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Biomedical subjects

Y Maeda

Publications and source records attributed to Y Maeda.

At least 649 records · Page 36Linked to original sources

Type 1 (insulin-dependent) diabetes mellitus with coexisting autoimmune thyroid disease in Japan.

Type 1 diabetes mellitus is known to be a heterogenous disease which is frequently complicated with other autoimmune thyroid diseases (AITD). The present study was designed to investigate the clinical characteristics and HLA antigens in Japanese Type 1 diabetic patients with AITD. Subjects were 25 Type 1 diabetic patients with AITD (13 Graves' disease and 12 Hashimoto's thyroiditis) and 32 Type 1 diabetic patients without AITD. Compared with Type 1 diabetic patients without AITD, age at onset of diabetes was later and positive ICA persisted much longer in the diabetic patients with AITD. Compared with normal controls, DR9 was increased in the patients with AITD, while DR4 was increased in those without AITD. Type 1 diabetic patients with AITD were characterized by the late onset of diabetes, persistent ICA and increased association with DR9. These results suggest that immunological and genetic heterogeneity may exist within Japanese Type 1 diabetic patients.

Adolescent↗

Endothelin-1 of canine basilar artery in vasospasm.

Cerebral vasospasm was induced in adult mongrel dogs by a two-hemorrhage method. The basilar arteries were quickly frozen after careful removal of surrounding blood clot and their level of immunoreactive endothelin-1, a strong vasoconstrictor produced by the endothelial and vascular smooth-muscle cells, was measured by sandwich-enzyme immunoassay. The levels of immunoreactive endothelin-1 (mean +/- standard deviation) were 112.9 +/- 7.0 pg/mg protein prior to vasospasm, 180.4 +/- 24.7 pg/mg protein on Day 2 after vasospasm, and 115.0 +/- 24.0 pg/mg protein on Day 7, showing a significant increase (p less than 0.01) in immunoreactive endothelin-1 only on Day 2. In addition, vasospasm was moderately reversed by the topical application of monoclonal antibody against endothelin-1 on Day 2 but rather resistant to topical monoclonal antibody on Day 7. It is suggested that endothelin-1 could act as a trigger in the early stages of cerebral vasospasm, but that the maintenance of cerebral vasospasm at later stages might be independent of endothelin-1.

Animals↗

Effects of inhibitors of protein kinase C and calpain in experimental delayed cerebral vasospasm.

Vasospasm was produced in adult mongrel dogs by a two-hemorrhage method, and the spastic basilar arteries were exposed via the transclival route on Day 7. Tonic contraction was produced in the normal canine basilar arteries by a local application of KCl or serotonin after transclival exposure. The exposed spastic and tonic basilar arteries then received a topical application of the following: 1-(5-isoquinolinesulfonyl)-2-methyl-piperazine (H-7), a potent inhibitor of protein kinase C acting at the catalytic domain; calphostin C, a specific inhibitor of protein kinase C acting at the regulatory domain; or calpeptin, a selective inhibitor of calpain. Both spastic and tonic basilar arteries were effectively dilated by H-7. Calphostin C caused only slight dilation of spastic basilar arteries but moderate dilation of tonic basilar arteries. Dilation in response to calpeptin was remarkable in the spastic basilar arteries but slight in the tonic basilar arteries. The doses of calphostin C and calpeptin required to obtain maximum effect were markedly lower in the tonic model than in the spastic model. The spastic and tonic models had a similar dose-dependent response to H-7 but quite a different response to calphostin C or calpeptin, suggesting a difference in the function of protein kinase C and calpain in the two models. Furthermore, the effect of calphostin C on the reversal of vasospasm was increased significantly after topical treatment with calpeptin. It is suggested that the majority of the catalytic domain of protein kinase C is dissociated from the regulatory domain, probably by a limited proteolysis with calpain, and is markedly activated in vasospasm.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Demonstration of PGL-I & LAM-B antigens in paraffin sections of leprosy skin lesions.

An investigation on the demonstration of PGL-I and LAM-B antigens in thirty-four paraffin embedded skin biopsies taken from leprosy patients who covered the whole spectrum of the disease and in four control specimens was carried out. Neither the PGL-I antigen nor the LAM-B antigen was demonstrated in the normal skin specimens that were used as negative control; and only the LAM-B antigen appeared in the tuberculosis specimens in which the PGL-I antigen was negative. The PGL-I antigen was demonstrated on thirty-three leprosy samples except one TT sample and the LAM-B antigen, on all samples by immunochemical staining technique. The antigens were identified as intracytoplasmic bacillary staining, in solitary, granular as well as debris patterns; and as soluble antigenic staining, in vacuolar or amorphous pattern. In LL and BL cases, the antigens were detected predominantly from macrophages and peripheral nerves in all five staining patterns; in BB cases, from macrophages mostly in the granular as well as debris patterns, from the nerves in the vacuolar pattern; while in TT and the majority of BT cases, they were mainly from nerve remnants inside the granuloma in the vacuolar or amorphous staining pattern. In addition, it is interesting to note that the immunochemical staining was able to differentiate the foamy change from the hydropic degeneration. We also found that the antigens distributed in arrector pili muscles and the walls of muscular vessels were obviously related to the unmyelinated nerve fibers innervating the smooth muscle cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Bacterial↗

[A new steroid therapy for difficult asthmatics--an induction and maintenance, two-step therapy].

Beclomethasone dipropionate (BDP) administered by inhaler is a very useful drug for the treatment of bronchial asthma. In this therapy, it is very important to use steroids systematically to induce a complete remission of asthma attack (first step) and then begin to use BDP a dose of more than 800 micrograms to maintain remission (second step). We treated 27 difficult asthmatics with this therapy and found this new method very useful. The characteristics of asthmatics were as follows. 1) The age ranged from 37 to 82, and the mean age (+/- S.E.) was 58.9 (+/- 2.6) years old. 2) The onset age ranged from 27 to 74 with a mean age (+/- S.E.) of 46.9 (+/- 2.6) year old. 3) The number of non-atopy was 22 cases. 4) The follow-up duration ranged from 5 to 45 months with a mean (+/- S.E.) of 15 (+/- 2.0) months. The results were as follows. 1) The complete remission rate was 48%, partial remission 37% and unchanged 15%. 2) There was a significant increase only in %VC. 3) The peripheral eosinophil count was decreased significantly. 4) The log value of PC20 concentration by acetylcholine increased significantly by a factor of 2.94 to 3.28. 5) After this therapy, the mean serum cortisol level at 9:00 a.m. was 10.1 (+/- 3.8, S.E.) micrograms/ml. There were only 2 cases whose cortisol level were under the normal. 6) There were many oral side effects, namely stomatitis with 5 cases and hoarseness with 8.

Adult↗

Effect of salmon calcitonin on the lethality of quinolinic acid, an excitatory amino acid.

The effect of salmon calcitonin (SCT) on the lethality of quinolinic acid (QA), an endogenous excitatory amino acid, was investigated in relation to the excitatory amino acid receptor/ion channel complex. SCT increased the LD50 value of QA in a bell-shaped fashion, but the difference was not significant. The non competitive N-methyl-D-aspartate (NMDA) receptor antagonists MK-801 and phencyclidine (PCP) inhibited QA lethality dose-dependently. SCT potentiated the inhibitory effects of these antagonists. The competitive and glycine site antagonists 3-((+-)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) and 7-chlorokynurenic acid (7ClK), respectively, inhibited QA lethality in a dose-dependent fashion. SCT did not potentiate the effect of either drug. These results suggest that SCT inhibits NMDA receptors by interacting with Ca ion channel.

Amino Acids↗

Development of a mandibular tracking device with six degrees of freedom using optoelectronic system.

The purpose of this study was to develop a prototype handy mandibular tracking device with six degrees of freedom using the optoelectronic kinematic data acquisition system and to evaluate its accuracy. The system consisted of the light-weight sensor part mounted on the mandibular incisor portion and two 2-D PSD cameras positioned in front of the patient. On the sensor part, three light emitting diodes (LEDs) were attached in triangular form. Displacements of the sensor part were detected by two cameras, transformed into electric signals, and sampled by A/D converter in a desktop computer. Since the overall accuracy of this system was about 0.03 mm in the displacement and 0.06 degrees in the rotation angles, this system was proven to be capable for the wide range of clinical application.

Humans↗

FK 224, a novel cyclopeptide substance P antagonist with NK1 and NK2 receptor selectivity.

We have discovered a novel cyclopeptide substance P (SP) antagonist, FK 224 (N-[N2-[N-[N-[N-[2,3-didehydro-N-methyl-N-[N-[3-(2-pentylphenyl )- propionyl]-L-threonyl]tyrosyl-L-leucynyl]-D-phenylalanyl]-L-allo- threonyl]-L-asparaginyl]-L-serine-nu-lactone), which inhibited [3H]SP binding to guinea pig lung membranes in a dose-dependent manner. According to Rosenthal analysis, the inhibitory effect of FK 224 on [3H]SP binding appears to be competitive. In order to clarify the receptor subtype selectivity of FK 224, we have studied the interaction of FK 224 with three tachykinin receptors (NK1, NK2 and NK3) by using receptor binding techniques and in vitro bioassays, and have also compared FK 224 with the novel nonpeptide antagonist, (+/-)-CP-96,345. In binding experiments, FK 224 dose-dependently inhibited [3H]SP binding to rat cerebral cortical membranes (NK1) and [3H]neurokinin (NK) A (NKA) binding to rat duodenum smooth muscle membranes (NK2), but did not affect [3H]eledoisin binding to rat cerebral cortical membranes (NK3). In bioassay experiments, FK 224 inhibited SP-induced contraction of guinea pig ileum (NK1) and NKA-induced contraction of rat vas deferens (NK2) in a dose-dependent manner, but did not affect NKB-induced contraction of rat portal vein (NK3). In contrast, (+/-)-CP-96,345 inhibited SP-induced contraction of guinea pig ileum, but not NKA-induced contraction of rat vas deferens or NKB-induced contraction of rat portal vein. In the presence of FK 224, SP dose-response curves and NKA dose-response curves were shifted to the right in parallel with no depression of the maximal contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of FK224, a novel compound NK1 and NK2 receptor antagonist, on airway constriction and airway edema induced by neurokinins and sensory nerve stimulation in guinea pigs.

FK224 (N-[N2-[N-[N-[N-[2,3-didehydro-N-methyl-N-[N-[3-(2- penthylphenyl)-propionyl]-L-threonyl]tyrosyl]-L-leucynyl]-D- phenylalanyl]-L-allo-threonyl]-L-asparaginyl]-L-serine-nu-lactone) is a novel neurokinin (NK) antagonist that exhibits selectivity for NK1 and NK2 receptors. The effects of FK224 on airway constriction and airway edema induced by NKs and nerve stimulation have been investigated in guinea pigs. FK224 inhibited the contraction of isolated guinea pig trachea induced by substance P (SP, 10(-8) M), NKA (10(-9) M) and NKB (10(-8) M) in a concentration-dependent manner, and the IC50 values were 2.6 x 10(-6), 1.3 x 10(-6) and 2.3 x 10(-7) M, respectively. Tracheal contraction induced by histamine and acetylcholine was not affected by FK224, suggesting a specific effect on NK-mediated responses. FK224 also inhibited the atropine-resistant contraction of isolated guinea pig bronchi induced by electrical field stimulation with an IC50 value of 3.5 x 10(-6) M. In in vivo experiments, FK224 given i.v. inhibited SP (13.5 micrograms kg-1)-, NKA (1.1 micrograms kg-1)- and capsaicin (3.1 micrograms kg-1)-induced airway constriction in guinea pigs with ED50 values of 0.39 mg kg-1, 0.36 mg kg-1 and 1.1 mg kg-1, respectively. FK224 also inhibited SP (1.3 micrograms kg-1)-, NKA (11 micrograms kg-1)- and capsaicin (100 micrograms kg-1)-induced airway edema with ED50 values of 0.14 mg kg-1, 0.29 mg kg-1 and 0.30 mg kg-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Recent advances in ovarian cancer chemotherapy].

The standard approach for epithelial ovarian cancer has been maximum cytoreductive surgery followed by combination therapy. Several prospective control studies individually failed to demonstrate improved survival advantage for the Adriamycin containing combination compare with cisplatin plus cyclophosphamide. The two drug combination of carboplatin plus cyclophosphamide will be thought to become the treatment of choice, because it is equally effective as and less toxic than a regimen of cisplatin plus cyclophosphamide. Clinical trials are also in progress with more dose-intense regimens based on considerable retrospective evidence that survival is correlated with the dose intensity of platinum compounds. Currently, high dose carboplatin plus Gm-CSF, two-drug combination of carboplatin and cisplatin and super high dose carboplatin combined with autologous bone marrow transplantation are undergoing clinical trials. Taxol and taxotere, most important cancer drugs after emergence of cisplatin compound, has been shown to have clinical activity in drug resistant ovarian cancer patients. Majority of patients even with advanced germ cell tumors of the ovary is now cured because of the development of effective platinum-based combination chemotherapy of PVB or BEP.

Antineoplastic Agents, Phytogenic↗

[Overt leukemia from MDS associated with marked basophilia].

A 52-year-old woman was admitted to our hospital because of leukocytosis. She had been diagnosed with RAEB in another hospital in past time. At the admission, the white cell count was 30,900/microliter with blasts (14.0%) and marked basophilia (49.0%). Bone marrow aspiration revealed with 30.2% blasts and 21.1% basophils. Having obtained those results, diagnosis of RAEB in transformation was made. After admission, number of basophils in peripheral blood increased gradually, and level of histamine in serum was elevated significantly. Multiple peptic ulcers in stomach and bowel and high fever were induced due to histaminemia. Despite several therapy she died because of respiratory failure and septisemia. Although the mechanism of basophilia in this patient could not be clarified, there was a possibility that basophilia in this patient might be differentiated from leukemic clone because almost basophils in peripheral blood were mature and those had many granules including metachromasia by stained with toluidine blue.

Basophils↗

[A case report of two mitral valve aneurysms with one perforation after two attacks of infective endocarditis].

Aneurysms of the mitral valve complicating infective endocarditis (IE) are uncommon. The patient was a 57-year-old man who was admitted to our hospital for a precise examination of heart failure. One year before, the first two-dimensional echocardiography showed an aneurysm of the anterior mitral leaflet possibly due to a previous attack of IE. Doppler color flow mapping detected a regurgitant jet from the mitral valve aneurysm into the left atrium during systole, which suggested perforation of the aneurysm, and an aortic regurgitant jet flowing against the anterior mitral leaflet. Because the patient's family refused cardiac catheter examination and surgery, we treated him in the out-patient clinic. A few weeks before his admission, he had discontinued taking diuretics because of uncomfortable urinary frequency. He gradually developed the symptoms of heart failure and entered our hospital. IE was suspected because of leucocytosis and slight fever. Two-dimensional echocardiography revealed a new aneurysm of the anterior mitral leaflet without perforation, located in the distal part of the old aneurysm. This time, his family consented to the surgical treatment. Aortic and mitral valve replacement was successfully performed. It was pathologically confirmed that the two mitral aneurysms had been caused by IE.

Aortic Valve↗

Induction of Fc epsilon RII/CD23 on PHA-activated human peripheral blood T lymphocytes and association of fyn tyrosine kinase with Fc epsilon RII/CD23.

Despite the evidence for the expression of Fc epsilon RII/CD23, a glycoprotein that is a low-affinity Fc receptor for IgE, obtained on T cell lines and some pathological T cells, that of Fc epsilon RII/CD23 on normal human T cells is still unclear. We studied the emergence of T cells bearing Fc epsilon RII/CD23 in short-term culture of normal human peripheral blood mononuclear cells stimulated with 15 microliters/ml phytohemagglutinin (PHA). Using two-dimension flow cytometry, more than 10% of Fc epsilon RII/CD23(+) cells were shown to co-express CD3 antigen. Both CD4(+) and CD8(+) T cells expressed Fc epsilon RII/CD23. The expression of mRNA for Fc epsilon RII/CD23 on PHA and IL-4 stimulated PBMC was demonstrated by northern blotting and in-situ hybridization. The mechanism of signal transduction through Fc epsilon RII/CD23 was dissected by transfection of cDNA coding for Fc epsilon RII to the human natural killer-like cell line YT, activation of which was easily detected by the induction of interleukin-2 receptor/p55 (Tac). Cross-linking of Fc epsilon RII/CD23 with H107 anti-Fc epsilon RII monoclonal antibody enhanced IL-2R/p55 expression on YT cells transfected with Fc epsilon RII cDNA (YTSER). A possible involvement of protein-tyrosine kinase in the Fc epsilon RII-mediated signal transduction was studied using YTSER. Fc epsilon RII was physically associated with an src-family tyrosine kinase p59fyn and not with p56lck, which was also found in YT cells. Recently it was reported that p59fyn was associated with T-cell antigen receptor. Our results collectively suggest the multiple function of p59fyn which may be implicated in the Fc epsilon RII-mediated activation signal in YT cells.

Blotting, Northern↗

[DNA ploidy pattern as an indicator of degree of malignancy and prognosis in gastric cancer].

We used fresh materials and paraffin blocks of advanced gastric cancer to examine the relationship of DNA ploidy pattern from flow cytometry (FCM) to degree of malignancy and prognosis. No significant relationship was found between the frequency of DNA aneuploid (DA) and the clinicopathological factors (depth of invasion, degree of progression, histological type, lymph node metastasis, ly, v etc.). FCM examination using fresh materials revealed significant difference in prognosis between the non-DA and DA groups for non-curative stage III or IV cases (p < 0.05). On the other hand, in terms of the relationship between DNA ploidy patterns from paraffin blocks and prognosis for curative resection cases of ss-gastric cancer, prognosis was significantly better in the non-DA group than in the DA (p < 0.01). These results indicate that the clinicopathological prognostic factors for gastric cancer are connected in a complex way and that DNA ploidy patterns alone are not superior to the prognosis determining factors used in the past.

Aged↗

Tumor dormancy and the effect of selected drugs on the tumor-dormant state.

An animal model for studying tumor dormancy was established by two-way selection of tumor-progressive and nonprogressive (tumor-dormant state) ddY mice in the same basal stock. In the tumor-progressive (prg) substrain of mice, Ehrlich ascites tumor cells (2 x 10(7)) subcutaneously inoculated into the dorsal skin formed a progressive solid tumor. In the tumor-dormant substrain (drm) of mice, the same tumor cells did not grow at all but formed a small caked nodule (1 to 3 mm in diameter) within 1 week. Some of the tumor cells persisted in the nodule at least 3 months without apparent mitotic figures. Such dormant tumor cells emerged and revealed outgrowth to overt solid tumors after they were transplanted into the dorsal skin of prg mice or into athymic mice (C57BL/6J nu/nu). To estimate the predisposition of drm mice to form tumors, the effect of certain drugs on the tumor-dormant state was examined. Estradiol, progesterone, dexamethasone, prostaglandin E2, Cyclosporin A, and collagenase all failed to promote the emergence of dormant tumor cells in drm mice.

Animals↗

Enzyme immunoassay with synthetic peptides to detect anti-HTLV-I antibodies.

We developed an enzyme immunoassay (EIA) system to detect antibodies to human T-lymphotropic virus type I (HTLV-I). This system uses chemically synthesized oligopeptides to capture anti-HTLV-I antibodies in serum. The two epitopes of HTLV-I proteins exhibiting the most specific antigen-antibody reaction reside within amino acids 100-130 of p19, a core protein encoded by gag, and amino acids 175-199 of gp46, an envelope glycoprotein encoded by env. This new assay uses synthetic peptides corresponding to these two regions modified by adding two lysine residues at the amino terminal of each peptide to facilitate the binding to the surface of the microtiter plate wells. We compared the performance of our EIA with gelatin-particle-agglutination (PA) and indirect-immunofluorescence (IF) assays, both of which use viral proteins purified from virus-carrying cell cultures. Mass screening by EIA with various synthetic peptides was more accurate than the current confirmatory IF assay.

Agglutination Tests↗

Lobster troponin C: amino acid sequences of three isoforms.

We have determined the amino acid sequences of the three major isoforms of lobster troponin C, using protein chemistry methods. Each isoform contains 150 amino acid residues, with a calculated Mr of 17,000 +/- 100. Sequence differences occur in all regions of the polypeptides, indicating that the isoforms are products of three different genes, rather than alternative transcripts of a single gene. Analysis of the sequences predicts that functional Ca(2+)-binding sites are present only in regions II and IV of four ancestral regions.

Amino Acid Sequence↗