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Biomedical subjects

M Mizuki

Publications and source records attributed to M Mizuki.

At least 37 records · Page 2Linked to original sources

Fas ligand in human serum.

The Fas ligand (FasL), a member of the tumor necrosis factor family, induces apoptosis in Fas-bearing cells. The membrane-bound human FasL was found to be converted to a soluble form (sFasL) by the action of a matrix metalloproteinase-like enzyme. Two neutralizing monoclonal anti-human FasL antibodies were identified, and an enzyme-linked immunosorbent assay (ELISA) for sFasL in human sera was established. Sera from healthy persons did not contain a detectable level of sFasL, whereas those from patients with large granular lymphocytic (LGL) leukemia and natural killer (NK) cell lymphoma did. These malignant cells constitutively expressed FasL, whereas peripheral NK cells from healthy persons expressed FasL only on activation. These results suggested that the systemic tissue damage seen in most patients with LGL leukemia and NK-type lymphoma is due to sFasL produced by these malignant cells. Neutralizing anti-FasL antibodies or matrix metalloproteinase inhibitors may be of use in modulating such tissue damage.

Animals↗

[Large granular lymphocyte leukemia].

Large granular lymphocyte leukemia (LGLL) is defined as clonal proliferation of LGLs in peripheral blood. The following studies were conducted to address some issues in chronic LGLL. (1) Chronic LGLL is characterized by the indolent course, and the diagnosis of leukemia is difficult in such patients as those without distinct organomegaly and/or any evidence of monoclonality. We performed immunohistological studies in a patient with persistent NK lymphocytosis. No organomegaly had been seen in the patient during a three-year-observation, who died from cerebrovascular accident. The autopsy findings revealed multi-organ infiltration including spleen, liver, bone marrow, lymph nodes and lung. These findings suggest that the cells of chronic LGLL have infiltrative capacity characteristic of malignant cells. (2) Lymphocytosis in chronic LGLL is usually stable for a long period. We found that both T- and NK-LGLL cells strongly expressed CD95, an apoptosis related protein. Anit-CD95 did not induce apoptosis, but suppressed proliferation induced by IL-2 or anti-CD3. These results suggest that CD95-CD95 ligand system is involved in the slow cell growth characteristic of chronic LGLL. (3) CD4+CD8+ double positive (DP) cases are rarely seen in LGLL, and the physiologic counterpart of the leukemic cells has not been determined yet. We found that the DP-LGLL had alpha alpha type in the CD8 subunit and did not express RAG-1, these findings being characteristic of peripheral T cells. We also found that they expressed IL-4 mRNA and secreted IL-4 on activation. These results strongly suggest that DP-T-LGLL represents an expansion of a rare subset of peripheral DP-T cells, possibly derived from IL-4 activated CD4 single positive T cells.

Aged↗

[LGL lymphoma].

We reported in this article two patients with large granular lymphocytic lymphoma (abbreviated as LGL lymphoma). One was the patient with LGL leukemia/lymphoma (patient 1) and other was the patient with NK-LGL lymphoma (patient 2). Because the gene of TCR delta was rearranged in the patient 1, the clonality of the LGL leukemia/lymphoma was confirmed. However, it is not determined yet whether the lineage of tumor cells is T cells or NK cells. The cytochemical features of the lymphoma cells of the patient 2 were studied. It was found that NK cell-derived lymphoma cells of the patient were positively stained with these two monoclonal antibodies that are reactive with T cell; one is anti-CD45RO (UCHL-1) and other is anti-CD3. Judging from the result, malignant NK-LGL cells in some patients are cytoplasmic CD3+ and UCHl-1+. It is emphasized that May-Grünwald-Giemsa stain of biopsied specimen of the lymphoma is required for making the diagnosis of LGL lymphoma.

Adult↗

[Swyer-James syndrome with pneumomediastinum and subcutaneous emphysema due to bronchial asthma].

A 24-year-old woman was admitted to our hospital due to moderate asthmatic attacks. Dyspnea and hypoxemia progressed gradually despite medication. A chest roentgenogram revealed left unilateraly hyperlucency with pneumomediastiumn and subcutaneous emphysema. Swyer-James syndrome was diagnosed. Several cases of Swyer-James syndrome with bronchial asthma airway hyperresponsiveness have been reported, but we know of no reports of Swyer-James syndrome with pneumomediastinum and subcutaneous emphysema due to prolonged asthmatic attacks. Pneumomediastinum and subcutaneous emphysema may be caused by abnormally high pressures in the bronchial lumen and alveolar space during asthmatic attacks, because the emphysematous lesion may be structurally weak.

Adult↗

A case of chronic necrotizing pulmonary aspergillosis due to Aspergillus nidulans.

A 55-year old man without immunosuppression clinically showed a coin lesion in the right lower lung on the chest radiographs. Aspergillus nidulans was isolated and identified in both trans-bronchial lung biopsy specimen and resected tissue. The specimens revealed characteristics of chronic necrotizing pulmonary aspergillosis pathologically. Very few reports on cases of pulmonary aspergillosis due to A. nidulans exist, and we were not able to find any reports of similar cases. This case may be the first reported case of chronic necrotizing pulmonary aspergillosis due to A. nidulans.

Adenocarcinoma↗

A case of malignant hemangiopericytoma: an immunohistochemical and ultrastructural study.

We report one case of malignant hemangiopericytoma which started with a tumor in the lower jaw and multiple nodules in the lung. The tumor quickly metastasized to the brain and chemotherapy was not at all effective. Hemangiopericytoma is generally diagnosed by its histological characteristics. Recently, however, electron microscopy and immunohistochemical methods have been used for its diagnosis. In our case, electron micrograph showed the growth of hemangiopericytoma cells around immature endothelial cells. In addition, the tumor cells reacted positively only with anti-vimentin antibodies, and the endothelial cells in the tumor tissue were positive for antifactor VIII antibodies. The observed features were consistent with the characteristics of hemangiopericytoma.

Antibodies, Monoclonal↗

[A case of pulmonary sarcoidosis with circulatory insufficiency of segmental and subsegmental branches of pulmonary arteries].

A 50-year-old woman was admitted to our hospital on April 4, 1992, because of progressive worsening of dry cough and exertional dyspnea. Moderate hypoxemia and obstructive ventilatory impairment were present. Her chest roentgenogram and CT films showed thickened bronchovascular bundles in the absence of significant parenchymal fibrosis. Transbronchial lung biopsy revealed the formation of noncaseous epithelioid cell granulomas. Pulmonary perfusion scintigraphy showed multiple perfusion defects predominantly in the upper lung fields. Pulmonary ventilation scintigraphy showed a normal pattern. After administration of prednisolone for 3 months, her chest roentgenogram and CT films demonstrated marked decrease of infiltrates, but there was no improvement of hypoxemia and perfusion defects on pulmonary perfusion scintigraphy. Pulmonary angiography revealed multiple stenoses and occlusions of segmental and subsegmental branches of pulmonary arteries. Long-term steroid treatment will be necessary for this rare form of pulmonary sarcoidosis to prevent the development of pulmonary hypertension.

Female↗

A HTLV-I carrier who showed various symptoms and antibodies of autoimmune diseases.

We report a 37-year-old female HTLV-I carrier with complicating primary biliary cirrhosis (PBC) and mixed connective tissue disease (MCTD). Serum anti-HTLV-I antibody titer was x256. Flower cells (4.5%) were found in the peripheral blood. Southern blot analysis showed no clonal integration in peripheral blood lymphocyte (PBL) DNA. Polymerase chain reaction showed the HTLV-I genome in PBL DNA. As cholestatic liver dysfunction and serum titer of anti-mitochondrial antibody were found, a clinical diagnosis of PBC was made. This patient later developed MCTD. These diseases responded well to prednisone. The pathogenetic relationship of HTLV-I infection with various autoimmune diseases is discussed.

Adult↗

[A case of chronic asthma with emphysematous change in a middle-aged woman].

A 32-year-old woman with chronic asthma is presented. She had suffered from dyspnea and breathlessness on exertion for 7 years. Her chest X-ray film on admission showed marked emphysematous changes and chest CT scan revealed low attenuation areas, however she was a non-smoker and had no previous childhood respiratory problems. She was administered prednisolone to treat the wheezing attack and hypoxemia. After treatment, her lung function and hypoxemia improved, but low attenuation areas of the chest CT scan remained unchanged. These facts suggest the possibility that bronchial asthma which is controlled poorly for a long time, may cause emphysematous change of the lung.

Adult↗

[Multiple myeloma and adhesion molecules].

The physiological role of fibronectin (FN) on the human plasma cells were examined using three PC cell lines, FR4ds, OPM1 and OPM1ds. FR4ds was reactive with anti-VLA-alpha 4 and anti-alpha 5. In contrast, OPM1 and OPM1ds were not reactive with anti-VLA-alpha 5. FN induced spreading in FR4ds and OPM1ds. Albumin blocked these spreadings. FR4ds with mature plasma cell phenotype of alpha 4+ and alpha 5+ was more sensitive for FN than OPM1 and OPM1ds with immature phenotype of alpha 4+ and alpha 5-. Spreading cells proliferated more than floating cells. All these cell lines showed chemotaxis toward FN. alpha 5+ FR4ds was more sensitive for FN than OPM1 and OPM1ds with alpha 5- phenotype. These new abilities of PC of spreading and chemotaxis we found are summarized to be an affinity to organs. It is likely that alpha 4+ and alpha 5- PC with low affinity to organs are stored in peripheral blood as a result. We examined the chemotaxtic activity of myeloma cells in bone marrow and these in pleural effusions in a patient with multiple myeloma. These cells in pleural effusions showed more chemotaxic activity than these in bone marrow. FN induced growth, production of Ig, and motility of PC, which resulted in the augmentation of humoral immunity.

Bone Marrow Cells↗

Monocytes appearing repeatedly after chemotherapies had an identical rearrangement pattern of immunoglobulin with leukemic blasts in a patient with CD13+ acute lymphoblastic leukemia.

We recently encountered a patient with acute lymphoblastic leukemia (ALL) who showed temporal monocytosis of an unusually high cell count (5,000-30,000 monocytoid cells/microliter) five times after treatment with different chemotherapies. The leukemic cells expressed B-cell-associated antigens, CD19 and CD10, E-rosette receptor, CD2 and monocyte/myeloid antigen, CD13 simultaneously. They were peroxidase-negative. One week after the initiation of conventional chemotherapy for ALL, the leukemic blasts had disappeared. Alternatively, monocytoid cells appeared along with the recovery from nadir status. They showed several features of monocytes; they were weakly dot-positive for nonspecific esterase, reactive with CD14 and CD13 and Fc gamma-receptor-positive. Furthermore, they migrated into a fungally infected joint space. Features incompatible with normal monocytes were the absence of peroxidase reactivity, the expression of B-cell-associated antigens, CD19 and CD10 and E-rosette receptor, CD2. Southern blot hybridization analysis revealed an unexpected result that HindIII digested DNA from both leukemic blasts and monocytoid cells had the same rearranged band of IgH. Thus, an identical clonality of monocytoid cells, temporally appearing after chemotherapies and leukemic lymphoblasts, was determined in this patient with CD13+ ALL.

Antigens, CD↗

Transformation of large granular lymphocytic leukemia during the course of a reactivated human herpesvirus-6 infection.

A patient with CD3+ large granular lymphocytic (LGL) leukemia developed transformation (TF). The phenotype of the leukemic cells was CD3+, CD4+ and CD8-. The leukemic cell count increased rapidly; the cells became large and the nuclear outline, which had been reniform, became lobulated. Anti-HTLV-1 and anti-HIV antibodies were negative in the serum of the patient and no HTLV-1 specific sequences were detected in the cDNA of the leukemic cells by polymerase chain reaction (PCR). Comparison of the karyotype abnormality of the leukemic cells before and after TF revealed an abnormality of the 21 trisomy in 90% of mitotic cells of the patient. Analysis of the cell cycle revealed that 13.7% of the leukemic cells were in DNA synthesis phase which was not previously found. The titer of anti-human herpesvirus-6 (HHV-6) immunoglobulin G which had been high at chronic phase (1:1640 compared to normal titer of less than 1:160), became 1:20,000 at TF. The titer of anti-HHV-6 immunoglobulin M also increased from less than 1:4 at the chronic phase to 1:120 at TF (normal value less than 1:4). A HHV-6-specific DNA sequence was detected by PCR in the peripheral mononuclear cells collected at TF but not at the chronic phase. These data suggests that TF occurs not only in CD3-negative but also in CD3-positive LGL leukemia. HHV-6 reactivation is therefore a possible cause in immunocompromised hosts whose general conditions are deteriorated.

Aged↗

[A case of Paragonimiasis westermani with pleural effusion eight months after migrating subcutaneous induration of the abdominal wall].

Patients with Paragonimiasis westermani show a typical ring form or nodular shadow on chest X-ray, cough, sputum, and hemosputum. Recently, case reports of Paragonimiasis westermani, accompanied by pneumothorax and pleural effusion, as for Paragonimiasis miyazakii, have been increasing. Paragonimus westermani often causes an ectopic infection in various organs such as the peritoneal cavity, pleural cavity, pericardium, liver, adrenal gland and brain. Cutaneous paragonimiasis is considered one of the typical forms of ectopic infection in its earlier phase, but a few unexpected cases of cutaneous Paragonimiasis westermani have also been reported. A 68-year old man, who had never eaten fresh-water crab or raw sliced meat of wild boar, noticed subcutaneous induration of the abdominal wall. The induration had been gradually moving upwards and to the right from the infraumbilical region for over 20 days, and then disappeared at the right upper lateral abdominal wall. Eight months later, he developed severe pain in the right lower chest, and a chest X-ray showed right pleural effusion. Laboratory examinations revealed eosinophilia (WBC 3940/mm3, eosinophil 9%), elevated ESR, and an elevated serum total IgE level (5517 IU/ml). Ouchterlony's double diffusion test performed with the patient's serum in agarose showed strong bands toward Paragonimus westermani antigen, compared to Paragonimus miyazakii antigen. Immunoelectrophoresis with the patient's serum showed specific bands toward Paragonimus westermani antigen. This patient was finally diagnosed as having Paragonimiasis westermani infection, and he responded to praziquantel administration. The clinical course of this patient appears to be rare in cases of Paragonimiasis westermani infection. The clinical course of this case resembled some cases of Paragonimiasis miyazakii infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Muscles↗

[Large granular lymphocytic leukemia].

We investigated the surface markers, cell-function, clonality, and the association of IL-2 receptors and a second messenger of src family of tyrosine kinase p56lck in IL-2 signal transduction of the leukemic cells of 12 patients with large granular lymphocytic leukemia (LGL leukemia). The leukemic cells of 5 patients were CD3+ and 5 of them were CD3-. In three patients with CD3- leukemia examined, one showed karyotype abnormality of 46, XY, -10, +mar and the delta gene of TCR was rearranged in one patient. The TCR of the leukemic cells of a patient MH with CD3+, CD4 and CD8 (double positive marker: DP) recognised rabbit IgG presented by macrophages. The recognition was class II restricted. We examined the expression pattern of CD8 subunits and found that DP leukemic cells commonly expressed CD8 alpha+ beta-. These results suggested that DP leukemic cells were CD4+ T cells and expressed CD8 alpha secondarily. The p75 IL-2 receptors were detected, however, the modulation of p56lck in the process of IL-2 signal transduction were not found out. There was no association between p75 and p56lck when leukemic LGL cells proliferated on stimulation with IL-2.

Antigens, CD↗

Pulmonary corpora amylacea contain surfactant apoprotein.

The case of a 53-year-old female with interstitial pneumonitis is described with special regard to biochemical characterization of pulmonary corpora amylacea which were found in the lung specimen obtained by bronchial biopsy from the patient. The main protein component in bronchoalveolar lavage (BAL) fluid of the patient was albumin, but proteins in the precipitate fraction of BAL fluid, where the corpora amylacea were recovered, predominantly consisted of 36 kD protein which was stained with the monoclonal antibody PE 10 to human pulmonary surfactant apoprotein by immunoblot. Histologically the pulmonary corpora amylacea were stained with eosin and PAS. The particles were stained immunohistochemically by immunoperoxidase reaction using PE 10, but not by antibodies to human albumin. The pulmonary surfactant apoprotein seems, therefore, to be not simply adsorbed in the particles, but to be contained in them. Thus, the surfactant apoprotein may, at least in this case, be involved in the formation of pulmonary corpora amylacea.

Apoproteins↗

[A case of multiple inflammatory tracheo-bronchial polyps associated with chronic sinusitis].

A 57 year-old woman was aware of breath odor and visited to our hospital. There were no abnormal findings in her physical examination and chest X-ray. Multiple polyps in the trachea and both main bronchi were discovered by fiberoptic bronchoscopy. They were 0.1-0.5 cm in diameter. In a histological examination, squamous metaplastic epithelial cells and numerous inflammatory cells infiltrating subepithelially were seen. No malignant cells were found. The patient had suffered from chronic sinusitis for 15 years, and it was suggested that the development of tracheo-bronchial polyps was associated with chronic sinusitis.

Bronchial Neoplasms↗

[A case of remarkable bronchial stenosis due to aspiration of delayed-release iron tablet].

This report describes a rare case of bronchial mucosal injury caused by aspiration of a delayed-iron tablet. A 44-year-old woman had been taking delayed-iron tablets (Feto-Gradumet) regularly because of iron deficiency anemia, and accidentally aspirated a tablet into her bronchus. After this accident, she had complained of wheezing and shortness of breath. On bronchoscopy, the bronchial mucosa of left lower lobe initially showed remarkable swelling and redness, and became corroded and narrowed gradually by iron toxicity over several months, although we tried to remove some fragments of tablet as completely as possible. While we had examined her bronchi repeatedly by bronchoscopy, the bronchial mucosa gradually normalized during 15 months, but moderate stenosis of the left basal bronchus remained. The pathological findings showed infiltration of inflammatory cells, edema and granuloma formation in the submucosal region. This report suggests that the bronchial injury was due to the toxicity of persistent ferrous sulfate eluted from the iron tablet which had adhered firmly to the wet bronchial wall for a long time.

Adult↗