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Biomedical subjects

H Funahashi

Publications and source records attributed to H Funahashi.

At least 19 recordsLinked to original sources
PubMed1992

Low frequency of rearrangements of the ret and trk proto-oncogenes in Japanese thyroid papillary carcinomas.

We investigated the frequency of rearrangements of the ret and trk proto-oncogenes in Japanese thyroid tumors. DNAs from 38 thyroid papillary carcinomas and 14 follicular adenomas were analyzed by Southern blotting. Rearrangements of the ret and trk proto-oncogenes were detected in one and two papillary carcinomas, respectively, but not in follicular adenomas. Analysis by a reverse transcriptase-polymerase chain reaction method showed that the ret rearrangement-positive tumor contained the PTC/retTPC chimeric transcript, which was reported to be found specifically in thyroid tumors and adenomatous goiter. We also found that rearranged mRNA of the trk proto-oncogene was expressed at high levels in one of two trk rearrangement-positive tumors. Our results indicated that the frequency of rearrangements of these proto-oncogenes in Japanese papillary carcinomas was much lower than that in Italian patients.

Adenoma↗
PubMed1992

ACTH increases expression of c-fos, c-jun and beta-actin genes in the dexamethasone-treated rat adrenals.

Our recent finding that ACTH increases c-fos mRNA in the adrenal gland of hypophysectomized rats indicates that the gene product FOS may play an important role(s) in mediating the action of ACTH. However, hypophysectomy employed in that study causes the disappearance of trophic hormones other than ACTH and may modify the effect of ACTH. Thus, in the present investigation, dexamethasone-treated rats were used. Since FOS functions only when it dimerizes with JUN (the product of c-jun gene), the changes in the levels of c-fos and c-jun mRNAs were studied together with that of beta-actin mRNA which is also affected by ACTH. Northern blot analysis was employed to determine the mRNA levels. It was demonstrated that ACTH increases the mRNAs coding c-fos and c-jun in the adrenal glands of dexamethasone-treated, ACTH-suppressed rats. The c-fos mRNA was not detectable before ACTH administration. After ACTH administration, the mRNA levels were transiently increased, the maximum level being observed at 30 min after ACTH. At 180 min post ACTH, the level returned to the unstimulated level. The mRNA coding c-jun was detectable before ACTH administration and it also increased rapidly after ACTH with maximal stimulation at 30 min. However, the mRNA level at 180 min post ACTH was still higher than the unstimulated level. The changes in beta-actin mRNA were approximately the same as those of c-jun mRNA. These results suggest that increased expression of c-fos, c-jun and beta-actin genes by ACTH may play an important role in mediating its action on the adrenals.

Actins↗
PubMed1992

Primary pigmented nodular adrenocortical disease (PPNAD): immunohistochemical and in situ hybridization analysis of steroidogenic enzymes in eight cases.

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare but an interesting adrenocortical disorder associated with ACTH-independent hypercortisolism. We have studied eight cases of the adrenals with PPNAD by immunohistochemistry of all steroidogenic enzymes involved in cortisol biosynthesis (P-45scc, 3 beta-HSD, P-450c21, P-45017 alpha, and P-45011 beta) and also by performing in situ hybridization of P-45017 alpha in seven cases in order to localize the sites of specific steroidogenesis in this unique disorder. Immunoreactivity of all the enzymes examined was intense in almost all of the cells in adrenocortical nodules, especially the cells with abundant eosinophilic cytoplasm in all the cases examined. The internodular cortex, which demonstrated atrophy in five cases, normal appearance in two cases and hyperplasia in one case, was negative for the enzymes with an exception of 3 beta-HSD. Hybridization signals of P-45017 alpha were condensed over the nodules in in situ hybridization study, suggestive of an increased production of the enzyme itself in cortical cells of the nodules. These results may be consistent with autonomous cortisol production by the nodular cells and indicate that almost all of the cells in the nodules produce cortisol, which can also explain the presence of hypercortisolism despite small sizes of adrenals in PPNAD. Immunoreactivity of steroidogenic enzymes is observed in a small cluster of cortical cells with abundant eosinophilic cytoplasm located at the zona reticularis but not in adjacent non-nodular cortex, which may support an abnormal development of the zona reticularis as a possible pathogenesis of this disorder.

3-Hydroxysteroid Dehydrogenases↗
PubMed1991

Dexamethasone-nonsuppressible cortisol in two cases with aldosterone-producing adenoma.

Forty-one patients with aldosterone-producing adenoma (APA) were subjected to a dexamethasone suppression test (DST) before surgery. Serum cortisol and urinary excretion of 17-hydroxycorticosteroids were suppressed by dexamethasone in 39 patients [DST(+)]. In two patients (cases A and B), they were not suppressed [DST(-)]. Clinical manifestations of the two DST(-) patients were similar to those of DST(+) patients. Hypertension, hypokalemia, high serum aldosterone levels, and suppressed PRA were found in all of the patients. The cut surfaces of the adenomas from all of the patients, including cases A and B, were golden yellow, which is typical of APA. However, atrophies of the adjacent normal tissues were evident exclusively in the two DST(-) patients. After removal of the affected adrenals, the serum cortisol level was suppressed by dexamethasone in one of the DST(-) patients (case B). These findings suggested autonomous cortisol production by APA. To evaluate whether cortisol could be produced from the adenoma tissue, the presence of several steroidogenic enzymes was studied by immunohistochemistry and mRNA analysis in the adenomas and the adjacent nonneoplastic adrenals from the 2 DST(-) and 5 DST(+) patients. Immunohistochemical analysis demonstrated that steroidogenic enzymes were expressed in APA tumor tissues from both DST(-) and DST(+) patients. In both groups, mRNAs coding steroidogenic enzymes were present not only in the nonneoplastic but also in the tumor tissues. Quantitative analysis of the mRNA levels revealed that in the adrenals from DST(+) patients, the mRNAs were more abundant in nonneoplastic tissue than in tumor tissue. However, in those from DST(-) cases, the mRNAs were much more abundant in the tumor tissues than in the nonneoplastic tissues. These results indicate that tumor cells of the two DST(-) patients autonomously synthesized not only aldosterone but also cortisol. The diameters of the tumors from the two DST(-) patients exceeded 3 cm, while those from other DST(+) patients were smaller. In patients with large APA, adrenal insufficiency should be anticipated upon removal of the tumor.

Adenoma↗
PubMed1991

[Study of hormone replacement therapy following total thyroidectomy in thyroid cancer--with special reference to the analysis of thyroid hormone peripheral effects, using indirect calorimetry].

Peripheral effects of thyroid hormones were examined using an indirect calorimetry in 18 patients with thyroid cancer before and after total thyroidectomy. Peripheral effects of exogenous thyroid hormones in TSH-suppression therapy after thyroidectomy were also studied. The subjects were maintained without hormone replacement for 3 weeks after total thyroidectomy. The ratio of resting energy expenditure to basal energy expenditure (REE/BEE) was determined before operation, before hormone replacement, and 1 and 5 weeks after the beginning of replacement, and the values were compared with changes in the blood thyroid hormone levels. Positive correlations were observed between the changes in endogenous thyroid hormone levels before and after total thyroidectomy and those in REE/BEE (free T3 vs. REE/BEE; r = 0.756, p less than 0.01), suggesting that evaluation of REE/BEE is clinically useful as an index of peripheral effects of thyroid hormones. Five weeks after the beginning of hormone replacement, T4 and free T4 were slightly range, and no enhancement of energy metabolism was noted. From these findings, the post-operative TSH suppression therapy carried out at our department is considered to be justifiable also from the viewpoint of energy metabolism.

Adult↗
PubMed1991

[Kinetics of PTH metabolism after total parathyroidectomy and autograft at forearm in patients with secondary hyperparathyroidism due to chronic renal failure].

Five patients with secondary hyperparathyroidism (2(0) HPT) due to chronic renal failure were investigated for PTH metabolism kinetics after total parathyroidectomy and autograft at the forearm (PTxG). We studied the kinetics of PTH for 24 hours after surgical treatment and gradually increased PTH levels when the parathyroid grafts became functional. It has been well known that the secreted intact PTH is peripherally cleaved in the region of reside 34 to yield amino- and carboxyl-terminal fragments. In this study, specific assays were used for intact PTH (INT-PTH), middle (HS-PTH, MM-PTH) and carboxyl-terminal (C-PTH) fragments. Half-lives were calculated from the mean values of all experiments by a two-compartment system; INT-PTH: 11.1 +/- 3.9 min, HS-PTH: 9.6 +/- 1.7 hrs., MM-PTH: 11.1 +/- 2.9 hrs., C-PTH: 10.1 +/- 1.2 hrs. (Mean +/- SD). The disappearance rate of biologically active intact PTH was rapid, whereas those of middle and carboxyl-terminal biologically inactive fragments were prolonged in the patients with chronic renal failure. The graft function was examined by PTH gradient between the venous samples in the grafted arm as compared to the non-grafted arm. PTH gradient of INT-PTH assay was over 1.5 one week following PTxG in all patients. This suggests that the intact PTH assay is a reliable predictor of clinical response to the graft function after PTxG.

Forearm↗
PubMed1990

Adrenocorticotropin increases expression of c-fos and beta-actin genes in the rat adrenals.

It is widely accepted that expression of protooncogenes is coupled with cellular proliferation and differentiation. Since ACTH stimulates not only steroidogenesis but also cellular proliferation, we investigated whether ACTH affects the expression of c-fos, c-myc, and beta-actin genes. The effect of ACTH on adrenal glands was studied in hypophysectomized rats. Changes in the mRNA levels were studied by Northern and dot blot analyses. It was demonstrated that ACTH induces increases in mRNAs encoding c-fos and beta-actin in adrenal glands of hypophysectomized rats. When stimulated by ACTH (5 IU/100 g BW), the mRNA levels of both genes increase rapidly; the maximum levels are observed at 30 min for c-fos and 6 h for beta-actin. Both mRNAs declined to near-control levels by 6-24 h. The levels of mRNAs encoding cholesterol side-chain cleavage cytochrome P-450 and 21-hydroxylase cytochrome P-450 began to increase 3 and 12 h after ACTH administration, respectively. This increase continued for 24 h after ACTH treatment. Increases in total adrenal RNA and adrenal weight occurred slowly after ACTH treatment. On the other hand, the levels of c-myc mRNA were very low and were not increased by ACTH administration. These results suggest that increased expression of c-fos and beta-actin genes by ACTH may have important roles in mediating its action on adrenals.

Actins↗
PubMed1990

Alteration in the expression of genes for cholesterol side-chain cleavage enzyme and 21-hydroxylase by hypophysectomy and ACTH administration in the rat adrenal.

The changes in steady-state levels of mRNA for cholesterol side-chain cleavage cytochrome P-450 (P-450scc) and steroid 21-hydroxylase cytochrome P-450 (P-450c21) caused by hypophysectomy and ACTH treatment were determined in rat adrenals. Hypophysectomy caused marked decreases in adrenal weight and total RNA per gland. Administration of ACTH resulted in increases in adrenal weight and total RNA. A significant correlation between the amount of RNA and adrenal weight was observed. Both P-450scc and P-450c21 mRNAs were decreased by hypophysectomy and increased by ACTH treatment. P-450scc mRNA decreased to 20% and P-450c21 mRNA to 76% of control values 1 day after hypophysectomy. ACTH caused a significant increase in P-450scc mRNA after 3 h. However, a significant increase in P-450c21 mRNA was observed 12 h after administration of ACTH. These results are concordant with previous studies in vitro utilizing cultured adrenocortical cells. Moreover, the induction of steady-state levels of P-450scc mRNA was faster than that observed by other investigators in studies in vitro. These results may indicate that integrity of the adrenal gland in vivo is important for the action of ACTH.

Adrenal Glands↗
PubMed1990

[Clinical efficacy of ifosfamide for liver metastasis of breast cancer].

Chemotherapy for liver metastasis of breast cancer has rarely been found effective. We devised a new regimen of chemotherapy for recurrent breast cancer mainly using ifosfamide. It was found clinically applicable and particularly effective for liver metastasis. The tumor decreased in size and the levels of various tumor-markers markedly decreased following drug administration. This treatment has made for longer survival for some patients. Side effects could be well controlled with steroid hormones and Na-bicarbonate.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

[Autotransplantation of parathyroid glands in thyroid carcinoma surgery and their postoperative function].

Total removal and subsequent autotransplantation of parathyroid glands were carried out in operations for thyroid carcinoma in 25 cases. For the purpose of fine dissection of paratracheal lymph nodes, before thyroidectomy more than 2 parathyroid glands were found and transplanted into greater pectoralis muscle. The patients who underwent surgery were studied for more than one year following operation to determine the short term and long term outcomes of the procedure. None of the patients received prophylactic calcium supplement therapy except for hypocalcemic symptoms. In thirteen patients, the parathyroid function was almost completely restored within 3 weeks without any postoperative substitution therapy, with an obvious surge in the plasma PTH level on 5P.O.D. The serum Ca level started to elevate on 7P.O.D. and recovered to 97.4% of the preoperative value 3 weeks after transplantation. As for the 12 patients who exhibited hypocalcemic symptoms, Ca lactate and hydroxycholecalciferol were administered for only 24.7 and 17.0 days, respectively. Serum levels of Ca and P, as well as the index of bone mineral content, were all within the extremely excellent range even one year after operation. None of the patients was on a substitution regimen. These results suggest that autotransplantation is a valuable alternative for the preservation of the parathyroid function in operations for thyroid carcinoma.

Adult↗
PubMed1988

Multiple functioning paraganglioma associated with polycythemia.

Multiple retroperitoneal functioning paraganglioma complicated by polycythemia is reported in the case of a girl who, at the age of 13 years complained of headache, palpitation, and faintness preoperatively. In the retroperitoneal cavity, there were 21 paragangliomas larger than 1 cm in diameter. All were removed surgically in two sections, the first in 1979 and the second in 1983. Bilateral adrenals were macroscopically normal, and her symptoms disappeared. Now the recurrence of retroperitoneal paraganglioma is likely, although there have been no symptoms for 8 years, since the first operation. It is difficult to conclude that the tumors were benign or malignant in this case. Though complication of polycythemia had been diagnosed before the operation, the symptom continued even with the serum erythropoietin level kept in the normal range. Association of polycythemia with paraganglioma is extremely rare, and it is also rare to find more than 10 paragangliomas. Only a limited number of reports have been made on each case in the literature.

Adolescent↗
PubMed1988

Total thyroparathyroidectomy in patients with thyroid cancers and changes in erythrocytic Mg levels following parathyroautotransplantation.

Parathyroid hormone (PTH) rapidly decreases in patients with thyroid cancers, even after autotransplantation following total thyroparathyroidectomy. Simultaneously, serum calcium (Ca) and erythrocytic Ca levels also decrease, and in some cases, tetanic symptoms caused by hypocalcemia may occur. Assuming that magnesium (Mg) might participate in the alteration of Ca and PTH levels, the postoperative changes in intracytoplasmic Mg levels of erythrocyte were determined for several days. In the present paper, red blood cells (RBC) were used as a substitute for general somatic cells and controls were taken from patients with breast cancers. Although the erythrocytic Mg levels of the patients with thyroid cancers showed almost no change until day 7, an apparent decrease was noted in the patients with breast cancers during the period from day 1 to day 7, with a significant difference being seen between the two groups. Assuming that the operative invasions were compatible between these two groups of patients, the difference may be explained by a rapid decrease of postoperative serum PTH in the patients with thyroid cancers.

Calcium↗
PubMed1988

Effect of parathyroid function on serum bone Gla protein.

The serum bone Gla protein (BGP) level was measured in patients with idiopathic hypoparathyroidism, and primary hyperparathyroidism, and normal volunteers. The mean serum BGP level was 4.5 +/- 0.20 micrograms/l in 40 normal volunteers. It was significantly lower in 12 patients with idiopathic hypoparathyroidism (1.6 +/- 0.21 micrograms/l, p less than 0.001) and significantly higher in 33 patients with primary hyperparathyroidism (13.0 +/- 1.3 micrograms/l, p less than 0.001). When a single intravenous injection of 30 micrograms of human PTH 1-34 was administered to the patients with idiopathic hypoparathyroidism, there was no significant change in serum BGP within the next 24 hours. Following a therapeutic oral dose of alfacalcidol, serum BGP was appreciably increased (p less than 0.001) from the preadministration value of 1.6 +/- 0.21 micrograms/l to 3.9 +/- 0.34 micrograms/l. In patients with primary hyperparathyroidism, the surgical excision of parathyroid adenoma led to a sharp decrease in serum PTH but a gradual decrease in serum BGP. The latter approximately paralleled the decline in serum alkaline phosphatase. Thus, serum BGP is a marker that reflects bone turnover status in parathyroid disease. It appears that the active form of vitamin D directly increases the secretion of BGP in existing osteoblasts and PTH mainly affects serum BGP to stimulate the bone remodeling cycles with its long term effect.

Adenoma↗
PubMed1987

[A case of von Hippel-Lindau disease with multiple abdominal disorders and renal cell carcinoma].

A 52-year-old male underwent right nephrectomy after a clinical diagnosis of renal cell carcinoma. He suddenly lost consciousness 3 days after the nephrectomy and expired 3 weeks later. An autopsy revealed a hemangio-blastoma in the forehead skin. Multiple cysts, cyst-adenomas and an islet cell tumor were also identified in the pancreas. Considering the presence of blindness and the familiar, prevalence of this disease, his case was diagnosed as a rare manifestation of von Hippel Lindau disease associated with renal cell carcinoma, complicated with abdominal disorders.

Adenoma, Islet Cell↗
PubMed1987

[A case report of multiple endocrine neoplasia type 2b].

A 10-year-old girl was admitted displaying a medullary thyroid carcinoma, accompanying neurinomas of the tongue, marfanoid habitus, megacolon, and scoliosis. Although her adrenal glands were found to be unremarkable on both CT and ultrasonogram examination an MIBG scintiscan showed a 131-1 uptake, suggesting the presence of medullary hyperplasia. Remarkable nodal involvement with invasive features witnessed in the upper mediastinum during tertiary surgery four years later, following a total thyroidectomy. The TCT and CEA profiling was not sufficient enough to predict a recurrence. At the present state there is difficulty in providing an early diagnosis; through node dissection, however, is considered to be necessary at time of primary thyroid operation in cases with MEN type 2b.

Carcinoma↗