Search PubMed⌕ Search

Biomedical subjects

K Hashizume

Publications and source records attributed to K Hashizume.

At least 199 records · Page 11Linked to original sources
PubMed1998

Collagen and elastin synthesis by desmoid tumor in vitro.

In order to characterize human desmoid tumors in vitro, the production of collagen and elastin and the expression of collagen types alpha1(I), alpha1(III) and transforming growth factor (TGF)-beta1 mRNA were investigated in six desmoid tumors; five derived from familial adenomatous polyposis patients and one from a sporadic case. The proportion of collagen production to total protein production was determined by 3H-imino acid incorporation, an indicator of collagen synthesis, using high-performance liquid chromatography (HPLC). The proportion of collagen production to total protein production was much higher in all six desmoid tumors compared with human skin fibroblasts (HSF). Quantitatively, the rate of elastin synthesis in desmoid tumor cells monitored by valine-proline peptide was also significantly higher than in HSF. Pro-alpha1(I) collagen mRNA was highly expressed in both desmoid tumors and HSF at approximately the same level, whereas pro-alpha1(III) collagen mRNA was more abundant in some of the desmoid tumors than the normal skin fibroblastic cell lines. Tumor growth factor-beta1 mRNA, which is believed to stimulate collagen synthesis, was expressed in both desmoid tumors and HSF to the same extent. These results demonstrate the increased formation of collagen and elastin in desmoid tumors in vitro and suggest that the increased synthesis of elastin rather than of collagen and TGF-beta1 may be involved in increased fibrogenesis by desmoid tumors.

Adenomatous Polyposis Coli↗
PubMed1998

Pheochromocytoma arising from an accessory adrenal gland in a patient with multiple endocrine neoplasia type 2A: transient development of clinical manifestations after hemorrhagic necrosis.

A case of pheochromocytoma arising from an accessory adrenal gland in a patient with multiple endocrine neoplasia type 2A (MEN 2A) is reported. This tumor resulted in autonecrosis which caused transient expression of clinical symptoms. Scintigraphy of the abdomen identified the existence of an additional accessory adrenal gland because of which the patient did not require a supplement of hydrocortisone after bilateral total adrenalectomy. Pheochromocytoma arising from an accessory adrenal gland is rarely reported, and spontaneous remission of clinical symptoms due to necrosis of the pheochromocytoma without a clinical emergency is also unusual. Accessory adrenal glands can be the cellular basis for pheochromocytoma, and the importance of continual follow up for pheochromocytoma in subjects with MEN 2A should be emphasized.

Adrenal Gland Neoplasms↗
PubMed1998

Hyperfunctioning thyroid adenoma concomitant with papillary thyroid carcinoma, follicular thyroid adenoma and primary hyperparathyroidism.

A case of 67-year-old woman with hyperthyroidism due to functioning thyroid adenoma is reported. The patient had concomitant follicular thyroid adenoma and primary hyperparathyroidism in addition to functioning adenoma. Histological examination of the excised thyroid tissue revealed occult papillary carcinoma within a functioning adenoma. Genetic analysis of such tumors indicated that functioning adenoma and papillary carcinoma may be etiologically independent. There have been a number of case reports on the coexistence of functioning thyroid adenoma and thyroid cancer or hyperparathyroidism, but none of the studies had examined the etiologic relationship of these lesions on a genetic basis. Furthermore, to our knowledge, this is the first report of the concurrence of four tumors in the neck, functioning thyroid adenoma, papillary thyroid carcinoma, follicular thyroid adenoma and parathyroid adenoma.

Adenoma↗
PubMed1998

[Aging and Hashimoto's thyroiditis].

Analysis of patients with persistent hypothyroidism due to Hashimoto's thyroiditis suggested that metabolism of thyroxine (T4), including deiodination to triiodothyronine (T3), was reduced in the elderly. The increase in the serum levels of T4 after oral administration of T4 was augmented in the elderly, whereas increase in the serum T3 level was not. Possibly due to the reduction in the pituitary deiodinase, suppression by T4 administration of serum thyrotropin (TSH) level was the same in elderly as in younger subjects despite a larger increase in the serum levels of T4 in the elderly. Consequently, the amount of T4 required to maintain a normal serum TSH level did not differ between elderly and younger subjects. Other characteristics of elderly patients with Hashimoto's thyroiditis were that goiter size was smaller, that hypothyroidism was more frequent, and that Graves' disease was less frequent.

Adult↗
PubMed1998

[TNM classification--pediatric tumors].

The clinical and postsurgical TNM classifications (cTNM and pTNM) for neuroblastoma (NB), nephroblastoma (WT) and soft tissue sarcomas were presented in 1982 by the TNM Committee in UICC in collaboration with SIOP. The Japanese TNM Committee proposed new pTNM systems (J-pTNM) for NB and WT, and new cTNM and pTNM system for primary liver carcinoma in infants and children (HT). These pTNMs were based on the staging systems developed by the Malignant Tumor Committee of the Japanese Society of Pediatric Surgeons. The proposal of subdivision of M category in NB was presented for testing the new telescopic ramifications of TNM. The TNM for HT was added as a new classification recommended for testing. The effectiveness of these TNM systems was assessed using NB, WT and hepatoblastoma (HB) cases which were registered in collaborating institutes. The analyses suggested that pTNM, especially the J-pTNM system in NB, WT and HT were effective for the assessment of prognoses, although cTNM systems were not enough to assess the extent of the disease.

Child↗
PubMed1998

[The effect of hippocampal dentate granule cell lesions upon the limbic seizure model of rats].

The purpose of this study was to determine the role of dentate granule cells upon limbic seizure of Wistar rat caused by unilateral intra-amygdaloid administration of kainic acid (KA). Stereotactic surgery was performed in Wistar rats and stainless steel injection chemitorode was inserted in the left amygdala. Left dentate granule cells lesion were induced by microinjection of colchicine. The rats obtained recovery period for 7 days, postoperatively. The rats were divided into two groups. One group were used for observation of symptoms and electroencephalographic findings during the limbic seizure for 6 hours after the KA injection. Another group was processed for measuring local cerebral glucose utilization (LCGU) during limbic seizure status. The histological study demonstrated a selective loss of dentate granule cells in the left hippocampus 7 days after the colchicine injection. After the KA injection, initiation of the spike discharge was significantly retarded not only in the hippocampus (from 6.01 min. to 37.25 min.) but also in the amygdala (from 2.96 min. to 10.8 min.). Progression, frequency and intensity of the KA induced seizures were also inhibited by the colchicine-induced dentate granule cells lesion. During limbic seizure status, LCGU obtained by 14C-deoxyglucose autoradiography were significantly decreased not only in the hippocampus but also in the amygdala on the site of KA injection. These data suggest that hippocampal dentate granule cells play an important role on initiation and progression of the KA induced limbic seizure. The result suggested that there was an acceleration mechanism of the limbic seizure between amygdala and hippocampus.

Amygdala↗
PubMed1997

Ligand-dependent heterodimerization of thyroid hormone receptor and retinoid X receptor.

The thyroid hormone receptors (TR) bind to cis-acting DNA elements as heterodimers with the retinoid X receptors (RXR). These heterodimers display distinct specificities in mediating the hormonal response to target gene transcription. We characterized the interaction between TRalpha1 and RXRalpha via their ligand binding domains (LBDs) and the effect of ligands on the interaction using a yeast two-hybrid system. The DNA binding domain (BD) of yeast Gal4 fusion to the LBD of TRalpha1 had no transcriptional activity on its own, but when it was coexpressed with the activation domain (AD) of yeast Gal4 fusion to LBD of RXRalpha conferred activation to a reporter gene harboring a Gal4 binding site, indicating that LBDs of TRalpha1 and RXRalpha interact with each other in solution. Furthermore, T3 and 9-cis-RA increased the reporter activity, and an additive effect was observed when both ligands were added, indicating that the TRalpha1.RXRalpha heterodimerization is augmented by their respective ligands in vivo. Using an in vitro pull-down experiment, we confirmed the ligand-dependent interaction observed in the yeast system. Matrix-bound glutathione S-transferase-RXRalpha specifically coprecipitated the 35S-labeled TRalpha1 above the control, and associated 35S-labeled TRalpha1 was increased by the addition of T3 and 9-cis-RA. These results imply a complex, sensitive cross-talk in vivo among nuclear receptors and their respective ligands through distinct hormonal signaling pathways.

Alitretinoin↗
PubMed1997

Expression, nuclear localization and interactions of human MCM/P1 proteins.

We report here the comparative analysis of human Mcm/P1 proteins (HsMcm2, -3, -5 and -7), including a characterization of their mutual interactions, cell cycle dependent expression and nuclear localization during the cell cycle and the quiescent state. The mRNA levels of these genes, which undergo cell cycle dependent oscillations with a peak at G1/S phase, may be regulated by E2F motifs, two of which were detected in the 5' upstream region of the HsMCM5 gene. In contrast, the protein levels of these Mcm proteins were found to remain rather constant during the HeLa cell cycle. However, their levels gradually increased in a variable manner as KD cells progressed from GO into the G1/S phase. In the GO stage, the amounts of HsMcm2 and -5 proteins were much lower than those of HsMcm7 and -3 proteins, suggesting that they are not present in stoichiometric amounts, and that only a proportion of these molecules actively participate in cell cycle regulation as part of Mcm/P1 complexes.

Amino Acid Sequence↗
PubMed1997

Sarcomatoid renal cell carcinoma with widespread metastases to liver and bones in a kidney transplant recipient.

A case of sarcomatoid renal cell carcinoma with widespread metastases to liver and bones in a cadaver renal transplant recipient is reported in this article. The patient underwent a kidney transplant at the age of 43 and was treated with various immunosuppressive agents after surgery. Twelve months after the transplantation, multiple tumors were found in the liver, and the patient died 8 months later. Pathological examination at autopsy revealed renal cell carcinoma with a sarcomatoid component in the right native kidney and metastases to liver and bones. It is unusual for renal cell carcinoma to undergo sarcomatous transformation and to metastasize to the liver before reaching other organs. We speculate that immunosuppressants may have altered malignant cell proliferation, invasion, and the form of metastasis in this case.

Adult↗
PubMed1997

The function of retinoid X receptors on negative thyroid hormone response elements.

Retinoid X receptors (RXRs) form heterodimers with thyroid hormone receptors (TRs). RXRs increase DNA binding affinity of TRs and T3-mediated transactivation on positive T3 response elements (TREs). However, the role of RXRs on negative TREs, and the relation of RXRs to the dominant negative effect of mutant TRs, are not defined. To clarify the function of RXRs on negative TREs, we performed transient cotransfection studies using the rat glycoprotein hormone alpha promoter fused to luciferase gene (alphaLuc), and human TRH promoter fused to luciferase gene (TRH-Luc) as reporters. We found that the JEG-3 cell-alphaLuc system was very sensitive to TR regulation. Using TRbeta1 wild-type (WT) expression vector, 6.2 ng/well (170 ng/10 cm dish), and 0.2 ng/well (11 ng/10 cm dish) caused maximal, and half maximal, inhibition of Luc activities in the presence of 1 nM T3. A T3 dose dependent inhibition study was also performed. From these studies, we determined that the appropriate conditions in which to study alphaLuc transactivation, in a linear portion of the dose response curve, was using 0.8 ng/well TRbeta1 expression vector and 0.1 nM T3. Under these conditions, TRbeta1 mutant R316H (GH), but not G345R (Mf), showed a weak dominant negative effect at a 1:1 ratio in the presence of 0.1 nM T3 although neither mutant had detectable T3 binding affinity. Moreover this dominant negative effect of R316H on the alphaLuc reporter was enhanced in the presence of RXRgamma. Mutant G345R showed a stronger dominant negative effect than did R316H when using a double palindromic TRE fused to herpes simplex thymidine kinase-Luc reporter as a positive TRE. These results conform to the clinical features of R316H which is associated with apparent pituitary resistance of thyroid hormone (PRTH). Mutant R316H also showed a weak dominant negative effect with TRH-Luc at a 1:1 ratio in the absence or presence of RXRgamma. However RXRgamma did not enhance the dominant negative effect as it did using alphaLuc reporter gene. Electrophoretic gel mobility shift assay (EMSA) showed that RXR alpha augmented the DNA binding affinity of wild type and R316H TRs as heterodimers on the previously reported negative TREs of glycoprotein hormone alpha promoter, suggesting that RXR does not produce its response by removing TRs from these TREs. RXR alpha augmented DNA binding affinity of TRbeta1WT, and R316H showed a weaker heterodimer band than did the wild type in EMSA. Using the TRH-Luc reporter, basal activity was increased by wild type TRbeta1. However a TRbeta1 DNA binding domain mutant, (C127S) which can not bind to DNA, did not increase the basal activity. This indicates that DNA binding of the TR is required for increasing basal activity of TRH promoter. These results indicate that (1) RXR-TR heterodimers play a role in basal transactivation and T3 suppression of negatively regulated genes, and (2) RXRs increase the dominant negative effect of some mutant TRs on specific negative TREs. (3) This effect occurs without removing TRs from the TRE. (4) The differential dominant negative effect of mutant R316H (negative TRE > positive TRE) may explain, at least in part, the presentation of R316H as PRTH. (5) Augmentation of basal activity by wild type TRs on a negative TRE requires DNA binding.

Animals↗
PubMed1997

Elevation of serum creatine kinase during treatment with antithyroid drugs in patients with hyperthyroidism due to Graves disease. A novel side effect of antithyroid drugs.

We describe 4 patients with Graves disease who had abnormal increases of serum creatine kinase (CK) concentrations during treatment with antithyroid medications. Three of the patients experienced myalgia and muscle cramps. All of the patients manifested an increase in serum CK levels 1 to 3 months after the administration of antithyroid drugs. Thyrotropin concentrations and cardiac systolic time indexes during the elevation of serum CK concentrations were not consistent with hypothyroidism. The mechanisms are not obvious, but it is likely that the rapid decrease of thyroid hormones in tissues may temporarily cause hypothyroid states, resulting in alterations in CK concentrations. It is suggested that hasty correction of thyrotoxicosis should be avoided in susceptible patients, unless the thyrotoxic conditions are critical.

Adult↗
PubMed1997

Inhibition of peroxisome proliferator signaling pathways by thyroid hormone receptor. Competitive binding to the response element.

Peroxisome proliferators (e.g. clofibric acid) and thyroid hormone play an important role in the metabolism of lipids. These effectors display their action through their own nuclear receptors, peroxisome proliferator-activated receptor (PPAR) and thyroid hormone receptor (TR). PPAR and TR are ligand-dependent, DNA binding, trans-acting transcriptional factors belonging to the erbA-related nuclear receptor superfamily. The present study focused on the convergence of the effectors on the peroxisome proliferator response element (PPRE). Transcriptional activation induced by PPAR through a PPRE was significantly suppressed by cotransfection of TR in transient transfection assays. The inhibition, however, was not affected by adding 3,5,3'-triiodo-L-thyronine (T3). Furthermore, the inhibition was not observed in cells cotransfected with retinoic acid receptor or vitamin D3 receptor. The inhibitory action by TR was lost by introducing a mutation in the DNA binding domain of TR, indicating that competition for DNA binding is involved in the molecular basis of this functional interaction. Gel shift assays revealed that TRs, expressed in insect cells, specifically bound to the 32P-labeled PPRE as heterodimers with the retinoid X receptor (RXR). Both PPAR and TR bind to PPRE, although only PPAR mediates transcriptional activation via PPRE. TR.RXR heterodimers are potential competitors with PPAR.RXR for binding to PPREs. It is concluded that PPAR-mediated gene expression is negatively controlled by TR at the level of PPAR binding to PPRE. We report here the novel action of thyroid hormone receptor in controlling gene expression through PPREs.

Animals↗