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Biomedical subjects

K Kuma

Publications and source records attributed to K Kuma.

At least 145 records · Page 8Linked to original sources

Expression of dipeptidyl aminopeptidase IV activity in thyroid carcinoma.

Dipeptidyl aminopeptidase IV activity staining was performed in various thyroid tissues to evaluate this enzyme activity as a thyroid tumor marker. A total of 195 thyroid tissues were tested for their enzyme activity expression. All papillary and follicular carcinomas, 40 cases and 3 cases, respectively, showed enzyme activity, although two other carcinomas, one medullary and one anaplastic, were not stained. Follicular adenoma expressed enzyme activity in 4 of 26 cases. Fifty-two cases with adenomatous goiter, 54 with Graves' disease and 13 with chronic thyroiditis were judged to be negative. Five normal thyroids expressed no activity except for occasional positive staining of capillary endothelia. These data suggest that dipeptidyl aminopeptidase IV activity staining is very useful for pathological diagnosis of thyroid tumors.

Dipeptidyl Peptidase 4↗

Monocytoid B-cell lymphoma arising in extranodal organs.

Six cases of monocytoid B-cell lymphoma (MBCL) developing in extranodal sites (thyroid, three; stomach, two; rectum, one) are described. Patients were all women aged 46 to 65 years (median, 53 years). Three patients with thyroid lymphoma presented with an increasing goiter, two with positive serum antithyroid antibodies, and one patient had chronic lymphocytic thyroiditis (CLTH). The histologic type of surgically resected specimens was a diffuse proliferation of atypical lymphoid cells with monocytoid appearance, i.e., abundant pale cytoplasm with distinct cell border and small reniform nucleus. These cells were CD20+, 22+, 24-, 9- showing their B-cell origin. The monoclonal nature of the proliferating cells was confirmed by restricted expression of immunoglobulin (Ig) light chain and/or gene rearrangement study in three cases. Two cases of thyroid lymphoma in which the monoclonality could not be confirmed had histologic appearances characteristic of malignant lymphoma. All three patients with gastric or rectal lymphoma had reactive lymphoid hyperplasia (RLH) near the tumors. These findings showed presence of MBCL in the extranodal sites with invariable coexistence with lymphoid follicles formed by CLTH in thyroid or RLH in stomach and rectum.

Aged↗

Evolution of RNA polymerases and branching patterns of the three major groups of Archaebacteria.

The amino acid sequences of the largest subunits of the RNA polymerases I, II, and III from eukaryotes were compared with those of archaebacterial and eubacterial homologs, and their evolutionary relationships were analyzed in detail by a recently developed tree-making method, the likelihood method of protein phylogeny, as well as by the neighbor-joining method and the parsimony method, together with bootstrap analyses. It was shown that the best tree topologies predicted by the first two methods are identical, whereas the last one predicts a distinct tree. The maximum likelihood tree revealed that, after the separation from archaebacteria, the three eukaryotic RNA polymerases diverged from an ancestral precursor in the eukaryotic lineage. This result is contrasted with the published result showing multiple origins for the three eukaryotic polymerases. It was shown that eukaryotic RNA polymerase I evolved much more rapidly than RNA polymerases II and III: The N-terminal half of RNA polymerase I shows an extraordinarily high evolutionary rate, possibly due to relaxed functional constraints. In contrast the evolutionary rate of archaebacterial RNA polymerase is remarkably limited. In addition, including the second largest subunit of the RNA polymerase, a detailed analysis for the branching pattern of the three major groups of archaebacteria was carried out by the maximum likelihood method. It was shown that the three major groups of archaebacteria are likely to form a single cluster; that is, archaebacteria are likely to be monophyletic as originally proposed by Woese and his colleagues.

Amino Acid Sequence↗

Heterogeneity of serum prolactin in patients with menstrual disorder in conjunction with hyperthyroxinemia.

Since the secretion of PRL is regulated by the hypothalamic-pituitary axis, an increase in large molecular size PRL in the serum is most likely due to secretion by the pituitary itself. The present study was performed to investigate the possible occurrence of PRL heterogeneity in 128 subjects with menstrual disorder in conjunction with hyperthyroxinemia (88 with untreated Graves' disease, 40 with subacute thyroiditis) and 50 age- and sex-matched healthy controls. All 128 patients in this study were suffering from amenorrhea or oligomenorrhea at the time of their initial visit. PRL heterogeneity was found in the sera of 5 of 88 (5.7%) patients with untreated Graves' disease, in 2 of 40 (5.0%) patients with subacute thyroiditis, but in none of the normal controls. PRL heterogeneity remained essentially unchanged in patients with Graves' disease over 6 months of treatment; however, in patients with subacute thyroiditis, either big-big PRL or big PRL decreased significantly along with a corresponding increase in little PRL associated with recovery from the illness within 6 months. The menstrual disorders in all patients were restored to normal after restoration to a euthyroid state. The underlying cause of the occurrence of PRL heterogeneity in patients with menstrual disorder in conjunction with hyperthyroxinemia is not known.

Adolescent↗

Natural course of Graves' disease after subtotal thyroidectomy and management of patients with postoperative thyroid dysfunction.

The Natural course of Graves' disease after subtotal thyroidectomy was studied in 67 patients who had subtotal thyroidectomy for Graves' disease and did not receive any medical treatment for 8 to 12 years after surgery. Postoperative thyroid status was determined by serum free thyroxine (T4), free triiodothyronine (T3), and thyrotropin (TSH) levels in the first period (1 year after surgery), second period (3.9 +/- 1.0 years), and third period (8.8 +/- 1.5 years). Serum thyroid stimulating antibody (TSAb) and TSH binding inhibitor immunoglobulin (TBII) activities were also measured. A total of 53 patients (79%) changed thyroid status during the observation period. One year after surgery, 50 percent of euthyroid subjects developed abnormal thyroid function in the next period. Reversible latent hypothyroidism was the most common type of thyroid dysfunction seen in up to 46% of patients. Interestingly, hyperthyroidism and hypothyroidism that developed in the postoperative period were temporary disorders in most cases. Serum TSAb and TBII activities did not help predict the postoperative changes of thyroid status. Our study indicates that the instability of the thyroid function is common after subtotal thyroidectomy.

Adult↗

A follow-up study of 85 patients with Graves' disease in remission who developed undetectable serum thyroid-stimulating hormone concentrations using sensitive TSH assays.

Eighty-five patients with Graves' disease in clinical remission after treatment for over 1 year by methimazole therapy (36 patients, group A) or subtotal thyroidectomy (49 patients, group B) who became undetectable for serum thyrotropin levels (TSH less than 0.05 mU/l), were further followed for 1 year or more. Eight patients in group A (22%) and 7 patients in group B (14%) relapsed. Eleven patients in group A (30%) and 5 patients in group B (10%) had fluctuating patterns of free T4 in the upper normal to slightly supranormal range indicative of subclinical hyperthyroidism. The remaining patients continued to have undetectable TSH levels or restored normal TSH levels and normal thyroid hormone concentrations in sera. The results of the present study indicate that the occurrence of undetectable serum TSH concentrations in Graves' disease patients previously treated with methimazole or surgery are not necessarily predictive of clinical relapse because the eventual outcome is variable.

Adult↗

Immunologic and immunohistochemical studies on chronic lymphocytic thyroiditis with or without thyroid lymphoma.

The local immunologic phenomena in the thyroid gland of 16 patients with chronic lymphocytic thyroiditis (CLTH) were investigated; 5 of these cases were associated with thyroid non-Hodgkin's lymphomas (NHL). All patients were admitted because of struma, growing slowly in patients with CLTH alone and rapidly in those with associated thyroid NHL. CLTH was confirmed by histologic findings, including the presence of lymphoid follicles or thyroid autoantibodies in the serum in all 16 patients. Immunologic study revealed that all thyroid NHL were of the B cell type. Surface maker study of suspended cells showed that the percentages of E-rosette-forming cells in patient with CLTH and thyroid NHL (38.0 +/- 10.0%) and in patients with CLTH alone (45.0 +/- 11.9%) were between those of B cell NHL of lymph node and B cell hyperplasia reported by others. Immunohistochemical studies confirmed the reactive nature of lymphoid follicles. Subset distribution of T and B lymphocytes in patients with CLTH and thyroid NHL markedly contrasted with that in patients with CLTH alone: an increased ration of CD8+ cells (suppressor/cytotoxic cell) to CD4+ cells (helper/inducer cell). There was a marked increase in the number of immunosuppressive acidic-protein(IAP)-containing macrophages in the thyroid lesion and serum IAP level in patients with thyroid NHL. These findings provide evidence of a difference in the local immunologic conditions in CLTH alone compared to CLTH complicated by thyroid NHL.

Adult↗

The incidence of thyroid stimulating blocking antibodies during the hypothyroid phase in patients with subacute thyroiditis.

The etiology of subacute (de Quervain's) thyroiditis (SAT) is uncertain, although it probably represents a nonspecific inflammatory response by the thyroid to a variety of viruses. It has been suggested that nonimmune processes are involved in SAT patients who have negative autoantibody titers. The disease has a variable course; although it is self-limited in most cases, some patients develop transient hypothyroidism, and others do not during the recovery period. The present study was performed to evaluate the occurrence of TSH receptor antibody (TRAb), measured by RRA (TSH binding inhibitor), TRAb measured by stimulation assay (thyroid-stimulating antibody), and TRAb measured by blocking assay [TSH-blocking antibody (TSH-BAb)] activity in 68 patients with SAT who had negative autoantibody titers. The patients were divided into 2 groups: group I, 31 patients who developed hypothyroidism during the recovery period; and group II, 37 patients who remained euthyroid during recovery. Positive immunoglobulin activity occurred in about 20% of group I patients during follow-up, but in only 3% of group II patients. About 20% of group I patients developed positive TSH-BAb activity and were hypothyroid, requiring exogenous hormone therapy for 1.2-3.5 yr, whereas hypothyroidism was relatively transient in group I patients who had negative TSH-BAb activity (2-6 months). Although increased TSH-BAb activity may account for hypothyroidism in some patients with SAT, the precise mechanism for the development of transient hypothyroidism in SAT remains enigmatic.

Adult↗

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.

Adult↗

RNA-binding protein-related sequence in a malaria antigen, clustered-asparagine-rich protein.

Members of the RNA-binding protein superfamily contain RNA binding domains of about 90 amino acids with a highly conserved motif 'GFGF'. Using the conserved motif with some variations G-(F/Y)-(G/A)-(F/Y)-(V/I)-X-(F/Y) as a probe, we screened protein sequences carrying identical amino acids in an NBRF-protein database. It has been found that the C-terminal portion of clustered asparagine-rich protein (CARP), a malaria antigen from Plasmodium falciparum, shows an unexpected sequence similarity with the RNA-binding protein superfamily for the C-terminal half of the RNA-binding domain. Dot matrix comparisons and alignment of these sequences as well as a statistical test have revealed highly significant sequence similarities. From these analyses, we conclude that the malaria antigen CARP belongs to a large family of the RNA-binding proteins. An evolutionary implication of the sequence similarity was also discussed.

Amino Acid Sequence↗

Compartmentalized isozyme genes and the origin of introns.

Both the mouse cytosolic malate dehydrogenase gene and its mitochondrial counterpart contain eight introns, of which two are present at identical positions between the isozyme genes. The probability that the two intron positions coincide by chance between the two genes has been shown to be significantly small (= 1.3 x 10(-3), suggesting that the conservation of the intron positions has a biological significance. On the basis of a rooted phylogenetic tree inferred from a comparison of these isozymes and lactate dehydrogenases, we have shown that the origins of the conserved introns are very old, possibly going back to a date before the divergence of eubacteria, archaebacteria, and eukaryotes. In the aspartate aminotransferase isozyme genes, five of the introns are at identical places. The origins of the five conserved introns, however, are not obvious at present. It remains possible that some or all of the conserved introns have evolved after the divergence of eubacteria and eukaryotes.

Amino Acid Sequence↗

Thyroid peroxidase in endemic goiter tissue.

Thyroid peroxidase (TPO) activity and TPO protein were analyzed in endemic goiter tissue under iodine deficiency and after iodine supplement. TPO was prepared from 9 endemic goiter tissues and 4 normal thyroid tissues by solubilizing enzyme with detergent. Four patients with endemic goiter received iodized oil injection 12 months before surgery. All patients had normal serum thyrotropin (TSH) and thyroid hormone levels before surgery. TPO activity was measured by iodinase assay and guaiacol assay. Endemic goiter TPO showed greater iodination activity than that of normal TPO (p less than 0.01). The guaiacol assay showed greater TPO activity in 6 of the 9 endemic goiter tissues than that of the normal tissue. Iodized oil treatment did not affect TPO activity or TPO proteins when compared with those in untreated endemic goiter tissues. TPO activity in endemic goiter tissue correlated with thyroid T4 5'-deiodinase activity and not with thyroid hormone content in thyroglobulin. Since thyroid T4 5'-deiodinase and TPO are under control of TSH, an increase in TPO activity in the presence of normal serum TSH may be explained by the increased sensitivity of endemic goiter tissue to TSH-one of the possible adaptation mechanisms of endemic goiter.

Adult↗

Sensitivity of thyroids to endogenous thyrotrophin in patients with Graves' disease.

T3 nonsuppressibility and TSH nonresponsiveness to TRH are characteristics of untreated hyperthyroid Graves' disease. Although the tests are commonly restored to normal during antithyroidal drug therapy, dissociation of TRH and T3 suppression tests have been observed in euthyroid Graves' disease and during drug therapy. Abnormalities of pituitary-thyroidal regulation and persistence of thyroid autoimmune disease have been found in Graves' patients following various modalities of therapy. The present study investigated in vivo sensitivity to endogenous TSH of thyroids in 144 Graves' disease patients following treatment with subtotal thyroidectomy, 131I, or antithyroidal drugs. After administration of TRH, thyroidal sensitivity to TSH was determined by the following: delta T3 (peak T3 minus basal T3), % increase in T3 (peak over basal), and the ratio of delta T3 to delta TSH. Significant differences in sensitivity to TSH in T3 nonsuppressible patients were found compared to suppressible patients regardless of their TSH responses to TRH or modality of therapy. These data suggest that measurements of serum T3 and TSH following TRH administration to determine in vivo thyroidal sensitivity may be substituted for the T3 suppression test as a confirmatory test for Graves' disease or as a prognosticator of relapse following therapy.

Adolescent↗

Unusual thyroid scintigrams in Plummer's disease during methimazole therapy. Conversion of hot to hypofunctional nodules.

Thyroid scintigrams of two women (aged 48 and 58) with Plummer's disease showed unusual radioiodine accumulation during treatment with methimazole (MMI). Before MMI therapy, the scintigrams revealed most of the radioiodine uptake only in the nodules of the patients and very little uptake in the non-nodular portions of the thyroid. After initiation of MMI therapy, scintigrams performed at three and eight months revealed that the hot nodules had become hypofunctional and that the surrounding tissues had normal radioiodine accumulation. The findings indicate that the nodules in Plummer's disease continue to concentrate MMI selectively compared with normal surrounding thyroid tissue during therapy.

Adenoma↗

Hashimoto's thyroiditis manifesting monoclonal lymphocytic infiltration.

Hashimoto's thyroiditis (HT) and lymphoma are sometimes difficult to distinguish between. Moreover, lymphoma sometimes develops in a thyroid gland from pre-existing HT. Open- or large-needle biopsy usually distinguishes between them; the specimen may be examined histologically and subjected to immunohistochemistry. Another possible method of examination is fine-needle aspiration biopsy (FNAB). The cells obtained may be evaluated cytologically, and subjected to flow cytometry, using various antibodies. In this study, anti-kappa and anti-lambda antibodies are especially important, as a gross predominance of kappa or lambda B lymphocytes infiltrating the thyroid is evidence for a B cell monoclone. In this study, 15 patients were selected because of their rapidly growing goitres. They all underwent FNAB. Five had cytology typical of HT, and no evidence of monoclonality on flow cytometry. They were diagnosed as HT without further histopathology. The remaining 10 patients had cytology suspected of lymphoma, or evidence of monoclonality on flow cytometry, or both. These patients underwent open- or large-needle biopsy. Only three of them were diagnosed histopathologically as lymphoma; the other seven were diagnosed histopathologically as HT, making 12 cases of HT in all. Five of these 12 cases, and one of the three cases of lymphoma showed flow cytometrical evidence of monoclonality; thus evidence of monoclonality from FNAB, while interesting, does not necessarily serve to differentiate between HT and lymphoma. Furthermore, the immunohistochemical assessment of monoclonality did not correlate with the flow cytometrical assessment. Follow-up evidence will be required to discover whether those patients with a B cell monoclone in their HT are the ones who develop a lymphoma.

Aged↗