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Biomedical subjects

S Hanada

Publications and source records attributed to S Hanada.

At least 91 records · Page 5Linked to original sources

Lymphatic mast cell response and effect of compound 48/80 on popliteal lymph node reaction in rats following intracutaneous injection of Staphylococcus aureus.

To investigate the significance of mast cells in the popliteal lymph node during the development of an inflammatory response, rats were inoculated with 12 x 10(7) colony-forming units of Staphylococcus aureus in the hind foot pad. Numerical changes in mast cells were then measured in the corresponding popliteal lymph node. Six days after inoculation, despite the enlargement of the responding lymph node, a marked decrease in granulated mast cell number, relative to the contralateral node, was observed in the cortical and medullary compartments. Popliteal lymph nodes from rats treated with compound 48/80 and then inoculated with S. aureus showed a higher cortical and medullary hypertrophic response and a significant increase in degranulated/weakly basophilic mast cell number in the lymph node tissue. The findings suggest that (1) Staphylococcus aureus induces a reduction in granulated mast cell number in the cortical and medullary compartments of regional lymph nodes; (2) pretreatment with compound 48/80 appears to contribute to the lymphoid cell proliferation and the hypertrophic response of lymph nodes induced by S. aureus; and (3) granulated mast cells have a regulatory role on lymphoid cell proliferation.

Animals↗

Miconazole as inflammatory agent--I. Cellular and pathophysiological effects.

1. Subcutaneous injection of miconazole into the rat paw evoked an acute, circumscribed and long-lasting inflammation. 2. Miconazole edema presented two defined phases of rapid swelling. 3. Miconazole edema was antagonized by chlorpheniramine, dexamethasone and phenylbutazone. 4. This edema was 1.5-2 times more intense than edema due to econazole. 5. It is suggested that miconazole paw edema might be useful in the process of screening anti-inflammatory drugs.

Animals↗

Expression of fos proto-oncogene product by monoclonal antibody FO-120 in smouldering adult T-cell leukaemia (ATL).

We investigated the expression of c-fos gene product in peripheral blood mononuclear cells of patients with smouldering adult T-cell leukaemia (ATL) and healthy human T-lymphotropic virus type-I (HTLV-I) carriers by an immunofluorescence assay, using a mouse monoclonal antibody (FO-120) specific for fos gene product. Peripheral blood mononuclear cells derived from healthy HTLV-I carriers were rarely positive for FO-120, less than 2% of the cells weakly reacted with FO-120, whereas positive cells were detected in more than about 10% of cells from patients with smouldering ATL. FO-120 appears to be a useful tool for detecting smouldering ATL in asymptomatic HTLV-I infected people without using molecular techniques.

Adult↗

Elevated levels of soluble factors in the cerebrospinal fluid in patients with adult T-cell leukaemia complicated with meningeal infiltration.

We measured some soluble factors in the cerebrospinal fluid (CSF) of patients with adult T-cell leukaemia (ATL) complicated with meningeal infiltration. Interleukin-4 (IL-4) was not detectable in the CSF of all cases with meningeal infiltration. Interleukin-6 (IL-6) was detected in a few patients with ATL. Measurement of IL-4 and IL-6 in CSF had no diagnostic value for meningeal infiltration of ATL cells. Soluble CD4 (sCD4) was highly elevated in all ATL patients with meningeal infiltration. Soluble interleukin-2 receptor (sIL-2R; sCD25) in CSF was markedly elevated in 13/18 ATL patients (72.2%) with meningeal infiltration. Levels of sCD4 and sCD25 in the CSF of ATL patients with central nervous system (CNS) symptoms were significantly higher than those of non-ATL patients with CNS symptoms. These observations indicate that sCD4 and sCD25 in the CSF are probably associated with meningeal infiltration of leukaemia cells that expressed CD4 and CD25 on the surface membrane and new markers for the meningeal infiltration of ATL cells.

CD4 Antigens↗

Monoclonal antibody HML-1 reactivity with adult T-cell leukaemia/lymphoma and other lymphomas.

Human T-cell leukaemia/lymphoma virus type 1 (HTLV-1), a causative virus of adult T-cell leukaemia/lymphoma (ATLL), is known to be transmitted by breast-feeding. Using a monoclonal antibody HML-1 which labels human intestinal intra-epithelial T lymphocytes, we have immunohistochemically examined ATLL tissues in order to evaluate the possibility that HTLV-1 infected intestinal T cells are the origin of ATLL cells. Previously this antibody was reported to react with intestinal T-cell malignant lymphomas but not with peripheral tumours, or any B-cell lymphomas. We investigated 181 patients with malignant lymphomas and found that 19 out of 113 ATLLs were positive for HML-1. T-cell malignant lymphomas excluding ATLL also reacted with HML-1 (7/24), but all the B-cell lymphomas 0/33) and non-neoplastic lymph node and skin lesions (0/10) were negative for HML-1. In patients with ATLL and other T-cell malignant lymphomas, the positivity level of HML-1 was relatively higher in stomach (3/7) and tonsil (2/6) than that in lymph nodes (15/100) and skin (8/47). We observed one HML-1 positive ATLL patient with tumour formation in the skin and lymphadenopathy and marked infiltration of the large intestine but minimal involvement of other organs. Although HML-1 was frequently expressed in gastric infiltration of ATLL, the level of positivity was too low in lymph nodes to support the hypothesis that HTLV-1 infected intestinal T cells are the origin of ATLL cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Successful treatment of chemotherapy-resistant adult T cell leukemia/lymphoma by irinotecan hydrochloride (CPT-11)].

A 62-year-old man was hospitalized in March 1990 due to upper abdominal discomfort and anorexia. The chest X-ray revealed an upper anterior mediastinal tumor, and abdominal ultrasound showed lymphadenopathy. Endoscopic examination of the stomach revealed a large, irregular ulcer, which was histologically confirmed to be malignant lymphoma by biopsy. Serum anti-HTLV-1 antibody was positive. A diagnosis of ATLL (lymphoma type) was made. The usual therapy for this disease, including the LSG4 and RCM protocols, was only transiently effective. Therefore, the patient was treated with CPT-11 (40 mg/m2) by intravenous infusion on 3 consecutive days with weekly repetition in November 1990. Complete remission was obtained after 2 weeks of treatment, and was maintained for 5 months. This case suggests that CPT-11 may be effective for the treatment of ATL.

Aged↗

Treatment of adult T-cell leukemia/lymphoma with MST-16, a new oral antitumor drug and a derivative of bis(2,6-dioxopiperazine). The MST-16 Study Group.

BACKGROUND: MST-16, a new orally administered bis(2,6-dioxopiperazine) analogue and an inhibitor of topoisomerase II, was given to 24 patients with adult T-cell leukemia-lymphoma (ATLL) in a Phase I-II multi-institutional cooperative study. METHODS: MST-16 was administered orally daily for 7 days, with courses repeated at intervals of 2-3 weeks in 24 patients. RESULTS: Two complete remissions (CR) and eight partial remissions (PR) were obtained in 23 evaluable patients who received 1200-2800 mg/day of MST-16. Among 13 acute-type ATLL, one CR and five PR were obtained. Among eight lymphoma-type ATLL, two PR were detected. Among two chronic-type ATLL, one CR and one PR occurred. Remissions were obtained at 7-232 days (median, 23 days) and lasted 43-374 days (median, 68 days). The major toxic effects were leukopenia (68%), anemia (52%), thrombocytopenia (35%), and gastrointestinal disorders (22%). CONCLUSIONS: MST-16 was shown to be effective in ATLL, which has no standard therapy. This drug deserves further clinical trials because it shows little cross resistance to currently available antitumor drugs.

Administration, Oral↗

Analyses of mixed melanogenesis in tyrosinase cDNA-transfected human amelanotic melanoma cells.

In the pigment cell the synthesis of tyrosinase and the formation of premelanosomes are independent, yet coordinated, processes. However, the interrelationship between the two processes has not been elucidated previously. In this study, an expression plasmid for human tyrosinase cDNA was constructed and transfected into a human amelanotic melanoma cell line, G-361. Stable transfected cells (G-CMHT-3) were obtained with high tyrosinase activity and distinct melanization occurred. As for the type of melanin, both pheo- and eumelanin contents increased in G-CMHT-3 cells. Interestingly, catalase activity as one of the other melanogenic enzymes was decreased in G-CMHT-3 cells. The decrease of catalase activity was considered to play a role in melanin-polymer formation, resulting in the increase of both pheo- and eumelanin contents. Under electron microscopic observation, dopa-oxidase-positive Golgi-associated endoplasmic reticulum of lysosome, coated vesicles, and premelanosomes were observed in pigmented G-CMHT-3 cells, and the expressed tyrosinase was considered to be well translocated to these organelles. In addition, the number of premelanosomes (stages I-III) as well as melanosomes (stage IV) increased in G-CMHT-3 cells compared to those in G-361 cells. It is also noted that G-CMHT-3 cells showed more normal phenotype premelanosomes with occasional transitional premelanosomes exhibiting partial melanin polymer formation within their concentric whorl-like internal membranes. Furthermore, the number of eumelanosomes in G-CMHT-3 cells was much larger than that in G-361 cells. These results suggest that the tyrosinase introduced by its cDNA transfection induced active and structurally non-aberrant premelanosome formation resulting in the upregulated pheo- and eumelanogenesis.

Humans↗

[A case of refractory multiple myeloma effectively treated with long-term oral etoposide].

A sixty-two-year-old man was admitted to our hospital for diarrhea and fatigue on September 1, 1988. Laboratory examination revealed anemia and a high serum protein level with increased gamma-globulin. Although he had no apparent bony lesions, the bone marrow picture showing an increase of abnormal plasma cells and serum immunoelectrophoresis indicating the presence of monoclonal protein of IgG-gamma type were compatible with multiple myeloma, stage IIIA. None of the following combinations of interferon alpha and ranimustine, cyclophosphamide and prednisolone, or melphalan and prednisolone were effective in reducing the level of serum M-protein. Therefore, we started daily oral administration of etoposide (25 mg/day) on February 21, 1989. Then the serum M-protein level was gradually reduced, and partial remission was achieved after 9 months' administration. After 27 months treatment the regimen was changed from daily to every second day administration, and finally stopped after 40 months. The patient has been in remission without etoposide to date.

Administration, Oral↗

Tumor necrosis factor-beta and hypercalcemia.

Hypercalcemia in hematological malignancy is frequently encountered in lymphoid malignancies such as adult T-cell leukemia (ATL) and multiple myeloma and is difficult to manage. As a causative agent of hypercalcemia in ATL, tumor necrosis factor-beta (TNF-beta), previously known as lymphotoxin, has been carefully studied and reviewed here. Bone resorption studies showed the presence of activity in culture supernatants of HTLV-I infected cells. Enzyme linked immunosorbent assays (ELISA) for TNF-beta detected elevated TNF-beta in the sera of ATL patients with hypercalcemia. Immunostaining by monoclonal anti-TNF-beta antibody demonstrated the presence of TNF-beta in both HTLV-I infected cell lines and freshly isolated ATL cells. Furthermore biological TNF-beta activity assay including inhibition of anti-TNF-beta antibody confirmed the conventional documentation of TNF-beta activity in the sera and culture supernatants of HTLV-I infected cell lines. These studies showed that the TNF-beta secreted from ATL cells might be one of the factors contributing to the hypercalcemia in patients with ATL functioning as an osteoclast activating factor (OAF).

Animals↗

[Adult T-cell leukemia with Ki-1 expression].

A 64-year-old man was admitted to our hospital complaining of fever and edema in February, 1990. Lymph node biopsy revealed diffuse lymphoma pleomorphic type according to the LSG classification. On hematological examination, leukocyte count was 23,500/microliters, of which 36% abnormal lymphocytes expressing CD2, CD3, CD4 and CD25 as same as the lymph node cells. Anti-HTLV-I antibody in serum was positive. From these data, the diagnosis of adult T-cell leukemia (ATL) was made. ATL cells in the blood and lymph node expressed CD30 (Ki-1). CD30 positive ATL cells derived from the blood was increased after short-term culture. The induction of Ki-1 antigen in cell lines and short-term cultured cells from ATL patients was accompanied by the appearance of the HTLV-I related antigen. Then, we suggest that there was some relation between expression of the Ki-1 antigen and activation by HTLV-I in ATL cells.

Antigens, CD↗

[Chronic myelogenous leukemia with blastic crisis in which expression of P-glycoprotein was associated with resistance to chemotherapy].

A 55-year-old woman with chronic myelogenous leukemia developed a lymphoid blast crisis (BC) 10 months after diagnosis. By using immunoblotting with a monoclonal antibody against P-glycoprotein (P-gp) C219, her leukemia cells from the first and 3rd crises were shown to be negative for the P-gp, while the cells of the 4th crisis were detected to have a high level of P-gp. This patient did not respond to chemotherapy with several anti-cancer agents in the 4th crisis, although complete remission was achieved in the first, second and third crises after administration of agents including vincristine and prednisolone. Therefore the expression of P-gp in the 4th BC might have been closely related to the resistance to chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Endoscopic analysis of gastric mucosal lesions in patients with adult T-cell leukemia during chemotherapy].

Gastric mucosal lesions in 13 patients with adult T-cell leukemia (ATL) were endoscopically studied at least at 2 occasions during chemotherapy for these patients. X-ray examinations by using barium meal showed deformities in 10 patients and abnormal mucosal pattern in 11 out of 13 patients with ATL. The endoscopic examinations revealed gastric ulcers in 5 patients, erosion in 8, diffuse bleeding in 2, tumorous mucosal folds in one, and submucosal tumor in one patient. In 9 out of 12 ATL patients, pathological study revealed that ATL cells had invaded the mucosal area of the stomach. The ulcers and erosions were improved by chemotherapy in 3 out of 5 and 5 out of 8 patients, respectively, whereas the erosion was not reduced in 2 and even aggravated in one patient. Interestingly, the gastric lesions formed by ATL cell invasion were improved by the administration of anticancer agents in 5 out of 9 patients. However, these lesions reappeared together with systemic lesions of ATL.

Adult↗

[Cyclic thrombocytopenia with chronic thyroiditis and ankylosing spondylitis].

A 58-year-old man with cyclic thrombocytopenia who was initially diagnosed as idiopathic thrombocytopenic purpura (ITP), concomitant with chronic thyroiditis and ankylosing spondylitis, was reported. Serum level of T 3 (0.48 ng/ml) and T 4 (2.1 micrograms/ml) were both subnormal and that of TSH (257.1 microU/ml) was markedly elevated. Thyroid test (6400X) and microsome test (6400X) was both positive, but anti-nuclear antibodies were negative. Radiographic findings of lumbar spine showed the typical "bamboo spine" and HLA B 27 was positive. Therapies for ITP, such as adrenocorticosteroids including steroid pulse therapy, high-dose intravenous gamma-globulin, danazol, slow infusion of vinca alkaloids and splenectomy, were only effective transiently. After these therapies platelet counts began to fluctuate from 0.4 X 10(10)/L to 34.4 X 10(10/L, therefore the diagnosis of cyclic thrombocytopenia was done. Interestingly low-dose methotrexate (MTX) was effective, and the cyclic fluctuation of platelet counts disappeared. These observations in this case were very suggestive of the pathogenesis of cyclic thrombocytopenia and mechanisms of cyclic change of platelet counts.

Humans↗

[Hemolytic anemia complicated with Behçet's disease and myelodysplastic syndrome].

A rare case of hemolytic anemia complicated with Behçet's disease and myelodysplastic syndrome (MDS) is described. A 41-year old woman suffering from hemolytic anemia was admitted in July of 1988 with right lower abdominal pain and a high fever. Her anemia was first pointed out in 1962 (at age 15), and diagnosed as hemolytic anemia in 1977 by a full hematological examination showing erythro-hyperplasia in bone marrow, Coomb's test was negative and corticosteroid therapy failed to improve her anemia. She had also been suffering from recurrent stomatitis and genital ulcer since the delivery of her first baby in July, 1972. Barium enema was performed and revealed a simple deep ulcer at the terminal ileum. Bone marrow examination showed morphological abnormalities of granulocytic and erythrocytic series. We thereby diagnosed her illness as incomplete Behçet's disease and MDS associated with hemolytic anemia. She was treated by ubenimex, blood transfusion and intravenous alimentation with discontinuing oral intake, and there was a satisfactory improvement in pancytopenia and ulcer.

Adult↗