[Studies on changes in histamine levels in the blood of infants and children. Part 6. Arachidonate metabolism via lipoxygenase affecting EIB episode in asthmatic children].
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Biomedical subjects
Publications and source records attributed to Y Horiuchi.
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Natural cell-mediated cytotoxicity (NCMC) was measured in 7 patients with Sjögren's syndrome without complication of connective tissue disease, 5 patients with Sjögren's syndrome associated with connective tissue disease other than rheumatoid arthritis (RA), 13 patients with Sjögren's associated with RA, and 29 patients with RA without Sjögren's. All 25 patients with Sjögren's syndrome showed a significantly suppressed NCMC. In the patients with RA but without Sjögren's, the NCMC for 21 female patients was rather enhanced when compared with controls, while 8 male patients did not differ from controls. The reduced NCMC in the Sjögren's patients did not seem to correlate with the presence of antilymphocyte antibody. A more accelerated rate of NCMC was demonstrated in the patients with RA who were receiving gold therapy.
The mode of genetic transmission of gout and increased activity of phosphoribosylphrophosphate synthetase (PRPPS) was studied in one family. Among 15 members of Family F, two male members had gout and had PRPPS activity of erythrocyte lysates three times higher than normal subjects. Five female members had activity 2.5 times higher than normal. The difference between the activities of male and female affected members was statistically significant (P less than 0.05). To examine the genetic trait of this abnormal PRPPS, the incorporation of 3H-adenine into erythrocytes or lymphocytes was studied using autoradiography. The number of grains which show the uptake of labeled adenine into cells revealed a normal distribution pattern in two normal persons and in two male patients, and a mixed pattern of the two cell populations in two female affected members. These results suggested mosaicism in female members and X-linked dominant transmission of this trait. Thermal inactivation of PRPPS of an affected female was intermediate between that from a normal subject and that from the affected males. This result showed the heterogeneity of the PRPPS from the hemolysate of an affected female. The genotype of PRPPS on the X-chromosome was assumed and the lod score between PRPPS and Xg was also estimated. From these findings and electrophoretical study, it was suggested that the abnormal enzyme was a mutant enzyme transmitted in an X-linked dominant trait, and that the mutation occurred on the structural gene of the PRPPS.
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The prick-test titration, allergen provocation test, acetylcholine inhalation test, total serum IgE measurement, histamine release test, and serum IgE, IgG, IgA, and IgM antibody determinations were carried out in atopic asthmatic patients who had never received immunotherapy with mite extract. Comparison of these procedures shows good correlation between them. Skin-test titration appears to be a fairly accurate and reliable method to determine causative allergens. The antigen inhalation provocation test tends to be positive among subjects with low thresholds to acetylcholine. This indicates that patients with airway tracts hyperreactive to acetylcholine are prone to asthma attacks even with exposure to small amounts of specific allergen and probably to various stimuli. Atopic subjects produce more IgE antibody and other antibodies than nonatopic subjects do. The quantity of specific antibodies to mite was lowest for IgM in atopic subjects.
Mitogen-induced cell-mediated cytotoxicity (MICC) of human peripheral blood granulocytes (PMN) and lymphocytes (PBL) was studied by using chicken erythrocytes as targets. The possible mechanisms were elicited bidirectionally by means of the MICC inhibition test and by functional analysis of lectin. In our preliminary data it was noted that PMN-mediated cytotoxicity was more potent than that of PBL. In addition, erythrophagocytosis or lysosomal enzymes released from PMN offered little contribution to cytotoxic activity of PMN. From the inhibition study it was realized that intact cytoskeletal structures, functionally preserved membrane lectin receptors, active DNA synthesis, and environmental divalent cations were mandatory for the full expression of MICC activity by both effectors. We also identified the cytotoxic activity of PHA-P as having a unique character that is thermostable and independent of the other biological activities.
Forty-two Japanese families, including 80 individuals with Werner's syndrome were studied, confirming that this syndrome is inherited as an autosomal recessive trait. The incidence of malignancy was relatively high in these families and individuals with Werner's syndrome, although the incidence was not so high as was reported previously. HLA typing revealed no significant linkage with Werner's syndrome. The frequency of Werner's syndrome in Japan was estimated using two methods which indicated approximately 300 cases among 100 million people.
An active principle inhibiting beta-lactamases, which was found in the culture of a bacillus strain was a mixture of known C14-C17 fatty acids. The mixture was separated into five components by high-performance liquid chromatography. Among these components, 12-methyltetradecanoic acid showed the strongest activity (I50: 20-146 microM). The anteiso fatty acids having the 1-methylpropyl group exhibited an interesting activity inhibiting beta-lactamases.
Rabbit antiserum to guinea pig IgE was prepared. This antiserum absorbed IgE antibodies to dinitrophenyl determinants when examined by passive cutaneous anaphylaxis. This antiserum also provoked contraction of tracheal rings from normal guinea pigs in vitro. This system is a new model for asthma in which only IgE among immunoglobulins reacts.
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The significantly reduced natural killer (NK) cell activity was demonstrated in the peripheral blood lymphocytes (PBL) from 20 female patients with systemic lupus erythematosus (SLE) when compared with NK activity in the age- and sex-matched controls. The reduced NK activity did not correlate with clinical parameters including daily prednisolone doses, serum CH50, antinuclear antibody titers, and antiDNA activities, circulating immune complex levels, and cytotoxic activities of antilymphocyte antibodies (ALA). The effects of prednisolone and aggregated human IgG on NK activity were only slightly suppressive in the in vitro studies. When normal PBL were pretreated with rabbit complement and SLE sera containing ALA, the NK activity of the surviving cells was markedly decreased. The decrease was specific and did not seem to be due to the physical hindrance of the dead cells. Other heterologous ALA of rabbit origin did not exert a suppressive effect on NK activity. These results suggest that the suppressed NK activity in SLE can be ascribed to an antiNK cell specific antibody in lupus sera, although the participation of circulating immune complexes was not completely excluded.
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The defective coupling factor F1 ATPase from a mutant strain (KF11) of Escherichia coli was purified to a practically homogeneous form. The final specific activity of Mg2+-ATPase was 6-9 units/mg protein, which is about 10-15 times lower than that of F1 ATPase from the wild-type strain. The mutant F1 had a ratio of Ca2+-ATPase to Mg2+-ATPase of about 3.5, whereas the wild-type F1 had ratio of about 0.8. The mutant F1 was more unstable than wild-type F1: on storage at -80 degrees C for 2 weeks, about 80% of its activity (dependent on Ca2+ or Mg2+) was lost, whereas none of the activity of the wild-type F1 was lost. The following results indicate that the mutation is in the beta subunit. (i) High Mg2+-ATPase activity (about 20 units/mg protein) was reconstituted when the beta subunit from wild type F1 was added to dissociated mutant F1 and the mixture was dialyzed against buffer containing ATP and Mg2+. (ii) Low ATPase activity having the same ratio of Ca2+-ATPase to Mg2+-ATPase as the mutant F1 was reconstituted when a mixture of the beta subunit from the mutant F1 and the alpha and gamma subunits from wild-type F1 was dialyzed against the same buffer. (iii) Tryptic peptide analysis of the beta subunit of the mutant showed a difference in a single peptide compared with the wild-type strain.
Human IgE biosynthesis in vitro was studied by co-culturing T and B cells from atopic patients and normal controls in the presence of 10 microliter/ml pokeweed mitogen for 7 days. IgE and anti-mite IgE ab in the culture media significantly correlated with those in plasma. Normal T cells suppressed in vitro production of IgE and IgE ab significantly more than did atopic T cells but no difference was found in IgG production. The culture of B cells alone (T-depleted fraction) produced IgE equally as well as the co-culture of T and B cells. Anti-mite IgE ab was also produced by B cells alone from mite-sensitive patients. However, IgE biosynthesis in vitro was not consistently affected by pokeweed mitogen. The results suggest a deficiency of the T suppressor system in atopy and the existence of T-independent IgE-producing cells.
4-N,6'-N,3-O-Tridemethylistamycin A0 (9) and 6'N,3-O-didemethylistamycin A0 (15) were synthesized from 3,2',6'-tri-N-benzyloxycarbonyl-3',4'-dideoxyneamine 1,6-carbamate (1) through an aziridine derivative 6 by an analogous procedure employed in the total synthesis of istamycin A0 (19). Acylation of 15 with glycine at the 4-methylamino group gave 6'-N,3-O-didemethylistamycin A (18) having interesting activities especially against pseudomonas, but 4-N,6'-N,3-O-tridemethylistamycin A (12) derived from 9 showed only weak activity. Therefore, the 4-N-methyl group of istamycin A (20) is essential for the antimicrobial activity.