Search PubMed⌕ Search

Biomedical subjects

H Osawa

Publications and source records attributed to H Osawa.

At least 145 records · Page 8Linked to original sources

Effects of bestatin (Ubenimex) on human T-cell colony formation.

The antitumor action of bestatin is considered to be an indirect action mediated by T-cells. Therefore, we investigated the effects of bestatin on the differentiation and proliferation of human precursor T-cells using a colony formation technique. Bestatin did not increase the overall number of T-cell colonies, but it significantly increased in CD4+ cell and significantly decreased in CD8+ cell subpopulations. It also induced CD4+.8+ cells. These findings indicated that bestatin acts on precursor T-cells to induce the differentiation of these cells into CD4+ cells.

Adult↗

Case report of amyloidosis-like glomerulopathy with hepatic involvement.

A few cases of nephrotic syndrome with the glomerular deposition of an amyloid-like material which did not stain with Congo red have been documented. But extrarenal deposits have not been previously reported in this disease. We describe here a case of nephrotic syndrome associated with the deposition of an amyloid-like material in the liver as well as in the renal glomeruli. The deposits were made up of fibrillar structures which resembled those of amyloid when viewed through the electron microscope but they did not stain with Congo red. This is the first report of amyloidosis-like glomerulopathy with extrarenal deposits.

Amyloid↗

[Gabexate mesilate induced remarkable transient reversal of thrombocytopenia in a ITP patient].

A 46-year-old woman was admitted to our hospital because of hemorrhagic tendency. Normal coagulation test results conflicted with the diagnosis of disseminated intravascular coagulation (DIC). Furthermore, we saw no evidence of autoantibodies, including antinuclear antibodies and splenomegaly, and there was no past history of infection or medication. Peripheral blood test showed marked decrease of platelets only. Bone marrow aspiration revealed increased megakaryocytes. Morphology of other blood components was normal. Thus, we diagnosed this case as idiopathic thrombocytopenic purpura (ITP). Administration of prednisolone and an immunosuppressants did not improve symptoms. So patient was temporarily discharged and treated with 6-MP at the outpatient department. She was rehospitalized for liver damage caused by the drug. Patient then developed sepsis from acinetobactor. We administered gabexate mesilate (FOY, 2,000 mg/day) for four days to prevent DIC. Platelet count, which was 1.5 X 10(4)/microliter before FOT administration, began increasing on the second day, reaching 25. 5 X 10(4)/microliter on the fourth. Count rapidly decreased to 2.8 X 10(4)/microliter on the seventh day after administration had been discontinued. Two-time FOY administration after patient's recovery from sepsis led to a definite, similar transient increase in platelet count. As ITP patients with transient increase in platelet count by FOY administration had not been reported, this case is thought to be an interesting case in the pathogenesis and treatment of ITP.

Female↗

A study on experimental focal glomerular sclerosis in rats: significance of intraglomerular lipid deposition.

The present study deals with intraglomerular lipid deposition and its relation to the development of focal glomerular sclerosis (FGS) in rats. Experimental FGS was induced by repeated administration of puromycin aminonucleoside (AN) and was observed from the 3rd to 6th month. At 3 months after the beginning of the experiment, FGS lesions, marked proteinuria and hyperlipidemia were observed. Sudan III-stained sections revealed intraglomerular deposition of lipid, especially in the sclerotic lesions. An immunofluorescent study demonstrated nodular or massive deposition of IgM, IgG and fibrinogen in the sclerotic areas. Significant positive correlation was observed between the degree of intraglomerular lipid deposition and glomerular damage. In order to examine the intraglomerular lipid, isolated glomeruli which were obtained by a sieving method were analyzed by thin layer chromatography. The intraglomerular lipid consisted of cholesterol ester with a small amount of triglyceride. The incidence of sclerosis and excretion of urinary protein attained peak levels at the 3rd month and then decreased, but hyperlipidemia was prolonged. It is suggested that hyperlipidemia and intraglomerular lipid deposition may contribute to the development of FGS in aminonucleoside nephrosis.

Animals↗

Evaluation of the efficiency of two IgA immune complex assays.

Two IgA immune complex assays, namely the anti-IgA inhibition of binding assay (a-IgA-InhBA) and the IgA polyethylene glycol assay (IgA-PEG assay) were evaluated using IgA aggregates (AIgA) of well defined sizes. AIgA was prepared by heat treatment. After ultracentrifugation the size of AIgA was found to be in a range between 7 S and 64 S. Five AIgA pools (greater than 64 S, 44-64 S, 24-43 S, 20-24 S and 9-19 S) and a pool of monomeric IgA were prepared to test the efficiency of the two assays. The IgA-PEG assay exclusively detected very large sized AIgA (greater than 64 S), whereas the a-IgA-InhBA detected also AIgA of intermediate size (9-19 S). The sensitivity of the latter assay was found to be size dependent. After ultracentrifugation of serum samples from patients with IgA nephropathy, IgA of large and intermediate macromolecular size was detected. It is concluded that the a-IgA-InhBA is useful for the detection of circulating IgA-containing immune complexes in IgA nephropathy.

Antigen-Antibody Complex↗

[Idiopathic thrombocytopenic purpura complicated with circulating lupus anticoagulant].

A 37 year-old female was admitted to our hospital because of hypermenorrhea, prolonged bleeding time, thrombocytopenia and the diagnosis of idiopathic thrombocytopenic purpura (ITP) was made. Though activated partial thromboplastin time (APTT) was markedly prolonged, her coagulation factors were within normal ranges. Activities of the circulating lupus anticoagulant (LAC) was suggested. Kaolin clotting time of the platelet poor plasma was used as a sensitive screening test using the mixture of normal and patient's plasma for the detect of LAC. As a result, LAC positive pattern was observed. The treatment with high-dose gammaglobulin brought out a transient increase of the platelet count, but the prolongation of APTT was not corrected. Both the platelet count and the prolongation of APTT were significantly improved after the treatment with betamethasone.

Adult↗

Mechanism of action of anti-IL-2R monoclonal antibodies. ART-18 prolongs cardiac allograft survival in rats by elimination of IL-2R+ mononuclear cells.

ART-18, a mouse IgG1 mAb recognizing the IL-2 binding domain of the rat p55 subunit IL-2R molecule, prevents graft rejection in various experimental models, although its mechanism of action in vivo, like that of anti-IL-2R mAb generally, remains elusive. These studies were designed to define whether IL-2R+ T effector cells were actually eliminated or their function merely inhibited by comparing directly the in vitro and in vivo efficacy of intact ART-18 and its F(ab)/F(ab')2 fragments. Addition of each mAb preparation profoundly suppressed MLR set up between naive LEW responders and x-radiated BN stimulators, suggesting that mAb fragments retained Ag binding functions in vitro. However, both ART-18 F(ab) and F(ab')2 were ineffectual in vivo as judged by their inability to affect acute (8 days) rejection of (LEW X BN)F1 cardiac allografts in LEW recipients (graft survival ca. 11 and 9 days, respectively, compared to ca. 21 days after therapy with intact ART-18, p less than 0.001). The sera levels of ART-18 and ART-18 F(ab')2 were 4 to 5 micrograms/ml, but only less than 0.5 micrograms/ml of F(ab) could be detected. The therapeutic failure of ART-18 fragments was unrelated to potential host sensitization, as rat antimouse F(ab) or F(ab')2 serum IgG titers remained in the same range as those against intact ART-18. The role of the Fc portion of Ig in the mode of action of ART-18 was then tested further by flow microfluorimetry analysis of host mononuclear spleen cells and immunoperoxidase stains of the graft infiltrate. IL-2R+ cells were abundant in rats treated with ART-18 fragments, comparable to acutely rejecting controls. In contrast, IL-2R expression was abolished in animals undergoing ART-18 therapy. The elimination of IL-2R+ cells is required to prolong cardiac allograft survival in rats after IL-2R targeted treatment with ART-18 mAb.

Animals↗

Interaction between C3 and IL-2; inhibition of C3b binding to CR1 by IL-2.

We previously reported that C3 has a role in the enhancement of the IL-2 dependent proliferation of helper T cells. Because the IL-2R has a structural homology with the complement proteins, such as CR1 and CR2, we studied the possible ligand crossreactions on CR1 and IL-2-receptor, and the direct interaction between C3 and IL-2. While C3 has an enhancing effect on the IL-2 dependent proliferation of HT-2, a CR1-positive mouse T-cell line, the growth of the CTLL-16 line (CR1-negative) is not affected by C3. It has been proven that neither the insolubilized C3 nor the soluble C3b-like C3 react with the IL-2 binding epitope of the IL-2 receptor. However, using human RBC we have demonstrated that the binding of aggregated C3 to CR1 is inhibited by rIL-2, in a dose-dependent manner. When RBC were incubated with rIL-2 and FITC-labelled Fab-anti-CR1 simultaneously, there was no inhibition in the fluorescence intensity. As detected by ELISA, rIL-2 was bound to the same extent by insolubilized C3, C3b, and C3c, while C3d coat had lower binding capacity. The receptor-binding epitope of IL-2 is intact in the complex of complement proteins and rIL-2, as demonstrated by the binding of DMS1, a monoclonal antibody reacting with the receptor site of IL-2. It is strongly suggested that C3b may play a role in the growth of CR1 positive T cells.

Cell Line↗

Studies on the formation of high-affinity IL-2 binding sites of an IL-2 receptor p55 + p75 heterodimeric complex: functional importance of a determinant on the p55 subunit defined by a monoclonal antibody AHT-107.

The monoclonal antibody (mAb) AHT-107 recognized a determinant distal to the interleukin 2 (IL-2) binding site on the p55 subunit of the IL-2 receptor (IL-2R) (the Tac antigen, CD25) of human T lymphoblasts, while the mAb AHT-54 recognized a determinant close to the IL-2 binding site as did the anti-Tac. The AHT-107 inhibited IL-2 dependent proliferation of human T lymphoblasts equally as well as did the AHT-54. Both mAbs inhibited the high-affinity binding and crosslinking of IL-2 to the p55 + p75 heterodimeric complex on forskolin-treated YT cells. Remarkably, the AHT-107 did not inhibit the low-affinity binding and cross-linking of IL-2 to the p55 molecule on human p55 cDNA-transfected cells, while the AHT-54 as well as anti-Tac did so. In contrast, the mAb PC61, that was previously reported to recognize a determinant distal to the IL-2 binding site on the mouse p55 subunit of IL-2R and to dissociate IL-2 from the high-affinity IL-2R complex by altering the conformation of the p55 molecule itself, inhibited the low-affinity binding and cross-linking of IL-2 to the p55 molecule on mouse p55 cDNA-transfected cells. Further, we showed that the AHT-107 did not dissociate IL-2 from the high-affinity IL-2R complex once formed on human T lymphoblasts.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Clinical study on splenic autotransplantation after splenectomy in idiopathic thrombocytopenic purpura].

Splenic autotransplantation after splenectomy for idiopathic thrombocytopenic purpura (ITP) is one of the effective treatments for maintaining the patients' immunity in children. We investigated this surgical method in 10 adult ITP patients. This method was extremely effective for thrombocytopenia. Cellular immunity of the patients was maintained as evidenced by the normal response of peripheral lymphocytes to phytohemagglutinin (PHA) and concanavalin-A (Con-A) after the operation. The mitogenic response of peripheral lymphocytes to PHA and Con-A might be a useful indication for predicting the effect of splenectomy.

Adult↗

A family case of IgA nephropathy and Henoch-Schönlein purpura nephritis.

We describe a family case of IgA nephropathy and Henoch-Schönlein purpura nephritis. This is the first report involving IgA nephropathy in a child and Henoch-Schönlein purpura nephritis in a parent. It is suggested that the two were related etiologically as well as clinicopathologically.

Adolescent↗

Regulation of in vivo immunological reactions by monoclonal antibody against lymphocyte activation antigen.

In vivo effects of a monoclonal antibody that recognizes rat lymphocyte activation antigen were studied. Spleen cells obtained from sheep red blood cell (SRBC)-immunized rats developed strong PFC response against SRBC. However, the 5C6-F4 treatment resulted in the inhibition of subsequent development of PFC response. The suppression of PFC response was due to the inhibition of generation of helper T cells, but not due to the preferential induction of suppressor cells. In addition, 5C6-F4 antibody was also found to inhibit the clinical expression of collagen-induced rat arthritis and the synovial inflammation in collagen-induced arthritis rats. Furthermore, the in vivo generation of cytotoxic cells against syngeneic tumor cells was also inhibited by 5C6-F4 antibody. The in vivo administration of 5C6-F4 antibody did not cause any pathological changes in brain, lung, liver, kidney, spleen, thymus, and lymph nodes.

Animals↗

[Multivariate statistical analysis of the postoperative recurrence factors in uterine cervical carcinoma].

In 211 patients with postoperative cervical carcinoma, we studied the relationship between the recurrence and various factors, and the interrelation among the factors. 1) Lymph node metastasis, clinical stage, number of complaints, adenocarcinoma and adenosquamous carcinoma, and number of pregnancies were associated with recurrence. Signs of myelic injury and large cell non-keratinizing carcinoma were associated with less recurrence. Maintenance chemotherapy markedly improved the prognosis. 2) Lymph node metastasis was frequently associated with an advanced stage, adenocarcinoma or increased erythrocyte sedimentation. Increased sedimentation was rarely associated with greater numbers of pregnancy or keratinizing carcinoma. Signs of myelic injury were rare in cases of advanced stage or large cell carcinoma and frequent in cases of long periods of illness. 3) Intrapelvic recurrence was related to early recurrence and maintenance chemotherapy, and extrapelvic recurrence to increased sedimentation, late recurrence, adenocarcinoma and no chemotherapy. 4) Early recurrence was associated with shorter periods of illness, lymph node metastasis and no chemotherapy, but late recurrence was associated with longer periods of illness, no lymph node metastasis, maintenance chemotherapy and adenocarcinoma. 5) The prognosis and the required periods of maintenance chemotherapy could be determined by Z = 4.3817.X1 + 1.2366.X2-0.0916.X3 + 2.3257.X4-1.9606.X5 + 1.6477.X6-0.1967.X7- 7.3047, with rates of inaccuracy of 13.9% for cases of no recurrence and 15.1% for recurrent cases.

Analysis of Variance↗

An ELISA that detects cell-associated and released rat IL-2 receptors in a soluble form.

A mouse anti-rat interleukin-2 receptor (IL-2R) monoclonal antibody (mAb), ART-65, has recently been developed which recognizes the rat IL-2R but binds to an epitope distinct from that recognized by the mAb ART-18. The availability of two mAb against the rat IL-2R molecule permitted the development of an enzyme-linked immunosorbent assay (ELISA) which detects soluble and solubilized rat IL-2R. Using this ELISA, time course studies of ConA and LPS-activated rat splenocytes revealed that IL-2R are released into their environment during the culture period, and that IL-2R can be detected in rat sera. The significance of the results is discussed.

Animals↗