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Biomedical subjects

K Kuma

Publications and source records attributed to K Kuma.

At least 163 records · Page 9Linked to original sources
PubMed1990

Presence of both stimulating and blocking types of TSH-receptor antibodies in sera from three patients with primary hypothyroidism.

A case report of three patients with primary hypothyroidism who had potent TSH-binding inhibitor immunoglobulins (TBII) and both thyroid stimulating (TSAb) and thyroid stimulation-blocking antibodies (TSBAb) has been described. Two patients displayed symptoms and signs indistinguishable from those in primary myxoedema (cases 1 and 2), and another patient had a history of Graves' disease (case 3). TBII, TSAb and TSBAb activities were 90.0, 1084.2 and 94.5% in case 1, 91.5, 826.6 and 95.8% in case 2, 76.0, 230.0 and 95.0% in case 3, respectively (normal range, less than 11.0%, less than 145.0 and less than 22.0%, respectively. The results indicate that both stimulating and blocking types of TSH-receptor antibodies exist in these patients. The possible mechanism whereby hypothyroidism developed has been discussed.

Adolescent↗
PubMed1990

Follow-up study of thyroid stimulating-blocking antibodies in hypothyroid patients.

It has been shown that hypothyroidism of some patients may be associated with increased activity of thyroid stimulating-blocking antibodies (TSBAb). The present study was undertaken to follow the course of thyroid blocking, stimulating immunoglobulins and TSH-binding inhibitor immunoglobulins (TBII) in six hypothyroid patients who had elevated TSBAb and were treated with T4. Four of the six had Graves' disease previously treated with antithyroidal drugs, one had Graves' disease treated with 131I and one had subacute thyroiditis and subsequently became hypothyroid. The patients were followed for 1-5 years. Blocking activity and TBII normalized in four of the six during T4 therapy, so T4 was discontinued and they remained euthyroid. These data indicate that it is important to monitor carefully thyroid function in hypothyroid patients treated with a fixed amount of T4 to avoid subclinical hyperthyroidism and its consequence, e.g. osteoporosis.

Adolescent↗
PubMed1990

Diffuse sclerosing variant of papillary carcinoma of the thyroid. A histopathological study of four cases.

We present four cases of an unusual diffuse sclerosing variant of papillary carcinoma of the thyroid occurring in Japanese women ranging in age from 17 to 42 years. Macroscopically, both lobes of the thyroid were involved, being diffusely enlarged and firm. Histologically, the tumor was characterized by squamous metaplasia of tumor cells, numerous psammoma bodies, extensive stromal fibrosis, severe lymphocytic infiltration with formation of lymph follicles, and thin bundles of smooth muscle cells in the fibrous stroma. The tumor islands were located mainly within the dilated lymphatic vessels and the metastatic tumor involved the bilateral cervical lymph nodes in all cases. It is assumed that papillary carcinoma of this type invades the thyroid lymphatics during the early stage and, without forming nodular lesions, disseminates to both lobes with extensive metastasis to the cervical lymph nodes. It should be noted that papillary carcinoma of this type often suggests chronic thyroiditis clinically because of the symmetrical enlargement of the thyroid and frequent positive anti-thyroid antibodies in the serum. Some workers have reported the prognosis to be unfavorable because of extensive lymphatic involvement, but the prognosis of this variant has not yet been defined.

Adolescent↗
PubMed1990

Thyroid response, especially to thyrotropin-binding inhibitory immunoglobulins, in euthyroid relatives of patients with Graves' disease: a clinical follow-up.

Three hundred and fifty-three euthyroid relatives of Graves' disease patients were tested for TSH binding inhibitory immunoglobulins (TBII). Eighteen had elevated levels of TBII, and 232 who had negative TBII levels also agreed to be followed for a period of 6-30 months. TBII was chosen as the critical screening measurement for this study, rather than thyroid-stimulating antibodies (TSAb) and thyroid-stimulating blocking antibodies (TSBAb), because of the availability and ease of use of TBII RIA kits. Eleven of the 18 subjects with elevated TBII were T3 nonsuppressible (group I), and 10 of the 11 were TRH unresponsive. Nine of these 10 subjects showed TSH levels below 0.05 mU/L. The remaining 7 subjects were T3 suppressible and TRH responsive (group II). Alterations in thyroid status occurred in 8 of the 11 subjects in group I during follow-up. One developed hypothyroidism, and 7 became hyperthyroid. The hypothyroid subject had initial titers of TBII, TSAb, and TSBAb that were markedly elevated, and TSAb disappeared when she became hypothyroid. Six of the 7 subjects who developed hyperthyroidism had elevated TSAb and negative TSBAb titers while they were euthyroid. All 7 subjects in group II remained euthyroid during the follow-up period. Only 2 of the 232 relatives who initially had negative TBII titers became hyperthyroid during the follow-up period. The results indicate that euthyroid relatives with a family history of Graves' disease who have elevated TBII levels and suppressed basal serum TSH concentrations have a much higher potential to develop hyperthyroidism than those who have normal or negative TBII levels.

Adolescent↗
PubMed1990

The occurrence of thyrotropin binding-inhibiting immunoglobulins and thyroid-stimulating antibodies in patients with silent thyroiditis.

Silent (painless) thyroiditis has been recognized as a clinical entity for over a decade and is characterized by spontaneously resolving thyrotoxicosis. Its etiology is uncertain; however, a few reports have indicated the occurrence of TSH binding-inhibiting immunoglobulins (TBII) and thyroid-stimulating antibodies (TSAb) in some of the patients. The present study was undertaken to evaluate thyroid function and the occurrence of TBII and TSAb and thyroid autoantibodies (antithyroglobulin and antimicrosomal) in 53 patients with silent thyroiditis during the course of their disease. The patients were divided into 2 major groups: I) those who developed transient hypothyroidism and II) those who did not. All patients initially had significantly increased concentrations of serum T4, free T4, and free T3, suppressed TSH levels, and decreased thyroid radioiodine uptake. TBII and TSAb were initially positive in 8 (15.1%) and 10 patients (18.9%), respectively. Forty patients were available for follow-up. TBII was positive in 6 of 24 (25.0%), and TSAb was positive in 8 of 24 (33.3%) of the patients who developed transient hypothyroidism during the course of their disease. Among the patients who did not become hypothyroid at any time, TBII was positive in only 2 of 16 (12.5%), and none of the patients became TSAb positive. The findings indicate that increased TSAb and TBII activity may be detected in patients with silent thyroiditis and, when present, are associated with transient hypothyroidism during the course of the disease.

Adolescent↗
PubMed1990

Changes in serum autoantibodies to thyroid peroxidase during antithyroid drug therapy for Graves' disease.

Thyroid microsomal antigen is considered to be identical with thyroid peroxidase (TPO). Although there have been many reports concerning changes in microsomal autoantibody during the course of antithyroid drug therapy for Graves' disease, little is known about this matter in relation to TPO autoantibody (TPOab). Therefore, in this paper, we studied serial changes in the latter autoantibody. Initial levels of serum TPOab (% immunoprecipitation) in 13 patients with hyperthyroid Graves' disease ranged from -11.3% to +84.5% (mean +/- SD, 38.9 +/- 31.8%). Of three patients with persistently increased serum TPOab throughout drug therapy, all had recurrence of hyperthyroidism after the drug was discontinued. Of seven patients whose TPOab levels were initially high but subsequently decreased, four had remission of the disease after drug therapy. Inhibition by TPOab of the TPO activity was also demonstrated by both guaiacol and iodide assays, and changes in this inhibitory activity during therapy varied among individuals. This inhibition was not correlated with disease remission. The decrease in serum TPOab observed in some antithyroid drug-treated patients may reflect a decline in disease activity or may be a direct effect of the drug.

Adolescent↗
PubMed1990

Thyroid-stimulating antibody and thyrotropin-binding inhibitory immunoglobulin activity in hypothyroid patients who subsequently developed thyrotoxicosis.

Although abnormal thyroid-stimulating and -blocking antibodies have been demonstrated in hyperthyroid and hypothyroid patients with autoimmune thyroid disorders, a direct correlation is not always observed. Thyroid-stimulating antibody, thyrotropin-binding inhibitory immunoglobulin, and thyroid-stimulating blocking antibody levels were determined in three hypothyroid patients who subsequently developed hyperthyroidism. Thyroid-stimulating antibodies levels were normal in one, elevated in another, and unmeasured in the third hypothyroid patient, but became elevated in all patients with the onset of hyperthyroidism. There was discordance, however, in one patient who had markedly elevated thyroid-stimulating antibodies and TSH-binding inhibitory immunoglobulin levels when she was hypothyroid. The data indicate that thyroidal responses to the abnormal stimulating antibodies may differ among patients with autoimmune thyroid disease.

Adult↗
PubMed1989

Possible disorder of B-cell-related surveillance and malignant lymphoma of the thyroid.

Malignant lymphoma of the thyroid has been shown to be of B-cell origin. To clarify its genetic origin, we have investigated HLA-A, B, C, and DR antigens, and the immunoglobulin G (IgG) heavy-chain allotype, Gm, in such patients. There was no correlation between the occurrence of malignant lymphoma of the thyroid and the HLA antigens tested, but patients with this lymphoma had significantly lower frequency of the Gm1,21 haplotype than healthy persons. These results suggested a disorder of surveillance related to B-cells may be involved in the pathogenesis of malignant lymphoma of the thyroid.

Adult↗
PubMed1989

Stable high level expression of human thyroid peroxidase in cultured Chinese hamster ovary cells.

An expression plasmid containing both human thyroid peroxidase and mouse dihydrofolate reductase cDNAs was transfected into chinese hamster ovary cells. The stably transformed cells constitutively expressed immunoreactive thyroid peroxidase on the cell surface. These cells were further used to establish a subline producing a large amount of thyroid peroxidase by selecting clones resistant to methotrexate. The molecular weight of the expressed thyroid peroxidase was the same as purified human thyroid peroxidase. This expressed protein had peroxidase activity when determined by guaiacol oxidation. Furthermore, the expressed thyroid peroxidase was immunoreactive to sera of patients with autoimmune thyroid disease in which autoantibodies to thyroid peroxidase appeared.

Animals↗
PubMed1989

Correlation of chromosome abnormalities with clinical characteristics in thyroid lymphoma.

Karyotypes from seven patients with thyroid lymphoma were studied before treatment. When the cytogenetic results were correlated with the clinical data, it became evident that there are two distinct groups of patients with thyroid lymphoma. In a group of patients with solely numerical abnormalities the disease is associated with a rather long duration from the onset of goiter to the time of operation for lymphoma, with abnormal thyroid function, and with positive tests for antithyroid autoantibodies. Two of four patients in this group showed trisomy 22; the remaining two showed a loss of a sex chromosome. The other group of patients with solely structural abnormalities is associated with a short duration from the onset of goiter to the time of operation, with normal thyroid function, and with the trend of negative tests for autoantibodies. Two of three patients in this group showed a 14q+ abnormality. These results indicate that there are two distinct type of thyroid lymphoma, chromosomal changes of which are implicated as pathogenetic factors in lymphomagenesis of different mechanisms.

Aged↗
PubMed1989

Mixed-valence hydroxides as bioorganic host minerals.

A range of naturally occurring divalent-trivalent metal cation hydroxides and modified artificial analogs have been synthesized and characterized. Structural and chemical properties of these minerals, determining their capability to selectively concentrate, order and alter molecules of prebiotic interest, include their anion exchange capacity and specificity, photochemical reactivity, production of nascent hydrogen, and catalytic efficiency. Properties relevant to these functions have been investigated and are discussed.

Aluminum↗
PubMed1989

Analysis of epidermal growth factor (EGF) receptor and effect of EGF on the growth of cultured Graves' and non-neoplastic human thyroid cells.

We analyzed epidermal growth factor receptors (EGF-R) and the growth stimulatory effects of epidermal growth factor (EGF) in the presence or absence of TSH on cultured human non-neoplastic and Graves' thyroid cells. All cells studied possessed EGF-R composed of two components. There was no significant differences in the binding characters of EGF-R among non-neoplastic thyroid cells whether they were obtained from thyroid tissues adjacent to malignant carcinoma or benign adenoma. Ten nM of EGF stimulated (3H)-thymidine (dTR) incorporation of non-neoplastic thyroid cells by about 50%. However, TSH had no effect on the growth of these cells. Both EGF-R binding parameters and cell proliferation effects of EGF and TSH were simultaneously examined in non-neoplastic thyroid cells from 8 patients. A significant inverse correlation (r = -0.757) was observed between binding affinity (Ka1) and EGF-induced increase of dTR incorporation. Binding capacity (Cmax) did not correlate significantly with dTR incorporation. In Graves' thyroid cells, all parameters of EGF-R were significantly lower than those of non-neoplastic thyroid cells, higher basal dTR incorporation was observed, and their goiter size significantly correlated with EGF-induced increase of dTR incorporation (r = 0.879) and also appeared to correlate inversely with Ka1. These data indicate a close relationship between the binding affinity of EGF-R and thyroid cell growth.

Cell Division↗
PubMed1989

Newcastle disease virus evolution. I. Multiple lineages defined by sequence variability of the hemagglutinin-neuraminidase gene.

We compared the hemagglutinin-neuraminidase gene sequence among 13 strains of Newcastle disease virus (NDV) isolated over the last 50 years. Although overall homology was remarkably high, the sequence variability demonstrated the existence of at least three distinct lineages, which must have co-circulated for considerable periods. The sequence variability also appears to reflect some accumulation of mutations over time. Strictly correlating with the lineages, the translation products could be classified into three size classes. One class lacked the interchain disulfide bond, and another represented unusual precursor protein of biologically inactive form. The lineages correlated to some extent with virulence and place of isolation of the strains. However, antigenic variations, which were neither cumulative nor progressive, did not correlate with the lineages. These analyses showing multiple lineages were greatly facilitated by a precise calculation of synonymous substitutions, which had been largely free from selective pressures and had occurred frequently and evenly throughout the coding region.

Amino Acid Sequence↗
PubMed1989

Newcastle disease virus evolution. II. Lack of gene recombination in generating virulent and avirulent strains.

Sequence analysis and comparison of the fusion glycoprotein genes of 11 Newcastle disease virus (NDV) isolates indicated a high degree of functional and structural constraint exerted on the change of the glycoprotein. However, synonymous nucleotide substitutions occurred frequently throughout the coding region. Facilitated by an analysis of synonymous difference (Ks) in pairwise strain comparison, we defined the branching orders of the strains and identified three distinct evolutionary lineages correlating with the virulence as expressed by mean death time (MDT) for chick embryo. The typically virulent strains with MDT of about 50 hr were associated with one lineage, while the typically nonvirulent strains with MDT of infinity were of another lineage. The third lineage consisted of both virulent and avirulent strains whose MDTs lay on a continuum from 50 to 120 hr. Synonymous substitutions were found to occur with almost the same rates in the adjacent hemagglutinin-neuraminidase and membrane protein genes as in the fusion protein gene, and the branching orders based upon the Ks for these genes were essentially identical to those derived from the fusion protein gene. Therefore, no gene exchange by recombination seems to have occurred to generate the strains of distinct lineages. Rather, the different strains appear to have evolved through various degrees of accumulation of point mutations. Besides these evolutionary features, the present study strongly supports the importance of the previously identified signals for gene expression and for the proteolytic activation of the gene product.

Animals↗
PubMed1989

Intrathyroidal HLA-DR-positive lymphocytes in Hashimoto's disease: increases in CD8 and Leu7 cells.

The peripheral and intrathyroidal HLA-DR-positive (DR+) lymphocyte subsets that were activated in vivo in patients with Hashimoto's disease (HD) were examined by two-color flow cytometry with monoclonal antibodies against CD3, CD4, CD8, Leu7, CD19, and HLA-DR antigens. The proportions of total DR+ cells in peripheral lymphocytes and the proportions of DR+ cells in the CD3+, CD4+, and Leu7+ lymphocytes were higher in patients with HD than in normal controls. Furthermore, the proportions of total DR+ cells among intrathyroidal lymphocytes isolated from thyroid tissue of individuals with HD were higher than those in their peripheral lymphocytes. Interestingly, the proportions of DR+ cells among the CD3+, CD8+, and Leu7+ lymphocytes in the thyroid were greatly increased. These data indicate that (i) CD3+ T, especially CD4+ T helper/inducer, lymphocytes and Leu7+ NK/K cells are activated in peripheral blood in Hashimoto's disease and that (ii) CD3+ T, especially CD8+ T suppressor/cytotoxic, lymphocytes and Leu7+ NK/K cells are predominantly activated in Hashimoto's goiter, suggesting an increase of cell-mediated cytotoxicity in the thyroid in Hashimoto's disease.

Adult↗
PubMed1989

Evolutionary relationship of archaebacteria, eubacteria, and eukaryotes inferred from phylogenetic trees of duplicated genes.

All extant organisms are though to be classified into three primary kingdoms, eubacteria, eukaryotes, and archaebacteria. The molecular evolutionary studies on the origin and evolution of archaebacteria to date have been carried out by inferring a molecular phylogenetic tree of the primary kingdoms based on comparison of a single molecule from a variety of extant species. From such comparison, it was not possible to derive the exact evolutionary relationship among the primary kingdoms, because the root of the tree could not be determined uniquely. To overcome this difficulty, we compared a pair of duplicated genes, elongation factors Tu and G, and the alpha and beta subunits of ATPase, which are thought to have diverged by gene duplication before divergence of the primary kingdoms. Using each protein pair, we inferred a composite phylogenetic tree with two clusters corresponding to different proteins, from which the evolutionary relationship of the primary kingdoms is determined uniquely. The inferred composite trees reveal that archaebacteria are more closely related to eukaryotes than to eubacteria for all the cases. By bootstrap resamplings, this relationship is reproduced with probabilities of 0.96, 0.79, 1.0, and 1.0 for elongation factors Tu and G and for ATPase subunits alpha and beta, respectively. There are also several lines of evidence for the close sequence similarity between archaebacteria and eukaryotes. Thus we propose that this tree topology represents the general evolutionary relationship among the three primary kingdoms.

Adenosine Triphosphatases↗