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H Shinomiya

Publications and source records attributed to H Shinomiya.

53 records · Page 3Linked to original sources
PubMed1987

Calcium ionophore A23187 does not stimulate lipopolysaccharide nonresponsive C3H/HeJ peritoneal macrophages to produce interleukin 1.

C3H/HeJ mice are hyporesponsive to the biologic effects of bacterial lipopolysaccharide (LPS). The defect in the strain of mice is believed to be due to the expression of a mutant allele designated Lpsd at the chromosome four locus. The molecular basis of this hyporesponsiveness is not known, but it may result from some defective membrane signal transductions. To examine this possibility, we compared the abilities of interleukin 1 (IL-1) production by C3H/HeJ macrophages with those by C3H/He macrophages (LPS responsive) after stimulation with the calcium ionophore A23187 or phorbol myristate acetate (PMA). A23187 induced IL-1 production by C3H/He macrophages, but it did not induce IL-1 production by C3H/HeJ macrophages and neither did LPS. However, it had the ability to increase intracellular free Ca2+ in C3H/HeJ macrophages as well as in C3H/He macrophages, this being examined by the changes in cytosolic Ca2+ in the macrophages by using Quin 2. In contrast, PMA was able to induce IL-1 production by both C3H/He and C3H/HeJ macrophages without increasing intracellular Ca2+. Since polymyxin B did not inhibit A23187- or PMA-induced IL-1 production by C3H/He macrophages, these results are not due to the little amount of LPS in culture medium, but due to their own characteristics. A calmodulin antagonist W-7 effectively inhibited A23187-induced IL-1 production by C3H/He macrophages. However, it hardly inhibited LPS-induced IL-1 production except at high concentration, and it caused no inhibition of the PMA-stimulated one. These results suggest that the blocking sites expressed phenotypically by the Lpsd are shared by LPS- and A23187-stimulated cellular processes, although the actions of LPS and A23187 are different from each other. In addition to the direct study with LPS or lipid A, A23187 should provide another useful approach to clarify the molecular mechanisms of Lpsd defect in C3H/HeJ macrophages.

Animals↗
PubMed1987

Preparation and characterization of polyclonal and monoclonal antibodies against human interleukin 1 alpha (IL 1 alpha).

Polyclonal and monoclonal anti-human IL 1 alpha antibodies (Ab) have been established. These Ab neutralized human recombinant IL 1 alpha (rIL 1 alpha) activity effectively, but did not interfere with human rIL 1 beta, murine rIL 1 alpha, or human rIL 2 activity. Fifty percent of rIL 1 alpha activity (25 U/ml, or 2.5 ng/ml) was neutralized by less than 0.06 microgram/ml of rabbit anti-IL 1 alpha Ab (R-38.3G) and by less than 0.13 microgram/ml of monoclonal Ab (clone 28(3B1], respectively. In other experiments, 10 micrograms/ml of rabbit anti-IL 1 alpha Ab could effectively neutralize 50% of 2000 U of rIL 1 alpha activity, and the same amount of monoclonal Ab neutralized 50% of 500 U/ml of rIL 1 alpha activity. Not only IL 1 alpha activity in the thymocyte costimulator assay, but also IL 1-dependent IL 2 production by a human leukemic cell line, HSB.2 subclone, were blocked by these polyclonal or monoclonal Ab. In addition, pI 4.9 IL 1 activity produced by the myelomonocytic cell line THP-1 and by the Epstein-Barr virus-transformed B cell lines, were neutralized by these Ab, suggesting that these cell lines also produce IL 1 alpha. The specificity of these polyclonal and monoclonal Ab was further confirmed by immunochemical method (Western blotting), in which anti-IL 1 alpha Ab reacted with rIL 1 alpha in a specific manner. Furthermore, an enzyme-linked immunosorbent assay system has been developed that can detect low levels of IL 1 alpha activity (less than 0.3 ng/ml or less than 3 U/ml), which is still less sensitive than thymocyte comitogenic assay and considerably less sensitive than the D10 assay. Finally, anti-IL 1 alpha Ab-conjugated affinity columns were prepared, by which IL 1 alpha activity, but not IL 1 beta activity, was specifically adsorbed and eluted effectively.

Antibodies, Monoclonal↗
PubMed1987

[Correlations between the features of first heart sound and opening snap and the shape and motion of the anterior mitral leaflet in patients with mitral stenosis].

To evaluate the relationship between the motion pattern and degree of organic change of the anterior mitral leaflet (AML) and the features of the mitral component of the first heart sound (M1) or the opening snap (OS), 37 patients with mitral stenosis (MS) were studied by auscultation, phonocardiography and echocardiography. Based on the features of M1 and OS according to auscultation and phonocardiography, the patients were categorized as group I, 18 patients with loud and snappy M1 and OS; group II, 12 patients with snappy M1 but small and dull OS; and group III, seven patients with small and dull M1 and OS. Intensities of M1 and OS were calculated by the ratios of their amplitudes to the aortic component of the second heart sound on the high frequency phonocardiograms recorded at points of the maximum intensities, respectively. Echocardiographic parameters related to productions of M1 and OS were obtained from M-mode and two-dimensional echograms of the AML; they were amplitudes and velocities on closing and opening, M1 area defined as that between end-diastolic and systolic echoes, OS area between systolic and early diastolic echoes, the doming area between the trailing edge of an early diastolic echo and a line projected from the anterior annulus to the tip of the leaflet, and the degree of systolic ballooning. Results were as follows: 1. Significant differences in the area of the mitral valve orifice were found among three groups. The area was maximum in group II, minimum in group III and intermediate in group I. 2. In group I, the body of the AML was pliable, resulting in a ballooning into the left atrium in systole and a marked doming toward the left ventricle in early diastole. Various parameters related to the production of M1 and OS in group I were significantly increased as compared with those of the other two groups. 3. In group II, the body of the AML was not pliable in spite of mild organic changes in the valve. The degree of early diastolic doming was mild. Compared to group III, the intensity of M1 in group II was significantly larger, but no significant difference was observed in the parameters related to the production of M1 between the two groups.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1985

Thomsen-Friedenreich antigen in bladder tumors as detected by specific antibody: a possible marker of recurrence.

TUR specimens of non-invasive transitional-cell carcinomas were examined for their expression of Thomsen-Friedenreich (T) antigen by indirect immunofluorescence staining using rabbit IgG antibody which was raised with desialated glycophorin. Nine (45%) out of 20 tumors of low grade (Grade I and II), and 5 (56%) of 9 tumors of high grade (III) were diffusely stained with anti-T (T-positive), whereas T-antigen in normal tissue was cryptic and stained only after neuraminidase treatment (cryptic T-positive). Of the T-negative tumors, 9 (45%) of the low grade but only one of the high grade tumors, were stained positively for the cryptic T-antigen. The rest of the tumors were devoid of the cryptic T-antigen. Eighty percent of both Tumors expressing T-antigen and those lacking the cryptic T-antigen recurred within two years. Recurrence was not influenced by initial histological grade.

Antibodies↗
PubMed1983

Inhibition of phagocytosis by erythrocyte membrane sialoglycoprotein on target liposomes.

Sialoglycoprotein (GP) of human erythrocytes was incorporated into liposomes and its effect on the Fc receptor-mediated phagocytic reaction of human PMN cells was examined. Whereas liposomes carrying 2,4-dinitrophenylated lipid were, upon opsonization with rabbit anti-DNP, readily ingested by PMN cells and induced the NBT-reducing reaction, these reactions were markedly suppressed when GP was incorporated into the target liposomes. The inhibitory activity was found in the glycophorin A and B fractions, but the latter was more active than the former on a weight basis. It was estimated that incorporation of only a single molecule of GP per vesicle of 6000 lipid molecules may be sufficient to protect the particle from phagocytosis, but there was an apparent antagonism between the suppressive GP and opsonizing antibody as, with more antibody, more GP became necessary to inhibit phagocytosis. The effect of GP was largely abolished by trypsin treatment of GP-bearing liposomes or by the addition of F(ab')2 of anti-GP.

Dose-Response Relationship, Immunologic↗
PubMed1983

Parallelism between regulatory effects of erythrocyte glycoproteins on phagocytosis and on the alternative complement pathway.

Major membrane glycoprotein fractions from erythrocytes of humans, rats, sheep and rabbits were isolated and reconstituted into dinitrophenyl (DNP)-haptenated liposomes, in an attempt to compare their effects on the phagocytic response of human polymorphonuclear leucocytes (PMN) and on the alternative pathway of human complement. These glycoproteins on liposomes, by themselves, barely induced the nitroblue tetrazolium blue (NBT)-reducing reaction in PMN cells, but exhibited a suppressive effect to a variable extent on the Fc receptor-mediated uptake of haptenated liposomes opsonized with IgG, as judged by NBT reaction. The rank order in the suppressive activity was human greater than rat, sheep greater than rabbit. In parallel to their effect on phagocytosis, these glycoproteins were also found to suppress the alternative pathway of human complement which was initiated by IgG molecules attached to the same liposome surface. The results are taken to suggest that a molecular mechanism analogous to that in the complement cascade might also be involved in the phagocytic recognition system.

Animals↗
PubMedDate not supplied

Single-allele correction of the Dmo1 locus in congenic animals substantially attenuates obesity, dyslipidaemia and diabetes phenotypes of the OLETF rat.

1. Whole-genome scans have identified Dmo1 as a major quantitative trait locus for dyslipidaemia and obesity in the Otsuka Long Evans Tokushima Fatty (OLETF) rat. 2. We have produced congenic rats for the Dmo1 locus through successive back-cross breeding with diabetic OLETF rats. Marker-assisted speed congenic protocols were applied to efficiently transfer chromosomal segments from non-diabetic Brown Norway (BN) rats into the OLETF background. 3. In the fourth generation of congenic animals, we observed a substantial therapeutic effect of the Dmo1 locus on lipid metabolism, obesity control and plasma glucose homeostasis. 4. We have concluded that Dmo1 primarily affects lipid homeostasis, obesity control and/or glucose homeostasis at fasting and is secondarily involved in glucose homeostasis after loading. 5. The results of the present study show that single-allele correction of a genetic defect of the Dmo1 locus can generate a substantial therapeutic effect, despite the complex polygenic nature of type II diabetic syndromes.

Alleles↗