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Biomedical subjects

T Akagi

Publications and source records attributed to T Akagi.

At least 181 records · Page 10Linked to original sources

Evaluation of pulmonary artery histopathologic findings in congenital heart disease: an in vitro study using intravascular ultrasound imaging.

OBJECTIVES: This study aimed to 1) compare in vitro intravascular ultrasound images of human pulmonary arteries with corresponding histologic sections, and 2) correlate the relation between intravascular ultrasound findings and Heath-Edwards pathologic grade of pulmonary vascular changes. BACKGROUND: The pathologic assessment of the pulmonary vascular bed is essential for diagnosis and management of congenital heart disease with pulmonary hypertension. METHODS: We evaluated and compared intravascular ultrasound images with histologic findings at identical sites in 40 pulmonary artery segments from 17 autopsy studies: group 1 = 7 patients with pulmonary hypertension (Heath-Edwards grade I to V, 20 segments); group 2 = 10 patients without cardiopulmonary disease (20 segments). RESULTS: In group 2, the pulmonary artery wall echo consisted of a single layer. In group 1, 1) all segments of pulmonary arteries from patients with pulmonary hypertension showed a three-layered appearance; 2) in patients with mild pulmonary hypertension (Heath-Edwards grades I and II), intravascular ultrasound demonstrated increased thickness of the echoluscent zone due to medial hypertrophy with no intimal reaction; 3) patients with severe pulmonary hypertension (Health-Edwards grade III or higher) had intravascular ultrasound findings of increased medial thickness and a bright inner layer from intimal hyperplasia; 4) percent wall thickness derived from intravascular ultrasound showed a significant correlation with that determined by histologic examination (r = 0.89, p = 0.0001, n = 20). CONCLUSIONS: Changes observed with intravascular ultrasound imaging correlate well with histopathologic grade. Thus, intravascular ultrasound may have significant utility in the evaluation of pulmonary vascular morphology in patients with pulmonary hypertension.

Adolescent↗

Homotypic cell aggregation via conformational change of CD44 molecule induced by anti-CD44 monoclonal antibodies.

The homotypic cell aggregation of leukocytes is an unique adhesive event which is caused by cellular activation. Anti-CD44 monoclonal antibody (mAb) induces homotypic cell aggregation of hematopoietic cell lines expressing CD44, but the mechanism of homotypic cell aggregation is poorly understood. We used four mAbs against CD44: TL-1 which was newly developed and seemed to react with a non-hyaluronate binding site, OS/37 and BU52 which recognized a hyaluronate binding site, and Hermes-3 which recognized a non-hyaluronate binding site. TL-1 treatment induced strong homotypic cell aggregation in several types of cell lines including a B cell line from a patient with leukocyte adhesion deficiency syndromes (LAD) and normal peripheral blood lymphocytes (PBL). OS/37 and BU52 also induced weak homotypic cell aggregation. None of these anti-CD44 mAbs-induced homotypic cell aggregations was blocked by antibodies against LFA-1, ICAM-1, VLA-4, or L-selectin. Interestingly, the TL-1-induced homotypic cell aggregation was blocked by Hermes-3 or OS/37, but not by BU52. BU52-induced homotypic cell aggregation was blocked by Hermes-3 or OS/37, but not by TL-1. OS/37-induced homotypic cell aggregation was blocked by Hermes-3, TL-1 or BU52. The blocking experiments with anti-metabolic agents revealed that the induced homotypic cell aggregation was energy-dependent and associated with intracytoplasmic actin filaments. This homotypic cell aggregation did not require de novo protein synthesis, because it was not affected by pretreatment with either cycloheximide or actinomycin D. FACS analysis revealed that TL-1 binding did not affect the intensity of expression of the CD44 molecule on the cell surface.

Animals↗

Eradication of Helicobacter pylori with lansoprazole and clarithromycin in gastric ulcer patients.

This study attempted to determine the efficacy of lansoprazole plus clarithromycin therapy in the eradication of Helicobacter pylori in gastric ulcer patients. The influence of H. pylori eradication on healing and relapse of ulcers was also studied. Thirty-nine patients received either lansoprazole 30 mg daily for 8 weeks (group 1) or clarithromycin 200 mg twice daily for 2 weeks and lansoprazole 30 mg daily for 8 weeks (group 2). Before treatment, H. pylori status was evaluated by a rapid urease test and histologic examination. H. pylori clearance and eradication were evaluated by a rapid urease test, polymerase chain reaction, and a [13C]urea breath test. Clearance of H. pylori was 0% in group 1 and was 33% in group 2. Eradication of H. pylori was 0% in group 1 and 21% in group 2. Although all five ulcers were healed in patients with H. pylori eradication, ulcers were not healed in the five patients without eradication. Relapse of ulcer was observed in three patients in whom eradication had failed. In this study, for H. pylori-positive gastric ulcer patients, better results were obtained when lansoprazole plus clarithromycin therapy was used, and H. pylori eradication was achieved.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Malignant fibrous histiocytoma of the right ventricle of the heart.

Right-sided cardiac malignant fibrous histiocytoma (MFH) is extremely rare, and to the authors' knowledge only three cases have been reported. In this study, a case of MFH in the right ventricle, the septum, and the pulmonary valves and artery in a 47 year old male is described. The tumor showed typical pathological features of MFH, such as cellular pleomorphism, storiform pattern and abundant mitoses. Immunohistochemical and electron microscopical findings were compatible with MFH, and excluded the possibility of leiomyosarcoma and angiosarcoma. Whole body examination, including Gallium scintigram, localized the primary site to the heart. The details of this case are presented with a review of the reported cases of cardiac MFH.

Heart Neoplasms↗

Correlation between the number of apoptotic cells and expression of the apoptosis-related antigens Fas, Le(y) and bcl-2 protein in non-Hodgkin's lymphomas.

The relationship between the number of apoptotic cells and the expression of apoptosis-related antigens was examined in 56 cases of non-Hodgkin's lymphomas and in 10 cases of reactive hyperplastic lymph nodes (RHL). Apoptosis was visually quantified by the in situ end-labeling (ISEL) method, and the expression of Fas, Le(y) antigens and bcl-2 protein was examined by immunohistochemistry. The expression of Le(y) antigen was observed in germinal centers of RHL and 45% of non-Hodgkin's lymphomas. The apoptotic cell count (AC) in follicular lymphomas was significantly less than that in diffuse lymphomas. The distribution pattern of apoptotic cells in follicular lymphomas was inverse to that in RHL. In follicular lymphomas, AC was lower in follicles than in interfollicular areas. In contrast, AC was higher in follicles than in interfollicular areas in RHL. Le(y) antigen-positive lymphomas showed a significantly higher AC than the negative cases. The Fas antigen-positive lymphomas showed a higher AC than the negative cases. However, AC in bcl-2 protein-positive and negative cases was not significantly different. These results suggest that Ley and Fas antigens appear to be involved in the apoptotic tendency of tumor cells in non-Hodgkin's lymphomas, whereas bcl-2 does not necessarily.

Apoptosis↗

Fetal arrhythmias: intrauterine diagnosis, treatment and prognosis.

Fetal echocardiography can provide useful information for the evaluation of fetal arrhythmias. Between 1980 and 1993, 44 fetuses with arrhythmias were diagnosed in utero at 12 and 40 weeks of gestation in Kurume University Hospital. Fetal bradycardia, tachycardia and ectopic beats were revealed in 17, seven and 20 fetuses, respectively, and their clinical features and prognosis were evaluated. In the 17 fetuses with bradycardia, eight were associated with congenital heart defect, and six of these developed to fetal hydrops. Of the 17 fetuses, four died in utero, one was terminated, and six died after birth. The other six cases survived. Three of these had a pacemaker implanted after birth. In the seven fetuses with tachycardia, transplacental anti-arrhythmic drugs were administered in five cases and conversion of the arrhythmia was achieved in four. None of the cases was associated with any congenital heart defect, and none died. Three infants had paroxysmal tachycardia postnatally. In the 20 fetuses with ectopic beats, arrhythmia was observed postnatally in 10, but all of these were resolved within 3 months after birth. Fetal bradycardias carried a poor prognosis in most cases and further studies are required to establish effective treatment. Some cases of fetal tachycardia developed recurrent tachycardia postnatally. Close follow-up of the newborn is therefore necessary.

Arrhythmias, Cardiac↗

Thrombotic thrombocytopenic purpura and myoglobinuric acute renal failure following radiation therapy in a patient with polymyositis and cervical cancer.

A 73-year-old woman was admitted to receive radiation treatment for uterine cervical cancer, however a complex series of events ensued, leading to death. She developed an acute exacerbation of polymyositis complicated by thrombotic thrombocytopenic purpura, rhabdomyolysis and acute renal failure. Radiation therapy may have produced an immune disturbance leading to the acute exacerbation of polymyositis. Auto-immune-mediated endothelial damage might have triggered a series of events leading to thrombotic thrombocytopenic purpura. Rhabdomyolysis seemed to be the main cause of acute renal failure.

Acute Kidney Injury↗

Kawasaki disease.

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Coronary Aneurysm↗

Inverse expression of bcl-2 protein and Fas antigen in lymphoblasts in peripheral lymph nodes and activated peripheral blood T and B lymphocytes.

To examine the regulatory mechanism of apoptosis in lymphoid cells, expression of both bcl-2 protein and Fas antigen was investigated in reactive lymph nodes, in resting lymphocytes from peripheral blood (PBLs), and in PBLs stimulated with pokeweed mitogen, interleukin-4 (IL-4) + anti-IgM antibody, IL-2 + anti-CD3 antibody, phytohemagglutinin + phorbol myristate acetate using immunohistochemistry and flow cytometry. Germinal center cells expressed a large amount of Fas antigen, which is associated with the induction of apoptosis in lymphoid cell lines, in contrast to the lack of bcl-2 protein as an apoptosis inhibitor. On the other hand, mantle zone lymphocytes expressed a high level of bcl-2 protein and less Fas antigen. This inverse expression of bcl-2 protein and Fas antigen was also shown in activated T and B lymphocytes from peripheral blood. These lymphoblasts fell into apoptosis dose-dependently in the presence of anti-Fas monoclonal antibody, but resting lymphocytes that expressed both bcl-2 protein and Fas antigen did not undergo apoptosis. These findings suggest that bcl-2 expression prevents the apoptosis of lymphoid cells induced by the Fas antigen-dependent mechanism and that apoptosis of lymphocytes is exquisitely controlled, at least in part, by regulation of the bcl-2 and Fas genes.

Animals↗

Primary osteosarcoma of the cerebrum with immunohistochemical and ultrastructural studies: report of a case.

A 57-year-old woman with primary intracerebral osteosarcoma is reported. The tumor was identified by computed tomography as a mass with hemorrhage in the right parietal lobe. The surgical and pathological examinations confirmed an osteosarcoma of intracerebral origin. She suffered from repeated local recurrence of the tumor and died about 1 year after the onset. The pathological findings showed features of osteoblastic osteosarcoma with numerous osteoclast-like multinucleated giant cells. Immunohistochemically, tumor cells were positive for vimentin, and partially for actin. Multinucleated giant cells were reactive with vimentin and CD68 antibodies. Ultrastructurally, tumor cells were rich with rough endoplasmic reticulum. These findings are consistent with the histological features of skeletal or extraskeletal osteosarcoma. This is the third case of primary intracerebral osteosarcoma reported in the literature and the first one analyzed ultrastructurally.

Brain Neoplasms↗

Promotional effects of azathioprine on peripheral B cell lymphomas in BALB/c mice induced by administration of 7,12-dimethylbenz[a]anthracene.

BALB/c mice either were injected subcutaneously with 25 micrograms/g or 50 micrograms/g body weight 7,12-dimethyl-benz[a]anthracene (DMBA) at the age of 13 weeks, or received repeated s.c. injections of azathioprine (0.1 mg/g) starting from the age of 6 or 18 weeks, or they received treatments with both agents. Of the 317 mice treated, 69 developed lymphomas by the age of 50 weeks. None of the 31 non-treated mice developed lymphomas during this period. The lymphomas, classified according to Pattengale-Taylor's classification for murine lymphomas/leukemias, were examined immunohistochemically and immunogenetically. The lymphomas induced with DMBA showed a male preponderance and a higher incidence of the B cell type, especially in the lymph node and spleen. Azathioprine induced predominantly T-lymphoblastic lymphomas in the thymus and these were found more frequently in females. Treatment with both DMBA and azathioprine remarkably increased the incidence of B lymphomas, especially follicular center cell lymphomas in the spleen, which are the predominant type of spontaneous lymphomas occurring in older BALB/c mice. Some of the treated mice also developed prelymphomatous lesions.

9,10-Dimethyl-1,2-benzanthracene↗

Bauhinia purpurea (BPA) binding to normal and neoplastic thyroid glands.

Biotinylated bauhinia purpurea agglutinin (BPA) was studied, using the ABC method, in different thyroid gland conditions (26 follicular adenomas, 39 papillary carcinomas, 15 follicular carcinomas, and 10 normal thyroids), to determine whether specific lectin binding patterns were developed during malignant transformation that could enable the distinction of carcinoma from adenoma. In normal thyroids, BPA was very rarely and faintly reactive with follicular cells. In neoplastic conditions, BPA binding profiles for follicular adenoma were essentially identical to those of normal follicles, whereas BPA unequivocally reacted with follicular carcinoma and papillary carcinoma. BPA reacted more strongly with cells of papillary structures than with those forming solid nests and follicles. In papillary carcinoma, BPA binding was observed mostly in the apical surface and cytoplasm of carcinoma cells, whereas a diffuse cytoplasmic binding pattern was predominant in follicular carcinoma. Neuraminidase treatment had little or no effect on either normal or adenomatous follicular epithelium, whereas in follicular carcinoma, the number of positive cells and the staining intensity was increased. These findings suggest that BPA would be useful for the differential diagnosis of papillary and follicular carcinomas, and less consistently so, for differentiating follicular carcinoma from follicular adenoma. Peanut agglutinin with similar sugar specificity was not reactive with follicular cells either in normal or neoplastic glands.

Adenocarcinoma, Follicular↗

bcl-2 regulation in normal resting lymphocytes and lymphoblasts.

Expression of the bcl-2 protein and bcl-2 mRNA at the individual cell level was semiquantitatively examined in normal quiescent peripheral blood lymphocytes and pokeweed mitogen- or concanavalin A and interleukin-2-induced lymphoblasts in vitro by microscopic fluorometry using immunofluorescence and fluorescein-labeled in situ hybridization. Approximately 90% of normal quiescent T and B lymphocytes expressed bcl-2 protein at a level which was compatible with that of bcl-2 mRNA. On the contrary, most mitogen-induced lymphoblasts showed a posttranscriptional suppression of bcl-2 protein expression. However, bcl-2 protein was not downregulated by the posttranscriptional suppression in all lymphocytes activated in vitro, but approximately 15% of the lymphoblasts still expressed bcl-2 protein at a higher level than nontransformed quiescent small lymphocytes; thus bcl-2 protein expression in lymphoblasts showed a distinct bimodal pattern. Furthermore, it was supposed that lymphoblasts with no detectable bcl-2 protein might fall into apoptosis but the remainder, expressing high levels of bcl-2 protein, could escape apoptosis. Thus, the bcl-2 gene may play an important role as a regulator of apoptosis in the human immune system.

Apoptosis↗

Enhancement of T cell receptor signaling of tumor-infiltrating lymphocytes by retrovirally mediated fyn gene transduction.

We conducted retrovirally mediated transduction of fyn gene into tumor-infiltrating lymphocytes (TILs) in an attempt to augment T cell receptor-CD3 complex signal transduction, using TILs obtained from six patients with epithelial ovarian cancer. The expression of the transduced gene was more than five times that of endogenous fyn gene. In all preparations, the cytolytic activity of the TILs against autologous tumor cells, but not allogeneic tumor cells, was significantly enhanced (P < 0.01) by transduction of fyn gene. In addition, when TILs were treated with anti-CD3 antibody to stimulate T cell receptor-CD3 complex, fyn-gene-transduced TILs showed about two times higher proliferation (P < 0.05) and secreted 2.2 to 11.7 times more tumor necrosis factor-beta (P < 0.05) than nontransduced TILs. These results could have important implications for TILs-mediated gene therapy for cancer.

Female↗

Malignant peripheral nerve sheath tumor with prominent intracytoplasmic vacuolation: report of a case.

A case of malignant peripheral nerve sheath tumor with uncommon features is reported. A mass was noted in the left thigh of a 16 year old man. Histologically, most areas of the tumor exhibited the typical appearance of malignant peripheral nerve sheath tumor, but some tumor cells had rounded nuclei and cytoplasm, resembling an epithelioid pattern. It was noted that some rounded tumor cells showed prominent intracytoplasmic vacuolation. Immunohistochemically, almost all of the tumor cells, including the rounded and vacuolated ones, were positive for S-100 protein and vimentin. Electron microscopic study revealed well-developed cytoplasmic processes, intracytoplasmic intermediate-sized filaments, basement lamina formation and extracellular long-spacing collagens. These findings were compatible with those of Schwann cell differentiation. Moreover, ultrastructurally, the vacuolated spaces contained a few granular materials and were derived from the dilatation of the rough endoplasmic reticulum. It is speculated that intracytoplasmic vacuolation in malignant peripheral nerve sheath tumor would be caused by degeneration of the tumor cells.

Adolescent↗

CD30 antigen in non-Hodgkin's lymphoma.

Expression of the CD30 antigen in lymphoid neoplasms and reactive lesions were examined immunohistologically using the monoclonal antibody BerH2. CD30 antigen was expressed in 17 of 18 patients with Hodgkin's disease (HD), all of three anaplastic large cell lymphomas (ALCL), 11 of 52 T-cell malignant lymphomas (TML) including ALCL, 13 of 153 B-cell malignant lymphomas (BML) including ALCL, two of three malignant histiocytosis and one of four plasmacytomas. Although a single case of small cell lymphoma was positive, in cases of mixed cellular morphology, neoplastic cells of larger or more pleomorphic nuclei tended to be stained more extensively and intensively. This antigen is expressed in TML significantly more often than in BML (P < 0.05). CD30 antigen was expressed less frequently at clinical stage I than those of stages II to IV. There was no significant relationship between CD30 antigen expression and that of proliferating cell nuclear antigen or CD43 antigen in non-Hodgkin's lymphomas (NHL). The CD30 antigen expression did not affect the prognosis of NHL overall, but in high grade TML, CD30 antigen-positive individuals tended to have a more favorable prognosis than those that were negative. In reactive diseases, some plasma cells, immunoblasts, interdigitating cells, follicular center cells and histiocytes were stained positively, but not always, and with variable intensity. These results suggest that CD30 antigen is expressed in various cell lineages to some extent and may relate to cellular activation in some instances. When making the histopathologic diagnosis of HD or NHL including ALCL, CD30-positive cell should be carefully interpreted.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers, Tumor↗

Aberrant expression of the monocyte/macrophage phenotype in a human T cell line immortalized by HTLV-I and an adult T cell leukemia/lymphoma cell line.

An HTLV-I-immortalized human T cell line (JP-2), a N-methyl-N'-nitro-N-nitrosoguanidine-treated JP-2 line (JP-2T), and an adult T cell leukemia cell line (ATL-1T) were examined morphologically and phenotypically. All of these cell lines expressed some T cell markers, including CD4, and showed rearrangement of T cell receptor (TCR) genes, but they lacked CD3 and TCR antigens and expressed some myelomonocytic markers (CD68, HL-21, CD15, CD16). JP-2 cells grew in suspension, but JP-2T and ATL-1T cells, which mostly adhered to the surface of culture vessels, showed macrophage-like morphological features and expressed more monocyte/macrophage markers (lysozyme, alpha 1-antitrypsin) and fibronectin. ATL-1T cells transplanted into SCID mice lost the macrophage features. These results suggest that HTLV-I infected T cells can express some macrophage features and that these cells may provide a model that will be useful in elucidating the phenotypic variability of T cell lymphomas.

Animals↗