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M Hosono

Publications and source records attributed to M Hosono.

At least 109 records · Page 6Linked to original sources
PubMed1994

A conserved epitope on H+,K(+)-adenosine triphosphatase of parietal cells discerned by a murine gastritogenic T-cell clone.

BACKGROUND/AIMS: H+,K(+)-adenosine triphosphatase (H+,K(+)-ATPase) of parietal cells is an organ-specific enzyme recognized by autoantibodies found in human and murine autoimmune gastritis (AIG). Murine AIG can be induced in BALB/c mice by thymectomy 3 days after birth and is a T cell-mediated disease. This study examined the specificity of T cells that cause AIG and the role of H+,K(+)-ATPase in this disease. METHODS: From an AIG mouse, a gastritogenic T-cell clone (II-6) was established, and its reactivity to synthetic peptides of H+,K(+)-ATPase was tested. RESULTS: II-6 cells are CD4+, V beta 14+, and interferon gamma producers. Adoptive transfer of II-6 cells to syngeneic nude mice resulted in AIG without the production of autoantibodies to parietal cells. The II-6 cells were responsive not only to murine but also to human and porcine parietal cells. Their proliferation was also induced by amino acids 891-905 (alpha 891) and 892-906 (alpha 892) of the alpha subunit of porcine and human H+,K(+)-ATPase, respectively. CONCLUSIONS: The T-cell response to a single epitope of H+,K(+)-ATPase, the amino acid sequence of which is conserved among at least three mammals tested, is sufficient to cause AIG. Autoantibodies to parietal cells are not detected in these AIG mice.

Amino Acid Sequence↗
PubMed1994

A newly designed radioimmunoconjugate releasing a hippurate-like radiometal chelate for enhanced target/non-target radioactivity.

Target-to-non-target ratio of radioactivity can be enhanced by the injection of monoclonal antibodies (MoAbs) labeled with metallic radionuclides, if some modality to accelerate the urinary excretion of radioactivity accumulated in non-target tissues could be introduced. In this study, a radioimmunoconjugate chemically designed to release a hippurate-like radiometal chelate was synthesized and tested in vivo. A 67Ga chelate of succinyldeferoxamine (SDF) was conjugated with a MoAb against osteogenic sarcoma (OST7, IgG1) through an ester bond using a new metabolizable MESS linker, N-[I4-(maleimidoethoxy)succinyl]oxy]succinimide (67Ga-DFO-MESS-OST7). When injected into normal mice, 67Ga-DFO-MESS-OST7 exhibited faster clearance of radioactivity from circulation with less accumulation in the liver, kidney and spleen than those observed with 67Ga-DFO-EMCS-OST7, which was prepared under identical conditions to 67Ga-DFO-MESS-OST7 except for using a non-metabolizable linker holding no ester bond to release 67Ga-SDF. Size exclusion HPLC analysis of the liver homogenate obtained from mice 24 h after injection of 67Ga-DFO-MESS-OST7 indicated that all the radioactivity was eluted in the high molecular weight fraction with most of it being present as the 67Ga-DFO-MESS-OST7 fraction. Reverse-phase HPLC analysis of urine sample from the same mice showed a single radioactivity peak at the same retention time as that of 67Ga-SDF. In athymic mice bearing osteogenic sarcoma, 67Ga-DFO-MESS-OST7 exhibited higher tumor-to-blood and tumor-to-organ ratio of radioactivity when compared with 67Ga-DFO-EMCS-OST7. These results indicated that 67Ga-DFO-MESS-OST7 achieved enhanced target-to-non-target ratio of the radioactivity, due to preferential cleavage of the ester bond in non-target tissues, followed by rapid urinary excretion of the resulting chelate (probably as 57Ga-SDF). These results also suggest that the present design would become an applicable modality for enhancing the target-to-non-target ratio of radioactivity by MoAbs.

Animals↗
PubMed1994

Soft-tissue tumors: diagnosis with Tc-99m (V) dimercaptosuccinic acid scintigraphy.

PURPOSE: To assess the potential of technetium-99m (V) dimercaptosuccinic acid (DMSA) scintigraphy for diagnosis of soft-tissue tumors. MATERIALS AND METHODS: Tc-99m (V) DMSA scintigraphy was performed in 76 patients with histologic proof of soft-tissue tumors. In 57 of these patients, gallium-67 citrate scintigraphy was performed within 2 weeks after Tc-99m (V) DMSA scintigraphy. RESULTS: Uptake of Tc-99m (V) DMSA was clearly detected in almost all sarcomas, metastatic carcinomas, highly recurrent benign tumors (ie, extra-abdominal desmoids and tenosynovial giant cell tumors), superficial and deep hemangiomas, and granulomatous soft-tissue lesions but was not found in other benign solid tumors of soft tissue. Uptake of Ga-67 citrate was clearly detected in all inflammatory lesions and metastatic carcinomas, eight of 14 sarcomas (57%), and two of 10 highly recurrent benign tumors (20%) but was not found in hemangiomas or benign soft-tissue tumors. CONCLUSION: Low-grade malignant and highly recurrent benign lesions, which often recur after surgery, were detected more accurately with Tc-99m (V) DMSA scintigraphy than with Ga-67 citrate scintigraphy.

Adolescent↗
PubMed1994

[Partial purification and properties of deoxyribonucleases from eggs and liver of Xenopus laevis. Comparison with deoxyribonuclease II from bovine spleen].

Deoxyribonucleases from eggs and the liver of Xenopus laevis were partially purified by DEAE-cellulose and heparin-Sepharose affinity column chromatographies. The fractions having egg and liver DNase activities were eluted on high performance liquid chromatography through TSK gel G3000SW at the molecular weights of 41.5 and 45 kDa, respectively. The frog DNases hydrolyzed a native DNA over a heat-denatured DNA, and also formed double-strand cuts not only in linear lambda-DNA but also in closed circular pBR322DNA. The pH optimum of the DNases was 4.5-5.0 in 50 mM acetate buffer. These enzyme activities were abolished by treatment at 80 degrees C for 5 min and pH 2, 3 or 12 for 1 h. The enzymes act in such a manner as deoxyribonuclease II (from bovine spleen)-type nuclease with respect to substrate specificity, optimum pH and cation dependence.

Animals↗
PubMed1994

Case report: uptake of pentavalent technetium-99m dimercaptosuccinic acid by pigmented villonodular synovitis: comparison with computed tomography, magnetic resonance imaging and gallium-67 scintigraphy.

The scintigraphic findings of a patient with pigmented villonodular synovitis are described and compared with the computed tomography and magnetic resonance imaging data. Intense uptake of pentavalent technetium-99m dimercaptosuccinic acid without gallium-67 citrate uptake indicates that pigmented villonodular synovitis has the features of a hyperplastic or neoplastic lesion rather than an inflammatory lesion from the point of view of nuclear medicine.

Adult↗
PubMed1994

Improved clearance of radiolabeled biotinylated monoclonal antibody following the infusion of avidin as a "chase" without decreased accumulation in the target tumor.

UNLABELLED: The techniques of radioimmunoimaging and radioimmunotherapy suffer from prolonged high background radioactivity because intravenously injected antibodies remain in the circulation and in the organs far longer than necessary for effective binding to the target. To decrease background and increase radionuclide excretion without decreasing the dose of radioactivity delivered to the target tumor, we used radiolabeled biotinylated antibodies followed by a "chase" avidin injection. METHODS: A mouse monoclonal antibody, OST7 (IgG1), which reacts with human osteosarcoma, was biotinylated and labeled with 125I, 131I or 99mTc. Radiolabeled biotinylated OST7 (10 micrograms) was administered intravenously into nude mice bearing human osteosarcomas and 30 micrograms of avidin was injected intravenously 6 or 24 hr later. RESULTS: Following avidin injection in mice pretreated with radiolabeled biotinylated antibodies, radioactivity was promptly cleared from the blood and deposited in the liver and spleen, after which radioiodine was rapidly detached from the antibody and excreted in the urine. The tumor-to-blood ratios at 6 and 24 hr after the injection of 125I-labeled biotinylated OST7 increased compared with the values before the avidin chase without any loss of tumor radioactivity. Furthermore, the tumor-to-background radioactivity ratio was improved and better images were obtained more rapidly after the injection of radiolabeled biotinylated antibodies than with conventional immunoscintigraphy. CONCLUSIONS: This method may find application in clinical radioimmunoimaging, especially using short half-life radionuclides such as 99mTc and 123I.

Animals↗
PubMed1994

Schwannoma of the extremities: comparison of MRI and pentavalent technetium-99m-dimercaptosuccinic acid and gallium-67-citrate scintigraphy.

The diagnostic value of MRI and scintigraphy was studied in patients with Schwannomas of the upper or lower extremities. MRI (T1- and T2-weighted imaging), pentavalent 99mTc-dimercaptosuccinic acid and 67Ga-citrate scintigraphy were performed in 11 patients with 12 histologically proven benign Schwannomas. All six tumors with a maximum diameter > or = 3 cm showed marked accumulation of pentavalent 99mTc-dimercaptosuccinic acid, whereas they showed no uptake of 67Ga-citrate. MRI detected all of the tumors, and the lesions had a signal intensity equal to or slightly less than that of skeletal muscle on T1-weighted images and hyperintense to that of subcutaneous fat on T2-weighted images. MRI was superior to detect small Schwannomas of the extremities. A positive 99mTc-dimercaptosuccinic acid scan and a negative 67Ga-citrate scan however is useful to distinguish sarcoma with myxoid change from Schwannoma.

Adolescent↗
PubMed1994

Effect of hyperthermia on tumor uptake of radiolabeled anti-neural cell adhesion molecule antibody in small-cell lung cancer xenografts.

UNLABELLED: This study was performed to examine the effect of hyperthermia on the intratumor accumulation of a monoclonal antibody (Mab) in an animal model. Mab NE150 (IgG1) recognizes the neural cell adhesion molecule (NCAM) expressed by human small-cell lung cancer (SCLC) cells. METHODS: Athymic mice inoculated with NCI-H69, an SCLC cell line, received an intravenous injection of 125I- and 111In-NE150 and the serial changes of the biodistribution were determined. Furthermore, athymic mice bearing NCI-H69 were either sham-treated or treated by a single hyperthermia at 42 degrees C or 43 degrees C for 1 hr, with the tumor-bearing leg in a water bath using pentobarbital anesthesia. Immediately after heating, the mice were given an intravenous injection of radiolabeled NE150, and the biodistribution was examined at 24 and 48 hr. RESULTS: NE150 localized well in the transplanted tumor when compared with a control Mab. In mice treated at 43 degrees C, there was a 1.34- to 1.67-fold increase in the tumor uptake of 125I- and 111In-NE150 compared to sham-treated mice at both 24 and 48 hr. In addition, a 1.84- to 2.22-fold increase of the tumor-to-blood ratio was demonstrated, since radiolabeled NE150 cleared faster from the circulation in the mice given hyperthermia. A histological study demonstrated the infiltration of neutrophils in the perivascular spaces, indicating an increase of tumor vascular permeability, which might be one of the main reasons for the enhancement of Mab uptake. CONCLUSION: Hyperthermia seems to be a potential method of achieving an increased tumor accumulation of Mab in the radioimmunotargeting of SCLC.

Animals↗
PubMed1994

Treatment of small-cell lung cancer xenografts with iodine-131-anti-neural cell adhesion molecule monoclonal antibody and evaluation of absorbed dose in tissue.

UNLABELLED: Human small-cell lung cancer (SCLC) is considered a feasible target for immunotherapy using a radiolabeled monoclonal antibody (Mab). A murine Mab, NE150 (IgG1), reacts with the neural cell adhesion molecule, which is identical to cluster 1 antigen of SCLC. METHODS: To estimate their therapeutic effects, NE150 and an isotype-matched control Mab were labeled with 131I and administered intravenously as a single dose into athymic mice inoculated with a NCI-H69 SCLC xenograft. The absorbed dose in organs was also examined based upon a long-term biodistribution study of 131I-NE150. RESULTS: Tumors (initial volume 563.4 +/- 223.5 mm3) treated with 11.1 MBq (300 microCi) of 131I-NE150 diminished and became invisible at days 30-33, demonstrating a 60-day mean growth delay to reach a tripled initial volume compared with sham-treated tumors. Cumulative absorbed doses were estimated to be 2310, 410, 500, 330, and 790 cGy for the tumor, liver, kidney, spleen and lung, respectively. CONCLUSION: Iodine-131-NE150 had potent therapeutic effects against SCLC transplants in athymic mice, however, careful assessment of the side effects, improvement of radioiodination and chimerization of the Mab might be necessary to achieve efficient targeting in clinical therapeutic applications.

Antibodies, Monoclonal↗
PubMed1993

Induction of renal pelvic carcinoma by phenacetin in hydronephrosis-bearing rats of the SD/cShi strain.

Carcinogenicity of phenacetin (PH) to the urinary tract was tested with the use of spontaneously hydronephrosis-bearing rats. In Experiment 1, 55 SD/cShi male rats were fed with 2% PH-containing diet for 85 weeks, and 32 SD/cShi male rats fed basal diet for 85 weeks served as controls. Forty-three of 53 rats fed with PH had renal pelvic carcinoma with lung metastases in three. The mean induction time was 78 weeks. Ureteral carcinoma and urinary bladder carcinoma were observed in 2 and 6 of 53 rats given PH, respectively. No urinary tract carcinoma was found in control animals. In Experiment 2, early lesions of the kidney affected by PH were also evaluated with the use of SD/cShi and Sprague-Dawley (SD) rats. Two groups of animals containing 6 SD/cShi or 6 SD male rats per group were fed 2% PH-containing diet for 8 weeks. Control animals containing 6 SD/cShi rats or 6 SD rats were fed basal diet for 8 weeks. Simple hyperplasia was found in 5 of 6 SD/cShi rats given PH and 2 of 6 SD/cShi control rats. Papillary necrosis was seen in 4 of 6 SD/cShi and 2 of 6 SD rats given PH. SD/cShi rats, especially those treated with PH, showed higher but not significant 5-bromo-2'-deoxyuridine labeling indices in the covering epithelium of the renal pelvis and papillae. In this short term experiment PH and its metabolites, N-hydroxyphenacetin and N-acetyl-p-aminophenol, were measured in urine and plasma by using high performance liquid chromatography. Significantly higher PH and slightly higher metabolites were detected in urine and plasma of SD/cShi rats compared to SD rats. These results indicated that the renal pelvis of SD/cShi rats had more sensitivity to PH carcinogenicity. This paper provides experimental proof of PH carcinogenicity toward the renal pelvis in an animal model.

Animals↗
PubMed1993

CD4+/CD8- thymocytes dominate the fetal thymus treated with a combination of anti-T cell receptor-beta and anti-CD4 antibodies.

Two major phenotypic changes characterize the development of a mature thymocyte from its CD4+/CD8+ (double positive or DP) precursor: the loss of expression of either CD4 or CD8 and the increase in the level of surface TCR. The specific surface interactions responsible for these changes are unknown, but studies using the fetal thymus as an experimental system have provided clues by identifying conditions that alter these maturational events. Development to the CD4+/CD8-/TCR-alpha beta high (single positive) phenotype is inhibited when thymocytes in fetal organ culture are exposed to antibodies directed against the CD4 molecule, the CD3 complex or the TCR-alpha/beta heterodimer. We show in this study, however, that treatment of fetal thymic lobes with a combination of anti-CD4 and anti-TCR-beta antibodies results in a marked increase in the proportion of mature CD4+/CD8-/TCR-alpha beta+ thymocytes and a decrease in the proportion of DP thymocytes. Although treatment of lobes with a combination of anti-CD4 and anti-CD3 epsilon antibodies also depletes cultures of DP thymocytes, the CD4+/CD8-/TCR+ population does not develop. Our results are consistent with the hypothesis that coengagement of CD4 and TCR biases development to the CD4 single positive phenotype and with observations that TCR engagement and CD3 engagement have different developmental consequences.

Animals↗
PubMed1993

Agglutinins from aquatic insects--tumor cell agglutination activity.

Agglutinins were identified in whole body extracts of aquatic insects by means of murine tumor cell agglutination, using sarcoma 180 ascites, Ehrlich, and MM-46 cells. Screening revealed agglutinins in 5 of 10 of the larvae tested, and in 2 of 6 of the water-dwelling adult insects; Gerris paludum insularis and Gyrinus japonicus. Only the agglutinin from adult G. paludum also agglutinated human erythrocytes. An ascites tumor was converted into a solid form in vivo after administration of G. paludum agglutinin. The observation that these aquatic insect agglutinins preferentially agglutinate tumor cells has considerable implications in terms of anti-tumor effects such as inhibition of cell proliferation and metastasis.

Agglutination↗
PubMed1993

Effects of intrathymic injection of organ-specific autoantigens, parietal cells, at the neonatal stage on autoreactive effector and suppressor T cell precursors.

Thymectomy on day 3 after birth (3d-Tx) induces autoimmune gastritis (AIG) in 81%, and oophoritis (AIO) in 25% of BALB/c mice at the age of 2 to 3 months. Intrathymic, but not intraperitoneal injection of syngeneic parietal cells into sex-matched BALB/c mice within 24 h of birth resulted in almost complete prevention of the development of AIG in these mice in which 3d-Tx was performed. The prevention induced was parietal cell specific, since the development of AIO was not inhibited in female mice. Moreover, the injection of BALB/c liver cells, Mls-matched (BALB/c) and -disparate (DBA/2) B blasts which resulted in V beta 6 T cell deletion, as well as the injection of staphylococcal enterotoxin B failed to prevent the diseases. These findings suggested that recognition of an autoantigen in the thymus is necessary for the induction of tolerance, and that involvement of Mls-1 antigens in the pathogenesis of AIG, as has been suggested previously (Schwartz, R. H., Cell 1989. 57: 1073), was unlikely. T cells that suppress the development of organ-specific autoimmune diseases in 3d-Tx mice seem to maintain the unresponsiveness of autoreactive T cells at the periphery in normal mice. In agreement with our previous observations, we found that intraperitoneal (i.p.) injection of spleen cells from 3-month-old normal mice into 3d-Tx mice on day 10 after birth prevented the development of AIG, whereas spleen cells from age-matched AIG+ (mice with AIG) or AIG- (mice without AIG) 3d-Tx mice failed to do this. This implies that the suppressor cells probably affect the differentiation of effector-precursor to effector. In fact, these suppressor cells did not inhibit the adoptive transfer of AIG to nu/nu BALB/c mice by spleen cells from 3d-Tx mice manifesting AIG. By negative selection using monoclonal antibody and complement, it was confirmed that the phenotype of the suppressor cell was CD4. In contrast to 3d-Tx, 10d-Tx did not induce AIG, indicating the peripheralization of the suppressor cell by that time. On the other hand, intrathymic injection of parietal cells immediately after birth did not affect suppressor cell generation, implying that some T cells, including suppressor cells, escape thymus selection. We postulate that these cells correspond to the precursors of the autoreactive effector T cells and suppressor T cells that are present in normal mice.

Animals↗
PubMed1993

Scintigraphic detection of xenografted tumors producing human basic fibroblast growth factor.

A murine monoclonal antibody 3H3 recognizes the basic fibroblast growth factor (FGF) and inhibits the growth of human glioblastoma cells both in vitro and in vivo. We studied the potential of a scintigraphic technique using the 3H3 antibody to detect tumors that produce basic FGF. 125I- and 111In-labeled 3H3 bound to U87MG human glioblastoma cells in vitro. U87MG cells were inoculated subcutaneously into nude mice. After development of the tumor, radiolabeled 3H3 was injected into the subcutaneous space surrounding the tumor. A high level of radioactivity from 3H3 was retained at the tumor, whereas an irrelevant antibody cleared rapidly from the injected site. Radiolabeled 3H3 was not retained in tumors that did not produce basic FGF. Scintigraphic detection of tumors expressing basic FGF would be valuable for the therapeutic application of the antibody.

Animals↗
PubMed1993

A human/mouse chimeric monoclonal antibody against CA125 for radioimmunoimaging of ovarian cancer.

Murine monoclonal antibody 196-14 recognizes the ovarian-cancer-associated antigen CA125, but the epitope it recognizes is different from that of monoclonal antibody OC125. We developed a human/mouse chimeric 196-14 using the variable regions of the murine 196-14 and human heavy-chain (gamma 1) and light-chain (kappa) constant regions. Cell binding and competitive inhibition assays using chimeric 196-14 labeled with 125I, 111In or 99mTc demonstrated that the in vitro immunoreactivity of the chimeric antibody was identical to that of the parental murine monoclonal antibody. However, in mice bearing human ovarian cancer xenografts, the clearance from blood was faster and absolute levels of accumulation in the tumor were lower for the 125I-labeled or 99mTc-labeled chimeric antibody than for the murine antibody labeled with the corresponding radionuclides. The tumor-to-blood radioactivity ratio was not significantly different between the chimeric antibody and the murine antibody, regardless of the radionuclide used for labeling. Chimeric antibody 196-14 labeled with 131I, 111In or 99mTc is promising for the radioimmunoimaging of ovarian cancer.

Adenocarcinoma↗
PubMed1993

Changes in CA125 release and surface expression caused by drugs in uterine cervix adenocarcinoma cells.

The effect of drugs on the release of CA125 antigen and the binding of anti-CA125 monoclonal antibody (MoAb) to malignant cells was evaluated in vitro. TMCC-1, uterine cervical adenocarcinoma cells, were exposed to dexamethasone (DEX), sodium n-butyrate (NaB), dibutyryl cyclic AMP (dbcAMP), retinoic acid (RA), calcitriol (VD3), and interferon-gamma (IFN-gamma). NaB, RA and VD3 increased CA125 release per cell and 125I-labeled anti-CA125 MoAb binding to the cells. DEX also increased the 125I-labeled anti-CA125 MoAb binding to the cells, and CA125 antigen release per cell was also slightly increased. IFN-gamma suppressed both CA125 release and 125I-labeled MoAb binding. A combination of DEX, VD3 and RA and increased the binding of MoAb to TMCC-1 cells, but the amount of bound MoAb was not significantly different from that obtained by single drug treatment. DbcAMP had no significant effect on enhancing MoAb binding. Drugs can increase the binding of anti-CA125 MoAb to malignant cells and they may be applied to increase the tumor uptake of radiolabeled MoAbs in vivo.

Adenocarcinoma↗