Biomedical subjects

T Manabe

Publications and source records attributed to T Manabe.

At least 127 records · Page 7Linked to original sources

PubMed1999

Preventive effects of exogenous phospholipases on inhibition by ferrous ions of [3H]MK-801 binding in rat brain synaptic membranes.

Prior treatment with ferrous chloride led to marked inhibition of [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne (MK-801) binding to an open ion channel associated with the N-methyl-D-aspartate (NMDA) receptor in a concentration-dependent manner at concentrations of higher than 1 microM in rat brain synaptic membranes. Both phospholipases A2 and C significantly prevented the inhibition when treated before the treatment with ferrous chloride, while neither superoxide dismutase nor alpha-tocopherol affected the inhibition even when treated simultaneously with ferrous chloride. Of various saturated and unsaturated free fatty acids, moreover, both oleic and arachidonic acids exclusively decreased the potency of ferrous chloride to inhibit binding when membranes were first treated with fatty acids, followed by the second treatment with ferrous chloride. These results suggest that membrane phospholipids may be at least in part responsible for interference by ferrous ions with opening processes of the native NMDA channel through molecular mechanisms associated with the liberation of unsaturated free fatty acids in rat brain.

Animals↗

PubMed1999

N-methyl-D-aspartate signaling to nuclear activator protein-1 through mechanisms different from those for kainate signaling in murine brain.

Protein de novo synthesis is mainly under the control at the level of gene transcription by transcription factors in cell nuclei in eukaryotes. The systemic administration of N-methyl-D-aspartate resulted in selective but transient potentiation of binding of a radiolabeled double-stranded oligonucleotide probe for the nuclear transcription factor activator protein-1 in murine hippocampus, without markedly affecting binding of probes for other transcription factors. By contrast, kainic acid induced more potent and more persistent potentiation of activator protein- binding in the hippocampus than N-methyl-D-aspartate. The protein synthesis inhibitor cycloheximide was effective in significantly preventing the potentiation by N-methyl-D-aspartate, but not that by kainic acid at the doses used. Moreover, kainic acid induced much more and longer expression of immunoreactive c-Fos protein in the hippocampus than N-methyl-D-aspartate. However, neither N-methyl-D-aspartate nor kainate induced expression of cyclic AMP response element binding protein phosphorylated at serine133 in the hippocampus from 10 min to 24 h after the administration. Instead, kainate was more potent than N-methyl-D-aspartate in facilitating both dephosphorylation at serine and phosphorylation at tyrosine of particular nuclear proteins in the hippocampus. These results suggest that N-methyl-D-aspartate and kainate signals may be differentially transduced into cell nuclei to express the activator protein-1 complex through molecular mechanisms which differ from phosphorylation of cyclic AMP response element binding protein at serine133 but involve serine dephosphorylation and/or tyrosine phosphorylation of particular nuclear proteins in the murine hippocampus.

Animals↗

PubMed1999

Predominant expression of nuclear activator protein-1 complex with DNA binding activity following systemic administration of N-methyl-D-aspartate in dentate granule cells of murine hippocampus.

The systemic administration of N-methyl-D-aspartate (100 mg/kg, i.p.) resulted in preferential but transient expression of the transcription factor activator protein-1 in the granule cell layers of the dentate gyrus in the murine hippocampus by maximally 700% 1 h later, without markedly affecting that in the pyramidal cell layers of the CA1 and CA3 subfields for 4 h. The potentiation was completely prevented by prior administration of the N-methyl-D-aspartate channel blocker dizocilpine at 10 mglkg. By contrast, kainate (40 mg/kg, i.p.) potentiated activator protein-1 DNA binding in adjacent areas around the pyramidal and granule cell layers, in addition to potentiating that in neuronal cell layers of the CA1 and CA3 subfields and the dentate gyrus. Light microscopic analysis revealed that kainate, but not N-methyl-D-aspartate, induced marked losses of the pyramidal cells in the CAI and CA3 subfields, without affecting the dentate granule cells, for 14 days after administration. Limited proteolysis by V8 protease and supershift, as well as immunoblotting assays using antibodies against c-Fos and c-Jun, invariably gave support for differential expression by N-methyl-D-aspartate and kainate of the activator protein-1 complex consisting of different partner proteins. Moreover, two-dimensional electrophoresis followed by immunoblotting analysis revealed the expression of several nuclear proteins immunoreactive with the anti-c-Fos antibody at molecular weights and isoelectric points clearly different from those of c-Fos itself in response to kainate, but not N-methyl-D-aspartate, in the hippocampus. These results suggest that in vivo N-methyl-D-aspartate signals are predominantly transduced into cell nuclei to express activator protein-1 complex through molecular mechanisms different from those for kainate signals in the granule cells of the dentate gyrus in the murine hippocampus.

Animals↗

PubMed1999

Bone marrow involvement in NPM-ALK-positive lymphoma: report of two cases.

Two cases of NPM-ALK-positive anaplastic large cell lymphoma (ALCL) with bone marrow involvement are reported. These cases were recognized within a group of NPM-ALK-positive ALCLs (n = 6) by using immunohistochemistry with the ALK1 monoclonal antibody. In case 1, the bone marrow showed diffuse infiltration of round to spindle-shaped lymphoma cells with moderate fibrosis. In case 2, lymphoma cells intermingling with hematopoietic cells could only be identified by immunohistochemical staining. In contrast to the four NPM-ALK-positive ALCL cases, which showed a cohesive growth pattern in the lymph nodes, the two cases reported here displayed lymphoma cells of smaller size, and they were classified as lymphohistiocytic variants histologically. ALK1 stained small-sized components more clearly than did CD30 (HRS-4). These results suggest that bone marrow involvement of NPM-ALK-positive ALCL may be frequently associated with a histological variant showing a small-sized cell component, and that ALK1 immunostaining is a useful tool to investigate lymphomas for bone marrow involvement.

Adolescent↗

PubMed1999

Energy filtering transmission electron microscopy using the new JEM-2010FEF.

The new JEM-2010FEF electron microscope provides useful techniques based on energy filtering as an omega-type energy filter is integrated into a thermal field-emission 200 kV transmission electron microscope. For example, the zero-loss imaging improves the contrast of high resolution lattice images as well as images of precipitates or lattice defects in alloys. The acquisition time for elemental mapping with core-loss electrons is one order in magnitude shorter than with energy-dispersive X-ray spectroscopy. The removal of inelastically scattered electrons enables us to observe weak lines in convergent-beam electron diffraction patterns from a thicker specimen with a probe size 1-2 nm in diameter. A combination of the field emission gun and sensitive recording media such as an imaging plate and a slow-scan CCD camera makes the energy filtering more powerful.

Journal Article↗

PubMed1999

Solid-pseudopapillary carcinoma of the pancreas.

A case of solid-pseudopapillary carcinoma (SPC) of the pancreas in a 34-year-old Japanese woman is presented. An abdominal ultrasonography revealed a mass, which measured 10 cm in diameter, in the body and tail of the pancreas. The tumor was resected and it was originally diagnosed as a non-functioning islet cell tumor. One year and five months later, the patient was re-admitted to hospital, and liver metastasis was confirmed by ultrasonography. The patient died 6 days after the second transcatheter arterial embolization (TAE) required for the metastasis. The autopsy showed small foci of liver metastasis. A retrospective examination of the tumor suggested the diagnosis of SPC because of its characteristic solid and pseudopapillary structures, immunohistochemical findings, and liver metastasis. This case suggests that capsular invasion, specifically found at the surgical margin of the peritoneal side, may be an important pathological finding that is suggestive of malignant potential in solid-pseudopapillary tumor. If there is such a finding in a surgical specimen, an intensive follow up should be advised to the clinician.

Adult↗

PubMed1999

Cutaneous granulocytic sarcoma mimicking immunoblastic large cell lymphoma.

A peculiar case of cutaneous granulocytic sarcoma without leukemic manifestation (so-called aleukemic leukemia cutis) that developed in the skin of the back of a 69-year-old man is reported. A skin biopsy specimen showed atypical cells with a prominent nucleolus proliferating around dermal blood vessels and along adnexa without epidermotropism. Atypical cells similar to those of the skin had infiltrated diffusely into the interfollicular area of an inguinal lymph node. Flow cytometric and immunohistochemical studies with a panel of monoclonal antibodies revealed neoplastic cells that had a biphasic phenotype of myeloid and T cell precursors. They expressed CD13, CD15, CD33, lysozyme, CD3epsilon, CD4, CD7 and terminal deoxynucleotidyl transferase (TdT). Gene analysis showed no rearrangement of the immunoglobulin heavy chain or T cell receptor beta and gamma genes. Ultrastructurally, the tumor cells exhibited a few intracytoplasmic electron-dense granules and well-developed rough endoplasmic reticulum with an occasional whorling arrangement. The initial diagnosis was immunoblastic large cell lymphoma, and the patient was treated with six courses of ProMACE-CytaBOM. In spite of the high-grade cytological characteristics of this tumor, the patient has been free of disease for 5 years.

Aged↗

PubMed1999

Immunohistochemical assessment of human bone marrow macrophages in hematologic disorders.

Changes in bone marrow macrophages may be associated with abnormal hematopoiesis in various hematologic disorders. We immunohistochemically evaluated the density of macrophages in bone marrow trephine biopsies. In reactive erythroid hyperplasia (hemolytic anemia and megaloblastic anemia), the macrophages slightly increased in density, extending their cytoplasmic processes between hematopoietic cells. In erythroid hypoplasia (pure red cell aplasia), they became rounded and frequently had hemosiderin granules. There was no significant difference in the macrophage density in the hematopoietic area between erythroid hyperplasia and hypoplasia. The macrophages increased in density in myeloproliferative disorders (polycythemia vera, chronic myelogenous leukemia and primary thrombocythemia). In myelofibrosis, some macrophages became extremely elongated along the line of the fibroblastic cells. In contrast, in conditions in which myelopoietic activity is considerably impaired (aplastic anemia, acute leukemia and multiple myeloma), they significantly decreased in density. These results suggest that the morphologic change in bone marrow macrophages is associated with erythropoietic activity and that there is a correlation between macrophage density and myelopoietic activity.

Antibodies, Monoclonal↗

PubMed1999

Platelet-activating factor receptor is not required for long-term potentiation in the hippocampal CA1 region.

From pharmacological studies, platelet-activating factor (PAF) has been proposed as a retrograde messenger for long-term potentiation (LTP) in the hippocampal CA1 region. We re-examined a possible contribution of PAF to LTP with a more specific approach using mice deficient in the PAF receptor. The PAF receptor-deficient mice exhibited normal LTP and showed no obvious abnormality in excitatory synaptic transmission. We also performed pharmacological experiments on the wild-type mice. Two structurally different antagonists of PAF receptors had no effects on LTP. Furthermore, the application of PAF itself caused no detectable changes in excitatory synaptic transmission. Thus, we conclude that the PAF receptor is not required for LTP in the CA1 region. Introduction

Animals↗

PubMed1999

Calcium-dependent mechanisms involved in presynaptic long-term depression at the hippocampal mossy fibre-CA3 synapse.

Long-term potentiation (LTP) and long-term depression (LTD) are induced presynaptically at the hippocampal mossy fibre-CA3 synapse. Activation of presynaptic metabotropic glutamate receptors (mGluRs) is necessary, but not sufficient for the LTD induction. Using mouse hippocampal slices, we attempted to identify additional presynaptic factors involved in the induction of mossy fibre LTD. Suppression of a rise in the presynaptic intracellular Ca2+ concentration ([Ca2+]i) with a membrane-permeable Ca2+ chelator, 1, 2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetraacetoxymethyl ester (BAPTA-AM), reduced the magnitude of LTD, whereas an increase in Ca2+ influx induced LTD, suggesting that an elevation of presynaptic [Ca2+]i is crucial for the LTD induction. A broad-spectrum protein kinase inhibitor, H-7, blocked LTD without affecting a presynaptic inhibition induced by an mGluR agonist. Furthermore, LTD was reduced by an inhibitor of calmodulin or Ca2+/calmodulin-dependent protein kinases. Thus, we conclude that mossy fibre LTD requires an increase in presynaptic [Ca2+]i and subsequent activation of Ca2+/calmodulin-dependent protein kinases. Because mossy fibre LTP may also require a rise in presynaptic [Ca2+]i, bidirectional long-term plasticity at the mossy fibre synapse is likely to be regulated by presynaptic Ca2+-dependent processes.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1999

Doc2alpha is an activity-dependent modulator of excitatory synaptic transmission.

Doc2alpha is a synaptic vesicle-associated Ca2 + -binding protein. To study the role of Doc2alpha in synaptic transmission and modulation, we generated homozygous null Doc2alpha mutant mice. In the CA1 region of hippocampal slices in the mutant mice, excitatory synaptic responses evoked with prolonged 5 Hz stimulation showed a significantly larger frequency facilitation followed by a steeper depression than those in wild-type mice, whereas there was no difference in synaptic transmission at lower frequencies or in paired-pulse facilitation. These results suggest that Doc2alpha regulates synaptic transmission when high Ca2 + concentrations in the presynaptic terminal are sustained. Furthermore, the mutant mice showed impairment in long-term potentiation and passive avoidance task. Thus, Doc2alpha may regulate transmitter release during repetitive synaptic activation, thereby contributing to memory formation.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1999

p53 mutations in tumor and non-tumor tissues of thorotrast recipients: a model for cellular selection during radiation carcinogenesis in the liver.

Concerns over cancer development from exposure to environmental sources of densely ionizing, high linear energy transfer (LET) radiation, such as alpha-particles from radon, is a current public health issue. The study of tumors attributable to high LET irradiation would greatly augment our insights into the biological mechanisms of carcinogenesis. Chronic low-dose-rate internal exposure to alpha-radiation from thorium dioxide deposits following intravascular administration of the radiographic contrast agent Thorotrast is known to markedly increase the risk of cancer development, especially that of hepatic angiosarcomas and cholangiocarcinomas. Although the mechanism is hypothesized to be via cellular damage, DNA being a major target, wrought by the high LET alpha-particles, the specific genes and the actual sequence of events involved in the process of transforming a normal cell into a malignant one are largely unknown. To shed some light on the molecular mechanisms of cancer development during a lifetime exposure to alpha-radiation, we analyzed the most commonly affected tumor suppressor gene in humans, p53, in 20 Thorotrast recipients who developed cancer, mostly of hepatic bile duct and blood vessel origin. Of the 20 cases, 19 were found to harbor p53 point mutations. Moreover, the accompanying non-tumor tissues from these patients also had p53 mutations, albeit at lower frequency. The distribution pattern of the point mutations was significantly different between the non-tumor and tumor tissues, with most mutations in malignant tissues located in the highly conserved domains of the p53 gene. Our results support the idea that p53 mutations are important in the genesis of Thorotrast-induced tumors but that these point mutations are a secondary outcome of genomic instability induced by the irradiation. Additionally, non-tumor cells harboring p53 mutations may gain some survival advantage in situ but mutations in the domains responsible for the formation of structural elements critical in binding DNA may be necessary for a cell to reach full malignancy.

Aged↗

PubMed1999

Basement membrane material in ovarian clear cell carcinoma: correlation with growth pattern and nuclear grade.

Stromal hyalinization in ovarian clear cell carcinomas has been suggested to be caused by deposition of basement membrane (BM) material, but the biological and diagnostic significance of this finding remains unknown. The distribution of BM material in 17 primary ovarian clear cell carcinomas was examined semiquantitatively using hematoxylin and eosin-stained sections and immunohistochemistry with antibodies to laminin and type IV collagen. For comparison, other surface epithelial tumors, including 8 serous tumors of low malignant potential, 10 serous adenocarcinomas, 6 mucinous tumors of low malignant potential, 5 mucinous adenocarcinomas, 6 endometrioid carcinomas, 4 Brenner tumors, 1 transitional cell carcinoma, and 3 undifferentiated carcinomas, were examined. Stromal hyalinization was found in all 17 clear cell carcinomas and was immunoreactive for type IV collagen and laminin. Other types of surface epithelial tumor lacked these findings. In clear cell carcinoma, areas showing a papillary pattern tended to show abundant deposition regardless of nuclear grade, whereas in solid, tubular, or cystic areas, the deposition was more prominent in areas showing high-nuclear-grade features (grade 2 and 3) than in areas with low-nuclear-grade features (grade 1). Dense deposition of BM material recognized as stromal hyalinization on hematoxylin and eosin-stained sections in primary ovarian clear cell carcinoma is a characteristic feature that is not seen in other ovarian surface epithelial tumors. This matrix production correlates with high-nuclear-grade features and papillary growth pattern.

Adenocarcinoma, Clear Cell↗

PubMed1999

Basaloid type adenoid cystic carcinoma of the breast.

We report a case of adenoid cystic carcinoma (ACC) of the breast with a prominent basaloid feature. The patient was a 62-year-old Japanese woman with a right breast mass, measuring 1.5 cm in diameter. Histologically, the tumor was composed of basal cell-like tumor cells, and it was originally diagnosed as invasive ductal carcinoma. The presence of PAS-positive basement membrane material around the tumor cell nests may be a diagnostic clue to ACC. The prognosis of ACC of the breast is considered to be favorable. However, basaloid type ACC may represent a poor prognosis, since our case revealed an aggressive behavior in spite of its small size.

Breast Neoplasms↗

PubMed1999

Bamboo-joint-like appearance of the stomach: a histopathological study.

A bamboo joint-like (BJL) appearance is an endoscopic finding characterized by swollen longitudinal folds transversed by erosive fissures or linear furrows, and it seems to be associated with Crohn's disease (CD). We performed gastroduodenoscopy in 1781 patients, and found BJL lesions in 15 (65.2%) of 23 CD patients and 20 (1.1%) of 1758 non-CD patients. Histological examination of the biopsy specimens showed sharp, fissure-like erosion or mucosal cleft in 7 (50%) out of 14 CD patients and one (20%) out of 5 non-CD patients. All cases with fissure-like erosion or, mucosal cleft revealed lymphoid aggregates, eosinophilic infiltration and edema in the superficial portion of the surrounding lamina propria. Epithelioid granuloma was seen at the base of the fissure-like erosion in two cases with CD. Our results indicated that fissure-like erosion or mucosal cleft in gastric biopsy specimens reflects the BJL appearance, and that such findings may provide a diagnostic clue to CD.

Adult↗

PubMed1999

Intraosseous epithelioid malignant peripheral nerve sheath tumor of the phalanx. Case report.

We report the first case of intraosseous epithelioid malignant peripheral nerve sheath tumor (MPNST) occurring in the phalanx. The patient was a 50-year-old Japanese man with an intramedullary lytic lesion of the proximal phalanx. Microscopically, the tumor was composed of epithelioid cells or polygonal cells, forming large cell nests with central necrosis. Most tumor cells were diffusely and strongly immunopositive for S-100 protein and vimentin, and negative for cytokeratin, epithelial membrane antigen, carcinoembryonic antigen, alpha-smooth muscle actin, and HMB-45. Laminin-positive material was discontinuously demonstrated between the individual tumor cells. Electron microscopy showed prominent external lamina. Our case indicated that laminin is useful for differentiating epithelioid MPNST from metastatic carcinoma and malignant melanoma.

Bone Neoplasms↗

PubMed1999

Clinicopathological features of serrated adenoma of the colorectum: comparison with traditional adenoma.

AIM: Serrated adenoma is a recently described category of colorectal adenoma. The aim of this study was to determine whether serrated adenomas have clinicopathological findings distinct from "traditional" adenoma. METHODS: Colonoscopy records for 1995-1998 were reviewed, and all traditional adenomas and serrated adenomas identified. Tumour site and endoscopic configuration were compared between the two types of adenoma. In polypectomised lesions, size and grade of dysplasia were compared between the two groups. RESULTS: There were 3305 traditional adenomas and 43 serrated adenomas. Serrated adenomas were more often found in the rectosigmoid colon than the traditional adenomas (67.5% v 41.2%, p = 0.0008). Polypectomy was more often done for serrated adenomas (27 of 43 lesions, 62.8%) than for traditional adenomas (626 of 3305 lesions, 18.9%, p < 0.0001). Size (mean (SD) maximum dimension, 12 (6) mm v 13 (3) mm) and incidence of high grade dysplasia (14.8% v 13.6%) in endoscopically removed specimens were not different between the two types. CONCLUSIONS: The therapeutic judgement applied to the management of traditional adenoma seems to be appropriate for serrated adenoma.

Adenoma↗

PubMed1999

Noncardiogenic pulmonary edema as the chief manifestation of a pheochromocytoma: a case report of MEN 2A with pedigree analysis of the RET proto-oncogene.

Pheochromocytomas are rare neoplasias of the adrenal medulla which generally present with paroxysmal or sustained hypertension. Cardiogenic pulmonary edema is a common feature of these tumors, but few cases have been described with noncardiogenic pulmonary edema. We report a pheochromocytoma with the principle manifestation of noncardiogenic pulmonary edema and characterize a genetic lesion associated with the disorder. A 30-year-old man was admitted with abdominal pain and breathlessness. x-Ray examination of the chest revealed a massive, diffuse infiltration of the left lung without cardiomegaly. No paroxysmal blood pressure fluctuations or heart failure were evident during the entire course, and the infiltrate and dyspnea resolved in three days without inotropic or diuretic agents. Serum norepinephrine and epinephrine levels were elevated twenty and fifty times above normal, respectively. The patient was ultimately diagnosed with multiple endocrine neoplasia type 2A (MEN 2A). Mutations in the RET proto-oncogene have been described recently in patients with MEN 2A. Mutation analysis of selected RET exonic sequences identified a germline mutation at codon 634 in exon 11 of the RET proto-oncogene. The mutation introduces a transition encoding a non-conservative substitution from TGC (Cys) to CGC (Arg) and creates a novel restriction site recognized by HhaI. We further screened for this mutation among four of the proband's relatives by HhaI restriction analysis. One asymptomatic family member was identified who subsequently elected prophylactic total thyroid removal. Histological examination of this specimen confirmed the presence of medullary thyroid carcinoma.

Adrenal Gland Neoplasms↗