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Biomedical subjects

H Funahashi

Publications and source records attributed to H Funahashi.

At least 163 records · Page 9Linked to original sources

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↗

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↗

[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↗

[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↗

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↗

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↗

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↗

[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↗

[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↗

[Study on extensive lymph node dissection: metastatic lymph nodes in papillary carcinoma of the thyroid].

Bilateral cervical lymph node dissection was performed in 71 cases of papillary thyroid carcinoma, considered to be relatively early cases because of mobility, irrespective of the size of tumor or presence of node enlargement. Of these, 33 cases received additional node dissection of the anterosuperior mediastinum through longitudinal sternotomy. The number of lymph nodes examined per subject averaged 89.9, the number of metastatic nodes was 13.8, and metastasis was noted in 88.7% of all cases. Lymph node metastasis tended to be more frequent on the affected side, but was simultaneously scattered over the whole cervical area. As to sites, metastasis of paratracheal nodes on the affected side occurred at a frequency of 66.2%, inferior and superior jugular nodes at 62.0% and 59.0% respectively, pretracheal nodes at 50.7%, and tracheoesophageal nodes at 47.9%. The high incidence of para- and pretracheal nodes suggests that the lymph flow in this direction is of great importance in metastasis. In fact, lymph nodes in the mediastinum, which were directly continuous with these nodes, showed as high as 39.4% metastasis in cases of anterosuperior mediastinal extirpation. This extensive node dissection is considered to be very preferable as at least the agony of survival with carcinoma can be lessened.

Adult↗

[Pituitary-adrenocortical response to surgical stress in male patients].

Effects of major surgical stress on the plasma levels of twelve kinds of steroid hormones, ACTH and renin activity, and on the excretion rates of urinary free cortisol and acid labile aldosterone etc. were studied in eleven male patients for seven days following operation. In another groups of patients, ACTH tests were carried out in order to investigate the effect of ACTH on the adrenal steroid hormone production. Also, an in vitro assay of the effect of ACTH on the adrenal tissue was performed. Surgical stress provoked marked increase in plasma levels of cortisol, despite little change in aldosterone levels. The postoperative plasma testosterone concentration showed a profound decrease throughout the observation period. The plasma renin activity reached the highest level on the first postoperative day, when plasma aldosterone was at the lowest level. It was concluded that the postoperative changes in the plasma steroid hormone levels were markedly influenced by other physical and humoral disorders provoked with surgical stress.

Adrenocorticotropic Hormone↗

[Ogilvie's syndrome--a case report and review].

Ogilvie's syndrome is caused from functional obstruction of the colon without mechanical stenosis and also termed as pseudo-obstruction of the colon. This disease is seen in patient who has other causative distress. The pathogenesis of this rare entity is unknown but it is suspected that there may be an underlying autonomic disturbance which causes non-mechanical obstruction of the colon. Most of the case reports on Ogilvie's syndrome have appeared in European and North American journals but are extremely rare in Japan. Some cases which have been categorized "spastic ileus" may be included in this syndrome. We recently experienced a patient with cerebral infarction who developed non-mechanical obstruction of the colon. This patient was treated successfully with an exploratory laparotomy and sigmoidostomy. It is considered that early diagnosis is an essential part of the initial management of this syndrome. Conservative treatment is indicated for most of the patients but a definitive surgical therapy is occasionally necessary.

Aged↗

[Sinus histiocytosis in the lymph nodes of breast cancer patients having undergone extensive radical mastectomy].

Sinus histiocytosis in the regional lymph nodes of 45 patients with breast cancer who had undergone extended radical mastectomy was studied by histological examination of 2,294 resected lymph nodes. Sinus histiocytosis was divided into three grades, marked, moderate, and mild to negative, by Ohmori's classification. The results indicated that: 1) sinus histiocytosis correlates fairly well with clinical stage, especially with the n-factor, and 2) the degree of sinus histiocytosis shows little difference between three groups of regional lymph nodes. The authors concluded that sinus histiocytosis dominates the prognosis and represents some aspect of a reticuloendothelial response of the whole body to carcinoma.

Breast Neoplasms↗

[Plasma steroid hormones in Cushing's syndrome: their relation to cause and clinical manifestations (author's transl)].

For the purpose of studying the relation of diversities of basic lesion as well as clinical manifestation to hormonal abnormality in Cushing's syndrome, 12 kinds of steroid hormones was simultaneously measured in plasma by using 2 types of Sephadex LH-20 column chromatography in a total of 30 patients comprosing 28 cases of Cushing's syndrome and 2 cases of adrenocortical carcinoma which had abnormal plasma steroid hormone levels without sign or symptom of Cushing's syndrome. In the group of Cushing's syndrome were included cases of pituitary ACTH-dependent hyperplasia (Hp.), adrenocortical adenoma(Ad.), bilateral nodular hyperplasia, ectopic ACTH syndrome as well as recurrent Cushing's syndrome following subtotal adrenalectomy. Twelve steroids measured in plasma were pregnenolone(Preg)., 17-OH pregnenolone(17Preg.), progesterone(Prog.), 17-OH progesterone(17Prog.), 11-deoxycorticosterone (DOC), corticosterone(B), aldosterone(Ald.), 11-deoxycortisol(S), cortisol(F), dehydroepiandrosterone(DHA), androstendione(A-dione) and testosterone(T), including precursors (Prec.: Preg., 17-preg., Prog., 17-prog.) as well as hormones belonging to the 3 systems in the biosynthetic pathways of steroid; i.e., glucocorticoids(Glu.C.'s: S,F), mineralocorticoids(Min.C.'s: DOC, B, Ald.) and sex steroids(And.'s: DHA, A-dione, T). In addition, steroidogenesis in isolated adrenal cells obtained surgically from patients with Cushing's syndrome due to Hp. and Ad, was observed. The results were as follows: (1) In cases due to Hp., plasma levels of Glu.C's and And.'s were slightly elevated, while levels of Min.C.'s were within the normal range. On the whole, however, the 3 systems were well balanced. (2) In cases due to Ad., elevated secretion of Glu.C.'s and Min.C.'s was observed, while secretion of And.'s was depressed. Among the 3 fractions of And.'s, depression of DHA and A-dione was characteristic of Ad.. (3) Elevation of And.'s in Hp. and Min.C.'s in Ad. in addition to elevation of Glu.C.'s was in fair correlation with moderate virilism in Hp. and with hypertension and hypokalemia in Ad. respectively. (4) In vitro experiments revealed that Ad. produces not only F but all 12 steroids hormones and that increased DOC and depressed DHA secretion reflected in their plasma levels were the characteristics of Ad. in steroidogenesis. Furthermore, isolated adenoma cells were found to produce Ald. at a higher rate than normal or hyperplasia adrenal cells. This finding may suggest that an intermediate type between Cushing's syndrome and primary hyperaldosteronism can exist in cases of adenoma. (5) In ectopic ACTH syndrome, plasma levels of Glu.C.'s, Min.C.'s and And.'s were equally but more markedly elevated as compared with Hp.. The increase of B was characteristic of this disorder and, coupled with a marked increase of F, seems to be the main cause of hypokalemic alkalosis frequently associated with this syndrome. (6) Nodular hyperplasia was accompanied by elevated Min.C...

Adenoma↗