value for differentiation between all HCM patients and 47 normal individuals was determined as 3.2/s. Both the left ventricular end-diastolic pressure (LVEDP) (19.6 +/- 6.1 mm Hg vs. 6.5 +/- 1.7 mm Hg, p < 0.0001) and the time constant of LV pressure decay during isovolumic diastole (tau) (44.0 +/- 6.7 ms vs. 32.1 +/- 5.5 ms, p < 0.0001) were increased in HCM patients compared with controls. The peak negative MVG was negatively correlated with both LVEDP (r = -0.75, p < 0.0001) and tau (r = -0.58, p < 0.0001). CONCLUSIONS: A reduced peak negative MVG reflects both prolonged relaxation and elevated LVEDP. The peak negative MVG might thus provide a noninvasive index of diastolic function, yielding unique information about auxotonic relaxation in patients with HCM.

Adult↗
PubMed2003

Gene and peptide analyses of newly defined lung cancer antigens recognized by HLA-A2402-restricted tumor-specific cytotoxic T lymphocytes.

We investigated tumor antigens recognized by HLA-A2402-restricted CTLs established from T cells infiltrating into lung adenocarcinoma. We report here three newly identified tumor antigen genes, including one unreported gene, temporarily referred to as clone 83, and two known genes, BTB domain containing 2 (BTBD2) and hairpin-binding protein. These genes were preferentially expressed in most of the cell lines of lung cancer and also of ovarian cancer and renal cell carcinoma at the mRNA level. The expression of these genes was confirmed in lung and other cancer tissue specimens. In normal tissues, clone 83 was expressed only in the colon, and hairpin-binding protein was not expressed at all, whereas BTBD2 was ubiquitously expressed. Clone 83, BTBD2, and hairpin-binding protein encoded two, one, and one epitope peptides that can be recognized by HLA-A2402-restricted CTLs, respectively. These epitope peptides possessed the ability to induce HLA-A24-restricted tumor-specific CTLs after in vitro stimulation in a culture of peripheral blood mononuclear cells from patients with lung cancer. These results suggest that these genes and peptides are potential candidates for cancer vaccines in HLA-A24(+) patients with lung cancer.

Adenocarcinoma↗
PubMed2003

Multifunctional Alloys Obtained via a Dislocation-Free Plastic Deformation Mechanism.

We describe a group of alloys that exhibit "super" properties, such as ultralow elastic modulus, ultrahigh strength, super elasticity, and super plasticity, at room temperature and that show Elinvar and Invar behavior. These "super" properties are attributable to a dislocation-free plastic deformation mechanism. In cold-worked alloys, this mechanism forms elastic strain fields of hierarchical structure that range in size from the nanometer scale to several tens of micrometers. The resultant elastic strain energy leads to a number of enhanced material properties.

Journal Article↗
PubMed2003

Identification of a CTL-directed epitope encoded by an intron of the putative tumor suppressor gene Testin of the common fragile site 7G region: a peptide vaccine candidate for HLA-B52+ and HLA-62+ cancer patients.

Although cytotoxic T lymphocyte (CTL)-directed epitopes binding to human histocompatibility leukocyte antigen (HLA)-A molecules have been well characterized, those binding to HLA-B molecules have not, largely due to their large diversity. In this study we report a unique cancer antigen gene, tentatively named Testin-related gene (TRG), which encodes CTL-directed epitopes on the HLA-B52 molecules most frequently expressed in Asians. TRG is located in an intron of the putative tumor suppressor gene Testin in the common fragile site 7G region at 7q31.2. TRG mRNA was expressed in the majority of cancer cells and cancer tissue tested, whereas it was scarcely expressed in the majority of normal tissues, and only low-level expression of TRG was detected in the heart, liver, and pancreas. One TRG peptide had the ability to induce HLA-B52-restricted CTL cytotoxic to TRG+ tumor cells in peripheral blood mononuclear cells (PBMC) of epithelial cancer patients. This peptide also induced HLA-B62-restricted and tumor-reactive CTL in PBMC of cancer patients. Therefore, this TRG-derived peptide might be appropriate for use in peptide-based immunotherapy for relatively large numbers of cancer patients throughout the world, given that 34% of Japanese, 27% of Chinese, and 13% of Caucasians express either HLA-B52 or HLA-B62 molecules

Cancer Vaccines↗
PubMed2003

Nicorandil inhibits oxidative stress-induced apoptosis in cardiac myocytes through activation of mitochondrial ATP-sensitive potassium channels and a nitrate-like effect.

The anti-anginal drug nicorandil has been shown to inhibit apoptosis by activating mitochondrial ATP-sensitive potassium (K(ATP)) channels. The possible contribution of the nitrate moiety of this drug to its anti-apoptotic effect has now been investigated in neonatal rat ventricular myocytes subjected to oxidative stress. Exposure of cultured myocytes to 100 micromol/l hydrogen peroxide (H(2)O(2)) increased the number of nuclei stained by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling technique as well as induced internucleosomal DNA fragmentation, loss of mitochondrial membrane potential, cytochrome c release into the cytosol, and activation of caspases-3 and -9, all of which are characteristics of apoptosis. Pretreatment of cells with nicorandil (100 micromol/l) inhibited these effects of H(2)O(2). Both the mitochondrial K(ATP) channel antagonist 5-hydroxydecanoate (5-HD) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), an inhibitor of soluble guanylyl cyclase, attenuated the anti-apoptotic effect of nicorandil in concentration-dependent manners. Coapplication of ODQ (10 micromol/l) and 5-HD (500 micromol/l) completely abolished nicorandil-induced cytoprotection. The effect of nicorandil was also reduced by an inhibitor of cGMP-dependent protein kinase (KT5823, 1 micromol/l). The nitric oxide donor (+/-)-S-nitroso-N-acetylpenicillamine (SNAP, 50 micromol/l) mimicked the protective effect of nicorandil in a manner sensitive to ODQ but not to 5-HD. A cell-permeable cGMP analog, 8-bromo-cGMP, also reduced H(2)O(2)-induced apoptosis. The inhibition of the H(2)O(2)-induced activation of caspase-3, but not that of caspase-9, by nicorandil in the presence of 5-HD or by SNAP was reversed by the addition of dithiothreitol to the enzyme assay. Nicorandil inhibits oxidative stress-induced apoptosis in cardiac myocytes through a nitric oxide/cGMP-dependent mechanism as well as by activating mitochondrial K(ATP) channels.

Adenosine Triphosphate↗
PubMed2003

Three or more median sternotomies for patients with valve disease: role of computed tomography.

BACKGROUND: We evaluated the effects of computed tomographic (CT) scan-guided third or fourth median sternotomies for valve operations on the incidence of resternotomy-related complications and early mortality. METHODS: Ninety patients undergoing valve replacement with third or fourth time sternotomy were divided into two groups. One group (CT group) consisted of 64 patients who had undergone routine CT scans preoperatively after 1991 to assess the possibility of sternotomy-related bleeding, and the other group (no CT group) comprised the remaining 26 patients who did not receive CT scans. RESULTS: Hospital death occurred in 4 patients (6%) in the CT group and in 6 patients (23%) in the no CT group (p = 0.0309). Multivariate analysis indicated NYHA class 4 (odds ratio [OR] = 6.99) and year of operation (OR = 1.05) to be predictors of hospital death. Preoperative CT scans revealed that 8 patients were considered to be high risk for resternotomy, they underwent femorofemoral bypass before sternal division was performed. Hemorrhage occurred upon sternal reentry in 2 of these 8 patients. The incidences of sternotomy-related injury were 19% (5/26) in the no CT group and only 3% (2/64) in the CT group (p = 0.0198). Multivariate analyses demonstrated a fourth sternotomy (OR = 4.31) to be a predictor of resternotomy-related injury. CONCLUSIONS: CT scans provide preoperative information on retrosternal adhesions. When a distended heart or expanded aorta has adhered to the sternum, femorofemoral cannulation should be performed before sternotomy. Third and fourth sternotomies, though demanding procedures, can be performed safely using the described strategy.

Blood Loss, Surgical↗
PubMed2003

Simultaneous assessment of wall motion and coronary flow velocity in the left anterior descending coronary artery during dipyridamole stress echocardiography.

OBJECTIVES: This study was designed to assess the feasibility and clinical meaning of simultaneous assessment of wall motion and coronary flow velocity (CFV) reserve in the left anterior descending coronary artery (LAD) by transthoracic approach for detecting LAD stenosis during dipyridamole stress echocardiography. BACKGROUND: Coronary flow reserve plays an important role, which can be evaluated by transthoracic Doppler echocardiography during vasodilator stress. METHODS: Dipyridamole stress test was performed in 110 patients with known or suspected coronary artery disease. CFV in the distal LAD was obtained at baseline and after dipyridamole infusion, and wall motion was also assessed up to the administration of atropine, if required. All patients underwent quantitative coronary angiography within 2 days of the stress test, and significant LAD stenosis was defined as > 50% stenosis. RESULTS: The success rate of both measurements was 92%. CFV reserve < 2 had a higher sensitivity (94% vs 72%, P <.01) and a lower specificity (65% vs 95%, P <.01) than wall-motion assessment for detecting significant LAD stenosis, and diagnostic accuracy between 2 methods was comparable (81% vs 82%). A total of 69 patients (73%) showed concordant results of the 2 methods, and diagnostic accuracy for detecting significant LAD stenosis was high (94%) in this subset of patients. CONCLUSIONS: The simultaneous assessment of CFV and wall motion was feasible in the majority of cases during dipyridamole stress echocardiography. Although diagnostic accuracy between the 2 tests was comparable, concordant results of the 2 methods provided accurate diagnosis in detecting significant LAD stenosis.

Adult↗
PubMed2003

Further analysis of the T-cell subsets and pathways of murine cardiac allograft rejection.

The present study examined the role of CD4+ and CD8+ T cells in cardiac allograft rejection when either the direct or indirect pathway was eliminated for the CD4+ portion of the response. To study the pathways in vivo, we used genetically altered mouse strains that lack class II antigens as either the donors or recipients for cardiac transplantation. In contrast to earlier published studies, which used different strain combinations, we found that either CD4- or CD8-depletion prolonged cardiac allograft survival moderately, but not indefinitely, in an MHC-mismatched, minor-matched combination. When the CD4+ indirect pathway was eliminated, rapid graft rejection occurred when both T-cell subsets were present and when either CD4+ or CD8+ T cells were depleted. When the CD4+ direct pathway was eliminated, rapid graft rejection occurred when both T-cell subsets were present, there was slow rejection when CD4+ T cells were eliminated, and no rejection was seen for more than 100 days when CD8+ T cells were eliminated. However, the long-surviving allografts on the recipients with only CD4+ cells and an indirect pathway did show evidence of chronic vasculopathy. Thus, either CD4+ or CD8+ T cells can mediate acute cardiac allograft rejection in these experiments when both pathways are available. In addition, CD4+ T cells can provide help for acute rejection through either the direct or indirect pathway. Finally, recipients who have only CD4+ cells and an indirect pathway do not demonstrate acute rejection, but do show evidence of chronic rejection.

Animals↗
PubMed2003

Gene expression of vitamin D hydroxylase and megalin in the remnant kidney of nephrectomized rats.

BACKGROUND: Regulation of vitamin D hydroxylase genes in the early stage of chronic renal failure is not fully understood. Using nephrectomized rats, we examined changes in mRNA levels of CYP27B1 (25-hydroxyvitamin D3-1 alpha-hydroxylase), CYP24 (25-hydroxyvitamin D3-24-hydroxylase), and vitamin D receptor in relation to megalin, recently found to participate in renal vitamin D metabolism. METHODS: A rat model of moderate renal failure was induced by 3/4 nephrectomy. Plasma parameters, including vitamin D metabolite concentrations, were measured at weeks 2, 4 and 8, and poly(A)+ RNA extracted from the remnant kidneys was subjected to Northern blot hybridization. RESULTS: Plasma creatinine concentration at week 2 was 0.40 +/- 0.02 mg/dL in the sham-operated and 0.93 +/- 0.15 mg/dL in the nephrectomized rats, and both values remained constant up to week 8. Plasma concentrations of 25(OH)D3, 1 alpha,25(OH)2D3, and 24,25(OH)2D3 were unchanged between nephrectomized and sham-operated rats at week 8. Intact parathyroid hormone (PTH) increased at week 8 in nephrectomized rats. CYP27B1 mRNA in nephrectomized rats did not vary at week 2, but increased approximately two- and four-fold at weeks 4 and 8, respectively, compared to the sham-operated rats. CYP24 and megalin mRNAs, on the other hand, began to decline as early as at week 2 in nephrectomized rats and kept decreasing throughout the experiment. The expression of vitamin D receptor was modestly but significantly decreased only at week 8. CONCLUSION: Coordinated and reciprocal alterations of the increase in CYP27B1 mRNA and the decrease in CYP24 mRNA may play a pivotal role in maintaining the plasma level of 1 alpha,25(OH)2D3 in the face of reduced nephron mass and/or megalin expression.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed2003

Liver regeneration in heparin-binding EGF-like growth factor transgenic mice after partial hepatectomy.

BACKGROUND & AIMS: Heparin-binding epidermal growth factor-like growth factor (HB-EGF), a member of the EGF family, is synthesized in the form of a membrane-anchored precursor (proHB-EGF), which subsequently is processed proteolytically to mature HB-EGF. This study describes the effects of HB-EGF on liver regeneration after 70% partial hepatectomy in proHB-EGF transgenic mice with liver-specific expression. METHODS & RESULTS: No significant differences in liver/body weight ratios and in bromodeoxyuridine (BrdU)-labeling index (the ratios of BrdU-positive hepatocyte nuclei) were found between adult transgenic and wild-type mice. However, in regenerating liver after partial hepatectomy, transgenic mice had higher liver/body weight ratios than wild-type mice and at 120 hours reached a level equal to that before partial hepatectomy. The BrdU-labeling index was about 5 times higher in the livers of transgenic mice compared with the wild type (51.5% vs. 10.2%, respectively; P < 0.01) at 48 hours after partial hepatectomy. Activation of microtubule-associated protein kinase after partial hepatectomy was higher and earlier in the transgenic mice as compared with the wild-type mice. Soluble HB-EGF was increased in the liver (at 8 min) after partial hepatectomy, indicating that the shedding of proHB-EGF occurred after partial hepatectomy. CONCLUSIONS: The transgenic expression of HB-EGF accelerates the proliferation of hepatocytes after partial hepatectomy, suggesting that HB-EGF functions as a hepatotrophic factor in vivo.

Animals↗
PubMed2003

Can minilaparotomy abdominal aortic aneurysm repair be performed safely and effectively without special skills?

BACKGROUND: The purpose of this study was to determine whether a surgeon without special skills can perform minimal incision abdominal aortic aneurysm repair as safely and effectively as traditional retroperitoneal aneurysmectomy. METHODS: After informed consent, eligible patients were randomized into minilaparotomy and retroperitoneal groups. The minilaparotomy repair consisted of a short transabdominal midline incision, intraabdominal retraction of the bowel, control of back bleeding with balloon catheters, and hand-sewn anastomoses. The retroperitoneal approach was performed through a left vertical-lateral abdominal incision. RESULTS: Twenty-six patients were randomly treated by minilaparotomy approach (n = 14) or retroperitoneal approach (n = 12) from December, 1999, to May 2001. Parameters for speed of recovery were indistinguishable and of no clinical significance. In the long-term follow-up (mean period, 27 months), no patients in the minilaparatomy group complained of discomfort from the incision, whereas 4 patients in the retroperitoneal group complained of discomfort (P < 0.05). CONCLUSIONS: Minilaparotomy approach can be performed safely and effectively without specialized skill. With regard to wound discomfort, the minilaparotomy technique is excellent. The minilaparotomy approach is therefore a useful alternative to traditional repair.

Aged↗
PubMed2003

Allorecognition and effector pathways of islet allograft rejection in normal versus nonobese diabetic mice.

Islet transplantation is becoming an accepted therapy to cure type I diabetes mellitus. The exact mechanisms of islet allograft rejection remain unclear, however. In vivo CD4(+) and CD8(+) T cell-depleting strategies and genetically altered mice that did not express MHC class I or class II antigens were used to study the allorecognition and effector pathways of islet allograft rejection in different strains of mice, including autoimmunity-prone nonobese diabetic (NOD) mice. In BALB/c mice, islet rejection depended on both CD4(+) and CD8(+) T cells. In C57BL/6 mice, CD8(+) T cells could eventually mediate islet rejection by themselves, but they produced rejection more efficiently with help from CD4(+) T cells stimulated through either the direct or indirect pathway. In C57BL/6 mice, CD4(+) T cells alone caused islet rejection when only the direct pathway was available but not when only the indirect pathway was available. In contrast, in NOD mice, CD4(+) T cells alone, with only the indirect pathway, could mediate islet and cardiac allograft rejection. These findings indicate that different mouse strains can make use of different pathways for T cell-mediated rejection of islet allografts. In addition, they demonstrate that NOD mice, which develop autoimmunity and are known to be resistant to tolerance induction, have an unusually powerful CD4(+) cell indirect mechanism that can cause rejection of both islet and cardiac allografts. These data shed light on the mechanisms of islet allograft rejection in different responder strains, including those with autoimmunity.

Animals↗
PubMed2003

Depolymerization of actin filament by cytochalasin E induces interleukin-8 production and up-regulates CD54 in the HeLa epithelial cell line.

We previously reported that the depolymerization of actin filament by cytochalasin E enhances low affinity Fcepsilon receptor II (CD23) expression on the human monocyte-like cell line, U937 (J. Clin. Immunol. 20: 235, 2000). In this study, we found that cytochalasin E strongly induces interleukin-8 through an epithelial cell line, HeLa, in dose- and time-dependent manners as assessed by enzyme-linked immunoassay and reverse transcription-polymerase chain reaction techniques. In addition, interleukin-8 production in the HeLa cells cultured with cytochalasin E was blocked in the presence of protein kinase C inhibitors, Go6976 and H-7. On the other hand, it was found that CD54 (intercellular adhesion molecule-1; ICAM-1) expression on the HeLa cells and the secretion of soluble CD54 were significantly up-regulated after culturing with cytochalasin E, and that these up-regulations of CD54 were also suppressed by Go6976. Taken together, these findings indicate that cytochalasin E activates protein kinase C under the depolymerization of actin filament, leading to the induction of interleukin-8 production and the up-regulation of CD54 in HeLa cells.

Actin Cytoskeleton↗
PubMed2003

Immunological evaluation of CTL precursor-oriented vaccines for advanced lung cancer patients.

Recent clinical trials of peptide vaccine for cancer patients have rarely resulted in tumor regression. One of the reasons for this failure could be an insufficient induction of anti-tumor responses in these regimens, in which peptide-specific memory cytotoxic T lymphocytes (CTLs) were not measured prior to vaccination. We investigated in this study whether pre-vaccination measurement of peptide-specific CTLs can provide any advantages in lung cancer patients receiving peptide vaccination with regard to safety and immunological responses. Ten patients with advanced lung cancer received vaccination with peptides under a regimen of CTL precursor-oriented vaccination, in which pre-vaccination peripheral blood mononuclear cells (PBMCs) were at first screened for reactivity in vitro to each of 14 peptides, followed by in vivo administration of only the reactive peptides. Profiles of the vaccinated peptides varied markedly among the 10 patients. This regimen was generally well-tolerated, although local skin reactions, diarrhea, and colitis were observed in 8, 2, and 1 patient, respectively. Increased CTL responses against the immunized peptides and tumor cells were observed in the post-vaccination PBMCs from 4 of 8 and 3 of 10 patients tested, respectively. Peptide-specific IgG became detectable in post-vaccination sera in 4 of 10 patients tested, and these 4 patients had a long progression-free survival. Furthermore, the median survival time of 9 patients with non-small cell lung cancer was 668.0 +/- 164.2 days. These results encourage further development of CTL precursor-oriented peptide vaccination for lung cancer patients.

Adenocarcinoma↗
PubMed2003

Immunological evaluation of peptide vaccination for patients with gastric cancer based on pre-existing cellular response to peptide.

There is no standard treatment modality for advanced gastric cancer (GC) at the present time. To develop a new treatment modality, we investigated the immunological responses of advanced GC patients (n = 13, 9 non-scirrhous and 4 scirrhous types) vaccinated with peptides to a regimen under which pre-vaccination peripheral blood mononuclear cells (PBMCs) were screened for their reactivity in vitro to each of 14 peptides on HLA-A24 or 16 peptides on -A2 allele, then only the reactive peptides (maximum: 4) were administered in vivo. This regimen was generally well tolerated, although grade I levels of fever and local skin reactions were observed in several patients. Delayed-type hypersensitivity (DTH) to the vaccinated peptides was observed in 4 patients. Increased cellular and humoral immune responses to the vaccinated peptides were observed in post-vaccination PBMCs from 4 of 8 patients and in post-vaccination sera of 8 of 10 patients tested, respectively. Prolonged survival was observed in patients showing cellular and humoral immune responses to the vaccinated peptides in the post-vaccination samples, including all 4 patients with the scirrhous type. These results encourage further development of peptide-based immunotherapy for GC patients.

Adenocarcinoma↗