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Biomedical subjects

T Kotani

Publications and source records attributed to T Kotani.

At least 145 records · Page 8Linked to original sources
PubMed1993

[Clinical application of recombinant thyroid peroxidase].

TPO is a major antigen corresponding to thyroid-microsomal autoantibodies. Anti-TPO autoantibodies are very important to diagnose autoimmune thyroid disease and to estimate its clinical course. An EIA for measuring anti-TPO autoantibodies (rhTPO-EIA) was developed using recombinant human TPO expressed in CHO cells and was compared with MCHA generally used in routine laboratory work. Sera from patients with various disorders were measured for their anti-TPO autoantibodies. Chronic thyroiditis and Graves' disease were highly positive, while thyroid cancer, adenoma, SLE, and RA were low in their positivity. The positive rate of anti-TPO autoantibodies were compatible with those of previous reports of each disorder. In the comparison between rhTPO-EIA and MCHA, the correlation coefficient was 0.486. Following absorption with thyroglobulin, sera were measured again and as a result, the correlation coefficient increased to 0.723. Therefore, MCHA was thought to be influenced in the presence of anti-thyroglobulin autoantibodies. The characteristics of TPO antigen and anti-TPO autoantibodies were also summarized.

Autoantibodies↗
PubMed1993

Nucleotide sequence of the cDNA encoding mouse thyroid peroxidase.

The nucleotide (nt) sequence of the cDNA encoding mouse thyroid peroxidase (TPO) has been determined. The TPO cDNA is 3281 nt long and its open reading frame encodes a protein composed of 914 amino acids (aa), including a putative initiation Met. The mouse TPO cDNA shows 75.3, 70.8, and 93.5% homology in the coding nt sequence with human, porcine, and rat TPO cDNAs, respectively. In the aa sequence, mouse TPO shows 73.4, 68.4, and 93.9% homology with human, porcine, and rat TPOs, respectively. Specifically, the aa sequence surrounding the proximal His residue, probably essential for TPO activity, is well conserved among these four organisms.

Amino Acid Sequence↗
PubMed1993

Increased tumor localization by monoclonal antibody A7 after F(ab')2 fragmentation in athymic nude mice bearing human pancreatic carcinomas.

Much recent research has been directed toward the use of monoclonal antibodies (MoAbs) for the immunodetection of solid tumors. In pancreatic cancer, conventional immunoscintigraphy using intact MoAbs remains disappointing. In this study, 125I-labeled F(ab')2 fragments produced by pepsin digestion of MoAb A7 were injected intravenously into nude mice bearing human pancreatic cancer, HPC-YS, xenografts that have previously been shown to react specifically with MoAb A7. The tumor tissue/blood ratio of 125I-labeled F(ab')2 fragments of MoAb A7 increased with time and was much higher than those for normal tissues. Moreover, the tumor tissue/blood ratio of 125I-labeled F(ab')2 fragments was greater than that of intact MoAb A7, although the F(ab')2 accumulation was less than that of intact MoAb A7 in the tumor. These results suggest that F(ab')2 fragments of MoAb A7 may be suitable carriers of radionuclides for immunodetection of human pancreatic cancer.

Animals↗
PubMed1993

Cranial fasciitis of childhood: a case report.

We present a case with cranial fasciitis in childhood and review the literature. A 7-year-old boy presented with hard mass on the scalp. He had sustained a bruise on the right temporal region about 2 years previously. Ultrasonic examination and CT scanning revealed the ossifying soft tissue mass in the right temporal scalp causing erosion and scalloping of the outer table of the skull. At surgery the lesion was firmly attached to the periosteum and the skull. The lesion was completely excised and the lytic bone curettaged. The tumor was composed of immature fibroblasts and diagnosed as cranial fasciitis in childhood. A brief review of the literature is included emphasizing the need to investigate further this completely benign lesion that is frequently confused with a malignant neoplasm.

Calcinosis↗
PubMed1993

Enhanced tumor localization of radiolabeled Fab fragments of monoclonal antibody A7 in nude mice bearing human pancreatic carcinoma xenografts.

Much recent research has been directed toward the use of monoclonal antibodies (MAb) for the immunodetection of solid tumors. In pancreatic cancer, the results of conventional immunoscintigraphy using intact MAb remain disappointing. Clear immunoscintigraphy with radiolabeled MAb requires a high tumor tissue/blood ratio of radioactivity and a low normal tissue/blood ratio of radioactivity. In this study, 125I-labeled Fab fragments produced by papain digestion of MAb A7 were injected intravenously into nude mice bearing a human pancreatic cancer (HPC-YS) xenograft previously shown to react specifically with MAb A7. The radioactivity of tumors and normal organs was subsequently measured. The tumor tissue/blood ratio of 125I-labeled Fab fragments of MAb A7 was 1.00 +/- 0.24 and 9.68 +/- 2.54 at 2 and 24 h after injection, respectively. The tumor tissue/blood ratio of radioactivity was significantly higher than those of normal organs at 24 h after injection. Moreover, the tumor tissue/blood ratio of 125I-labeled Fab fragments of MAb A7 was greater than that of intact MAb A7, although the 125I-labeled Fab accumulation level was much less than that of 125I-labeled intact MAb A7 in the tumor. When mice bearing tumors which did not react with MAb A7 were studied, 125I-labeled Fab fragments did not specifically localize to the tumors. These results suggest that Fab fragments of MAb A7 may be suitable carriers of radionuclides for the immunodetection of human pancreatic cancer.

Animals↗
PubMed1993

Production, binding and cytotoxicity of human/mouse chimeric monoclonal antibody-neocarzinostatin conjugate.

A human/mouse chimeric Fab monoclonal antibody A7 (chFabA7) was covalently coupled to neocarzinostatin (NCS) by the SPDP method at various chFabA7:NCS substitution ratios. The antigen-binding activity of the conjugate, examined by ELISA using fixed antigen-positive colon cancer cells, was identical to that of the parent chFabA7 when one mole of NCS was conjugated, but was reduced with 2 or 3 moles of conjugated NCS. By means of a colony-forming assay, the cytocidal effect of the conjugate on antigen-positive cancer cells was found to be stronger than that of free NCS, whereas in antigen-negative cancer cells it was similar to that of free NCS. This effect was attenuated by adding an excess amount of monoclonal antibody A7. These findings indicate that the conjugate has an antigen-specific cytocidal action, and thus chFabA7-NCS is a promising tool for targeting cancer chemotherapy.

Animals↗
PubMed1993

Expression of dipeptidyl aminopeptidase IV activity in human lung carcinoma.

Dipeptidyl aminopeptidase IV (DAP IV) staining was examined in various histological types of lung carcinomas to evaluate this enzyme activity. A total of 45 lung carcinomas were examined for their enzyme activity. Almost all (93.1%) cases of adenocarcinoma were positive for DAP IV activity, whereas all cases of squamous cell carcinoma, small cell carcinoma, large cell carcinoma and carcinoid were negative. DAP IV activity of microsomes in lung carcinomas was significantly higher in papillary adenocarcinomas than in squamous cell carcinomas. These data suggest that DAP IV may be a good marker to distinguish adenocarcinoma from other histological types of lung carcinoma.

Adenocarcinoma↗
PubMed1993

Magnetic resonance imaging in a dog with choroid plexus carcinoma.

Choroid plexus carcinoma was diagnosed in a 10-year-old maltese dog with chief complaint of progressive ataxia and head tilt. No abnormalities was observed on hemogram, radiographs of the skull, and electroencepharograph (EEG). Neurological examination suggested central vestibular lesions. On the magnetic resonance imaging (MRI) examination, images after contrast enhancement with Gadolinium DTPA-dimeglumine showed a rough circular lesion with an increased signal intensity in caudal fossa. This lesion was histopathologically confirmed to be choroid plexus carcinoma.

Animals↗
PubMed1993

Immunohistochemical observations of macrophages and perisinusoidal cells in carbon tetrachloride-induced rat liver injury.

In rat liver injured by carbon tetrachloride, ED-1-positive monocytes and resident macrophages significantly increased in number in damaged perivenular zones on days 2 and 4 after single or double dosing, peaking on day 2 and being two-fold more after the 2nd dosing. ED-2-positive resident macrophages significantly increased in number only on day 4 after the single dosing and on days 2, 4 and 6 after the 2nd dosing with a peak on day 2. A significant increase in number of muscle actin-positive perisinusoidal cells was seen on day 4 and on days 2 and 4 after the 1st and 2nd dosings, respectively, reaching a peak on day 4 and being more remarkable after the 2nd dosing.

Actins↗
PubMed1993

Immune recognition of hormonogenic sites of human thyroglobulin: studies of Graves' sera and a murine monoclonal antibody with thyroid hormone antibody activity.

We synthesized four peptides (HTg-1, 1-10; HTg-2, 2547-2558; HTg-4, 2592-2603 and HTg-6, 2737-2748) and two peptides (HTg-3, 2582-2591 and HTg-5, 2687-2694) with or without hormonogenic acceptor tyrosine of human thyroglobulin (hTg). They were iodinated with 127I or 125I. 127I-labeled peptides were tested for their ability to displace 125I-T4 binding to thyroid hormone autoantibodies (THAA) in two cases of Graves' disease and to a murine anti-hTg monoclonal antibody with anti-T4 activity (mAb). 125I-labeled peptides were tested for the direct binding to the aforementioned antibodies. None of the peptides displaced 125I-T4 binding to THAA or to a mAb, or exhibited increased binding to THAA and to a mAb. 125I-T4 binding to a mAb was equally displaced by hTgs obtained from a normal thyroid gland (NTg) and a case of Hürthle cell adenoma with undetectable iodine content (CTg). 125I-T4 binding to serum gamma globulin in each patient's serum was completely displaced by NTg, but CTg displaced 125I-T4 binding 2% and 5% in Case 1 and Case 2, respectively. It was speculated that the mAb recognizes a topological epitope around the hormonogenic site of hTg, while that of THAA in our two cases recognizes only T4 or an iodine dependent topological epitope(s) of hTg.

Animals↗
PubMed1993

Enhanced lymphatic delivery of monoclonal antibody following OK432 pretreatment.

The effect of OK432 on the lymphatic delivery of monoclonal antibody (Mab) was investigated by injecting [125I]-Mab A7 into BALB/c mice pre-treated with OK432, and measuring the radioactivity in the regional lymph nodes. The [125I]-Mab A7, when administered subcutaneously to the foot pad, preferentially accumulated in the ipsilateral popliteal and para-aortic lymph nodes. Treatment with OK432 prior to antibody injection significantly enhanced the accumulation of Mab A7 in these regional lymph nodes. These findings suggest that pretreatment with OK432 may constitute a promising method of enhancing the lymphatic delivery of Mab, and improving the efficacy of therapy directed against lymphatic malignancies.

Animals↗
PubMed1993

[A new application of immunoconjugate to reduce the local recurrence of colorectal cancer].

To examine whether or not immunoconjugate-A7-NCS can contribute for the reduction of local recurrence of colorectal cancer, the present study was undertaken. The study included examination of local retension, lymphatic delivery and inhibitory effect on tumor development after local administration of A7-NCS. The result showed that locally injected A7-NCS showed a high local retension, a high regional lymph node accumulation and a high inhibitory effect on tumor development. This finding indicates that A7-NCS can be a new promising tool for reducing the local recurrence of colorectal cancer.

Animals↗
PubMed1993

[Effect of succinylcholine on serum potassium concentration in children with chronic renal failure].

Serum potassium (K+) levels were measured after intravenous injection of succinylcholine (SCh) in 10 children with chronic renal failure, 10 normal children aged 1 to 10 years and 10 children with chronic renal failure after pretreatment with pancuronium prior to SCh. Arterial blood gas was maintained within normal ranges. The serum K+ level increased significantly during 10 minutes after SCh in normal children. There was no significant difference between serum K+ levels in normal children and those in children with chronic renal failure. Administration of pancuronium in small doses (20 micrograms.kg-1) prior to SCh (1 mg.kg-1) was not effective to prevent serum K+ elevation completely. Our results indicate that the administration of SCh in children with chronic renal failure might be possible without increasing serum potassium level.

Child↗
PubMed1992

Local administration of monoclonal antibody-drug conjugate: a new strategy to reduce the local recurrence of colorectal cancer.

This report investigates the application of monoclonal antibody A7 and its drug conjugate in locally controlling colorectal cancer. The experimental protocol consisted of local retention, lymphatic delivery, normal organ distribution, systemic toxicity, and tumoricidal effects. When 125I-labeled monoclonal antibody (Mab) A7 was injected into the pelvis and the thigh of Balb/c mice, a high local retention unrelated to antigen-antibody interaction was observed at the injected site for 24 h after injection. An analysis of local retension properties related to antigen-antibody interaction, conducted by intratumorally or peritumorally injecting 125I-Mab A7 into the tumor-bearing athymic nude mice, revealed a significantly higher tumor localization of Mab A7 in comparison to i.v. injection. 125I-Mab A7 accumulated to a great extent in the ipsilateral regional lymph node but not in the contralateral regional lymph node. Normal organ accumulation of Mab A7 was lower in the locally injected group than in the i.v. injected group. Intratumoral injection of Mab A7-neocarzinostatin (A7-NCS) led to the complete remission of established tumor in 5 of 6 antigen-positive xenograft-bearing mice but exhibited a complete remission in only 1 of 6 antigen-negative xenograft-bearing mice. A single local injection of A7-NCS inhibited tumor development in 12 of 16 and 5 of 15 antigen-positive tumor-bearing mice and antigen-negative tumor-bearing mice, respectively, whereas neither a systemic injection of A7-NCS and NCS nor a local injection of NCS and saline had a notable inhibitory effect on tumor development. Systemic toxicity of NCS was markedly reduced when it was locally administered in the antibody-conjugated form. These findings indicate that local injection of immunoconjugate is a promising new field for controlling the local recurrence of colorectal cancer.

Animals↗
PubMed1992

Identification of thyroiditogenic epitope on porcine thyroid peroxidase for C57BL/6 mice.

C57BL/6 mice show thyroid lesions when immunized with porcine thyroid peroxidase (pTPO) emulsified in CFA. We attempted to clarify a thyroiditogenic epitope on pTPO. Thyroid peroxidase treated with cyanogen bromide was fractionated by reverse phase chromatography, and six fractions (A to F) were obtained. Two of these fractions (D and E) stimulated lymph node cells (LNC) primed with pTPO in vitro and induced thyroiditis in vivo. Tricine-SDS-PAGE and rechromatography showed that fraction D consisted solely of a fragment of Mr 9500 Da and that fraction E contained mainly fragments of Mr of 5400 and 9500 Da. The fragment of fraction D was rechromatographed and 20 NH2-terminal amino acids were analyzed. This segment was found to correspond to residue 726-745 of pTPO deduced from cDNA at a probability of 80%. Four peptides ranging from residue 746-827 were first synthesized and tested for their thyroiditogenicity. Only Pep-2 (29 amino acids) could stimulate LNC primed with pTPO and induce thyroiditis. Pep-2 was divided into two smaller peptides (Pep-2-1 and -2-2) and their thyroiditogenicity was tested again. Pep-2-1 corresponding to residue 774-788, GPA-QITCTPRGWDSP, had thyroiditogenicity as well as the ability to stimulate LNC. It was thought that this segment was at least one of the thyroiditogenic epitopes on porcine thyroid peroxidase for C57BL/6 mice.

Amino Acid Sequence↗