Biomedical subjects
N Amino
Publications and source records attributed to N Amino.
Changes in natural killer cell activity in normal pregnant and postpartum women: increases in the first trimester and postpartum period and decrease in late pregnancy.
Changes in the activity and number of natural killer (NK) cells in peripheral blood in normal pregnant and postpartum women were examined. NK activity was measured in a 4-h 51Cr-release assay and evaluated by conventional relative lytic units and absolute lytic units which represent the total NK activity within a fixed volume of circulating blood. The number of NK cells was analyzed with FITC-conjugated monoclonal antibodies and by use of an automated flow cytometer. Unexpectedly, the relative NK activity increased in the first trimester and also for 1 month postpartum compared to the activity in normal non-pregnant controls. On the other hand, absolute NK activity decreased in the third trimester compared to the activity in normal non-pregnant controls. The percentage of CD57+ cells decreased in the second trimester, but the percentage of CD16+ cells did not change during pregnancy or the postpartum period. The absolute counts of CD57+ cells and CD16+ cells decreased in the second and third trimesters and increased transiently in the postpartum period. These findings indicate that the increased NK activity in the first trimester and at 1 month postpartum is induced by increased cytotoxic activity of individual NK cells, and that the decreased NK activity in late pregnancy is induced by a decrease in the numbers of NK cells. These physiological changes may play an important role in implantation in early pregnancy, protection of the fetal allograft in late pregnancy and in the natural defense against infection during the puerperal period.
Detection of thyroid microsomal and thyroglobulin antibodies by new sensitive radioimmunoassay in Hashimoto's disease; comparison with conventional hemagglutination assay.
We evaluated clinical usefulness of thyroid microsomal antibody (MCAb) and thyroglobulin antibody (TGAb) measured by new sensitive radioimmunoassays (RIA). These assays are simple and reproducible; the intra- and inter-assay coefficients of variation were 3.6-6.8% and 6.6-13.2% in the MCAb assay, and 3.2-7.7% and 7.6-12.3% in the TGAb assay, respectively. In 126 patients with Hashimoto's disease, the antibody activity determined by this RIA correlated with that determined by the hemagglutination assay (HA) (r = 0.848 for MCAb, r = 0.686 for TGAb, p less than 0.001). MCAb was detected by RIA in all of 115 HA-positive and 4 of 11 HA-negative patients, and TGAb by RIA in all of 84 HA-positive and 29 of 42 HA-negative patients: the prevalence of MCAb was 94% and that of TGAb was 90% in the disease. Moreover, some showed high antibody activity only in RIA. In another group of 14 patients with biopsy-proved Hashimoto's disease with no antibody activity by routine HA tests, serum MCAb was detected in 3 (21%), TGAb in 11 (79%), and both activities in 2 (14%). Our results indicate that (1) the RIA tests are more sensitive than the conventional HA test, and that (2) the present RIA test for TGAb is more sensitive than that for MCAb in detecting autoimmune abnormalities, especially in patients with biopsy-proved Hashimoto's disease who give negative results in the HA test.
The stability of immunological and biological activity of human thyrotropin in buffer: its temperature-dependent dissociation into subunits during freezing.
The stability of thyroid-stimulating hormone (TSH) in buffer under various storage conditions was studied with regard to its immunoreactivity measured by an immunoradiometric assay and its bioactivity by a sensitive FRTL-5 cell bioassay. The immunoreactivity was well retained at 4 degrees C or 24 degrees C throughout the study period of 90 days. At -20 degrees C, however, it decreased proportionately with the storage time. The mean reduction was 42.1% at 90 days compared with that when stored at -80 degrees C. The bioactivity showed a similar course of change with its reduction of 44.3% at -20 degrees C in 90 days. The loss of both activities was attributed to the dissociation of human (h) TSH molecule into its subunits. The concentration of the alpha subunit of hTSH in those samples stored at -20 degrees C gradually increased from the initial undetectable level to that almost equivalent on a molar basis to the loss of immunoreactivity. The enrichment of albumin in the buffer to a level of more than 1.0% was effective in preventing the occurrence of such a phenomenon. These data indicate that hTSH, when frozen at -20 degrees C in buffer is gradually dissociated into its subunits, despite its outstanding stability for 90 days at both 4 degrees C and 24 degrees C. However, no apparent inconsistency between immunological and biological activities, was observed at any temperature between -20 degrees C and 24 degrees C.
Novel IgA antibody to bovine thyrotropin in a healthy man.
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[Prediction of occurrence of thyroid disorders in neonates born to mothers with thyroid disorders].
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[Converse changes in serum levels of immunoglobulins (IgG, A and M) and complement components (C3, 4) during pregnancy].
Sequential changes in serum levels of the immunoglobulins IgG, A and M and of the complements C3 and C4 during pregnancy and the postpartum period were studied in 8 healthy women. Serum IgG and A levels decreased gradually during pregnancy, but increased significantly during the first three months following delivery. Serum IgM level also decreased during pregnancy, reaching its minimum during the second trimester, but increased thereafter. In contrast, C3 and C4 levels increased significantly during pregnancy and reached their maximum levels during the last trimester. After delivery, levels of these two components decreased gradually for the next six months. The complement system may operate as a compensatory autoregulatory mechanism in the suppression of the humoral immune system during pregnancy.
[Effect of plasma on analysis of lymphocyte subsets].
We examined the effect of plasma on the analysis of lymphocyte subsets with a flow cytometer using whole blood cells. Removal of plasma from whole blood by washing them before labelling the lymphocytes with fluorescein-conjugated antibodies reduced the proportion of CD5+CD19+ cells and increased the proportions of CD16+ CD57- and CD16+ CD57+ cells, as compared with those measured without washing, but did not change the proportions of CD5+ CD19-, CD5- CD19+, CD4+ CD8-, CD4- CD8+ and CD16- CD57+ cells. Removal of plasma from whole blood also reduced the fluorescence intensity of CD4 and CD5 antigens and increased that of CD8, CD16, CD19 and CD57 antigens on each lymphocyte subsets. Characteristics of the changed lymphocyte subsets were to have a surface antigen with weak immunofluorescence on the flow cytometric analysis such as CD5 and CD16, and to have an unclear borderline between the positive and negative cells. Therefore, even slight changes in the fluorescence intensity of these antigens could change the proportion of CD5+ CD19+, CD16+ CD57- and CD16+ CD57+ cells. However, these changes were not observed, when using the washed blood cells as samples after readdition of plasma to them. These data suggest that removal of plasma from blood before labelling the lymphocytes with fluorescein-conjugated antibodies is necessary to make the sample condition equal for flow cytometric analysis of lymphocyte subsets.
[Mixed type cryoglobulinemia with discrepancy of platelet counts measured with an automated cell counter and by manual counting method].
We experienced an abnormal blood sample which showed larger numbers of white blood cells and platelets counted by the electric resistance system and of platelets in mechanical counting by the flow system, than those in manual counting. Many precipitates were observed in this blood sample at room temperature or 4 degrees C, but were not observed at 37 degrees C. The precipitates were clarified to be caused by the mixed type (IgA, IgG and IgM) cryoglobulin by using an immunofluorescence method and an ouchterlony method. These data indicate that precipitation of cryoglobulin at room temperature induce falsely high value of platelet count in mechanical counting systems.
[Examination of the inhibitor to factor VIII in non-haemophilic patient].
We examined an inhibitor to factor VIII in non-haemophilic patient who had been developed widely spread ecchymosis and intramuscular bleeding. He had no previous personal or family history of abnormal bleeding tendency. His laboratory data was all normal except examination for blood coagulation. Coagulation studies showed prolonged activated partial thromboplastin time (48 sec) and decreased factor VIII activity (8%). The activity of the inhibitor to factor VIII was demonstrated to be 4.0 Bethesda unit. By the studies of dilution and time response curve, this inhibitor was found to inhibit up to 90% of factor VIII activity but not 100%. This inhibitor was shown to be IgG by protein-A affinity chromatography. In addition, bleeding time was prolonged in the patient. The value of von Willebrand factor antigen was 200%, but that of Ristocetin cofactor was 93%. Since the gel filtration analysis indicated that this inhibitor also suppressed Ristocetin cofactor activity, the relatively low value of Ristocetin cofactor might occur through the action of the inhibitor. These data suggest that patient's inhibitor react to factor VIII high molecular subunit.
Automated determination of creatine kinase activity in serum with use of thermostable glucokinase.
We measured creatine kinase (CK, EC 2.7.3.2) activity in serum with a new reagent system utilizing thermostable glucokinase (EC 2.7.1.2). Automated determinations were performed with Toshiba's Model TBA-80S Biochemical Analyzer. Precision studies demonstrated within-run and between-run CVs of 0.4%-2.4% and 2.8%-3.1%, respectively. The response linearity was confirmed for CK activity up to 1000 U/L at 37 degrees C. CK activities correlated well (r = 0.997) with those obtained by the manual method recommended by the German Society for Clinical Chemistry (measuring at 37 degrees C) involving hexokinase (EC 2.7.1.1). However, CK activities measured by our method were consistently higher than those of the hexokinase method at reaction temperatures of 30, 37, and 40 degrees C. These data indicate that the new method with thermostable glucokinase is better than that with thermo-unstable hexokinase for determination of CK activity in serum.
[Etiology and physiopathology of Hashimoto's disease ].
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Receptors in disease: an overview.
Hormones and certain other signal molecules bind to plasma membrane or intracellular receptors producing signals that initiate their physiological effects. Recent understanding of receptors has resulted in recognition of several categories of receptor-related abnormalities. (a) Congenital receptor abnormalities such as receptor deficiency syndrome. LDL receptor defect in familial hypercholesteremia and primary androgen resistance are examples. (b) Postreceptor coupling abnormalities such as pseudohypoparathyroidism type Ia where there are reduced levels of guanine nucleotide receptor cyclase coupling protein. (c) Acquired receptor abnormalities, such as presence of circulating antireceptor antibodies. Such antibodies have been implicated in the pathophysiology of many diseases including Graves' disease and myasthenia gravis.
Digoxin-like immunoreactivity in Chinese medicine.
Immunoreactive digoxin-like activity was observed in Chinese medicine, KYUSHIN tablet, taken popularly in Japan without prescription. The antibodies used in the assays of digoxin reacted with Chan-su, the major effective component of KYUSHIN, which contained cardiotonic steroids with similar chemical structure as digoxin. One tablet of KYUSHIN had digoxin-like immunoreactivity equivalent to 1.9, 1.5, and 72 micrograms of digoxin measured by three different commercial kits. These different equivalences may be attributed to differences in cross-reactivity of the antibody used in the immunoassays. Two healthy volunteers took two KYUSHIN tablets three times a day, a typical dose, and digoxin-like immunoreactivity reached almost 0.4 micrograms/L in 0.5 day. Therapeutic drug monitoring should be interpreted carefully in patients taking Chinese medicines, many of which contain the Chan-su component.
Relationship between proliferation and cell cycle-dependent Ca2+ influx induced by a combination of thyrotropin and insulin-like growth factor-I in rat thyroid cells.
The mechanism of cell proliferation by a combination of thyroid-stimulating hormone (TSH) and insulin-like growth factor-I (IGF-I) was studied in rat thyroid (FRTL-5) cells. IGF-I stimulated an approximately 3.5-fold increase in the rate of Ca2+ influx sustained for at least 6 h in TSH-pretreated cells but not in quiescent cells. The significant cell proliferation was observed when TSH-primed cells were incubated with IGF-I for 24 h but not for 12 h. IGF-I stimulated the rate of Ca2+ influx in a dose-dependent manner that was similar to that for induction of DNA synthesis. Both Ca2+ influx and DNA synthesis observed in response to IGF-I in TSH-primed cells were inhibited by cobalt. In addition, the stimulations of Ca2+ influx and DNA synthesis by IGF-I were dependent on extracellular Ca2+ in TSH-pretreated cells. When TSH-primed cells were pretreated with pertussis toxin, both IGF-I-induced Ca2+ influx and DNA synthesis were abolished. However, pertussis toxin did not block the priming action of TSH or forskolin. When calcium entry was induced by Bay K8644, it stimulated cell growth in TSH-primed cells but not in quiescent cells. Moreover, cobalt and lanthanum inhibited DNA synthesis even when added several hours after the addition of Bay K8644 but not when added 24 h after the growth factor in TSH-primed cells. These findings suggest that at least two important mechanisms may work in response to IGF-I only in the TSH-primed G1 phase of the cell cycle: first, IGF-I can activate directly or indirectly the Ca2+ channel via a pertussis toxin-sensitive substrate in TSH-primed cells; and second, a long lasting calcium entry by IGF-I may be a cell cycle-dependent mitogenic signal.
The distinct roles of alpha- and beta-subunits of human thyrotropin in the receptor-binding and postreceptor events.
The roles of alpha- and beta-subunits of human TSH (hTSH) were studied by investigating the inhibitory effects of monoclonal antibodies on the biological activity of hTSH. Four monoclonal antibodies directed toward different epitopes on the beta-subunit (hTSH beta) inhibited completely the receptor binding of hTSH to FRTL-5 rat thyroid cells. In contrast, five monoclonal antibodies directed toward different epitopes on the alpha-subunit had little or no effect on the receptor binding. Furthermore, four of five alpha-subunit-specific antibodies and three of four hTSH-specific antibodies inhibited both hTSH-induced cAMP accumulation and thymidine uptake in FRTL-5 cells, in a dose-response manner. One hTSH (alpha-beta heterodimer)-specific antibody which did not recognize the free subunits also had the inhibitory effect on both the receptor binding and hTSH-induced cAMP accumulation. These results strongly suggest that hTSH beta is indispensable for recognizing the receptors on FRTL-5 cells and that the alpha-subunit is required for signal transduction in postreceptor step(s). In addition, it is also suggested that the highly conformational structure of hTSH is absolutely essential for the biological activity.
Low prevalence of thyrotropin receptor antibody in primary hypothyroidism in Japan.
The prevalence of TSH receptor antibody (TRAb), measured by RRA assay (TSH-binding inhibitor immunoglobulin, TBII) and biological stimulation-blocking assay (thyroid-stimulation blocking antibody, TSBAb), was examined in 134 consecutive patients with primary hypothyroidism due to autoimmune thyroiditis [83 patients with goitrous Hashimoto's disease (group A) and 51 with primary atrophic hypothyroidism (group B)]. In group A, TBII was detected in 6 patients (7%), TSBAb in 7 (8%), and both in 4 (5%). Similarly, in group B, TBII was detected in 7 patients (14%), TSBAb in 7 (14%), and both in 5 (10%). TBII with TSBAb activity was low or moderate in group A, but strongly positive in group B. No relationship was apparent in either group between TBII or TSBAb activity and any clinical or laboratory parameter examined. Moreover, no clinical or laboratory findings distinguished patients with TRAb from those without. The low prevalence of TRAb in primary hypothyroidism suggests that intrathyroidal cell-mediated destructive mechanisms may be more important in the pathogenesis of hypothyroidism in autoimmune thyroiditis.
Massage therapy on neck: a contributing factor for destructive thyrotoxicosis?
A 57-year-old woman with Hashimoto's disease is described who developed transient destructive thyrotoxicosis subsequently after she underwent physical massage therapy over her shoulder to neck, together with the goiter, for muscle stiffness in that part. This case supports the concept that physical vigorous manipulation might be a contributing factor for thyrotoxicosis in cases predisposed with autoimmune thyroiditis.