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Biomedical subjects

K Sugino

Publications and source records attributed to K Sugino.

At least 55 records · Page 3Linked to original sources

Identification of activins A, AB, and B and follistatin proteins in Xenopus embryos.

There are several lines of evidence that activin is a crucial molecule for mesoderm induction in early Xenopus embryos. However, it is not known what kind and what amounts of activin proteins exist in cleavage stage embryos. Three isoforms of activins, A, AB, and B, were demonstrated to be present at least in part as a complex with abundant follistatin, an activin-binding protein, in early Xenopus embryos (stage 1-5). These results suggest that activin stored in eggs has an important role for mesoderm induction during early Xenopus embryogenesis and that follistatin can modulate the function of activin in signaling developmental changes.

Activins↗

The enucleation of thyroid tumors indeterminate before surgery as papillary thyroid carcinoma: should immediate reoperation be performed?

The management of patients with thyroid nodules which are indeterminate as papillary thyroid carcinoma (PTC) before surgery but identified as such after surgery still poses great difficulty for the surgeon. Immediate reoperation is often not performed due to the indolent biological characteristics of this disease and the increased risk of associated surgical complications. We conducted a study to determine whether or not immediate reoperation should be performed. The prognosis of 91 patients with PTC who underwent enucleation only was compared with that of 321 control patients with non-advanced PTC who underwent radical surgery during the same period. There were no deaths due to PTC in either group. Distant metastasis was observed in 1.1% and 0.6% of the enucleation and control patients, respectively, while local recurrence was observed in 3.3% and 8.1%, respectively. These results suggest that immediate reoperation is not necessary for patients who have undergone enucleation only.

Adolescent↗

An analysis of lymphocyte subsets in the regional lymph nodes of patients with papillary thyroid carcinoma.

Lymphocyte subsets in the lymph nodes regional to papillary thyroid carcinoma were determined using flow cytometry to ascertain the differences in local immunological responses between elderly and young patients. Lymph nodes from age-matched patients with benign thyroid tumors were used as controls. No significant alterations in lymphocyte subsets were observed in the lymph nodes from the young patients regardless of whether metastasis was present, whereas those from the elderly patients showed significant decreases in pan T cell (CD2+, CD3+) and cytotoxic T cell (CD8+, CD8+CD11b-) populations, and a significant increase in B cells (CD19+) compared with those from both the young patients and the age-matched controls. These results indicate that local immunological alterations occur in elderly patients with papillary thyroid carcinoma, and we believe that immunological changes are one of the clinical characteristics of this tumor.

Adolescent↗

Hemiaplasia of the thyroid associated with Graves' disease: report of three cases and a review of the literature.

We recently treated three additional patients with hemiaplasia of the thyroid associated with Graves' disease, making a total of eight such cases. All eight of these patients were women and their chief complaints were goiter in five cases, whereas exophthalmos or palpebral edema were noted in six cases. All eight patients underwent surgery for Graves' disease. The left lobe was absent in six cases and the right lobe in two, whereas the isthmus was absent in six cases and the pyramidal lobe in four. A total of 102 cases of hemiaplasia of the thyroid, including our present three cases, have been reported in the world literature since 1970, with 32 of them consisting of hemiaplasia associated with hyperthyroidism. Of these, the cause of hyperthyroidism was Graves' disease in 22 cases, an autonomously functioning thyroid nodule in 7, and thyrotoxic multinodular goiter in 3. The left lobe was absent in 19 cases while the right lobe was missing in 12, and laterality was unknown in 1 case.

Adolescent↗

Solid cell nests of the thyroid in medullary thyroid carcinoma.

Solid cell nests of the thyroid gland were studied in 44 patients with medullary thyroid carcinoma. In 10 (22.7%) patients, solid cell nests were revealed in the vicinity of tumour foci (five cases) or in the contralateral thyroid lobe and isthmus (four cases); in one case the location was indeterminate. In all seven cases in which immunohistochemical studies were carried out, solid cell nests showed negative staining for thyroglobulin, calcitonin and chromogranin A, findings which were distinct from those in medullary thyroid carcinoma. It is therefore suggested that solid cell nests of the thyroid are not precursors of this tumour.

Adolescent↗

[The "addiction trends" seen among the wives of alcoholics. Report 2].

It has been known that wives of alcoholics tend to show an unhealthy relation with their husbands. The test called ASTWA (Addictions Screening Test for Wives of Alcoholics), which we developed earlier and reported in the previous paper in detail, might be useful for both wives and therapists for helpful suggestions. In this report, the present authors try to evaluate the ASTWA scores obtained from the wives, which consist of "a total score," "caring trends", "dominating trends," "obsessive traits," and "trends toward lowering of self-esteem," making clear each of the critical points between normal and abnormal sifting trends with the help of a normal control study. The results are demonstrated graphically as in the YG Test. In this way, the reliability, the validity, and the usefulness of ASTWA were confirmed in the process of this study. A prospective study concerning the prognosis of alcoholism of their husbands in relation to the results of ASTWA was carried out. In the non-intervened group, wives of the abstinence group tended to show a lower score than in those of the slipped group in terms of the total score, the dominating trends, the obsessive traits, and the trends toward lowering of self-esteem. In the group in which three months of initial therapy for wives have been completed, a significant parallel correlation was found between the ASTWA results and the prognosis of abstinence of their husbands. These results suggest that the total score, the caring trends, dominating trends, and the involved traits would indicate a degree of healthiness or unhealthiness in the marital relationship, particularly in terms of a circular cause and effect relation in developing alcoholism, and also would be a prospective indicator of the prognosis of alcoholism of their husbands.

Alcoholism↗

[Clinical evaluation of diazepam suppository for premedication in children].

Anesthesiologists need a safe and effective premedication before general anesthesia and want to help decrease anxiety and minimize psychologic trauma to children. Therefore, we evaluated diazepam suppository (0.5 mg.kg-1 body weight) administered to 21 children before minor surgery under general anesthesia. We evaluated the sedative effect of the diazepam suppository (tablet) on the arrival at the operating room, during anesthesia induction and in the recovery room. On the arrival at operating room, 86% of children were sedated, and 65% of children could be induced smoothly under mask. There was no delayed emergence. Plasma diazepam level at induction was 376.5 +/- 28.4 ng.ml-1, which is the level needed for sedation. We conclude that diazepam suppository is a useful drug for premedication in children.

Anesthesia, General↗

Molecular heterogeneity of follistatin, an activin-binding protein. Higher affinity of the carboxyl-terminal truncated forms for heparan sulfate proteoglycans on the ovarian granulosa cell.

Follistatin (FS), an activin-binding protein, is a monomer derived from two polypeptide core sequences of 315 (FS-315) and 288 (FS-288) amino acids originated from alternatively spliced mRNA. To define the structural heterogeneity of native FS, we purified six molecular forms of FS from porcine ovaries. Protein chemical analysis revealed that the structural differences among the six isoforms were caused by truncation of the carboxyl-terminal region and/or the presence of carbohydrate chains, resulting in the formation of FS-315, FS-288, and FS composed of 303 amino acids (FS-303) in various forms of glycosylation on the two potential Asn-linked glycosylation sites. The majority of FS isolated from porcine ovaries was FS-303, which may have been derived from FS-315 by proteolytic cleavage of the 12 COOH-terminal amino acids. All six molecular species have almost the same activin binding activity (Kd = 540-680 pM). By contrast, the COOH-terminal truncated form, FS-288, showed much higher affinity for the rat granulosa cell surface than FS-303, whereas FS-315 had no affinity. FS-288 bound to heparan sulfate-Sepharose CL-4B, but FS-315 did not, suggesting that the truncated forms of FS bind to heparan sulfate proteoglycans on the cell. COS cells transfected with the FS-288 DNA expressed the FS-288 protein, which adhered to the cell surface, but cells transfected with the FS-315 DNA secreted the expressed protein into the medium, which did not bind to the cell surface. In rat anterior pituitary culture, FS-288 (ED50 = 2 ng/ml) was more potent in suppressing follicle-stimulating hormone release than FS-303 (ED50 = 10 ng/ml) and FS-315 (ED50 = 20 ng/ml). These results suggest that cell-associated FS traps activin more tightly in the matrix, thereby more effectively blocking the activity of activin on heparan sulfate proteoglycans of the cell surface and that cell-associated FS plays an important role in controlling the various actions of activin in a paracrine or autocrine manner.

Activins↗

Isolation and characterization of Xenopus follistatin and activins.

Xenopus follistatin and activins were purified from a Xenopus laevis cell line (XTC-F1) by four purification steps consisting of consecutive affinity chromatography on dextran sulfate-Sepharose and Sulfate Cellulofine, fast protein liquid chromatography gel permeation, and reverse-phase high performance liquid chromatography (HPLC). Our results thus obtained indicated that almost equimolar amounts of activins A, AB, and B were found to be present as a complex with follistatin (activin-binding protein) in the conditioned medium of XTC-F1 cells. Reverse-phase HPLC of the complex gave Xenopus follistatin and activins A, AB, and B. The purified Xenopus follistatin showed four major bands in a molecular mass range from 34 to 39 kDa by SDS-polyacrylamide gel electrophoresis under nonreducing conditions. The ability of each form of the protein to specifically bind activin was determined by activin-binding assay and ligand blotting analysis. Each protein was found to have the same NH2-terminus and its sequence was very homologous to that of mammalian follistatin. Several criteria including immunoblotting analysis and various functional assays revealed the existence of three isoforms of activins A, AB, and B in Xenopus, as in mammals. Xenopus activins significantly induced both ventral and dorsal mesoderm in explants of Xenopus blastula cells that would otherwise form epidermis. In a dose-dependent manner of each isoform of activin, the induced explants were able to differentiate into blood-like cells, coelomic epithelium, mesenchyme, muscle, and notochord. The induction patterns of three Xenopus activins were essentially the same. The mesoderm induction by the purified Xenopus activins was shown to be inhibited stoichiometrically by the purified Xenopus follistatin. These results indicate that Xenopus XTC-F1 cells secrete several molecular forms of follistatin/activin-binding protein and three isoforms of activins AB and B in addition to activin A.

Activins↗

Surgical treatment of locally advanced thyroid cancer.

Eighty-four patients with locally advanced thyroid cancer treated during the period from 1965 to 1989 were studied in order to evaluate the appropriateness of radical surgery. There were 57 patients who underwent palliative surgery (palliative group) and 27 patients who underwent radical surgery (radical group). Forty-six of the patients in the palliative group and all 27 in the radical group were aged 40 years or more. The survival rates as analyzed by the Kaplan-Meier method revealed no significant difference between patients aged 40 or more in the palliative group and those in the radical group. The control of local disease, however, was much more difficult in the palliative group. From the view of survival rates, the superiority of radical surgery could not be demonstrated, but radical surgery did control local neck disease better. In the palliative group, the survival rate of patients aged under 40 was significantly better than that of patients aged 40 or more. It may thus be better to avoid radical surgery in patients under 40 if it would result in a severe deterioration in their quality of life.

Adolescent↗

Follow-up evaluation of patients with Graves' disease treated by subtotal thyroidectomy and risk factor analysis for post-operative thyroid dysfunction.

Eight-year follow-up evaluation and analysis of factors related to postoperative thyroid dysfunction were made in 216 patients with Graves' disease treated by subtotal thyroidectomy. The postoperative status of thyroid function were as follows according to hypersensitive TSH level: 65 patients (30.1%) were euthyroid, 25 (11.5%) had overt hyperthyroidism requiring treatment, 14 (6.5%) had subclinical hyperthyroidism with normal thyroid hormone and suppressed TSH, 21 (9.8%) were overt hypothyroid requiring thyroid hormone replacement and 91 (41.1%) had latent hypothyroidism without hormone replacement. In order to know factors related to postoperative thyroid function, age, sex, preoperative levels of TSH receptor antibody (TRAb), thyroid antibody titers, degree of lymphocyte infiltration, duration of medical treatment, weight of the resected thyroid tissue and weight of the remnant thyroid tissue were determined. No factor except thyroid remnant and antimicrosomal antibody titer was related to postoperative thyroid function. The weight of remnant should be less than 6 g to avoid recurrent hyperthyroidism. As recurrence of hyperthyroidism was observed more than 5 yr after surgery, long follow-up is needed.

Adolescent↗

[Hyalinizing trabecular adenoma of the thyroid].

We experienced a very rare case of hyalinizing trabecular adenoma of the thyroid. The histopathological features of this case included the following. 1) In puncture-aspiration cytodiagnosis, tumor cells aggregated around pink-stained hyaline acellular areas in an ellipsoidal or spindly configuration, with a part of the cytoplasm appearing as filamentous with unclear borders. In addition, a large number of intranuclear "holes" and nuclear grooves were evident. 2) In biopsy, tumor cells appeared in ellipsoidal or spindly configuration, with cytoplasm that easily stained with thyroglobulin but did not stain with calcitonin. The nuclei were irregular in size and some of the nuclei appeared strongly atypical, occasionally seen with cytoplastic inclusion body in the nucleus. These cells showed funicular structures in a radical arrangement with a hyaline material at the center. The hyaline material was stained positively with PAS or Laminin, but not with Cong red.

Adenoma↗

[Regional lymph node recurrence in patients with papillary thyroid carcinoma who did not undergo neck dissection].

It is important and difficult problem to manage patients with thyroid nodules which are indeterminate as papillary thyroid carcinoma (PTC) before surgery and identified as PTC after surgery. This paper highlighted whether immediate reoperation for such patients should be undergone or not. The prognosis of 196 patients with PTC who underwent lobectomy or subtotal thyroidectomy without neck dissection were studied (non-dissection group). The controls consisted of 783 patients with non-advanced PTC who underwent radical surgery during the same period (dissection group). There was no death due to PTC in both groups. Distant metastasis was observed 1.5% in non-dissection group and 2.2% in the dissection group. Local recurrence was observed 9.7% in the non-dissection group and 11.2% in the dissection group. The results suggested that immediate reoperation for the patient's who did not undergo neck dissection, is not necessary. It is thought that all of lymph node metastasis detected only by histology does not always behave in same.

Adult↗

[Outcome of surgical treatment for Graves's disease and a correlation between its clinical course and values of TSH receptor antibodies (TRAb)].

Two hundreds and sixteen patients with Graves' disease who underwent subtotal thyroidectomy at Ito Hospital during 1983 and 1984 were studied in order to known about the relationship between the prognosis and preoperative values of TRAb. There were 65 euthyroid patients (30.1%), 112 hypothyroid (51.8%), and 39 hyperthyroid (18.1%). No relationship between postoperative thyroid function and preoperative values of TRAb was observed. Postoperative values of TRAb were significantly higher in hyperthyroid group than in euthyroid group and hypothyroid group at any period. Postoperative values of TRAb were negative in about 90% of the patients of euthyroid group. On the other hand, negative postoperative values of TRAb were also observed in about 40% patients of hyperthyroid group. It is concluded that postoperative thyroid function could not be estimated from preoperative values of TRAb and much care is thought to be necessary to estimate the prognosis from postoperative values of TRAb.

Adolescent↗

Isolation and characterization of activin receptor from mouse embryonal carcinoma cells. Identification of its serine/threonine/tyrosine protein kinase activity.

The activin receptor protein was isolated from the mouse embryonal carcinoma (EC) cell line P19 by three cycles of affinity chromatography on an activin A-immobilized column. The purified receptor had a specific and high affinity for activins A, AB, and B (Kd = 345 pM), but not for transforming growth factor beta. The purified activin receptor was identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and ligand blotting analysis as a single protein of 70 kDa. The amino acid sequence of the first 18 NH2-terminal residues revealed that the receptor is a member of the activin receptor family. The purified receptor phosphorylated itself and exogenous substrate proteins on serine, threonine, and tyrosine residues, indicating that the activin receptor is a transmembrane serine/threonine/tyrosine protein kinase. These results suggest that signal transduction of activin employs a novel pathway via a new class of cellular receptor in EC P19 cells.

Activin Receptors↗

Isolation and characterization of native activin B.

To examine whether activin binds to follistatin, an activin-binding protein, to form a complex in vivo, we attempted to purify activin-follistatin complex from porcine follicular fluid. Our results thus obtained indicated that almost equimolar amounts of activins A, AB, and B are present as a complex with follistatin in the follicular fluid. Reverse-phase high performance liquid chromatography of the purified complex yielded follistatin and activins A, AB, and B. The activity of the purified activin B was found to be significantly lower than those of other activins in various assay systems such as stimulation of follicle-stimulating hormone secretion, induction of erythrodifferentiation, and potentiation of expression of gonadotropin receptors on ovarian cells. Moreover, binding of 125I-activin A to erythroleukemic cells which are activin-responsive was competed by activin B with approximately 10-fold lower potency compared with other activins. In contrast to these results, activin B was proved to have a potent Xenopus mesoderm-inducing activity, comparable with that of other activins. This indicates that, unlike activins A and AB, activin B can only elicit mesoderm-inducing activity and cannot function in other biological systems, suggesting a specific role of activin B in early development and unknown biological functions.

Activins↗

Follistatin inhibits activin-induced differentiation of rat follicular granulosa cells in vitro.

The effect of follistatin on activin-induced granulosa cell differentiation was investigated in freshly harvested granulosa cells from diethylstilbestrol (DES)-treated rats. Activin induced a remarkable change in granulosa cellular morphology from elongated fibroblast-like to round cells, which follistatin prevented. Follistatin itself had no influence on the cellular morphology. We studied the action of follistatin on activin-induced differentiation of granulosa cells cultured in a chemically defined medium. Addition of activin (30 ng/ml) to the culture increased the FSH binding site approximately 2-fold compared with the control (spontaneous expression) level, whereas follistatin reduced the activin-induced expression level to the control level in a concentration-dependent manner. Activin (30 ng/ml) markedly augmented FSH-induced hCG binding and progesterone production by approximately 20-fold, and these effects were suppressed by follistatin in a concentration-dependent manner. Similarly, addition of follistatin to the culture induced a concentration-dependent decrease of activin-enhanced inhibin-producing activity, but had no effect on FSH-induced inhibin production. These results suggest that follistatin/activin-binding protein binds to activin stoichiometrically to suppress the activin-induced differentiation of rat granulosa cell in vitro, but follistatin itself has no direct effect on activin-independent reactions.

Activins↗