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Y Shishiba

Publications and source records attributed to Y Shishiba.

At least 37 records · Page 2Linked to original sources

[99mTc-MIBI scintigraphy for the detection of parathyroid lesions in patients with hyperparathyroidism].

The usefulness of 99mTc-MIBI scintigraphy for the detection of parathyroid lesions was evaluated in 17 patients with hyperparathyroidism. Delayed image was used to evaluate the lesions. Detectability of MIBI for parathyroid lesions was 86% (18/21). The smallest lesion detected was parathyroid hyperplasia weighted 270 mg. Ectopic parathyroid adenoma and bone metastases of parathyroid carcinoma were clearly demonstrated. Detectability of MIBI scintigraphy for the lesions including ectopic and metastatic lesions was the highest among those of ultrasonography, CT and MRI methods. MIBI scintigraphy was thought to be useful for the detection of parathyroid lesions, especially for ectopic and metastatic lesions.

Bone Neoplasms↗

Inhibition of parathyroid hormone-related protein release by extracellular calcium in dispersed cells from human parathyroid hyperplasia secondary to chronic renal failure and adenoma.

The relationship between parathyroid hormone-related protein (PTHrP) release from parathyroid cells and extracellular calcium ion concentration was investigated in three cases of parathyroid hyperplasia secondary to chronic renal failure and in four cases of parathyroid adenoma. Amounts of PTHrP released from individual parathyroid cells dispersed from surgical specimens were estimated by cell immunoblot assay. Parathyroid cells from both hyperplasias and adenomas showed significant suppression in the release of PTHrP with increase in extracellular calcium ions, but the amounts of PTHrP released from adenoma cells were significantly larger than from hyperplasia cells. The maximal value for PTHrP released within 120 minutes from adenoma cells was 2.91 +/- 2.11 x 10(-2) fmol/cell ([Ca2+], 0.4 mmol/L), and the minimal value was 1.32 +/- 0.35 x 10(-2) fmol/cell ([Ca2+], 2.0 mmol/L). On the other hand, the maximal value for PTHrP released from hyperplasia cells was 1.79 +/- 1.56 x 10(-2) fmol/cell ([Ca2+], 0.4 mmol/L), and the minimal value was 0.32 +/- 0.19 x 10(-2) fmol/cell ([Ca2+], 2.0 mmol/L). These results demonstrate actual release of PTHrP from abnormal parathyroid tissues into the extracellular space with the response to extracellular calcium ions depending on the cell status. Given the lack of definite histological criteria to differentiate between hyperplasias and adenomas in the parathyroid gland, the presently demonstrated significant difference in the ability to release PTHrP is important in pointing to parathyroid hyperplasia secondary to chronic renal failure as a distinct pathological entity separate from parathyroid adenoma.

Adenoma↗

Growth hormone and prolactin gene expression in human densely and sparsely granulated somatotroph adenomas by in situ hybridization with digoxigenin-labeled probes.

We studied growth hormone (GH) and prolactin (PRL) messenger ribonucleic acids (mRNAs) in 14 cases with densely granulated somatotroph (DG) adenomas and 10 cases with sparsely granulated somatotroph (SG) adenomas using in situ hybridization with digoxigenin-labeled probes and correlated these data with their immunohistochemical results. A good correlation between in situ hybridization results and immunohistochemical data was found in most cases examined. The DG adenomas generally had a diffuse and intense GH immunoreactivity and GH hybridization signal, whereas in SG adenomas the number of cells exhibiting a GH mRNA signal and the strength of the GH mRNA signal in these cells were relatively lower than those of DG adenomas, indicating that lower expression of the GH mRNA signal is responsible for lower GH production in SG adenomas. In addition, PRL mRNA expression differed in the two types of adenoma; in DG adenomas, seven cases (50%) expressed PRL mRNA signal with a focal or scattered distribution despite normal serum PRL levels, but two showed no PRL immunoreactivity. In contrast, in SG adenomas, only one case contained a few cells possessing a PRL mRNA signal despite having no PRL immunoreactivity. It can be concluded that DG and SG adenomas, which have been considered variants of the same tumor, display definite differences as to GH or PRL gene expression in each type of adenoma.

Adenoma↗

Effects of dibutyryl cyclic AMP on hyaluronan and proteoglycan synthesis by retroocular tissue fibroblasts in culture.

Deposition of glycosaminoglycan is one of the histological features of Graves' ophthalmopathy. Although retroocular tissue fibroblasts are considered to be responsible for glycosaminoglycan accumulation, it is not known what is stimulating the fibroblasts. There are studies which are in support of and against the role of anti-TSH receptor antibodies in the pathogenesis of Graves' ophthalmopathy. TSH-receptor antibodies increase cAMP as a second messenger in thyroid cells. We studied the effects of dibutyryl cyclic AMP (Bt2 cAMP) on glycosaminoglycan synthesis by retroocular tissue fibroblasts in order to known whether cAMP can modulate glycosaminoglycan synthesis. Retroocular tissue fibroblasts mainly synthesize hyaluronan, the large chondroitin sulfate proteoglycan and the small chondroitin sulfate proteoglycan as glycosaminoglycan in cell culture. The amount of hyaluronan synthesis was measured as [3H]glucosamine incorporation into macromolecule susceptible to hyaluronidase digestion (from Streptomyces hyaluronlyticus). The amount of proteoglycan synthesis was measured as [35S]sulfate incorporation into macromolecules in medium and cell layer fraction. Proteoglycans in medium were further separated into the large proteoglycan and the small proteoglycan on a Superose 6 column. Bt2 cAMP increased both hyaluronan and proteoglycan synthesis by retroocular tissue fibroblasts, especially stimulating the secretion of the large proteoglycan synthesis by retroocular tissue fibroblasts, especially stimulating the secretion of the large proteoglycan. Effects of Bt2 cAMP on glycosaminoglycan synthesis were then compared with those in adult skin fibroblasts. Although the magnitude of response between the two was indistinct, the stimulation of the large proteoglycan synthesis by Bt2 cAMP was more prominent in retroocular tissue fibroblasts. The results suggest that the regulation of glycosaminoglycan synthesis by retroocular tissue fibroblasts is different from that by adult skin fibroblasts. Although further studies are required to determine its actual role, cAMP stimulates glycosaminoglycan synthesis by retroocular tissue fibroblasts and underlies the mechanism in Graves' ophthalmopathy.

Adult↗

Analysis of proteoglycan synthesis by retro-ocular tissue fibroblasts under the influence of interleukin 1 beta and transforming growth factor-beta.

Retro-ocular tissue fibroblasts are supposed to be responsible for the deposition of glycosaminoglycan in Graves' ophthalmopathy. We have reported in a preliminary fashion that interleukin 1 beta (IL-1 beta) and transforming growth factor-beta (TGF-beta) increased the rate of [35S]sulfate incorporation into proteoglycans two to five times the control in culture of retro-ocular tissue fibroblasts. The increase in the rate of [35S]sulfate incorporation into proteoglycan will occur as a result of: (a) net increase of proteoglycan synthesis; (b) elongation of glycosaminoglycan chains; (c) increased number of glycosaminoglycan chains; (d) oversulfation of glycosaminoglycan chains; (e) increase in cell number; (f) decreased rate of degradation. We have analyzed which mechanism is important for the increase of [35S]sulfate into proteoglycans observed in human retro-ocular tissue fibroblasts under the influence of cytokines. The last two possibilities (e, f) were ruled out because during the observation period there was no consistent proliferation of the cells and no decrease in the rate of degradation of proteoglycan examined by pulse-chase experiment. Cytokines did not change the size of glycosaminoglycan chains released from proteoglycan as measured by alkaline borohydride treatment, ruling out (b). Disaccharide analysis by HPLC after chondroitin sulfate ABC digestion revealed that glycosaminoglycan mainly contains monosulfated chondroitin disaccharides and that oversulfation was not observed under the influence of IL-1 beta or TGF-beta, ruling out (d). The capacity to synthesize glycosaminoglycan chain in the presence of an artifical acceptor of chain elongation, beta-D-xylodide, was increased significantly by IL-1 beta but not obviously so by TGF-beta.(ABSTRACT TRUNCATED AT 250 WORDS)

Connective Tissue↗

Development of Graves' ophthalmopathy and uveitis after radioiodine therapy for Graves' disease in a patient with HTLV-I associated myelopathy (HAM).

HTLV-I carriers or patients with HTLV-I associated myelopathy (HAM) are prone to immune-mediated inflammatory disorders. We present a 44-year-old female with HAM who developed Graves' disease. She developed severe Graves' ophthalmopathy shortly after 131I therapy, concurrently with a remarkable increase in TSH-receptor antibody titer. Ophthalmopathy was aggravated in spite of prednisolone therapy and euthyroidism being maintained by thyroxine replacement. Uveitis also developed after 131I therapy and iridocyclitis finally required trabeculotomy. This case suggests that HAM patients may have a higher risk of immune-mediated Graves' ophthalmopathy after 131I therapy.

Adult↗

Successful treatment by surgical removal of bone metastasis producing PTH: new approach to the management of metastatic parathyroid carcinoma.

A 62-year-old woman had primary hyperparathyroidism due to parathyroid carcinoma. In spite of surgical removal of the enlarged parathyroid gland, intractable hypercalcemia persisted. 99mTc-methoxyisobutylisonitrile scanning revealed bone metastatic lesions, although conventional 201T1-chloride scanning failed to demonstrate those lesions. Octreotide inhibited parathyroid hormone (PTH) secretion, although various means such as bisphosphonates, calcitonin and hydration were effective to reduce serum calcium level to some extent but failed to reduce PTH secretion at all. The CT-guided transcutaneous tumor marking facilitated the subsequent orthopedic surgery for successful removal of the metastatic focus of PTH secretion from the iliac bone.

Bone Neoplasms↗

Effects of transforming growth factor beta 1 and L-ascorbate on synthesis and distribution of proteoglycans in murine osteoblast-like cells.

Proteoglycans synthesized by osteoblasts are incorporated into bone matrix and thought to play a role in bone metabolism. Transforming growth factor (TGF) beta affects the synthesis of matrix proteins, including proteoglycans, in various stromal cells, and proteoglycans, especially decorin, are associated with matrix collagen. In the present study, the effects of TGF-beta 1 and L-ascorbate, a factor essential for collagen synthesis, on the synthesis and distribution of proteoglycans were examined using murine osteoblast-like MC3T3-E1 cells. TGF-beta 1 stimulated the synthesis of proteoglycans in MC3T3-E1 cells. Among various proteoglycans, the synthesis of decorin was preferentially enhanced by TGF-beta 1, and the effect was more pronounced on secreted decorin compared to that associated with the cell/matrix layer. TGF-beta 1 also stimulated the initiation and elongation of the dermatan sulfate glycosaminoglycan chain, resulting in a larger molecular size of decorin. TGF-beta 1 influenced the synthesis of a heparan sulfate proteoglycan only slightly. L-ascorbate had no effect on the synthesis of proteoglycans, but increased those associated with the cell/matrix layer. Furthermore, when L-ascorbate was added to the culture along with TGF-beta 1, the percentage of proteoglycans associated with the cell/matrix layer increased from 25.8 +/- 1.0 to 41.0 +/- 0.5%. These data demonstrate that TGF-beta 1 markedly stimulates the synthesis of proteoglycans, especially decorin, mainly as a secreting form, that the accumulation of decorin into matrix is enhanced by L-ascorbate, and that the effects of TGF-beta 1 and L-ascorbate are additive.(ABSTRACT TRUNCATED AT 250 WORDS)

3T3 Cells↗

Endocrine and morphological study of a clinically silent somatotroph adenoma of the human pituitary.

Silent somatotroph adenomas are defined as tumors showing morphological features consistent with GH production, but no clinical evidence of GH excess. We report here the case of a 46-yr-old woman with a large pituitary macroadenoma, slightly elevated serum GH levels, high serum insulin-like growth factor-I levels, and abnormal GH dynamics, but no acromegaly. The endocrinological abnormalities receded after transphenoidal surgery despite tumor persistence, as shown by neuroimaging. The reverse hemolytic plaque assay, performed for the first time in a silent GH cell adenoma, demonstrated that the number of GH cells releasing GH and the amount of GH discharged from individual cells were less than those in clinically functioning somatotroph adenomas. Thus, it is conceivable that this tumor secreted only small quantities of GH and for only short periods, providing an explanation for the lack of acromegaly. It appears that silent somatotroph adenomas do not represent a distinct entity. It is more likely that there is a continuous spectrum from clinically functioning, sparsely granulated somatotroph adenomas with high serum GH levels to silent somatotroph adenomas with normal serum GH levels. The cause of the lack of GH oversecretion in silent GH cell adenomas has yet to be elucidated.

Adenoma↗

Growth hormone-producing pituitary adenomas: correlations between clinical characteristics and morphology.

In this study, we compared the clinical and endocrinological characteristics, neuroimaging findings, surgical outcome, and conventional histological findings (including immunohistochemistry) with the electron microscopic appearance of 31 growth hormone (GH)-producing adenomas. By electron microscopy, these 31 tumors were divided into 23 densely granulated somatotroph adenomas (DG adenomas) and 8 sparsely granulated somatotroph adenomas (SG adenomas). SG adenomas more frequently affected younger women, but no significant correlation was found between the adenoma type and the characteristic signs and symptoms of acromegaly, the incidence of diabetes mellitus or hypertension, or the basal serum GH and insulin-like growth factor I levels. A distinct response of GH to thyrotropin-releasing hormone, bromocriptine, or GH-releasing hormone was significantly more common in patients with DG adenomas than in those with SG adenomas, whereas the incidence of a response to gonadotropin-releasing hormone or oral glucose was not significantly different between the two groups. An analysis of neuroimaging findings and surgical results indicated that SG adenomas were more likely to be macroadenomas with suprasellar extension or invasive tumors and had a lower surgical cure rate. However, postoperative radiotherapy seemed to be similarly effective in both types of adenoma to prevent a tumor recurrence and to reduce postoperative GH basal level in serum. Light microscopy showed that DG adenomas were mainly acidophilic and were immunopositive not only for GH but also for prolactin (43%), the beta subunit of thyroid-stimulating hormone (26%), and the alpha subunit of glycoprotein hormone (87%), whereas SG adenomas were almost all chromophobic and only revealed immunopositivity for GH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

Recovery from lymphocytic hypophysitis associated with painless thyroiditis: clinical implications of circulating antipituitary antibodies.

Lymphocytic hypophysitis usually occurs in the antepartum or postpartum period and recovery of pituitary dysfunction has not been documented in most cases reported previously. We present a 50-year-old woman with lymphocytic hypophysitis who spontaneously recovered from panhypopituitarism over 18 months with the disappearance of an intrasellar mass. Although lymphocytic hypophysitis is thought to be an autoimmune disease, the clinical and pathogenetic significance of circulating antipituitary autoantibodies has not been clarified. Antipituitary antibodies were studied by immunofluorescence in blood samples obtained during the whole clinical course in this particular patient. Antibodies against rat pituitary cytosol were positive during the period of hypopituitarism and became negative when pituitary function recovered. Antibodies reacting with intact prolactin-secreting rat GH3 and corticotropin-secreting mouse AtT-20 cells were also positive during her period of hypopituitarism. They remained positive for several years after the recovery of pituitary function. We conclude that circulating antibodies against rat pituitary cytosol are good markers of pituitary inflammation in this patient. The other point to be emphasized in this case is the simultaneous development of painless thyroiditis and lymphocytic hypophysitis. We have discussed the pathogenic relationship of these two diseases on the basis of similar cases reported previously.

17-Hydroxycorticosteroids↗

The presence of immunoreactive parathyroid hormone-related protein in parathyroid adenoma cells.

Parathyroid hormone-related protein (PTHrP) was first identified in human malignant tumors associated with humoral hypercalcemia of malignancy. We immunohistochemically examined the distribution of PTHrP both in 7 normal parathyroid glands and in a 20 parathyroid adenomas. Sixty-five percent of parathyroid adenomas (13 cases) were positive for PTHrP, whereas only one normal parathyroid gland was positive for PTHrP in the area of transitional oxyphil cells. Many parathyroid adenomas (12 cases) were composed of both PTHrP-positive cells and--negative cells, and these two different type of cells showed a tendency to form nodules respectively in parathyroid adenoma. Although both chief cells and oxyphil or transitional oxyphil cells were positive for PTHrP in parathyroid adenoma, oxyphil or transitional oxyphil cells were more responsible for PTHrP production than chief cells. Chief cells are thought to produce parathyroid hormone mainly in parathyroid adenoma. On the other hand, little is known concerning the function and role of oxyphil or transitional oxyphil cells. Our results suggest that oxyphil or transitional oxyphil cells in parathyroid adenoma may have some functional roles different from those of chief cells through the production of PTHrP.

Adenoma↗

Comparison of the incidence of association of periodic paralysis and hyperthyroidism in Japan in 1957 and 1991.

Periodic paralysis has been known to be associated with thyrotoxicosis in Japan. The incidence was 8.6% among male and 0.4% among female thyrotoxic patients according to a survey performed in the three major thyroid clinics in Japan in 1957. To determine the changes in the incidence during the intervening 34 years, the same type of survey was carried out again in 1991 at the same three major thyroid clinics previously involved. The incidence of paralysis in 1991 was 4.3% among male and 0.04% among female thyrotoxic patients, indicating more than a 40% decrease in the incidence. The possible cause of the decrease is related to the changes in food consumption, namely, to the fact that less carbohydrate and more potassium were taken in 1991 than in 1957.

Diet↗

Effect of growth factors on hyaluronan and proteoglycan synthesis by retroocular tissue fibroblasts of Graves' ophthalmopathy in culture.

One of the pathological changes seen in Graves' ophthalmopathy is the deposition of glycosaminoglycans such as hyaluronan and proteoglycan in retroocular connective tissue. We analyzed glycosaminoglycans synthesized by retroocular tissue fibroblasts in culture derived from an individual not suffering from thyroid disease and from three patients with Graves' ophthalmopathy. Retroocular tissue fibroblasts synthesized both hyaluronan and proteoglycan, the latter composed mainly of chondroitin sulfate. This contrasts with the proteoglycan synthesized by adult skin fibroblasts which was composed of dermatan sulfate and heparan sulfate proteoglycan. Chondroitin sulfate proteoglycan secreted by retroocular tissue fibroblasts consisted of large and small chondroitin sulfate proteoglycans (CS-PG), their size being determined by the Sepharose CL-6B column. The effects of IGF-1 and PDGF on hyaluronan and proteoglycan synthesis were studied separately and in combination. Both IGF-1 and PDGF increased the synthesis of hyaluronan and proteoglycan in a dose-dependent manner. IGF-1 predominantly stimulated secretion of small CS-PG, while PDGF increased large CS-PG markedly when studied in retroocular tissue fibroblasts. In contrast, IGF-1 stimulated secretion of small proteoglycan while PDGF had little effect on proteoglycan synthesis in skin fibroblasts. Thus, glycosaminoglycan synthesized by retroocular tissue fibroblasts has a unique composition and each component is regulated independently, at least in part.

Blood↗

Immunoglobulin G of patients with circumscribed pretibial myxedema of Graves' disease stimulates proteoglycan synthesis in human skin fibroblasts in culture.

Hyaluronic acid and proteoglycan accumulate in the affected skin of Graves' disease patients with pretibial myxedema (PTM). We aimed to determine whether an autoantibody IgG circulating in PTM patients stimulates proteoglycan synthesis in human skin fibroblasts, resulting in PTM. IgGs were purified from 14 normal subjects, 11 Graves' disease patients with PTM. 5 Graves' disease patients with active ophthalmopathy and 15 Graves' disease patients with neither PTM nor ophthalmopathy. Human skin fibroblasts were incubated with the IgGs and labeled with [35S]sulfate. The medium and cell layer were separated and the proteoglycan was extracted. The 35S radioactivity in the proteoglycan fraction was measured. Compared with normal IgGs or with those of Graves' disease without PTM or ophthalmopathy, PTM IgGs significantly increased the incorporation of the 35S into the proteoglycan. The effect of PTM IgG was dose-dependent. As PTM IgG did not alter degradation of the 35S labeled proteoglycan, an increase in 35S incorporation reflects increased synthesis. The effect was mediated through a mechanism other than adenylate cyclase activation. The present study demonstrates the presence of an autoantibody in PTM IgG that stimulates proteoglycan production through human skin fibroblasts. This is not correlated with the thyroid stimulating antibody activity. It is suggested that the activity of this antibody leads to the development of PTM.

Adult↗