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Biomedical subjects

T Mimura

Publications and source records attributed to T Mimura.

At least 19 recordsLinked to original sources

Proliferative activity in thyroid tumors.

To clarify the proliferative activity of papillary thyroid carcinoma, the bromodeoxyuridine (BrdU) labeling index (LI) of 61 various thyroid tumors was investigated using an in vitro labeling technique and immunohistochemical staining with anti-BrdU monoclonal antibody. The mean LI (+/- standard deviation) of 31 papillary carcinomas, 12 adenomas, 10 adenomatous goiters, 3 follicular carcinomas, and 2 medullary carcinomas were 1.2% (+/- 1.3%), 0.6% (+/- 0.3%), 0.7% (+/- 0.6%), 1.5% (+/- 2.2%), and 0.7% (+/- 0.6%), respectively. The LI of the papillary carcinomas ranged from 0.1% to 4.6%, and approximately 66% of these showed less than a 1% similarity with almost all benign tumors. However, the LI of the two malignant lymphomas and the one anaplastic carcinoma were more than 13%. When the LI of the papillary carcinomas was compared with their various prognostic factors, there was no correlation with tumor size, nodal status, or morphologic features. However, the patients who were 50 years of age or older tended to have relatively high LI, and the LI of the papillary carcinomas correlated with patient age. According to these results, the biologic characteristics of papillary carcinomas vary with age and high proliferative activity may contribute to the poor prognosis of this tumor in elderly patients.

Adenoma

A novel class of enkephalinase inhibitors containing a C-terminal sulfo group.

A new series of sulfonic acids were synthesized and tested for their enkephalinase inhibitory activity. Among them, the most potent was N-(2-benzyl-3-mercaptopropionyl)metanilic acid 10i with an IC50 value of 0.27 nM. Several other analogues (10a,b,j,n,o,gg,hh) showed the inhibitory activity comparable to or greater than thiorphan (IC50 = 2.6 nM), a C-terminal carboxyl-containing inhibitor of enkephalinase. Thus compounds containing a C-terminal sulfo group, instead of the C-terminal carboxyl group, were found to show a remarkably high level of inhibition of enkephalinase. The analgesic activity of 10b, (S)-10b, and (R)-10b was also evaluated by the phenylbenzoquinone writhing test.

Analgesics

Collection of acrosome-reacted human sperm using monoclonal antibody-coated paramagnetic beads.

A monoclonal antibody (MAb) against human acrosome-reacted sperm was attached to paramagnetic polystyrene beads. Human sperm prepared by the swim-up method were 1) incubated in m-BWW, 2) incubated and ionophore treated, or 3) incubated with 5% seminal fluid. After treatment, sperm were mixed with the beads and incubated for 1 hr. Variously treated sperm showed different binding abilities to the beads. Sperm bound to the beads were collected by a magnet and subjected to triple staining. Most of the collected sperm were acrosome reacted. The results suggested that the beads can be used to estimate the acrosomal status of sperm, and that the use of antibody-coated paramagnetic beads provides a convenient way of collecting acrosome-reacted sperm. The acrosomal status detected by the beads was also compared with the ability of sperm to fuse with zona-free hamster eggs. It was found that greater bead-binding ability correlated with more sperm fusing with zona-free hamster eggs.

Acrosome

Autoantibodies to nucleolin cross-react with histone H1 in systemic lupus erythematosus.

IgM autoantibodies to nucleolin and histone H1 are strongly associated in the serum of patients with systemic lupus erythematosus. IgM eluted from immobilized nucleolin specifically stained histone H1 blotted to nitrocellulose; conversely, IgM eluates prepared from immobilized histone H1 stained nucleolin blots. We conclude that the linkage of anti-nucleolin and anti-histone H1 autoantibodies in SLE is due, at least in part, to immunologic cross-reactivity between these two autoantigens, which share certain similar structural features.

Adult

Autoantibodies to CD45 in systemic lupus erythematosus.

Autoantibodies to surface antigens on lymphocytes and other cells of the immune system may contribute to the development of immunoregulatory and other cellular immune abnormalities in patients with active systemic lupus erythematosus. Of special interest in this respect are autoantibodies to CD45 (leukocyte-common antigen, T200), a plasma membrane protein tyrosine phosphatase implicated in the regulation of lymphocyte functional activity, including cytotoxicity, proliferation, and differentiation.

Antibody Specificity

Juvenile angiofibroma of the maxillary sinus. A case report.

The clinicopathological features of a rare case of juvenile angiofibroma originating from the maxillary sinus of a 13-year-old boy are reported. This tumor was composed of angiomatous and fibrous structures. The analysis of nucleolar organizer regions (NOR) of the various components of this tumor indicated that the fundamental elements were the fibroblastic cells, rather than the vascular endothelial cells.

Adolescent

Increase of migration of cultured endothelial cells by angiotensin-converting enzyme inhibitor derived from tuna muscle.

The influence of angiotensin-converting enzyme (ACE) inhibitory octapeptide derived from tuna muscle (tuna AI) on the bovine aorta endothelial cell (BAEC) migration was investigated, as compared with captopril. BAEC migration was quantitated 6 d after release from contact inhibition by a teflon fence assay. The culture grown in the presence of tuna AI (1 and 10 microM) clearly exhibited an increase in migration, compared with the control. The media collected from tuna AI (1 and 10 microM)-stimulated BAECs significantly exhibited the interleukin (IL) -1 activity that was detected by the thymocyte costimulation assay with phytohemagglutinin. Although tuna AI was a weaker ACE inhibitor than captopril, the increasing effect of tuna AI on the migration and the IL-1 generation in BAECs was slightly greater than that of captopril. In quiescent BAECs, tuna AI (1 microM) apparently induced c-myc and platelet derived growth factor (PDGF) A-chain messenger ribonucleic acid (mRNA) expressions within 30 min, which persisted for 6 h. In contrast, captopril induced a very low expression of c-myc mRNA, and had no relation to PDGF A-chain mRNA expression. These results suggest that the increase of BAEC migration by tuna AI, unlike captopril, is likely related to the induction or activation of IL-1, and c-myc and PDGF mRNAs, in addition to the inhibition of the conversion of endogenous angiotensin I to angiotensin II.

Amino Acid Sequence

Homology of an acrosome-reacted sperm-specific antigen to CD46.

MH61 is an acrosome-reacted sperm-specific monoclonal antibody. The antibody-coated beads effectively analyze the acrosomal status of human sperm. However, the nature of the antigen was not known. The antigen was purified by immunoprecipitation and SDS-PAGE followed by blotting on PVDF paper. The N-terminal sequence of the antigen was analyzed by an automated protein sequencer. An exactly matching sequence was found in CD46, that is also known as a membrane cofactor protein.

Acrosome

Studies on thermophile products. IV. Structural elucidation of cytotoxic substance, BS-1, derived from Bacillus stearothermophilus.

A new cytotoxic substance designated as BS-1 was isolated from the autolysate and culture filtrate of Bacillus stearothermophilus UK563. On the basis of spectral data, the structure of BS-1 was determined as bis(2-hydroxyethyl) trisulfide and confirmed by direct comparison with the synthetic compound. BS-1 exhibited potent cytotoxicity against leukemia P388-D1, leukemia P388, mastocytoma P815, lymphoma EL4 and lymphoma MOLT4.

Antineoplastic Agents

Inhibitory effect of bis(2-aminohexyl) disulfide and bis(2-amino-3-phenylpropyl) disulfide on several mouse inflammations.

The anti-inflammatory profile of the analogues of bis(2-aminopropyl) disulfide dihydrochloride with butyl (compd. II) and phenyl (compd. III) instead of the methyl group was studied in several mouse models related to phagocyte functions. The test samples were administered 2-3 h before the inflammatory stimulation or the peak of inflammation. Subcutaneously administered, compds. II and III significantly inhibited serotonin-induced paw edema in a dose-dependent manner (50% inhibitory dose values: 10 and 5 mg/kg, respectively), when orally administered at 25 mg/kg, these compounds were significantly effective, but their potencies were weaker. Neither compound had any irritant activity when administered at a dose of 12.5 micrograms/5 microliters/paw into the paw. In a sheep red blood cells (SRBC)-induced delayed-type hypersensitivity (DTH) reaction model, compd. II (25 mg/kg, s.c.) significantly inhibited the DTH responses when administered at two different times in relation to the time of challenge. However, there was only slight inhibition by compd. III (25 mg/kg, s.c.) on paw edema formation when administered 14 h after secondary immune response. In a model of experimental acute hepatic failure induced by successive injections of Propionibacterium acnes and lipopolysaccharide, both compounds increased mouse survived, compared with the control mice, and kept the serum levels of components involved in hepatic failure to nearly normal levels. These results demonstrate that compds. II and III possess an inhibitory effect on inflammation related to phagocytes.

Amines

Studies on thermophile products. V. Immunosuppressive profile in vitro of Bacillus stearothermophilus component, Fr.5-B.

The immunosuppressive profile of Bacillus stearothermophilus UK563 component, Fr.5-B, is presented in in vitro studies. Fr.5-B (0.1-1000 ng/ml), provided it was added at the initiation of mixed leukocyte reaction (MLR), inhibited dose-dependently the incorporation of tritiated thymidine ([3H]TdR) into mouse spleen cells and human peripheral blood lymphocytes. Even the addition of Fr.5-B 48 h after the onset of culture suppressed mouse MLR, unlike cyclosporin A (CYA). Fr.5-B significantly inhibited cytotoxic T lymphocyte generation determined by [3H]TdR-release micro-cytotoxicity assay by using mouse mastocytoma P815 as targets. Moreover, this component decreased dose-dependently the expression of class II major histocompatibility molecules (Ia) on mouse peritoneal macrophages induced by concanavalin A supernatant. The present results revealed the unique immunosuppressive property of Fr.5-B which was different from that of CYA.

Animals

Inhibitory effects of bis(2-aminohexyl)disulfide and its analogues on polymorphonuclear leukocyte functions in vitro.

Water soluble analogues of the anti-inflammatory compound, bis(2-aminopropyl)disulfide dihydrochloride (compd. I) with a butyl (II), phenyl (III), benzyl (IV) or pyrrolidinyl group (V) instead of the methyl group were synthesized, and their effects on the functions of cells related to inflammation were studied in vitro. Compounds II, III and IV showed much higher inhibitory activity than compd. I on formyl Met-Leu-Phe (FMLP)-induced O2(-)-generation of polymorphonuclear leukocytes (PMNs) and platelet aggregation. Compound II showed the strongest activity among the compounds (IC50 values: 2.6 microM). The inhibition of O2(-)-generation of PMNs by compd. II was the most effective when FMLP was used as a stimulant rather than when phorbol myristate acetate, A-23187 and opsonized zymosan were used. However, compd. II was not an O2(-)-scavenger. Compounds II, III and IV significantly inhibited a series of activation processes in PMNs, chemotaxis, phagocytosis and lysosomal enzyme release at doses ranging from 10 to 100 microM. Under these doses, compds II, III and IV did not affect the histamine release from mast cells or the hemolysis of erythrocytes. These results strongly suggest that the anti-inflammatory action caused by compd. II and its analogues was at least partly due to inhibition of several functions of PMNs and platelets.

Amines

Preparation of biologically active and site specifically radioiodinated recombinant human insulin-like growth factor-I.

Recombinant human insulin-like growth factor-I (rhIGF-I) was iodinated using a lactoperoxidase-catalyzed labeling method. The labeled products were separated into more than five fractions by ion-paired reverse-phase high performance liquid chromatography (HPLC). A fraction (peak 1), which showed the highest yield and radioactivity, was found to be biologically active in the BALB/c 3T3 cell proliferating system. The site of the iodination was investigated by S-pyridylethylation followed by trypsinization and separation with HPLC using reverse phase columns. From the amino acid analysis of the peaks which were radioactive, the iodination site of peak 1 was revealed to be Tyr-24 and Tyr-60. This is the first report of the biological activity of radioactive peptide hormone with a defined labeled site.

3T3 Cells

[Prognostic factors in patients with invasive differentiated thyroid carcinoma who underwent palliative resection].

In order to determine surgical strategy for locally advanced thyroid carcinoma, a multivariate analysis of prognostic factors was carried out with 70 patients of locally advanced thyroid carcinoma who underwent palliative surgery. Multivariate analysis was conducted by Cox's proportional hazard model. The patients have been followed up from 5 to 26 years. We have demonstrated the influence of age, sex, distant metastasis, pathological findings, numbers of adjacent organs, infiltrated, extent of resection, external irradiation and 131I therapy on survival. The result of this study showed that age had an impact on survival. The survival rate of the patients under 40 years was much better than that of the patients 40 years and over. The result implies that aggressive surgery and postoperative adjuvant therapy should be considered in the old patients, but not always be indication in the young patients.

Adenocarcinoma

Evaluation of acrosomal status using MH61-beads test and its clinical application.

OBJECTIVE: To evaluate the acrosomal status of viable sperm by MH61-beads test and its clinical application. DESIGN: Acrosomal status was evaluated using immunobeads coated with MH61 monoclonal antibody, which is specific for acrosome-reacted sperm. When viable sperm was coincubated with MH61-beads for an appropriate length of time, the formation of a sperm-bead complex was observed with a phase-contrast microscope, and the number of sperm binding to MH61-beads increased with the progression of the acrosome reaction. Using this agglutination, we developed the MH61-beads test to assess sperm function. SETTING: Department of Obstetrics and Gynecology, Osaka University Hospital. PARTICIPANTS: Forty-three volunteers and 20 males in our in vitro fertilization (IVF) and embryo transfer program. MAIN OUTCOME MEASUREMENT: The results of MH61-beads test were compared with the percentage of acrosome-reacted sperm detected by Pisium satinum agglutinin staining on 30 volunteers, with the results of sperm penetration assay (SPA) in 43 volunteers, and with the outcome of IVF in 20 patients. RESULTS: The results of MH61-beads test showed good reproducibility and correlated with the results of SPA using zona-free hamster eggs and IVF. CONCLUSIONS: The MH61-beads test, the results of which reflect the acrosomal status of sperm, may provide useful information concerning the fertilizing ability of sperm.

Acrosome

A strong inhibition of HIV-induced cytopathic effects by synthetic (1----6)-alpha-D-mannopyranan sulfate.

The anti-HIV effects of mannopyranan sulfate (1) were investigated by using MT-4 cells, namely, an HTLV-I-carrying CD-4 positive cell-line, in vitro. Stereoregular (1----6)-alpha-D-mannopyranan, which had been synthesized by ring-opening polymerization of a 1,6-anhydromannose derivative, was sulfated with piperidine-N-sulfonic acid to provide 1. N.m.r. analysis of 1 indicated that the reactivity of hydroxyl groups was in the order, 3-OH greater than 2-OH much greater than 4-OH. Mannopyranan sulfate having degree of substitution (d.s.) of 1.19-1.83 effectively inhibited HIV-induced cytopathic effects at a concentration of greater than 3.3 micrograms/mL. The anticoagulant activity and the adsorption on concanavalin A of 1 indicated the possibility of selective binding of 1 having d.s. of 1.19-1.83 to HIV-protein.

Anticoagulants

Autoantibodies to human stress proteins. A survey of various rheumatic and other inflammatory diseases.

Unselected sera from patients with various rheumatic, inflammatory bowel, and autoimmune skin diseases (n = 268) were examined against human cell lysate by immunoblotting procedures, to determine the prevalence of autoantibodies to stress proteins (heat-shock proteins) hsp60 (homolog of Escherichia coli groEL and mycobacterial 65K antigens), hsp73, and hsp90. Using standard, sensitive and specific assay conditions, IgG and IgM autoantibodies to these stress proteins were not demonstrable, or were detected infrequently, in sera from control subjects (n = 36) and from patients with rheumatoid arthritis, Sjögren's syndrome, ankylosing spondylitis, Reiter's syndrome, systemic lupus erythematosus, and systemic sclerosis. Autoantibodies to hsp60 were relatively more common (greater than or equal to 20% of sera) in patients with mixed connective tissue disease, polymyositis/dermatomyositis, psoriatic arthritis, inflammatory bowel disease, epidermolysis bullosa acquisita, and bullous pemphigoid. Anti-hsp73 autoantibodies were detected in 20% or more of the sera from patients with Lyme disease and ulcerative colitis. Taken together, these data extend the spectrum of autoimmune and inflammatory diseases in which humoral anti-stress protein autoreactivity develops. However, the paucity of humoral autoreactivity to stress proteins in patients with systemic lupus erythematosus and rheumatoid arthritis argues against a direct role of anti-stress protein autoantibodies in the pathogenesis of these disorders.

Autoantibodies