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Biomedical subjects

N Okabe

Publications and source records attributed to N Okabe.

At least 127 records · Page 7Linked to original sources

Analysis of peripheral T lymphocyte subpopulations in Graves' disease.

To detect possible changes in the T lymphocyte subpopulations in patients with Graves' disease, T mu and T gamma lymphocytes and "active" T lymphocytes were counted in the peripheral blood lymphocytes. Antithyroid autoantibodies were also measured in correlation with T lymphocyte subset analysis. We found no alteration whatever in T lymphocyte subpopulations, although there was a slight increase in the proportion of "active" T lymphocytes and T gamma lymphocytes in the untreated group, as compared to treated group, but the difference was not statistically significant. There was no correlation between T lymphocyte subpopulations and antithyroid autoantibodies. These data indicate that the defects in T gamma lymphocytes with suppressor function, probably does not explain the etiology of Graves' disease, despite the hypothesis that defects in suppressor cells may lead to the production of thyroid stimulating immunoglobulins and antithyroid autoantibodies in Graves' disease.

Autoantibodies↗

Effects of antithyroid drugs on lymphocyte proliferative responses to lectins: relationship between insulin autoimmune syndrome and methimazole.

Using peripheral blood lymphocytes from 8 healthy individuals and 5 patients with untreated Graves' disease, direct effects of methimazole (MMI) and propylthiouracil (PTU) on lectin-induced lymphocyte proliferative response were studied. Lymphocytes were cultured for 72 hr in the presence of lectins and antithyroid drugs. Lymphocyte DNA synthesis was counted by incorporation of 3H-thymidine. MMI at 1,000 microM enhanced lectin-induced lymphoproliferation of peripheral blood lymphocytes from both patients with Graves' disease and healthy individuals, at every point of culture time, while PTU showed a tendency toward suppression. These results suggest that this lympho-stimulation by MMI may be a causative factor related to insulin autoimmune syndrome, as deduced from the clinical reports that insulin autoimmune syndrome is, sometimes, found in patients with Graves' disease treated with MMI. This lympho-stimulation was evident regardless of the time of MMI addition, thus indicating that MMI is, by its action, a lymphoid stimulator and may lead to the insulin autoimmune syndrome in predisposed subjects with underlying Graves' disease.

Autoimmune Diseases↗

The crystal structure of a major metabolite of thyroid hormone: 3,3',5'-triiodo-L-thyronine.

Two independent conformations of the thyroinactive thyroid hormone metabolite, 3,3',5'-triiodo-L-thyronine (rT3) were determined by X-ray diffraction methods. The conformations show significant difference in the lettering geometry when compared with those of the thyroactive thyroxine (T4) and 3,5,3'-triiodo-L-thyronine (T3). The diphenyl ether conformation of the two conformers of rT3 is an anti-skewed one, in which the torsion angles, phi (C5-C4-O4-Cl') are 8 degrees and -6 degrees, and phi' (C4-O4-Cl'-O6') are 86 degrees and 87 degrees. This conformation is in contrast to a twist-skewed one of T4 and T3. The difference in the binding abilities between T4, T3 and rT3 to thyroxine binding carrier proteins in serum or to a nuclear receptor protein may be explained by the characteristic solid-state conformations of these metabolites.

Models, Molecular↗

[The adverse effects of thioureylene antithyroid drugs (author's transl)].

The aims of the present study were to investigate the incidence of adverse effects of thioureylene antithyroid drugs and to see if there were any factors related to the development of the adverse effects. Methimazole or propylthiouracil was administered to 151 patients with Graves disease; 76 untreated cases and 75 treated cases. The overall incidence was 22.4% among the 76 untreated cases. The incidences were 26.7% (13/45 cases) for methimazole and 16.1% (5/31 cases) for propylthiouracil, respectively, which were significantly higher than those previously reported. Fourteen out of 17 cases with the adverse effects were given the other thioureylene. The successive incidence of the adverse effects was 28.6% (4 cases), which was not significantly different from that under the drug of first choice. The result suggests that methimazole and propylthiouracil may not have cross-reaction each other. On the other hand, antinuclear antibody and anti-DNA antibody became positive in 2 out of the 4 cases. It would be a significant phenomenon, since antinuclear antibody was positive in only 3% of cases before the drug treatment. Thus, an immunological mechanism seemed to be involved in the problems, although there was no correlation between antithyroid autoantibodies and the development of the adverse effects. The adverse effects were observed within 2 months of administration of less than 250 tablets in total in most of the cases. The results imply that allergic mechanism rather than accumulating or toxic effect may concern the development of adverse effects of the thioureylenes.

Adult↗

The effect of guanidine hydrochloride on the conformation of bovine pancreatic DNAase I as measured with circular dichroism.

The denaturation of bovine pancreatic DNAase I (EC 3.1.21.1) by guanidine hydrochloride (GdnHCl) has been investigated with circular dichroism in the presence and absence of 1 mM Ca2+ at the wavelength region of 210-240 nm at 12.25 and 36 degree C. The change of the molar ellipticity at 220 nm by GdnHCl titration showed cooperative transition at each temperature and the midpoints of the titrations occurred near 2 M GdnHCl. At each temperature, the denaturation of DNAase I in the presence of 1 mM Ca2+ occurred a little slowly as compared with that in the absence of Ca2+. This suggests that 1 mM Ca2+ can to some extent stabilize the secondary structure of DNAase I against GdnHCl denaturation. The apparent free energy for the denaturation of DNAase I obtained by GdnHCl titration was calculated as 9.3 +/- 0.3 kcal/mol and 8.9 +/- 0.2 kcal/mol at 25 degree C in the presence and absence of 1 mM Ca2+, respectively. The possible regions for the alpha -helix and beta -structure of DNAase I were predicted from the amino acid sequence by probability calculation of Chou, P.Y. and Fasman, G.D., Adv. Enzymol. 47, 45-148. The characteristic feature is that the NH2-terminal half of DNAase I is rich in beta -structure and the COOH-terminal half contains mainly alpha -helix.

Animals↗

Cold-adapted recombinant influenza A virus vaccines in seronegative young children.

Two live, attenuated, intranasally administered influenza virus vaccines were evaluated in 21 seronegative young children at Vanderbilt Children's Hospital (Nashville, Tennessee). The vaccines were derivatives of a cold-adapted master strain, influenza A/Ann Arbor/6/60 virus, containing the hemagglutinin and neuraminidase of one of two contemporary strains, influenza A/Hong Kong/123/77 (H1N1) or A/Alaska/6/77 (H3N2) virus. Both vaccine strains replicated in seronegative young children without evidence of genetic instability. In addition, both vaccine strains caused no identifiable clinical reactions, were not transmitted to other seronegative children, and gave long-lasting immunity. In a subsequent naturally occurring epidemic of influenza A/Bangkok (H3N2) virus, children previously vaccinated with the related strain, influenza A/Alaska (H3N2) virus, were significantly protected as judged by serologic evidence of reinfection.

Antibodies, Viral↗

Minor conformational changes of yeast tRNAPhe anticodon loop occur upon aminoacylation as indicated by Y base fluorescence.

The Y base fluorescence of highly purified yeast tRNAPhe was measured in order to detect possible conformational changes of the anticodon loop, which were induced as a consequence of aminoacylation. A small enhancement of Y base fluorescence intensity in the order of 5% was observed in situ during aminoacylation. The rotational mobility of the Y base of Phe-tRNAPhe and tRNAPhe was determined by measuring the fluorescence polarization at various temperatures between 5 degrees C and 35 degrees C. Differences in the fluorescence polarization of the Y base between these tRNAs were however not observed. These results confirm that minor changes in the microenvironment of the Y base occur upon aminoacylation, whereas significant conformational changes of the anticodon loop can be excluded.

Anticodon↗

Circular dichroism studies on the interaction between human serum albumin and thyroxine.

The Cotten effects induced by the interaction of thyroxine (T4) with human serum albumin (HSA) have been examined at various molar ratios of T4 to HSA. The results suggested the following three distinct modes of interaction, depending on the molar ratio (n). 1. The first mode of interaction appeared at n=0-1. A large difference CD amplitude attributable to T4 was observed in the region between 280 nm and 325 nm. This suggests that the T4 molecule binds tightly to a highest affinity site of HSA. The difference CD spectra of HSA in the presence and absence of T4 bound at the highest affinity site showed that the peak at 292 nm might be induced by an intrinsic dissymmetry owing to an asymmetric carbon atom in the T4 molecule, while a CD band at 325 nm might be due to perturbation of the beta-ring chromophore of T4 by certain intrinsic loci of HSA at the binding site. 2. As the second mode of interaction at n=1 approximately 5-8, T4 molecules may bind loosely to HSA with various conformations, because the difference CD amplitude at 325 nm was decreased. 3. The third mode was detected at n greater than 5-8. The difference CD patterns is quite distinct from the others and is very similar to the CD band of T4: L-lysine mixture.

Binding Sites↗

Humoral and cellular immune responses of seronegative children vaccinated with a cold-adapted influenza A/HK/123/77 (H1N1) recombinant virus.

Humoral and cell-mediated immune responses of young, seronegative children were assessed after intranasal vaccination with a cold-adapted influenza. A/HK/77 (H1N1) CR 35 recombinant virus. Vaccines shedding influenza virus experienced a rise in hemagglutinin-inhibition antibody 15 to 30 days after vaccination. Vaccinees showed low but significant lymphocyte transformation to A/USSR (H1N1) by day 8 after vaccination, which decreased to prevaccination levels at 30 to 34 days. The lymphocyte transformation response occurred before serum antibody rises were detected by hemagglutinin-inhibition assay. No change in lymphocyte responsiveness was observed after vaccination as measured by phytohemagglutinin stimulation. Lymphocytes responded to in vitro incubation with inactivated influenza (H1N1) virus by producing interferon. The interferon produced was of type I and was observed in vaccinees and nonvaccinees both before and after vaccination.

Antibodies, Viral↗

Operative and postoperative choledochofiberoscopy.

Choledochofiberoscopy is effective for both diagnosis and therapy. It is a valuable diagnostic technic because it permits a definite diagnosis and it allows the surgeon to determine the operative method by direct viewing and by biopsy of the biliary tract wall. Choledochofiberoscopy is therapeutically valuable because it permits cleaning of the bile duct, the removal of retained or remnant stones in the common and intrahepatic ducts, and the removal of granuloma and benign tumor with forceps under direct vision.

Biliary Tract Surgical Procedures↗