Biomedical subjects
Publications and source records attributed to Y Abe.
The clinical significance of infarct-associated pericarditis was examined in 201 consecutive patients with acute Q-wave myocardial infarction with successful direct percutaneous transluminal angioplasty. A pericardial rub was a reliable clinical sign of extensive myocardial damage in patients with direct angioplasty.
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We have developed a local type experimental model of angiitisin rabbits. Repeated intracutaneous injections of erythrogenic toxins types A and C (ETA, ETC) along the intermediate auricular artery of the rabbit ear produced subacute type arteritis, characteristic of lymphocyticinfiltration, simulating Kawasaki disease angiitis. Staphylococcal enterotoxin B (SEB) and toxic shock syndrome toxin 1 (TSST) also induced similar lesions, indicating superantigens as inflammogens in vivo. Conversely, the Arthus reaction included acute type angiitis when tested similarly in rabbits immunized to human serum albumin. The ear artery was infiltrated by heterophil leukocytes, often together with venules and capillaries affected, resembling periarteritis nodosa and leukoclastic vasculitis in human disease.
A solid phase adsorption experiment was performed to detect anti-ETA alpha(NY5 strain ETA) nonneutralizing antibody. Toxin was applied to the Protein A-Sepharose column retaining IgG bound after pretreatment with test serum. Mitogenic activity recovered in the effluent and in the eluate containing the IgG was measured separately in rabbit lymphocyte culture. A significantly increased recovery in the eluate was found in combination with decreased recovery in the effluent of three sera from Kawasaki disease and one from Streptococcus pyogenes infection among 13 ELISA-positive, antimitogen assay (AMA)-negative sera tested. The nonneutralizing antibody may play an important role in the immune protection against ETA by binding to nonmitogenic epitope(s) on ETA and enabling to handle the toxin not as a superantigen but as a conventional peptide antigen.
To elucidate the penetrability of carteolol, a beta-adrenoceptor antagonist (beta-blocker) into the brain of rats, intracerebral and serum concentrations of the compound were determined in male rats receiving single or repetitive oral administration of carteolol hydrochloride at 30 mg/kg. The time-course of the intracerebral concentration of carteolol following single IV administration of the compound at 10 and 30 mg/kg was also studied in male rats. A high-performance liquid chromatography method was used to determine the intracerebral and serum concentrations. Following single oral dosing, the intracerebral concentration of carteolol reached a maximum of 0.074 microgram/g at 2 h postdosing and declined with a half-life of 3.7 h, and the Cmax and AUC of carteolol in the brain were 12.5% and 19.8% of those in serum. The intracerebral and serum concentrations of carteolol were determined in male rats receiving repetitive oral dosing of the compound once daily for 7 days. The concentration of carteolol in the brain and serum at 1 h postdosing varied within a range of 0.059-0.091 microgram/g and 0.321-0.443 microgram/ml, respectively, throughout the dosing period, showing no changes in the penetrability of the compound into the brain due to repeated dosing. The concentration of carteolol in the brain and serum increased in a dose-dependent manner in rats receiving a single IV administration of the compound. The elimination half-life of carteolol in the serum and brain was 0.6-0.8 h and 1.3-1.7 h, respectively, in rats following single IV dosing of the compound. The half-life in the brain was about twice as long as that in the serum. The brain to serum concentration ratio was 0.306:0.499. From the above results, it was concluded that carteolol is distributed from the circulation to the brain with low penetrability.
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STATEMENT OF PROBLEM: Retentive force control of clasp retainers is one of the most essential factors for the successful function of removable partial dentures. However, it is not yet known how the friction coefficients differ among restored abutments and clasp materials, and how the friction coefficients affect the retention of clasps. PURPOSE: The purposes of this study were to clarify the friction coefficients among restored abutments and clasp materials and to estimate the effect of friction coefficients on the retention of clasps. MATERIAL AND METHODS: The coefficients of static friction between three clasp materials (type IV gold, high Pd, and cobalt-chromium [Co-Cr] alloys) of two surface treatments (polished and sandblasted) and four abutment materials (human enamel, porcelain, type IV gold, and high Pd alloys) were evaluated under three conditions (dry, wet with water, and wet with saliva), and theoretically, the effect of the friction coefficients on clasp retention was estimated. RESULTS: The friction coefficients under various conditions ranged from 0.08 (polished Co-Cr clasp on type IV abutment in dry condition) to 0.37 (sandblasted Co-Cr clasp on high Pd abutment in dry condition). The theoretical estimation clarified that the retentive force of the clasp was linear to the friction coefficient. CONCLUSION: The retentive force increased linearly with increasing friction coefficient between abutment material and clasp material according to the newly developed formula. This study suggested that clasp designs should be changed depending on abutment materials.
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The FSH receptor is a member of the family of G protein-coupled receptors that activate adenylyl cyclase. The binding of agonist to cell surface receptors leads to a reduction in the intensity of the response to continuous stimulation, a process that is usually referred to as desensitization. Although the exact mechanism is not fully understood, the molecular cloning of the FSH receptor has made it possible to study desensitization in transfected cell lines. In this experiment FSH-induced desensitization was studied using Chinese hamster ovary cells expressing a functional human FSH receptor (CHO-FSHR cells). Stimulation of the CHO-FSHR cells with 10 ng/ml human FSH resulted in a decreased sensitivity to a second FSH stimulation. This decrease in FSH-induced cAMP production was observed within 2 h, and exposure of cells to FSH for 20 h led to a 70-80 % inhibition of cAMP formation. Moreover, the desensitization effect observed in CHO cells was mimicked by forskolin and, therefore, was mediated by cAMP. Incubation of cells with 125I-FSH showed an efficient internalization of the ligand in the CHO-FSHR cells. The CHO-FSHR cells rapidly internalized approximately 30% of the receptor-associated 125I-FSH by 2 h and 50% by 4 h. The responsiveness of individual CHO-FSHR cells to FSH was studied and administration of human FSH (30 ng/ml) induced a rapid rise in cytosolic calcium, reaching a peak at 6 sec. The data that human FSH can increase intracellular calcium in cells transfected with the FSH receptor cDNA reveal the possibility for the human FSH receptor to couple to both adenylyl cyclase and phospholipase C cascades.
We performed a randomized, open prospective study to determine the effect of 1 alpha-hydroxyvitamin D3 [1 alpha (OH)D3] on hyperthyroidism in patients with untreated Graves' disease. At the time of entry into the study, 30 patients were randomly assigned to receive a daily dose of 30 mg methimazole (MMI) (group A, n = 15) or the same dose of MMI supplemented with 1.5 micrograms 1 alpha (OH)D3 (group B, n = 15). These treatment regimens were continued for 24 weeks, and physicians were allowed to adjust MMI dosage during follow-up visits. Blood samples were collected, and serum concentrations of free triiodothyronine (FT3), free thyroxine (FT4), T3, T4, thyrotropin (TSH), alkaline phosphatase (ALP), and TSH-receptor antibody (TRAb) were determined. During the follow-up periods, all patients became euthyroid. The dose of MMI was not significantly different between these two groups. In contrast, decreases in mean serum FT3 and FT4 levels, as well as in mean serum T3 and T4 levels, were greater in group B. Correspondingly, the reciprocal increase in the mean TSH level was more prominent in group B. Mean TRAb levels did not differ between the two groups. Mean serum ALP levels in group B were significantly lower than in group A at 24 weeks. Thus, we suggest that concomitant administration of 1 alpha (OH)D3 is useful for treating hyperthyroidism in patients with Graves' disease.
Although the close relationship between the thymus and neuroendocrine system during the aging process has been well documented, influence of the thymus on the cognitive function of the central nervous system remains unknown. Male ddY mice were thymectomized 3-4 weeks after birth. Learning behavior, tested in a step-down test and in a spatial memory task, was significantly impaired in thymectomized mice at 10 months, but not before 5 months, after thymectomy. Reduced immune response was also not obvious before 10 months. These results suggested that thymectomy in young adult life in mice not only impaired the immune response, but also deteriorated the learning and memory ability, and that learning disorders in thymectomized mice could be utilized as a new screening model for cognitive enhancer.
OBJECTIVES: The purpose of this study was to elucidate the in vitro antimicrobial effect of tissue conditioners containing silver-zeolite on Candida albicans and nosocomial respiratory infection-causing bacteria, Staphylococcus aureus and Pseudomonas aeruginosa. METHODS: Five commercially available tissue conditioners were selected: Visco-gel (VG), GC Soft-Liner (SL), Fitt (FT), SR-Ivoseal (IV) and Shofu Tissue Conditioner (TC). Samples, 10 x 10 x 2.5 mm in size, contained silver-zeolite (SZ sample) and no SZ (N sample). The antimicrobial effects of these two samples were evaluated as a percentage of viable cells (CFU) in a microbial suspension (100 microliter) in phosphate-buffered saline with or without immersion in artificial saliva for four weeks. The borderline of the antimicrobial effect was determined at 0.1% viable cells. RESULTS: With the SZ samples, all tested microbes were killed under both conditions of no immersion and immersion in saliva. In non-immersed N samples, however, no cells of C. albicans (except with VG) and S. aureus survived, whereas the percentage of viable cells of P. aeruginosa was similar to that found in the control. However, with immersion in saliva, viable cells of C. albicans in some N samples (VG, SL and TC) increased compared with non-immersion samples by more than 0.1%. CONCLUSION: Tissue conditioners containing SZ have been shown to have antimicrobial effects for four weeks on C. albicans and nosocomial respiratory infection-causing bacteria in saliva in vitro.
Birch pollen is a very common cause of nasal allergy (pollinosis) not only in Scandinavia, Europe, Canada, and the northern part of the United States but also in Hokkaido, Japan. We have previously reported a positive association between the HLA-DR9 phenotype and the development of birch pollen allergy in Japanese subjects. However, there is little information about T cell epitopes of birch pollen which are presented by HLA class II molecules other than HLA-DR9. Therefore, we analyzed the difference in T cell epitope usage in patients who had HLA-DR9 versus those who did not. Seven Japanese patients with birch pollinosis were studied. Some groups of peptides representing T cell epitopes (Betula verrucosa; Bet VI peptides, p7-33, p23-46, p138-160) appeared to be shared by the majority, while another peptide (Bet VI p72-95) was recognized predominantly by patients who expressed HLA-DR9 and/or HLA-DQ3 molecules. Moreover, seven T cell clones and eight T cell lines were generated from two patients who did not have HLA-DR9 or HLA-DQ3. Using some of these T cell clones/lines, we investigated the relationship between HLA class II molecules and antigenic peptides. One of these T cell clones recognized antigenic peptides in the context of the HLA-DQ1 molecule. To our knowledge, this is the first indication that the epitope on Bet VI can be presented by the HLA-DQ molecule.
Human glioma usually shows intrinsic multidrug resistance because of the blood-brain barrier (BBB), in which membrane-associated P-glycoprotein (P-gp), encoded by the human multidrug resistance gene MDR1, plays a role. We studied drug sensitivity to vincristine (VCR), doxorubicin (DOX) and nimustine (ACNU) in both intracerebrally and subcutaneously xenotransplanted human glioma. We examined the levels of MDR1 and murine mdr3 gene expression in the xenografts by reverse transcriptase polymerase chain reaction and the localization of P-gp by immunohistochemistry. Six of seven subcutaneously transplanted xenografts (scX) were sensitive to the above three drugs. In contrast, all three intracerebrally transplanted human glioma xenografts (icX) were resistant to P-gp-mediated drugs VCR and DOX, but were sensitive to the non-P-gp-mediated drug ACNU. Neither icX nor scX showed any MDR1 expression. Intracerebrally transplanted human glioma xenografts showed an increased level of murine mdr3 gene expression, whereas scX showed only faint expression. The localization of P-gp was limited to the stromal vessels in icX by immunohistochemistry, whereas scX expressed no P-gp. Our findings suggest that the P-gp expressed on the stromal vessels in icX is a major contributing factor to multidrug resistance in human glioma in vivo.
1. An orally active, nonpeptide bradykinin (BK) B2 receptor antagonist, FR173657 (E)-3-(6-acetamido-3-pyridyl)-N-[N-[2-4-dichloro-3-[(2-methyl-8-quinolin yl) oxymethyl]phenyl]-N-methylaminocarbonyl-methyl] acrylamide) has been identified. 2. This compound displaced [3H]-BK binding to B2 receptors present in guinea-pig ileum membranes with an IC50 of 5.6 x 10(-10) M and in rat uterus with an IC50 of 1.5 x 10(-9) M. It did not inhibit different specific radio-ligand binding to other receptor sites. 3. In human lung fibroblast IMR-90 cells, FR173657 displaced [3H]-BK binding to B2 receptors with an IC50 of 2.9 x 10(-9) M and a Ki of 3.6 x 10(-10) M, but did not reduce [3H]-des]Arg10-kallidin binding to B1 receptors. 4. In guinea-pig isolated preparations, FR173657 antagonized BK-induced contractions with an IC50 of 7.9 x 10(-9) M, but did not antagonize acetylcholine or histamine-induced contractions even at a concentration of 10(-6) M. FR173657 caused parallel rightward shifts of the concentration-response curves to BK at concentrations of 10(-9) M and 3.2 x 10(-9) M, and a little depression of the maximal response in addition to the parallel rightward shift of the concentration-response curve at a concentration of 10(-8) M. Analysis of the data yield a pA2 of 9.2 +/- 0.2 (n = 5) and a slope of 1.5 +/- 0.2 (n = 5). 5. In vivo, the oral administration of FR173657 inhibited BK-induced bronchoconstriction dose-dependently in guinea-pigs with an ED50 of 0.075 mg kg-1, but did not inhibit histamine-induced bronchoconstriction even at 1 mg kg-1. FR173657 also inhibited carrageenin-induced paw oedema with an ED50 of 6.8 mg kg-1 2 h after the carrageenin injection in rats. 6. These results show that FR173657 is a potent, selective, and orally active bradykinin B2 receptor antagonist.
1. Stellettamide A (ST-A), a novel marine toxin isolated from a marine sponge, inhibited high K+(72.7 mM)-induced contraction in the smooth muscle of guinea-pig taenia coli with an IC50 of 88 microM. 2. In the taenia permeabilized with Triton X-100, ST-A inhibited Ca2+ (3 and 10 microM)-induced contractions with an IC50 of 46 microM for 3 microM Ca2+ and 105 microM for 10 microM Ca2+. In the permeabilized taenia, calyculin-A (300 nM), a potent inhibitor of type-1 and type-2A phosphatases, induced sustained contraction in the absence of Ca2+. ST-A had no effect on this contraction. 3. ST-A inhibited Mg2+-ATPase activity in native actomyosin prepared from chicken gizzard with an IC50 of 25 microM. 4. In a reconstituted smooth muscle contractile system containing calmodulin, myosin light chain (MLC) and MLC kinase, ST-A inhibited MLC phosphorylation with an IC50 of 152 microM. The inhibitory effect of ST-A was antagonized by increasing the concentration of calmodulin. 5. ST-A inhibited calmodulin activity, assessed by Ca2+/calmodulin-dependent enzymes, (Ca2+-Mg2+)-ATPase of erythrocyte membrane, with an IC50 of 100 microM and phosphodiesterase prepared from bovine cardiac muscle with an IC50 of 52 microM. The inhibitory effect on phosphodiesterase activity was antagonized by increasing the calmodulin concentration. 6. Interaction between ST-A and calmodulin was demonstrated by instantaneous quenching of the intrinsic tyrosine fluorescence of calmodulin by ST-A (3-300 microM). Similar results were obtained in the presence or absence of Ca2+ suggesting that ST-A binds to calmodulin and that Ca2+ is not essential for the binding of ST-A to calmodulin. 7. These results suggest that ST-A, isolated from marine metabolites, is a novel inhibitor of calmodulin.