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Biomedical subjects

K Endo

Publications and source records attributed to K Endo.

At least 703 records · Page 39Linked to original sources
PubMed1988

Role of cyclic AMP during histamine release. Histamine release is not directly related to increase in cyclic AMP levels in rat mast cells activated by concanavalin A, anti-IgE, antigen, prostaglandin D2 and isoproterenol.

Activation of mast cells by bridging of IgE-receptors or concanavalin A (Con A) results in a rapid initial rise and fall in cyclic AMP (cAMP) levels followed by a second rise in cAMP levels and histamine release (Sullivan, T. et al. (1976) J. Immunol. 117, 713-716; Lewis, R.A. et al. (1979) J. Immunol. 123, 1663-1668; Ishizaka, T. et al. (1981) Proc. Natl. Acad. Sci. U.S.A. 78, 6812-6816). trans-4-Guanidinomethylcyclohexanecarboxylic acid 4-tert-butylphenyl ester (GMCHA-OPhBut), a strong trypsin inhibitor and an anti-allergic agent (Muramatu, M. et al. (1982) Hoppe-Seyler's Z. Physiol. Chem. 363, 203-211; Takei, M. et al. Agents Actions, in press), strongly and dose-dependently inhibited the initial and second rises in cAMP levels, and release of histamine from rat mast cells by Con A, anti-IgE and antigen. Addition of GMCHA-OPhBut after the initial rise in cAMP inhibited the second rise in cAMP and histamine release. These results suggested a possible participation of a trypsin-like proteinase, probably pH 7 tryptase present in rat mast cells, in the activation of adenylate cyclase by the above secretagogues, and the initial rise in cAMP was not directly related to the latter events. The second rise in cAMP is induced by prostaglandin D2 (PGD2), a metabolic product of arachidonic acid. PGD2 elevated the cAMP levels in mast cells whereas no histamine was secreted. GMCHA-OPhBut did not inhibit the increase in cAMP by PGD2. Therefore, the strong inhibitory effect of GMCHA-OPhBut on the second rise in cAMP might depend on the inhibition of an earlier process than the activation of adenylate cyclase by PGD2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Evaluation of TSH-receptor antibodies as prognostic markers after cessation of antithyroid drug treatment in patients with Graves' disease.

Clinical usefulness of thyroid-stimulating antibodies (TSab) and TSH-binding inhibitor immunoglobulins (TBII) for predicting the prognosis in patients with Graves' disease after cessation of antithyroid drug treatment was evaluated, and compared with that of T3 suppression test and goitre size. Among 46 patients who had been euthyroid on a maintenance dose of antithyroid drugs for at least one year and had discontinued taking medicine, 16 relapsed within one year (group 1), 7 relapsed later than 1 year (group 2), and 23 patients remained in remission for more than 1 year (group 3). Incidence of TSab, TBII, T3 nonsuppressibility and large goitre (transverse diameter longer than means of the values for the 46 patients: greater than or equal to 4.36 cm in females; greater than or equal to 4.74 cm in males) determined at the time of discontinuation of treatment was 87.5% (14/16), 56.3% (9/16), 78.6% (11/14) and 81.3% (13/16) in group 1; 66.7% (4/6), 28.6% (2/7), 50.0% (3/6), and 57.1% (4/7) in group 2, and 56.5% (13/23), 24.1% (5/23), 35.7% (8/23), and 26.1% (6/23) in group 3, respectively. All relapsed patients showed remarkable increases in both TSab and TBII activities at the time of relapse. High incidence of TSab in patients remaining in remission suggests that a reduced functional reserve of the thyroid, probably owing to destructive changes and/or shrinkage of the gland, may cause impaired responses to TSab and is involved in the cause of remission. Development of blocking type of TBII was not considered to be a cause of remission. Remission was predictable in all patients with any two of the indices such as negative TSab, positive T3 suppressibility, and small goitre.

Adolescent↗
PubMed1988

A case report of a "necrotizing" entero-colo-proctitis in the adult.

We experienced a patient who died of diarrhea after an operation for glioblastoma. The mucosa of the small and large intestines were entirely denudated. Although the etiology is not clear, this case is supposed to be a very rare one of "necrotizing" enterocolitis in the adult occurring after an operation on a brain tumor.

Adult↗
PubMed1988

Clinical evaluation of tumour imaging using 99Tc(V)m dimercaptosuccinic acid, a new tumour-seeking agent.

Considering the favourable nuclear properties of 99Tcm over 67Ga, we have developed a new tumour-seeking agent, 99Tc(V)m dimercaptosuccinic acid (Tc(V)-DMSA). In order to evaluate the clinical usefulness of Tc(V)-DMSA scintigraphies, 492 patients were studied with Tc(V)-DMSA, and in some cases, where possible, the results were compared with conventional 67Ga citrate scintigraphies. There was a high degree of usefulness of Tc(V)-DMSA in patients with head and neck tumours, medullary thyroid carcinomas and soft tissue tumours. But in patients with carcinomas of the lung, liver and gastrointestinal tract, malignant melanoma and lymphoma, Tc(V)-DMSA was of no or little use.

Drug Evaluation↗
PubMed1988

Sipple's syndrome with liver tumors examined by iodine-131 MIBG and technetium-99m(V)-DMSA.

This case report describes the localization and categorization of tumors using 99mTc(V)-dimercaptosuccinic acid and [131I]metaiodobenzylguanidine scans in a very uncommon case of medullary thyroid carcinoma associated with pheochromocytoma (Sipple's syndrome) and hepatocellular carcinoma. Technetium-99m(V)-dimercaptosuccinic acid showed accumulation only in medullary thyroid carcinoma, but [131I]metaiodobenzylguanidine scans were positive in both medullary thyroid carcinoma and pheochromocytoma. In advanced Sipple's syndrome, combined use of [99mTc(V)]dimercaptosuccinic acid and [131I]metaiodobenzylguanidine may be useful for the categorization of tumor mass lesions and planning appropriate therapy.

3-Iodobenzylguanidine↗
PubMed1988

Semiquantitative in vitro binding assay of indium-111-labeled monoclonal antibodies to human cancer and normal tissues.

We have developed a simple in vitro method for the semiquantitative assessment of the radiolabeled antibody binding to cancer and normal tissues. Indium-111-labeled F(ab')2 fragments of 17-1A and 19-9 monoclonal antibodies with well-characterized specificity for gastrointestinal cancer demonstrated similar binding properties between cultured cancer cells and membrane fractions of homogenates prepared from tumor tissues. All of the 17 colon cancer specimens and seven (64%) of 11 gastric cancer specimens obtained by surgery showed positive binding with 17-1A. Specific binding of 19-9 was observed in 9 (53%) colon cancers and 4 (36%) gastric cancers. However, some normal colon tissues were also positive with 111In-labeled 17-1A. Relative levels of CA 19-9 antigen expression, determined by the binding with radiolabeled antibodies, correlated with percent positive cells determined by the immunohistochemical assays. Furthermore, membrane fractions could be cryopreserved without losing antibody-binding activity. These results indicate that this assay can be used for testing the immunoreactivity of radiolabeled anti-tumor antibodies and in vitro binding properties to cancer and normal tissues.

Antibodies, Monoclonal↗
PubMed1988

Relationship between in vitro binding activity and in vivo tumor accumulation of radiolabeled monoclonal antibodies.

The relationship between in vitro cell binding and in vivo tumor accumulation of radiolabeled antibodies was studied using 125I- and 111In-labeled monoclonal antibodies to human osteosarcoma, and a human osteosarcoma xenograft (KT005) in nude mice. Three monoclonal antibodies--OST6, OST7, and OST15--raised against human osteosarcoma recognize the same antigen molecule. Although the binding of both 125I- and 111In-labeled OST6 to KT005 cells was higher than that of radiolabeled OST7 in vitro, 125I-labeled OST6 showed a faster clearance from the circulation and a lower accumulation in the transplanted tumor than 125I-labeled OST7. In contrast to the radioiodinated antibodies, the in vivo tumor accumulation of 111In-labeled OST6 was higher, although not significantly, than that of 111In-labeled OST7. OST15 showed the lowest binding in vitro, and its in vivo tumor localization was also lower than the others. The discrepancy in tumor uptake between OST6 and OST7 labeled with either 125I or 111In may have been a result of differing blood clearance. These results suggest that binding studies can be used to exclude from in vivo use those antibodies which show very poor binding in vitro, while in vivo serum clearance may be a better test for choosing antibodies with similar binding.

Animals↗
PubMed1988

[A case of metastasis of gastric cancer to spermatic cord].

A 63-year-old man underwent total gastrectomy and partial resection of the transverse colon for Borrman IV gastric cancer on August 27, 1985. On August 8, 1986, 11 months after the operation, he visited our department with chief complaint of swelling of both groins. The spermatic cord was swollen to about 3 cm in diameter from both groins to inside of the scrotum and was hard as a club. The diagnosis of bilateral spermatic cord metastasis of gastric cancer was established and a biopsy was carried out. Histopathologically the diagnosis of spermatic cord metastasis of gastric cancer was confirmed.

Genital Neoplasms, Male↗
PubMed1987

Recognition of ovarian cancer antigen CA125 by murine monoclonal antibody produced by immunization of lung cancer cells.

In studies aimed at developing monoclonal antibodies against lung adenocarcinomas, we produced a murine monoclonal antibody designated 130-22 by immunizing mice with lung cancer cells. Since in immunoperoxidase staining experiments this antibody was reactive not only with lung adenocarcinomas but also with ovarian carcinomas, we examined its relationship to the ovarian cancer marker CA125, an antigen recognized by monoclonal antibody OC125 produced by immunization of mice with ovarian carcinoma cells. Although CA125 antigen was adsorbed by 130-22 antibody, 125I-labeled 130-22 did not compete with OC125, indicating that although these two antibodies recognized CA125 antigen, they reacted with separate antigenic determinants. The antigen defined by both antibodies was thought to be heat-labile glycoprotein with a molecular weight of over 1,000,000. A series of immunoradiometric assays was developed using combinations of two monoclonal antibodies in a simultaneous forward sandwich mode. Mixed monoclonal antibodies may provide a more sensitive assay for the detection of CA125 than the homologous assay, in which OC125 was used both as a tracer and as a catcher. These results indicate that CA125 is an antigen with two separate epitopes present in both ovarian and lung adenocarcinomas and that combination use of monoclonal antibodies reactive with different antigenic determinants will give certain advantages to the immunoradiometric assay of cancer markers.

Adenocarcinoma↗
PubMed1987

Preparation of 67Ga-labeled antibodies using deferoxamine as a bifunctional chelate. An improved method.

Radionuclides or anti-cancer drugs may be coupled to antibodies for specific transport to target tissues. We have previously reported that several proteins could be rapidly and efficiently labeled with gallium (67Ga) by using deferoxamine (DFO) as a bifunctional chelating agent. In the present paper, we have described the use of hetero-bifunctional agents for the conjugation of DFO with antibodies and investigated the effect of coupling agents on in vitro properties and biodistribution of 67Ga-labeled antibodies. 67Ga-labeled monoclonal antibodies retained antigen-binding activity when prepared under optimum conditions. The use of hetero-bifunctional reagents, such as succinimidyl 6-maleimido-hexanoate (EMCS) or N-succinimidyl-3-(2-pyridyldithio)-propionate (SPDP), which link thioether bonds and disulfide bridges prevented the formation of polymerized antibodies. Although high non-specific uptake in the liver was observed with radiolabels prepared by the homo-bifunctional agent glutaraldehyde, uptake in the liver was low with conjugates linked by hetero-bifunctional agents. 67Ga-labeled antibodies with thioether bonds showed in vivo stability, but the clearance from the circulation was the fastest with the radiolabel holding disulfide bonds. The coupling reagents used to link DFO and antibodies greatly influenced both in vitro properties and in vivo distribution of labeled antibodies and 67Ga-labeled antibodies provide a good model for the study of coupling methods and biodistribution of antibody conjugates.

Animals↗
PubMed1987

Disposition characteristics of mitomycin C-dextran conjugate in normal and tumor-bearing muscles of rabbits.

Disposition characteristics of the macromolecular prodrug of mitomycin C (MMC), mitomycin C-dextran conjugate (MMC-D), in normal and tumor (VX2 carcinoma)-bearing rabbit thigh muscles were studied using the in situ vascular perfusion technique. Three types of cationic MMC-D (MMC-Dcat) and two types of anionic MMC-D (MMC-Dan) with different carrier molecular weights were used. After bolus arterial injection in normal muscles, 83-96% of injected MMC-D was recovered in the venous outflow regardless of the carrier size or charge, whereas less than 60% of MMC was recovered in the same system. By applying statistical moment analysis to the outflow pattern of these drugs, pharmacokinetic parameters representing their disposition characteristics were obtained. Smaller intrinsic clearance (CLint) and distribution volume (V) were noted for MMC-D than for MMC, indicating low extravascular diffusion of MMC-D. In the tumor-bearing muscle, blood contamination from other parts of the body increased and a shortage of flow recovery due to the neovascularization of the tumors occurred. The disposition parameters of MMC-Dcat with a molecular weight of 500,000 (T-500) indicated some tissue distribution and sequestration in the tumor preparation. After constant infusion of [14C]MMC-D (T-500) for 4 h, tissue radioactivity concentrations were determined in various tissues. A higher radioactivity was observed in the viable region of the tumor and the lymph node compared with the normal muscle tissue and the necrotic region of the tumors. 131I-Labeled human serum albumin also gave similar results. In conclusion, higher tumor localization of antitumor agents may be made possible by the application of macromolecular prodrugs.

Animals↗
PubMed1987

Radiolocalization of xenografted human lung cancer with monoclonal antibody 8 in nude mice.

A monoclonal antibody (MAb) 8 [immunoglobulin G3 (IgG3)], directed against a Mr 48,000 human lung cancer-associated antigen, was radiolabeled with either 125I or 131I, and its biodistribution was studied in nude mice bearing human lung cancer (TKB-2) over a 7-day period. 125I-labeled MAb 8 increased its binding to the tumor during the period, while the binding of 125I-labeled control IgG3 declined after initial uptake. At Day 7, percentages of injected dose of 125I-labeled MAb 8 bound to the tumor rose to 7.4%, which was a 4.4-fold increase from Day 1 and 16-fold binding of 125I-labeled control IgG3 at the same day. Tumor:blood ratios became 2.7:1 at Day 7, and tumor:liver, tumor:spleen, and tumor:kidney ratios were more than 9:1. Normal organs showed no significant uptake of 125I-labeled MAb 8, compared with those of 125I-labeled control IgG3. A clear image of the xenografted tumor was obtained at Day 5, and it further improved at Day 7, when 60% of whole body radioactivity was localized to the tumor. Autoradiography of the mouse with tumor confirmed the excellent localization of 125I-labeled MAb 8 to the tumor, although the radioactivity of the tumor was not uniformly distributed. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis showed that most of the radioactivity was present at the tumor in the form of degraded immunoglobulin. MAb 8 has a potential usefulness in the diagnosis and treatment of lung cancer.

Animals↗