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Biomedical subjects

S Hanada

Publications and source records attributed to S Hanada.

At least 109 records · Page 6Linked to original sources
PubMed1991

Tumor necrosis factor-beta in the serum of adult T-cell leukemia with hypercalcemia.

Serum tumor necrosis factor-beta (TNF-beta) from patients with adult T-cell leukemia (ATL) was studied by a sandwich enzyme-linked immunosorbent assay (ELISA) developed in our laboratory using biotinylated monoclonal anti-TNF-beta and recombinant TNF-beta. Seven of eight patients with hypercalcemia showed elevation of serum TNF-beta. On the other hand, TNF-beta could not be detected by the ELISA in 28 patients without hypercalcemia. The lower detection limit in this assay was 100 pg/mL, corresponding to 500 pg/mL by the conventional method. In two patients serum TNF-beta level decreased after treatment in association with the level of serum calcium. Furthermore, immuno-staining using anti-TNF-beta and avidin-biotin complex showed the presence of cytoplasmic TNF-beta in not only human T-cell leukemia virus type I infected cell lines, but also freshly isolated cells from ATL patients with hypercalcemia. The actual biologic activity of TNF-beta in serum was confirmed by a conventional bioassay in a patient with hypercalcemia, and its cytotoxic activity was inhibited by the addition of anti-TNF-beta antibody in the assay. These results suggested that serum TNF-beta might be one of the factors contributing to the hypercalcemia, at least in patients with ATL.

Adult↗
PubMed1991

Histamine release from rat mast cells induced by econazole.

1. Econazole released histamine from rat mast cells in vitro. This response was not affected by the addition of calcium or by prior treatment of mast cells with EDTA or cromoglycate. 2. Rat mast cells treated with econazole were stained by the vital dye trypan blue. 3. The intradermal injection of econazole increased vascular permeability. This response was antagonized by chlorpheniramine and cyproheptadine. 4. Our results demonstrate that econazole releases histamine by the "nonselective" mechanism. It is suggested that econazole inflammatory effects may be due to histamine release from mast cells.

Animals↗
PubMed1991

Preparation and biological activity of 2-[4-(thiazol-2-yl)phenyl]propionic acid derivatives inhibiting cyclooxygenase.

A series of 2-[4-(thiazol-2-yl)phenyl]propionic acids substituted at various positions were prepared by the reaction of diethyl 2-methyl-2-(4-thiocarbamoylphenyl)malonates with alpha-bromoaldehyde diethyl acetals or alpha-haloketones followed by hydrolysis of esters. The inhibition of prostaglandin H synthetase (cyclooxygenase) was assayed by use of an enzyme preparation from guinea pig polymorphonuclear leukocytes. Examination of the structure-activity relationship of these compounds indicated that the substitution pattern with halogens at position 3 (R1) of the benzene ring and a methyl group in position 4 (R2) and/or 5 (R3) of the thiazole ring were favorable for inhibitory activity. The compounds bearing bulky alkyl or polar functional groups at the R2 position were weak inhibitors. The potent inhibitors of cyclooxygenase were tested for their ability to reduce carrageenin-induced inflammation of rat paws. These derivatives had strong anti-inflammatory activity based on their strong inhibition of cyclooxygenase, with some exceptions, including those with a thiomethyl group at R1.

Animals↗
PubMed1991

[Surface phenotypic diversity of CD4 or CD8 in ATL].

A 51-year-old woman was admitted to our hospital complaining of lymphadenopathy in June, 1987. Lymph node biopsy revealed diffuse lymphoma, mixed cell type according to the LSG classification. On hematological examinations, leukocyte has counted 12,400/microliters, of which 15% abnormal lymphocytes containing human T cell lymphotropic virus type-1 (HTLV-1) proviral DNA into the cellular DNA. She was diagnosed as adult T-cell leukemia (ATL). The abnormal lymphocytes in the peripheral blood expressed CD4 but lymph node cells expressed CD8. Thirty months after initial diagnosis, abnormal lymphocytes began to increased and reached 30,500/microliters. Surface phenotype of abnormal lymphocytes changed CD3+ CD4+ CD8- OKla1+ to CD3- CD4- CD8- OKla1-. This change is considered to show the surface phenotypic diversity in ATL cells.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1990

Expression of P-glycoprotein in adult T-cell leukemia cells.

We have examined the expression of P-glycoprotein (P-gp) in adult T-cell leukemia (ATL) samples from 25 patients. Based on immunoblotting with a monoclonal antibody against P-gp, C219, 8 of 20 ATL patients were P-gp positive at the initial presentation. All 6 patients at the relapsed stage were P-gp positive, and refractory to chemotherapy. The expression of MDR1 mRNA in P-gp-positive ATL cells was increased at the relapsed stage of one patient. P-gp of this patient was photolabeled with [3H]azidopine and the labeling was inhibited with nimodipine, vinblastine and progesterone. These results suggest that P-gp expressed in ATL cells from patients at relapsed stage has the same binding site(s) for the drugs as that in multidrug resistant cells, and is correlated with the refractory nature of the cells to chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1990

Expression of the multidrug transporter, P-glycoprotein, in acute leukemia cells and correlation to clinical drug resistance.

The overexpression of a cell-surface glycoprotein termed P-glycoprotein (P-gp) is frequently associated with multi-drug resistance (MDR) in cell lines in vitro. To evaluate the implications of P-gp expression in clinical drug resistance, the authors examined the expression of P-gp in leukemia cells from patients with acute myelogenous leukemia (AML) and those with acute lymphoblastic leukemia (ALL) at initial presentation and relapse, using immunoblotting with a monoclonal antibody against P-gp, C219. Nine of 17 patients with AML and four of 11 patients with ALL had P-gp-positive results at the initial presentation, and most P-gp-positive patients did not respond to chemotherapy. Four of seven patients at the relapsed stage and all three patients with preceding myelodysplastic syndrome had P-gp-positive results. The expression of P-gp and clinical refractoriness to chemotherapy were highly correlated. These data indicate that the expression of P-gp is closely related to clinical drug resistance in acute leukemia.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1990

Expression of the multidrug transporter, P-glycoprotein, in chronic myelogenous leukaemia cells in blast crisis.

The overexpression of a cell-surface glycoprotein termed P-glycoprotein (P-gp) is frequently associated with multidrug resistance (MDR) in cell lines in vitro. To evaluate the implications of P-gp expression in clinical drug-resistance, we examined the expression of P-gp in fresh leukaemia cells from chronic myelogenous leukaemia (CML) patients in blast crisis. By using immunoblotting with a monoclonal antibody against P-gp, C219, we showed that leukaemia cells from three CML patients in blast crisis were P-gp negative at the stage when these patients were in complete remission, and that the cells showed high levels of P-gp expression at times when the same patients had relapsed and had not responded to chemotherapy. Six out of 11 patients (nine in the refractory state) were P-gp positive and they rarely responded to chemotherapy. These data suggest that the expression of P-gp is closely associated with drug-resistance in CML.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1990

Lupus nephritis with adult T cell leukemia.

A 64-year-old Japanese male patient with lupus nephritis associated with adult T cell leukemia (ATL) is described. Percutaneous renal biopsy demonstrated findings consistent with membranous lupus nephritis. To our knowledge, this is the first case of lupus nephritis complicated by ATL, suggesting that human T cell leukemia virus type I may be correlated not only to outbreaks of ATL but also to lupus nephritis/systemic lupus erythematosus.

Humans↗
PubMed1989

The prevalence of human T-cell leukemia virus type I infection in patients with hematologic and nonhematologic diseases in an adult T-cell leukemia-endemic area of Japan.

In order to clarify the prevalence of human T-cell leukemia virus type I (HTLV-I) infection in the Kagoshima district, Japan, a highly endemic area for HTLV-I, antibodies for HTLV-I (anti-HTLV-I) were examined in the sera of 6167 from healthy residents and patients with various hematologic and nonhematologic diseases. In healthy residents, including blood donors, the prevalence of anti-HTLV-I was 11.9% (562/4741 persons). The prevalence increased with age, and was significantly higher in in females than in males (P less than 0.01). The prevalence of anti-HTLV-I in blood donors was 8.5%. In In hematologic diseases, the prevalence of anti-HTLV-I was 98.3% in ATL, 28.9% in lymphoproliferative disorders except ATL, and 10.6% in myeloproliferative disorders. In nonhematologic diseases, the prevalence of anti-HTLV-I was shown to be 29.5% in pulmonary tuberculosis, 25.8% in leprosy, 33.8% in chronic renal failure (CRF), 21.9% in autoimmune diseases, and 47.8% in strongyloidiasis. The various diseases except myeloproliferative disorders had significantly higher prevalence of anti-HTLV-I than healthy residents (P less than 0.01 or 0.05). For autoimmune diseases, the prevalence of anti-HTLV-I in patients with blood transfusion (55.6%) was higher than in those without blood transfusion (8.7%), and healthy residents. In hemodialysis patients with CRF who had received blood transfusions the prevalence of anti-HTLV-I increased with the number of blood transfusions. Therefore, HTLV-I transmission via blood transfusion would partially explain these high prevalence of anti-HTLV-I. However, the prevalence of anti-HTLV-I in hemodialysis patients with CRF was statistically higher than that in healthy residents, regardless of blood transfusion (P less than 0.01). Furthermore, hemodialysis patients showed significantly higher prevalence of anti-HTLV-I than healthy residents, even at a younger age. Patients with pulmonary tuberculosis and leprosy showed the same results as hemodialysis patients. These results suggest that possibility that HTLV-I infection has some relation not only to ATL but also to other diseases. Therefore, it seems very important to halt the spread of HTLV-I transmission as soon as possible.

Adolescent↗
PubMed1989

An enzyme-linked immunosorbent assay for immune complex of HTLV-I.

A sandwich enzyme-linked immunosorbent assay (ELISA) for immune complexes of human T cell leukemia virus type I (HTLV-I) was developed using monoclonal antibody (MoAb) 3G1 which recognizes a different epitope on HTLV-I to that with which natural human anti-HTLV-I antibody binds. The assay was capable of titrating artificial immune complexes not only at antigen-antibody equivalence but also at antibody excess. Although the antigen-antibody ratios could not be determined in the individual sera from patients with overt ATL, the level of immune complexes in three out of four sera was estimated to be 250 +/- 36 ng/ml. Immune complexes of HTLV-I could not be identified in sera obtained from one patient with overt ATL, three healthy HTLV-I carriers and three normal human controls.

Adult↗
PubMed1989

Lymphocyte subpopulations of peripheral blood in tsutsugamushi disease.

We examined lymphocyte subpopulations in the peripheral blood and serum concentrations of immunoglobulin (Ig) in 8 patients with tsutsugamushi disease. In 7 of the 8 cases, there was a 4-fold or greater increase in IgG and IgM antibody titers between the initial and convalescent serum specimens. In one case, there was no increase, but IgM antibodies were detected with diagnostically significant antibody titers. The percentages of CD8- and CD2-positive lymphocytes measured before treatment were found to be significantly higher than during the recovery stage of patients with tsutsugamushi disease. The CD4/CD8 ratio in the peripheral blood calculated before treatment was significantly lower than that during the recovery stage. Serum concentrations of IgG and IgM in patients during the recovery stage were significantly higher than pretreatment levels, respectively.

Adult↗
PubMed1989

Adult T cell leukemia in hemodialysis patients from the Kagoshima district, an area in which human T cell leukemia virus type I is highly endemic.

We report 2 cases of adult T cell leukemia (ATL) from hemodialysis (HD) patients with chronic renal failure (CRF) in the Kagoshima district, an endemic area of human T cell leukemia virus type I(HTLV-I) in Japan. The positivity of antibodies to ATL-associated antigen(anti-ATLA) in HD patients, regardless of whether or not blood transfusions were given, has been higher than in healthy persons in the district (p less than 0.01). ATL is considered to break out from HTLV-I carriers. Further study should be conducted to clarify the relationship between HTLV-I infection and CRF, and moreover, attention should be directed not only to treatment of HD but accompanying ATL as well, particularly in HTLV-I-endemic areas.

Aged↗
PubMed1989

[Pharmacological studies of a non-steroidal analgesic and antipyretic drug of LFP83].

Pharmacological properties of LFP83, a non-steroidal analgesic and antipyretic drug, were studied in mice, rats and rabbits. LFP83 is a prodrug of flurbiprofen (FP) which is its active major metabolite in vivo. In experimental models of acetic acid writhing, the Randall and Selitto method, arthritic pain, yeast fever, LPS fever, carrageenin edema and adjuvant arthritis, LFP83 (i.v.) showed remarkable analgesic, antipyretic and antiinflammatory activities; and it was more potent than ketoprofen (i.m.) and aspirin DL-lysine (i.v.). The analgesic activity of LFP83 was equal to or more potent than that of pentazocine, and its duration was longer than those of aspirin DL-lysine and pentazocine. In addition, the analgesic potency of LFP83 was approximately the same or more potent than that of FP (p.o.), and the onset of this analgesic effect began earlier. On the other hand, the ulcerogenic activity of LFP83 on rat gastric mucosa was less than that of FP (p.o.) in both single and consecutive (7 days) administrations. The safety index (UD50/ED50) of LFP83 was three to ten-fold higher than that of FP (p.o.). As mentioned above, LFP83 is a potent analgesic, antipyretic and antiinflammatory drug; and in comparison to oral FP, it has a more potent and immediate effect, weak gastric irritation and high safety index.

Analgesics↗
PubMed1989

[Expressions of 2H4 and 4B4 antigens on ATL cells].

We studied the expression of 2H4 and 4B4 on the surfaces of leukemia cells from 17 patients with adult T-cell leukemia (ATL) as well as of cells belonging to 2 T-cell lines derived from ATL patients. The effects of the supernatants obtained from culture fluids of the ATL cells and the T-cell lines on IgG production of a human B-cell line, CESS cells, were also examined. On the surfaces of the ATL cells from 15 out of 17 cases and of the cells of 2 T-cell lines 4B4 obviously existed at higher percentage than 2H4 and more than 80% of ATL cells from 16 out of these 17 cases showed the expression of T4 (CD4). These findings revealed that the most of ATL cells had a helper-inducer phenotype. Supernatants (Sups) of culture fluids of ATL cells from 4 patients and those of 2 T-cell lines were added at various concentrations to the CESS cells. In only 1 Sup from ATL patient enhanced the IgG production of the CESS cells at lower concentration. However, other 5 Sups suppressed the IgG production of the CESS cells in proportion to the increase of Sup added. These results showed that phenotypical type of ATL cells does not always correspond to their functions, and the ATL cells may produce humoral factors that regulate B cell functions.

Adult↗
PubMed1989

[A molecular basis for multidrug resistance and reversal of the resistance].

Multidrug-resistance is frequently characterized by enhanced drug efflux resulting from a membrane glycoprotein of 170,000 daltons (P-glycoprotein). Analysis of cloned cDNAs for the human MDR 1 gene, whose product is the P-glycoprotein, indicates that P-glycoprotein is an energy-dependent drug-efflux system for cytotoxic hydrophobic anticancer drugs. We have demonstrated that a photoanalog of a reversing agent, SDB-ethylenediamine, specifically binds to P-glycoprotein. The binding site on P-glycoprotein seems to be identical with that of anticancer agents and other reversing agents. On the other hand, the radioactive photoactive dihydropyridine calcium channel blocker, [3H] azidopine, photolabels P-glycoprotein in membrane vesicles from multidrug-resistant cells. This photolabeling is almost completely inhibited by excess dihydropyridine analogs that reverse or lower drug-resistance. In contrast, the labeling is not significantly inhibited by analogs that do not reverse resistance. These results suggest that it may be possible to quickly screen for dihydropyridine analogs that reverse multidrug resistance by measuring the inhibition of [3H] azidopine labeling of P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

[Pharmacokinetic and clinical studies on cefodizime in gynecologic field].

Pharmacokinetic and clinical studies on a new cephalosporin antibiotic, cefodizime (THR-221, CDZM), were performed and the results obtained are summarized as follows: 1. At about 84 minutes after a bolus injection of 1 g dose of CDZM, the drug was transferred well into tissues of internal genital organs and remained there at therapeutic levels for 285 minutes. The drug was also transferred quickly and sufficiently into exudate from pelvic dead space and its levels were still kept at high levels at 6 hours after administration. 2. CDZM was given to 8 women affected with gynecologic infections. The outcome of CDZM therapies showed that the drug was effective in all 8 of patients (100%) clinically and bacteriologically. 3. Notable adverse effects or abnormal laboratory test results were not observed except for 2 patients with transient and slight elevation of transaminase levels. Based on these results, it may be concluded that CDZM is a highly effective and a very safe antibiotic for the treatment on infectious diseases in gynecologic field.

Adult↗
PubMed1989

[Clinicopathological studies of the gastrointestinal tract in adult T-cell leukemia patients].

We analysed the digestive symptoms and the gastrointestinal (GI) tract lesions in 61 patients with adult T cell leukemia (ATL). Digestive symptoms were found in 36 patients (59.0%) at the onset of leukemia, and in 45 patients (73.8%) at the first medical examination. X-ray examination of the GI tract was made in 22 patients, and abnormal stomach mucosa patterns were found in 20 patients (90.9%). Endoscopic examination of the GI tract was carried out in 18 patients, and it revealed that most of the stomach mucosa was accompanied by edema and redness. Erosions and ulcers also were found in many patients. A granular shadow, which was noted during the x-ray examination, could not be confirmed by endoscopy. A pathological examination of biopsied specimens was made in 13 patients, and infiltration of leukemic cells into the stomach was observed in 10 of the 13 cases. These findings suggest that leukemic infiltration into digestive tracts is related to the development of digestive symptoms in ATL patients.

Adult↗