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Biomedical subjects

Koji Yamamoto

Publications and source records attributed to Koji Yamamoto.

At least 19 recordsLinked to original sources
PubMed2006

Time-dependent changes in adhesive force between chondrocytes and silk fibroin substrate.

In tissue engineering for cartilage repair using scaffold, initial chondrocyte-material interactions are significantly important for the following cell behaviors such as phenotypic expression and matrix synthesis. Silk fibroin scaffold is considered to be one of the useful materials in/on which chondrocytes can proliferate without dedifferentiating into fibroblast-like cells and can organize a hyaline-like tissue. For the purpose of seeking some useful aspects for designing scaffold, initial adhesive force of chondrocytes to the surface of fibroin substrate was measured by using a lab-made apparatus applying the cantilever beam method. It was found that the adhesive force per unit spreading area of chondrocytes on fibroin substrate had a clear peak between 6 and 12h after seeding. From the results of immunofluorescence staining for actin and vinculin during this period, it could be thought that an immature formation of actin fibers which was uniquely observed at the periphery of cells attaching to fibroin substrate did not contribute to the increase of adhesive force. Results in this study suggested that surface of the fibroin substrate was gradually covered with some substances which inhibit the adhesion during this period. These cell-material interactions have a possibility to be useful information for designing the adhesive performance of scaffold surface in cartilage regeneration.

Animals↗
PubMed2006

Elevation of the post-translational modification of proteins by O-linked N-acetylglucosamine leads to deterioration of the glucose-stimulated insulin secretion in the pancreas of diabetic Goto-Kakizaki rats.

Many nuclear and cytoplasmic proteins are O-glycosylated on serine or threonine residues with the monosaccharide beta-N-acetylglucosamine, which is then termed O-linked N-acetylglucosamine (O-GlcNAc). It has been shown that abnormal O-GlcNAc modification (O-GlcNAcylation) of proteins is one of the causes of insulin resistance and diabetic complications. In this study, in order to examine the relationship between O-GlcNAcylation of proteins and glucose-stimulated insulin secretion in noninsulin-dependent type (type 2) diabetes, we investigated the level of O-GlcNAcylation of proteins, especially that of PDX-1, and the expression of O-GlcNAc transferase in Goto-Kakizaki (GK) rats, which are an animal model of type-2 diabetes. By immunoblot and immunohistochemical analyses, the expression of O-GlcNAc transferase protein and O-GlcNAc-modified proteins in whole pancreas and islets of Langerhans of 15-week-old diabetic GK rats and nondiabetic Wistar rats was examined. The expression of O-GlcNAc transferase at the protein level and O-GlcNAc transferase activity were increased significantly in the diabetic pancreas and islets. The diabetic pancreas and islets also showed an increase in total cellular O-GlcNAc-modified proteins. O-GlcNAcylation of PDX-1 was also increased. In the diabetic GK rats, significant increases in the immunoreactivities of both O-GlcNAc and O-GlcNAc transferase were observed. PUGNAc, an inhibitor of O-GlcNAcase, induced an elevation of O-GlcNAc level and a decrease of glucose-stimulated insulin secretion in isolated islets. These results indicate that elevation of the O-GlcNAcylation of proteins leads to deterioration of insulin secretion in the pancreas of diabetic GK rats, further providing evidence for the role of O-GlcNAc in the insulin secretion.

Acetylglucosamine↗
PubMed2006

Epstein-Barr virus BZLF1 gene, a switch from latency to lytic infection, is expressed as an immediate-early gene after primary infection of B lymphocytes.

We demonstrate here that the Epstein-Barr virus (EBV) BZLF1 gene, a switch from latent infection to lytic infection, is expressed as early as 1.5 h after EBV infection in Burkitt's lymphoma-derived, EBV-negative Akata and Daudi cells and primary B lymphocytes. Since BZLF1 mRNA is expressed even when the cells are infected with EBV in the presence of anisomycin, an inhibitor of protein synthesis, its expression does not require prerequisite protein synthesis, indicating that BZLF1 is expressed as an immediate-early gene following primary EBV infection of B lymphocytes.

B-Lymphocytes↗
PubMed2006

Disseminated intravascular coagulation in acute leukemia: clinical and laboratory features at presentation.

BACKGROUND: Although there are two major scoring systems for the clinical diagnosis of disseminated intravascular coagulation (DIC), the validity of these systems for leukemia-associated DIC remains to be confirmed. METHODS: By analyzing 125 newly diagnosed acute leukemia patients, we investigated clinical and laboratory features of leukemia-associated DIC, and determined the validity of the two established criteria. RESULTS: A total of 36 patients (29%) were diagnosed with DIC according to expert opinion, a method regarded as the de facto gold standard. Leukemia-associated DIC is characterized by rare manifestation of organ failure because of thrombosis and no relevance of the platelet count for the diagnosis. The results of receiver operating characteristics analysis favored fibrin degradation product (FDP) rather than D-dimer as the fibrin-related marker test. Although prothrombin time, plasma fibrinogen, and serum FDP levels were significantly different for patients with and without DIC, multivariate analysis identified FDP levels to be the only factor associated with DIC diagnosis. The cut-off level of 15 microg/mL for FDP was found to be the most effective to differentiate DIC from non-DIC, resulting in diagnostic sensitivity and specificity of 92% and 96%, respectively. The diagnostic results for our patients produced with this FDP-based system were at least comparable with or superior to those obtained with the two currently available scoring systems. CONCLUSIONS: Our findings suggest that an FDP-based criterion may be applicable for the diagnosis of leukemia-associated DIC. Although it appears to be simple and practicable enough for clinical use, prospective validation of this criterion is needed.

Acute Disease↗
PubMed2006

Attenuated stress-induced catecholamine release in mice lacking the vasopressin V1b receptor.

Vasopressin V(1b) receptor is specifically expressed in the pituitary and mediates adrenocorticotropin release, thereby regulating stress responses via its corticotropin releasing factor-like action. In the present study we examined catecholamine release in response to two types of stress in mice lacking the V(1b) receptor gene (V(1b)R(-/-) mice) vs. wild-type mice. There were no significant differences in the basal plasma levels of catecholamines between the two genotypes. In response to stress induced by forced swimming, norepinephrine (NE), but not epinephrine (E) or dopamine (DA), was increased in wild-type mice, whereas the increases in NE and DA were not observed in V(1b)R(-/-) mice. In wild-type mice, E, but not NE or DA, was increased in response to social isolation stress, whereas the increase in E was not observed in V(1b)R(-/-) mice. These results suggest that the V(1b) receptor regulates stress-induced catecholamine release. Because it has been suggested that arginine-vasopressin (AVP) is related to the development of depression, we also evaluated immobility time in the forced swimming test, and we found no significant change in V(1b)R(-/-) mice. Taken together, these findings suggest that, in addition to the previously elucidated effect on the hypothalamic-pituitary-adrenal axis, vasopressin activity via V(1b) receptors regulates stress-induced catecholamine release.

Animals↗
PubMed2006

Computer-aided diagnosis scheme for identifying histological classification of clustered microcalcifications by use of follow-up magnification mammograms.

RATIONALE AND OBJECTIVES: Our purpose in this study was to investigate the usefulness of follow-up magnification mammograms (i.e., both current and previous magnification mammograms) in a computer-aided diagnosis (CAD) scheme for identifying the histological classification of clustered microcalcifications. MATERIALS AND METHODS: Our database consisted of current and previous magnification mammograms obtained from 93 patients before and after 3-month follow-up: 11 invasive carcinomas, 19 noninvasive carcinomas of the comedo type, 25 noninvasive carcinomas of the noncomedo type, 23 mastopathies, and 15 fibroadenomas. In our CAD scheme, we extracted five objective features of clustered microcalcifications from each of the current and previous magnification mammograms by taking into account image features that experienced radiologists commonly use to identify histological classifications. These features were then merged by a modified Bayes discriminant function for distinguishing among five histological classifications. For the input of the modified Bayes discriminant function, we used five objective features obtained from the previous magnification mammogram (previous features), five objective features obtained from the current magnification mammogram (current features), and the set of the five previous features and the five current features. RESULTS: The classification accuracies with the five current features were higher than those with the five previous features. These classification accuracies were improved substantially by using the set of the five previous features and the five current features. For the set of the five previous features and the five current features, the classification accuracies of our CAD scheme were 81.8% (9 of 11) for invasive carcinoma, 84.2% (16 of 19) for noninvasive carcinoma of the comedo type, 76.0% (19 of 25) for noninvasive carcinoma of the noncomedo type, 73.9% (17 of 23) for mastopathy, and 86.8% (13 of 15) for fibroadenoma. CONCLUSION: Our CAD scheme with use of follow-up magnification mammograms improved classification performance for mammographic clustered microcalcifications.

Algorithms↗
PubMed2006

Computer-aided diagnosis scheme using a filter bank for detection of microcalcification clusters in mammograms.

Mammography is considered the most effective method for early detection of breast cancers. However, it is difficult for radiologists to detect microcalcification clusters. Therefore, we have developed a computerized scheme for detecting early-stage microcalcification clusters in mammograms. We first developed a novel filter bank based on the concept of the Hessian matrix for classifying nodular structures and linear structures. The mammogram images were decomposed into several subimages for second difference at scales from 1 to 4 by this filter bank. The subimages for the nodular component (NC) and the subimages for the nodular and linear component (NLC) were then obtained from analysis of the Hessian matrix. Many regions of interest (ROIs) were selected from the mammogram image. In each ROI, eight features were determined from the subimages for NC at scales from 1 to 4 and the subimages for NLC at scales from 1 to 4. The Bayes discriminant function was employed for distinguishing among abnormal ROIs with a microcalcification cluster and two different types of normal ROIs without a microcalcification cluster. We evaluated the detection performance by using 600 mammograms. Our computerized scheme was shown to have the potential to detect microcalcification clusters with a clinically acceptable sensitivity and low false positives.

Algorithms↗
PubMed2006

[Preparation and characterization of (5-methyl-2-oxo-1,3-dioxol-4-yl) methyl thiamine sulfides].

A new type of S-protected thiol-type thiamines (prodrugs), which have a (5-methyl-2-oxo-1,3-dioxol-4-yl) methyl group recognized as a biologically safe promoiety, were designed, prepared, and confirmed to show higher serum thiamine levels after oral administration to rats than after that of thiamine itself and bisbentiamin as standards. Thus it was shown that the promoiety should be also used for improvement of poor oral absorption of drugs with a mercapto group, in addition to the absorption of drugs with carboxyl, amino, and hydroxyl groups.

Administration, Oral↗
PubMed2006

Clinical protocol for angiogenesis by intramyocardial injection of autologous bone marrow mononuclear cells in patients with severe coronary artery disease: TACT-NAGOYA-HEART.

BACKGROUND: Despite recent improvements in the treatments of coronary artery disease (CAD), there are a considerable number of patients who can not receive complete revascularization because of severe or total arterial occlusion. Intramyocardial injection of autologous bone marrow mononuclear cells (ABMMCs) has been shown to induce neovascularization of ischemic myocardium. METHODS AND RESULTS: The study will investigate the safety and feasibility of intramyocardial injections of ABMMCs and test the hypothesis that this treatment would promote neovascularization and improve left ventricular (LV) global and/or regional function in patients with severe CAD who have no other option. ABMMCs (approximately 10(6) cells) will be injected into the area of ischemic myocardium where the coronary artery is not graftable, in combination with bypass surgery to the other coronary branches. Myocardial perfusion and LV global and regional function will be evaluated, based on the micromanometer-tipped catheter method, single-photon emission tomography, and myocardial enhanced and color tissue Doppler echocardiography at baseline and during 12 month follow-up. CONCLUSIONS: This project will demonstrate that intramyocardial injection of ABMMCs with or without coronary artery bypass surgery could be a safe and effective method for therapeutic neovascularization, resulting in an improvement of cardiac function in patients with severe CAD.

Bone Marrow Cells↗
PubMed2006

Recurrent intramural hematoma of the small intestine in a severe hemophilia A patient with a high titer of factor VIII inhibitor: a case report and review of the literature.

A 17-year-old man with severe hemophilia A (factor VIII <1%) developed intermittent left upper quadrant pain. He had a high titer of factor VIII inhibitor (1024 Bethesda units/mL) and was diagnosed with intramural hematoma of the jejunum. He was managed conservatively with activated prothrombin complex concentrate (APCC), resulting in the resolution of symptoms. He developed recurrent intramural hematoma of the small intestine over the next 54 months, and was successfully treated with APCC. This case highlights a rare clinical manifestation in hemophilia patients, and also indicates the effectiveness of APCC instead of exploratory surgery for intramural hematoma. Cases of intramural hematoma of the gastrointestinal tract among hemophilia patients are also reviewed.

Adolescent↗
PubMed2005

The relationship between variables of 123-I-metaiodobenzylguanidine cardiac imaging and clinical status of the patients with diastolic heart failure.

BACKGROUND: The status of cardiac sympathetic nerve activity in patients with diastolic heart failure has not been fully understood. 123-I-metaiodobenzylguanidine cardiac images are valuable for evaluating cardiac sympathetic nerve activity. METHODS: We obtained 123-I-metaiodobenzylguanidine cardiac images from 34 consecutive patients with moderate heart failure and an ejection fraction of > or = 45%. RESULTS: The decay-corrected washout rate of 123-I-metaiodobenzylguanidine correlated with each plasma concentration of brain natriuretic peptide (standardized correlation coefficient=0.305, p<0.05), New York Heart Association functional class (standardized correlation coefficient=0.364, p<0.02), and exercise capacity (standardized correlation coefficient=-0.388, p<0.04). A multiple regression analysis revealed that the washout rate independently predicted plasma concentration of brain natriuretic peptide (standardized regression coefficient=0.367, p<0.02). In a univariate regression, the washout rate did not significantly correlate with the presence of ischemic heart disease (p=0.254); in a multivariate regression, the presence of ischemic heart disease did not predict the washout rate. For the 14 patients with sinus rhythm, there was a marginal negative correlation between the E/A velocity ratio of the transmitral flow and washout rate (standardized correlation coefficient=-0.518, p<0.07). CONCLUSIONS: In diastolic heart failure, cardiac sympathetic nerve activity increases proportionally to severity of the disease.

3-Iodobenzylguanidine↗
PubMed2005

Diagnostic efficacy of thin slice CT in osteoid osteoma of the thoracic spine: report of two cases.

We present a 24-year-old man and a 31-year-old woman who complained of persistent back pain with osteoid osteoma of the thoracic spine. Computed tomography (CT) revealed a round sclerotic lesion in the posterior element of the thoracic spine, although their plain radiographs showed no abnormalities except a slight scoliosis. The patients underwent total excision of the tumor via a posterior approach. They are currently asymptomatic with no recurrence of the lesion and have returned to full activity. The thin slice CT is one of the most important diagnostic tools for osteoid osteoma of the spine.

Adult↗
PubMed2005

A patient with adult extrahepatic portal obstruction, of which distinction from intrahepatic cholangiocarcinoma was difficult.

A 51-year-old Japanese male with chief complaints of slightly high fever and epigastralgia was hospitalized at our facility. The inflammatory response was enhanced, and liver dysfunction was observed. Abdominal ultrasonography demonstrated a hyperechoic lesion occupying the left portal vein, and abdominal plain CT indicated a low density of the lesion with a clear boundary, measuring about 3 cm x 2 cm, between the porta hepatis and segment IV of the liver. Contrast CT showed no enhancement in the arterial and portal phases, but a reduction in the density inside the tumor in the equilibration phase was noted. MRI showed hypointensity by T1-weighted imaging and hyperintensity by T2-weighted imaging. Angiography demonstrated an obstruction of the left portal vein and superior mesenteric vein, and endoscopic retrograde cholangiography revealed a constriction in the left intrahepatic bile duct. Since the possibility of intrahepatic cholangiocarcinoma could not be excluded, extended left hepatectomy combined with caudate lobectomy was performed. The tumor, measuring 31 mm x 21 mm x 20 mm, was pathohistologically diagnosed as an extrahepatic portal obstruction. Extrahepatic portal obstruction is an important disease that is sometimes difficult to rule out oncologic origin.

Bile Duct Neoplasms↗
PubMed2004

Targeted disruption of mouse ortholog of the human MYH9 responsible for macrothrombocytopenia with different organ involvement: hematological, nephrological, and otological studies of heterozygous KO mice.

Among three different isoforms of non-muscle myosin heavy chains (NMMHCs), only NMMHCA is associated with inherited human disease, called MYH9 disorders, characterized by macrothrombocytopenia and characteristic granulocyte inclusions. Here targeted gene disruption was performed to understand fundamental as well as pathological role of the gene for NMMHCA, MYH9. Heterozygous intercrosses yielded no homozygous animals among 552 births, suggesting that MYH9 expression is required for embryonic development. In contrast, MYH9+/- mice were viable and fertile without gross anatomical, hematological, and nephrological abnormalities. Immunofluorescence analysis also showed the normal cytoplasmic distribution of NMMHCA. We further measured the auditory brainstem response and found two of six MYH9+/- mice had hearing losses, whereas the remaining four were comparable to wild-type mice. Such observation may parallel the diverse expression of Alport's manifestations of human individuals with MYH9 disorders and suggest the limited requirement of the gene for maintenance and function of specific organs.

Animals↗
PubMed2004

Aging and plasminogen activator inhibitor-1 (PAI-1) regulation: implication in the pathogenesis of thrombotic disorders in the elderly.

Thrombotic cardiovascular diseases increase in incidence in the elderly, a tendency dependent on the age-related changes in vascular and hemostatic systems that include platelets, coagulation, and fibrinolytic factors as well as in the endothelium. The hypercoagulability of and advanced sclerotic changes in the vascular wall may contribute to the increased incidence of thrombosis in the elderly. One of the important key genes for aging-associated thrombosis is plasminogen activator inhibitor-1 (PAI-1), a principal inhibitor of fibrinolysis. The expression of PAI-1 is not only elevated in the elderly but also significantly induced in a variety of pathologies associated with the process of aging. These conditions include obesity, insulin resistance, emotional stress, immune responses, and vascular sclerosis/remodeling. Several cytokines and hormones, including tumor necrosis factor-alpha, transforming growth factor-beta, angiotensin II, and insulin, positively regulate the gene expression of PAI-1. The recent epidemic in obesity with aging in the industrialized society may heighten the risk for thrombotic cardiovascular disease because adipose tissue is a primary source of PAI-1 and cytokines. Emotional or psychosocial stress and inflammation also cause the elevated expression of PAI-1 in an age-specific pattern. Thus, PAI-1 could play a key role in the progression of cardiovascular aging by promoting thrombosis and vascular (athero)sclerosis. Further studies on the genetic mechanism of aging-associated PAI-1 induction will be necessary to define the basis for cardiovascular aging in relation to thrombosis.

Adipose Tissue↗
PubMed2004

Synthesis and structure-activity relationships of potent 3- or 4-substituted-2-cyanopyrrolidine dipeptidyl peptidase IV inhibitors.

Dipeptidyl peptidase IV (DPP-IV) inhibitors have attracted attention as potential drugs for use in the treatment of type 2 diabetes because they prevent degradation of glucagon-like peptide-1 (GLP-1) and extend its duration of action. A series of 2-cyanopyrrolidines are among the most potent of DPP-IV inhibitors. We focused our attention on substitutions at the 3- or 4-position of 2-cyanopyrrolidines and synthesized and evaluated various derivatives. Among them, the 4-fluoro derivative was found to exhibit better DPP-IV inhibitory activity and higher plasma drug concentrations after oral administration to rats than the 4-unsubstituted derivative. We report here on the synthesis and biological data of the aforementioned derivatives.

Adenosine Deaminase Inhibitors↗