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Biomedical subjects

M Yamamoto

Publications and source records attributed to M Yamamoto.

At least 91 records · Page 5Linked to original sources
PubMed2004

Immunohistochemical identification of intracytoplasmic lumens by cytokeratin typing may differentiate renal oncocytomas from chromophobe renal cell carcinomas.

Renal oncocytomas and chromophobe renal cell carcinomas (RCCs) share a common phenotype and both originate from the intercalated cells of the collecting duct. This makes it very difficult to differentiate between the two tumors immunohistochemically. Therefore, we studied the results of immunohistochemistry focusing on certain characteristic structures that are occasionally present in renal oncocytomas. We carried out Hale's colloidal iron staining and immunohistochemistry for various cytokeratins (cytokeratins 7, 8, 10, 10/13, 14, 18, 19 and 20, and AE1/AE3) in four oncocytomas and six chromophobe RCCs. In addition, one renal oncocytoma and one chromophobe RCC were studied using electron microscopy. Two renal oncocytomas and one chromophobe RCC were completely unstained by colloidal iron. There was no evident difference between the immunohistochemical characteristics of oncocytomas and those of chromophobe RCCs. However, in all four renal oncocytomas we identified intracytoplasmic ring-like positive reactions for some cytokeratins (at least 3 antigens of cytokeratins 7, 8 and 19, and AE1/AE3), which corresponded ultrastructurally to the intracytoplasmic lumens (ICLs). In contrast, no such structures were found in any of the chromophobe RCCs using the antibodies employed. Therefore, immunohistochemical identification of ICLs by cytokeratin typing may be useful for differentiating between renal oncocytomas and chromophobe RCCs and be more sensitive in this respect than colloidal iron staining.

Adenoma, Oxyphilic↗
PubMed2004

The distribution and role of myofibroblasts and CD34-positive stromal cells in normal pancreas and various pancreatic lesions.

To elucidate the distribution and role of myofibroblasts and CD34-positive stromal cells in various pancreatic lesions, we performed an immunohistochemical study using a streptoavidin-biotin immunoperoxidase technique. We selected 43 pancreatic lesions from 1 biopsied, 22 surgically resected and 12 autopsied specimens: acute pancreatitis (n=3), chronic non-obstructive pancreatitis (n=4), obstructive pancreatitis (n=7), islet cell tumor (n=4), serous cystadenoma (n=7), mucinous cystadenoma (n=6), and invasive ductal carcinoma (n=12). In normal pancreas, myofibroblasts and CD34-positive stromal cells were predominantly present in the peridcutal and periacinar areas, respectively. Both myofibroblasts and CD34-positive cells were observed in the stroma of chronic pancreatitis. In four islet cell tumors, myofibroblasts were present in the stroma of the tumor center, but no CD34-positive stromal cells were identified. Additionally, myofibroblasts and CD34-positive stromal cells were located in the inner layer and the outer layer of the capsule of three islet cell tumors, respectively. In nine of the thirteen cystadenomas, only myofibroblasts were recognized in the cyst wall. In the remaining four cystadenomas, a small number of CD34-positive cells were observed in the cyst wall. In 12 invasive ductal carcinomas, the stroma possessed a lot of myofibroblasts, but there were no or few CD34-positive stromal cells. In conclusion, it seems that the abundant amount of CD34-stromal cells in the main lesions is characteristic of chronic inflammatory lesions. Myofibroblasts and CD34-positive stromal cells may play a role in regulating the tumor growth in the capsule of islet cell tumors of the pancreas.

Acute Disease↗
PubMed2004

[Natural Y-grafting using internal thoracic artery branches for off-pump coronary artery bypass].

The excellent long-term patency rates achieved utilizing the internal thoracic arteries (ITAs) have stimulated a variety of approaches to expand the use of these conduits in coronary revascularization. The ITA divides at the level of the fifth or sixth intercostal space into the superior epigastric and musculophrenic branches. If these terminal branches of the ITA are large and long enough for grafting, they can be used to construct a "Y" anastomosis to the coronary arteries. We experienced 2 patients who underwent multivessel off-pump coronary artery bypass (OPCAB) using these ITA branches. In both patients the bilateral ITAs and the right gastroepiploic artery were taken down using the skeletonization technique as in situ grafts. One patient had 5 grafts including the right ITA terminal branches which were used for the left anterior descending branch (LAD) and diagonal branch. Another patient had 6 grafts including the left ITA terminal branches which were used for the posterolateral branch (PL)1 and PL2. Postoperative angiography revealed widely patent grafts in both patients. We believe that one of the advantages of applying the off-pump technique when the ITA branches are used is that it might be easier to arrange the angle of constructing a natural "Y" configuration compared with conventional coronary artery bypass grafting (CABG). In conclusion, the terminal branches of the ITA, if of suitable size, should be considered for "Y" grafts to diseased coronary arteries when performing complete arterial revascularization with only in situ grafts.

Aged↗
PubMed2003

Acute myeloid leukemia in elderly patients: experience of a single center.

Acute myeloid leukemia (AML) is a disease predominantly of older adults. Treatment of AML in the elderly is complicated not only by comorbidities but also by the high prevalence of poor prognosis markers. Thirty-one consecutive unselected patients with AML older than 60 years (representing 33% of all AML cases diagnosed at our institution during the same period) were followed over a period of 5 years (1997-2002). A high incidence of AML with multilineage dysplasia (45%) and no favorable cytogenetic abnormalities but 62% intermediate and 38% unfavorable karyotypes were found. Sixteen patients (52%) were selected for induction of intensive cytotoxic treatment and complete remission was achieved only by some of these intensively treated patients (7 of 16). Of these, 3 remained alive without disease (median: 11 months), 1 patient died shortly after complete remission, and 3 patients relapsed and died from refractory disease. Only 1 patient that was refractory to intensive cytotoxic treatment remained alive with disease under supportive care. Fifteen patients (48%) were managed with palliative/supportive care: 7 received palliative treatment and supportive care, 8 received supportive care only, and 4 patients remained alive with disease under supportive care (median: 9 months). Mortality rate was 74% and overall survival at two years was 12%. To the best of our knowledge, there is no previous report regarding elderly patients with AML in Brazilian subsets. The present data are similar to previously reported studies showing that elderly AML patients are not only older but also biologically distinct from younger AML patients, particularly in terms of the high incidence of poor prognostic karyotypes and resistance to therapy.

Acute Disease↗
PubMed2003

Essential Bacillus subtilis genes.

To estimate the minimal gene set required to sustain bacterial life in nutritious conditions, we carried out a systematic inactivation of Bacillus subtilis genes. Among approximately 4,100 genes of the organism, only 192 were shown to be indispensable by this or previous work. Another 79 genes were predicted to be essential. The vast majority of essential genes were categorized in relatively few domains of cell metabolism, with about half involved in information processing, one-fifth involved in the synthesis of cell envelope and the determination of cell shape and division, and one-tenth related to cell energetics. Only 4% of essential genes encode unknown functions. Most essential genes are present throughout a wide range of Bacteria, and almost 70% can also be found in Archaea and Eucarya. However, essential genes related to cell envelope, shape, division, and respiration tend to be lost from bacteria with small genomes. Unexpectedly, most genes involved in the Embden-Meyerhof-Parnas pathway are essential. Identification of unknown and unexpected essential genes opens research avenues to better understanding of processes that sustain bacterial life.

Bacillus subtilis↗
PubMed2003

The Lotus japonicus Sen1 gene controls rhizobial differentiation into nitrogen-fixing bacteroids in nodules.

A Lotus japonicus mutant, Ljsym75, which forms ineffective symbiotic nodules and defines a new locus involved in the process of nitrogen fixation, was characterized in detail in order to identify the stage of developmental arrest of the nodules. No nitrogen-fixing activity was detectable in Ljsym75 nodules at any stage during plant development, and plant growth was markedly retarded. Ljsym75 plants formed twice as many nodules as the wild-type Gifu, and this phenotype was not influenced by the application of low concentrations of nitrate. Although the ineffective nodules formed on Ljsym75 were anatomically similar to effective Gifu nodules, Ljsym75 nodules senesced prematurely. Microscopic examination revealed that bacteria endocytosed into Ljsym75 nodules failed to differentiate into bacteroids. Moreover, the bacteria contained no nitrogenase proteins, whereas leghemoglobin was detected in the cytosol of the nodules. These results indicate that Ljsym75 is required for bacterial differentiation into nitrogen-fixing bacteroids in nodules, and thus the Ljsym75 gene was renamed sen1 (for stationary endosymbiont nodule). Linkage analysis using DNA markers showed that Sen1 is located on chromosome 4.

Chromosome Mapping↗
PubMed2003

Sarcoplasmic reticulum Ca2+ release is not a dominating factor in sinoatrial node pacemaker activity.

Recent work on isolated sinoatrial node cells from rabbit has suggested that sarcoplasmic reticulum Ca2+ release plays a dominant role in the pacemaker potential, and ryanodine at a high concentration (30 micromol/L blocks sarcoplasmic reticulum Ca2+ release) abolishes pacemaking and at a lower concentration abolishes the chronotropic effect of beta-adrenergic stimulation. The aim of the present study was to test this hypothesis in the intact sinoatrial node of the rabbit. Spontaneous activity and the pattern of activation were recorded using a grid of 120 pairs of extracellular electrodes. Ryanodine 30 micromol/L did not abolish spontaneous activity or shift the position of the leading pacemaker site, although it slowed the spontaneous rate by 18.9+/-2.5% (n=6). After ryanodine treatment, beta-adrenergic stimulation still resulted in a substantial chronotropic effect (0.3 micromol/L isoproterenol increased spontaneous rate by 52.6+/-10.5%, n=5). In isolated sinoatrial node cells from rabbit, 30 micromol/L ryanodine slowed spontaneous rate by 21.5+/-2.6% (n=13). It is concluded that sarcoplasmic reticulum Ca2+ release does not play a dominating role in pacemaking in the sinoatrial node. The full text of this article is available at http://www.circresaha.org.

Action Potentials↗
PubMed2003

Sonographic evaluation for peripheral pulmonary nodules during video-assisted thoracoscopic surgery.

BACKGROUND: The clinical value of sonographic guidance during video-assisted thoracoscopic surgery (VATS) was studied in 26 patients with peripheral pulmonary nodules. METHODS: Twenty-six patients underwent VATS between June 2000 and March 2001 for primary lung cancer (n = 15), pulmonary metastasis (n = 6), and various benign tumors (n = 5). RESULTS: Sonographic guidance successfully visualized peripheral pulmonary tumors in 21 of the 26 patients (81%). Among them, rich intratumoral blood flow signal was identified in 8 of the 15 primary lung cancers by using color Doppler sonography. The peak velocity was 26 +/- 12.8 cm/s in primary lung cancer and 9.4 +/- 1.7 cm/s in pulmonary metastasis, respectively (p <0.01). CONCLUSION: Sonographic guidance during VATS is helpful for locating lesions and determining the extent of surgical resection. The color Doppler method was also useful for evaluating intratumoral blood flow, which yielded significant information for differentiating primary lung cancer, metastatic tumors, and various benign tumors.

Aged↗
PubMed2003

Inactivation of Ret/Ptc1 oncoprotein and inhibition of papillary thyroid carcinoma cell proliferation by indolinone RPI-1.

Genetic alterations causing oncogenic activation of the RET gene are recognized as pathogenic events in papillary and medullary thyroid carcinomas. Inhibition of Ret oncoprotein functions could thereby represent a specific therapeutic approach. We previously described the inhibitory activity of the 2-indolinone derivative RPI-1 (formerly Cpdl) on the tyrosine kinase activity and transforming ability of the products of the RET/PTC1 oncogene exogenously expressed in murine cells. In the present study, we investigated the effects of RPI-1 in the human papillary thyroid carcinoma cell line TPC-1 spontaneously harboring the RET/PTC1 rearrangement. Treatment with RPI-1 inhibited cell proliferation and induced accumulation of cells at the G2 cell cycle phase. In treated cells, Ret/Ptc1 tyrosine phosphorylation was abolished along with its binding to Shc and phospholipase C(gamma), thereby indicating abrogation of constitutive signaling mediated by the oncoprotein. Activation of JNK2 and AKT was abolished, thus supporting the drug inhibitory efficacy on downstream pathways. In addition, cell growth inhibition was associated with a reduction in telomerase activity by nearly 85%. These findings in a cellular context relevant to the pathological function of RET oncogenes support the role of Ret oncoproteins as useful targets for therapeutic intervention, and suggest RPI-1 as a promising candidate for preclinical development in the treatment of thyroid tumors expressing RET oncogenes.

Animals↗
PubMed2003

Reduced phosphorylation of cyclic AMP-responsive element binding protein in the postmortem orbitofrontal cortex of patients with major depressive disorder.

In this study, we examined the amounts of cAMP-responsive element binding protein (CREB) and its phosphorylated form in homogenate preparations from postmortem orbitofrontal cortices of antidepressant drug-free patients with major depressive disorder and age-matched controls by immunoblotting. Immunoreactivies of both CREB and phosphorylated CREB were significantly decreased in depressive subjects compared to controls. The immunoreactivity of phosphorylated CREB was diminished to a greater extent than that of CREB in depressive patients. It has been indicated from animal studies that a transcription factor likely mediates neural plasticity in the mammalian brain and neural tissues. Our results suggest that alterations in the cAMP signaling system, especially in CREB, may be involved in the pathophysiology of depression and be potential targets for antidepressant treatment.

Aged↗
PubMed2003

A critical period for retinoic acid teratogenesis and loss of neurophilic migration of pontine nuclei neurons.

Abnormalities in the pontine nuclei (PN) and inferior olive are hallmarks of human retinoic acid (RA) teratogenesis. This study shows that RA exposure of the mouse at a specific embryonic stage alters morphological structures that derive from the wall of the IVth ventricle to form components of the precerebellar system (the inferior olivary nucleus and the PN). The study employs both normal and a RAREhspLacZ transgenic RA reporter mouse. It is shown that abnormalities in the PN and inferior olive result from exposure at a critical period of embryonic day 9.5 and 10.5. The abnormalities in the PN are due to a failure in their usual neurophilic migration. The compact stream of cells that leads from the anterior rhombic lip to the ventral pons is instead scattered widely over the anterior medulla. Given that the RA exposure occurs after the resolution of rhombomere identity this suggests that teratogenic RA interferes with a regulatory event that overlays this original pattern.

Abnormalities, Drug-Induced↗
PubMed2003

Role of adapters in Toll-like receptor signalling.

Toll-like receptors (TLRs) play a critical role in the detection of invading pathogens within the body and the subsequent immune response. Individual TLRs recognize distinct microbial components. The TLRs are a type 1 transmembrane receptor that possess an extracellular leucine-rich repeat domain and cytoplasmic domain homologous with that of the interleukin 1 receptor (IL-1R) family. Upon stimulation, TLR recruits the IL-1R-associated kinase (IRAK) via the adapter MyD88, ultimately leading to the activation of nuclear factor-kappaB. Cytokine production in response to all TLR ligands is completely abolished in MyD88-deficient cells, indicating that MyD88 is an essential signalling molecule shared among members of the IL-1R/Toll family. However, several novel adaptor molecules have recently been identified. Evidence is now accumulating showing that differential utilization of these adaptors may activate overlapping as well as distinct signalling pathways, and ultimately give rise to distinct biological effects exerted by individual TLR family members.

Adaptor Proteins, Signal Transducing↗
PubMed2003

A novel p63 sterile alpha motif (SAM) domain mutation in a Japanese patient with ankyloblepharon, ectodermal defects and cleft lip and palate (AEC) syndrome without ankyloblepharon.

We present a sporadic case of a Japanese female infant with ectodermal dysplasia, complete cleft lip and palate, severe skin erosions at birth and recurrent scalp infection. She had typical clinical features of ankyloblepharon, ectodermal defects and cleft lip and palate (AEC) syndrome without ankyloblepharon. Histological and immunohistochemical analyses showed reduced granular cell layers and aberrant expression of the p63 protein in the suprabasal keratinocytes. Mutation analysis of the exon 13 of p63 gene revealed a heterozygous in-frame 3-bp insert (c. 538-539 ins TTC) encoding additional amino acid residues (F). This is the first report of sterile alpha motif domain mutation except for single nucleotide transitions.

Abnormalities, Multiple↗
PubMed2003

Analysis of B-cell clonality in the hepatic tissue of patients with Sjögren's syndrome.

OBJECTIVE: We investigated the incidence of B-cell clonality in the minor salivary gland and liver (extra-glandular lesion) of patients with Sjögren's syndrome (SS). We also compared B-cell clonality in the minor salivary gland and liver in the same individuals, and compared its incidence among patients with various liver diseases, such as primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH). METHODS: A minor salivary gland biopsy was performed on 35 patients with SS (30 patients with primary SS, and five patients with secondary SS). A liver biopsy was performed on nine patients with SS associated with bile duct lesions, two patients with PBC, one patient with AIH, one patient with drug-induced liver dysfunction, and three patients with viral hepatitis. DNA was extracted from each tissue sample and then subjected to Polymerase Chain Reaction (PCR). B-cell clonality was analysed by assessing the rearrangement of the immunoglobulin heavy chain (IgH) gene by PCR. RESULTS: B-cell clonality was confirmed in the minor salivary gland biopsy sample in 23 of the 35 patients (65.7%), and in the liver biopsy sample (non-exocrine organ involvement) in seven of the nine patients (77.8%). The presence or absence of B-cell clonality was investigated in both the minor salivary gland and liver in seven patients, but B-cell clonality was confirmed in both tissues in only one patient, and the pattern of clonality in the minor salivary gland differed from that in the liver. B-cell clonality was detected in the liver of the PBC and AIH patients. CONCLUSION: B-cell clonality is a phenomenon that is observed frequently in SS lesions in the salivary glands and liver. The appearance of B-cell clonality was shown to be attributable to antigen-driven clonal expansion.

Adolescent↗
PubMed2003

In vitro evaluation of the cytocompatibility of a glass-lonomer cement sealer.

The purpose of this study was to evaluate the cytocompatibility of two different types of root canal sealers in cell culture. Human periodontal ligament cells were cultured with set materials from an experimental glass-ionomer cement sealer (KT-308) and a commercially available zinc oxide-eugenol-based sealer (Canals) for 1, 3, and 7 days. Cytotoxic effects were evaluated from the morphological changes under a light microscope. Canals induced severe degenerative alteration of human periodontal ligament cells. In contrast, human periodontal ligament cells adjacent to KT-308 showed normal morphology and growth during the culture period. These results suggest that the glass-ionomer cement sealer, KT-308, is cytocompatible and has good potential as a root canal sealer.

Cells, Cultured↗
PubMed2003

Cyclooxygenase-2 promoter for tumour-specific targeting of adenoviral vectors to melanoma.

Novel therapeutic strategies are warranted for the treatment of metastatic melanoma as conventional therapies are inefficient. Conceptually, these strategies should be systemic and tumour-targeted. Gene therapy and viral oncolysis represent promising new approaches for cancer treatment that allow for the incorporation of molecular targeting strategies. In this regard, we analysed cyclooxygenase-2 (cox-2) expression as a potential new target for melanoma gene therapy. By reverse transcription polymerase chain reaction analysis, we showed cox-2 mRNA expression in all of the six tested melanoma cell lines, thus establishing cox-2 as a tumour marker for melanoma of potential interest for targeted therapeutics. Next, we analysed the activity and specificity of the cox-2 promoter within adenoviral vectors by luciferase assays. For this purpose, melanoma cell lines, primary melanoma cells and normal melanocytes were infected with adenoviruses containing cox-2 promoter sequences driving the luciferase reporter gene. The results demonstrated activity of the cox-2 promoter in melanoma cell lines and primary melanoma cells, but not in non-malignant primary epidermal melanocytes. Thus, we established herein the tumour specificity of the cox-2 promoter with potential applications for transcriptional targeting of adenoviral vector-based cancer gene therapy or virotherapy to melanoma.

Adenoviridae↗