Nihon Naibunpi Gakkai zasshi最新文献

To elucidate the significance of long-term administration of dexamethasone in order to differentiate the 4 types of hyperaldosteronism, blood pressure, serum electrolytes, plasma renin activity (PRA) and diurnal rhythm of plasma aldosterone (PAC) were studied before and after long-term dexamethasone (Dex) administration in patients with aldosterone-producing adenoma (APA), idiopathic hyper aldosteronism (IHA), unilateral adrenal hyperplasia (UAH) and Dex suppressible hyperaldosteronism (DSH). The results were as follows: 1) In APA with ACTH-dependent aldosterone secretion, long-term Dex administration induced a significant depression of PAC associated with an elevation in serum potassium (s-K). In almost all patients with APA, the diurnal rhythm of PAC, parallel to that of ACTH, completely disappeared following Dex administration. 2) In most patients with IHA, PAC was mainly influenced by the renin-angiotensin system. Dex did not affected on s-K, but it induced a slight decrease in PAC in some patients with IHA. 3) In UAH having similar pathophysiological findings of the adrenal cortex as IHA, Dex decreased PAC. 4) In DSH, Dex at a dose of 6 mg/day decreased PAC to normal value in association with normalization of blood pressure and s-K. From these results, hyperaldosteronism inducing a decrease in PAC and an increase in s-K by Dex is possibly diagnosed as APA, while the patients with no change of s-K by Dex may be diagnosed as IHA. Even if PAC is suppressed with Dex and ACTH-independent, the hyperaldosteronism may be UAH. It may be possible that factors other than aldosterone are important to induce hypokalemia in patients with IHA. Furthermore, it is suggested that UAH is a precedent pathophysiological condition of aldosterone-producing adenoma in the adrenal cortex. It is concluded that the measurement of s-K and diurnal rhythm of PAC before and after Dex administration are useful for discriminating APA and IHA.

We established two human thyroid tumor cell lines. One cell line (hPTC) was established from the tissue of a papillary thyroid carcinoma surgically excised from a 27-year-old female patient. The other cell line (hAG) was established from the tissue of an adenomatous goiter excised from a 59-year old female patient. Synthesis of cAMP by hPTC and hAG increased when they were stimulated by TSH. hPTC and hAG continued to divide as a monolayer in a tissue culture for three years and two years, respectively. We assessed the efficacy of anticancer drugs (doxorubicin:ADR, cisplatin:CDDP, nimustine:ACNU, bleomycin:BLM, cyclophosphamide:CPA, aclarubicin:ACR) with resard to hPTC. The hPTC cells were cultured in 24-well plates in the presence of the anticancer drugs for 48 hours, and the cellular DNA of the live cells was measured with diaminobenzoic acid. ADR had the lowest ED50 (0.029 mu g/ml) and the clinical blood concentration was 13.8 times that of the ED50. The clinical blood concentration divided by ED50 for the other anticancer drugs are, in order of higher values, 2.3 for CPA, 1.7 for BLM, 1.2 for CDDP, 0.5 for ACR, and less than 0.1 for ACNU. ADR showed time-independent effects since a 2-hour exposure of ADR to the hPTC cells resulted in the significant reduction of the cellular DNA content of the live cells even after 48 hours. The effects of the other anticancer drugs were time-dependent. We then studied the difference of the effects of ADR on hPTC and hAG. ED50 for hPTC was significantly low (0.035 mu g/ml) compared to that for hAG (0.460 mu g/ml). Since free radical formation is one of the major anticancer mechanisms of ADR the effects of free radicals on ED50's for hPTC and hAG were measured by adding glutathione (GSH), N-acetylcystein (NAC), buthionine sulfoximine (BSO), and alpha-tocopherol (alpha-toco) into the culture media. GSH catches up with free radicals in the extracellular fluid. NAC promotes production of GSH in the cytoplasm, but BSO interferes with the production of GSH in the cytoplasm. alpha-toco catches up with free radicals on the plasma membrane. GSH and alpha-toco did not effect ED50 for hPTC and hAG. However, NAC increased ED50 for hPTC and hAG, and BSO reduced ED50 for hPTC and hAG. The effects of NAC and BSO on ED50 for hPTC were greater than those for hAG.(ABSTRACT TRUNCATED AT 400 WORDS)

A case of an 18-year-old female with polyglandular autoimmune syndrome (PGA) type 1 complicated by slowly progressive IDDM was described. She had epilepsy at the age of 5, and mucocutaneous candidiasis and hypoparathyroidism at 7 years. At the age of 18, the patient noticed thirst and body weight loss. On admission, she had uneven teeth and chronic mucocutaneous candidiasis. Plasma blood glucose was 312 mg/dl without ketosis, hemoglobin Alc 9.1%, serum calcium 3.5 mEq/l, serum phosphorus 6.0 mg/dl. A CT scan of her brain revealed calcification in the bilateral basal ganglia. Serum intact PTH was less than 10 pg/ml. Ellsworth-Howard's test showed hyperresponsiveness in the secretion of urinary phosphorus and cyclic-AMP. Other endocrinological studies showed no abnormality except for mild hyporesponsiveness in the secretion of urinary C-peptide (39.6 mu g/day). After admission, she was initially treated with diet alone with positive islet cell antibody (ICA). Three months later she was treated with low dose insulin, and ICA became negative. Then 5 months later it became positive again. Sixteen months later she had IDDM with positive ICA and without the secretion of urinary C-peptide. On the basis of these results, we diagnosed this case as PGA type 1 with the manifestations of hypoparathyroidism, chronic mucocutaneous candidiasis and slowly progressive IDDM. This is the second case report in Japan about PGA type 1. Furthermore, this case demonstrates for the first time in Japan that slowly progressive IDDM is complicated by PGA type 1. The patient had this HLA typing: A 24(9), BW52(5), BW60(40), CW3, DR2, DRW12, DQW7. More investigation is necessary to clarify the mechanism of PGA type 1.

The author established three variant cell lines which were proliferative in the serum-free medium. These three cell lines were derived from MCF-7, a human breast cancer cell line. These 3 variants (MCF-S1, MCF-S2 and MCF-S3) proliferate estrogen (E2)-dependently, but the amounts of E2 receptor and progesterone receptor in the cells are different from each other among the variants. The author compared the effects of hormonal therapeutic agents, tamoxifen (TAM), 3-hydroxytamoxifen (3-OH-TAM), toremifene (TORE), and medroxyprogesterone acetate (MPA) on MCF-7 and the established variant cells. Although TAM showed little effect on the growth of any cell lines in the absence of E2, it considerably inhibited the growth of MCF-S2 cells and MCF-7 cells in the presence of 10(-10)M E2. TORE also provided no inhibitory effect at less than 10(-7)M concentration on any cells in the absence of E2, but it dose-dependently inhibited DNA synthesis of MCF-S2 cells in the presence of E2. On the other hand, although 3-OH-TAM markedly inhibited the growth of any cell lines at a concentration of less than 10(-6)M in the presence of E2, it dose-dependently inhibited the DNA synthesis of any cell lines in the absence of E2, and the effect was remarkable in the case of MCF-S2 or MCF-S3. MPA showed a tendency to increase the proliferation of any cells in the absence of E2, conversely in the presence of E2, and it slightly inhibited DNA synthesis at concentrations of over 10(-8)M. These results suggest that the effect of hormonal agents on breast cancer cells may depend on either hormonal levels or the characteristics of the cancer cells. The effect of the hormonal agents are diverse, and a hormonal agent which does not work well on one cancer cell population may work well on another population.

An attempt was made to determine the clinical evaluation of subtotal thyroidectomy in 58 patients with Graves' disease. The weight of the remnant thyroid gland was measured during the operations. Postoperative thyroid volume was measured by ultrasonography (thyroid volume = pi abc/6; a is length, b width, and c thickness). Postoperative thyroid function including serum TSH, free triiodothyronine (FT3), free thyroxine (FT4), thyroglobulin (Tg), TSH receptor antibodies (TRAb), and antimicrosomal antibodies (MCHA) was examined. Fifty-eight patients were divided into the three groups, according to postoperative thyroid function; 39 (67.2%) in remission, 7 (12.1%) with relapse and 12 (20.7%) in a hypothyroid state. Postoperative thyroid volume in patients with relapse was significantly (p < 0.05) greater than that in patients in remission and in a hypothyroid state. Remnant thyroid weight in patients with relapse was significantly (p < 0.05) heavier than that in patients in remission and in a hypothyroid state. However, there was no significant difference in an estimated total thyroid weight among the three groups. A significant correlation was noted between the remnant thyroid weight and the postoperative thyroid volume (R = 0.58, p < 0.001). On the other hand, there was a significant correlation between serum Tg level and the postoperative thyroid volume (R = 0.45, p < 0.01). Serum level of Tg in patients with relapse was significantly (p < 0.05) higher than that in patients in remission and in a hypothyroid state. The prevalence of negative MCHA in patients in remission appeared relatively higher than that in patients with relapse and in a hypothyroid state. In patients with a remnant thyroid weight of less than 4.0 g, there was no recurrence following subtotal thyroidectomy, but a higher prevalence of hypothyroid state (43%) was observed compared to those of larger remnant thyroid weight. In patients with a remnant thyroid weight of 4.0 to 6.0 g, there was a lower prevalence of recurrence (5.9%) compared to those with a larger remnant thyroid weight, while most patients showed remission (73.5%). On the other hand, the highest prevalence of recurrence (23.5%) was obtained in patients with a remnant thyroid weight of more than 6.0 g. These observations indicate that postopertive thyroid state does not depend upon an estimated total thyroid weight, but depends upon a remnant thyroid weight. In addition, a remnant thyroid weight is closely associated with thyroid volume measured by ultrasonography after subtotal thyroidectomy, which reflected the serum level of Tg.

A 74-year-old woman with primary hyperparathyroidism and ischemic heart disease was treated with percutaneous ethanol injection into a single parathyroid adenoma which was confirmed by fine-needle aspiration biopsy. The changes in intact parathyroid hormone (int-PTH), serum calcium, serum phosphate, and alkaline phosphatase after percutaneous ethanol injection therapy (PEIT), and also ultrasonic findings of the injected adenoma were examined before and after PEIT. The values of int-PTH and serum calcium remained high for a few hours after the ethanol injection. About 24 hrs later, however, rapid lowering of the serum concentrations of int-PTH and serum calcium was observed, reaching normal levels about 36 hrs later. Although these parameters recurred once, the patient received another three ethanol injections within three months, which normalized these values. In ultrasonic findings, the parathyroid adenoma was well demarcated and hypoechoic before PEIT. Twenty-four hours after the ethanol injection, the adenoma became hyperechoic with a small hypoechoic lesion as viable tissue. Then the tumor shrank gradually and no apparent side-effects was observed in a total of four PEIT. Since in Japan, PEIT for primary hyperparathyroidism has not been widely performed, we propose that this therapy could be a useful alternative treatment in patients in whom parathyroid surgery would not be indicated such as the elderly, patients with high surgical risks, hypercalcemic crisis and patients who refuse surgery.

IRS-1 (insulin receptor substrate-1) is a major substrate for the insulin receptor tyrosine kinase. After phosphorylation by the insulin receptor, IRS-1 binds to the specific molecules which possess SH2 (src homology 2) domain such as 85 kDa subunit of phosphatidylinositol 3 kinase and may mediate insulin signals. The regulation of IRS-1 has been analyzed in animal models of insulin resistance, and its mechanism has been studied in culture cells. In animal models of insulin resistance, phosphorylation of IRS-1 was mainly regulated by the insulin receptor tyrosine kinase both in liver and muscle. However, IRS-1 protein level was differently regulated in muscle and liver. In muscle, IRS-1 protein decreased with dexamethasone treatment and in hypoinsulinemic states such as starvation and streptozotosine-induced diabetes and showed no change in hyperinsulinemic states such as obesity. In liver, IRS-1 protein increased with dexamethasone treatment and hypoinsulinemic states and decreased in hyperinsulinemic states. In cultured cell such as 3T3-L1 or 3T3-F442A adipocytes, IRS-1 was negatively regulated both by insulin and dexamethasone by different mechanisms. Insulin regulates the IRS-1 expression at protein level mainly by decreasing the half life of IRS-1 protein, and dexamethasone regulates it at mRNA level mainly by decreasing the half life of IRS-1 mRNA.

Bacterial lipopolysaccharide (LPS) and other immunostimulants induce an isoform of nitric oxide synthase (iNOS) in vascular smooth muscle (VSM) which produces large quantities of nitric oxide (NO) and profound vasodilation. This process has been implicated as the cause of gram-negative septic shock. It has been demonstrated that interferon-gamma (IFN) markedly potentiates cytokine-induced NO synthesis in various cell types. However, little is known about the mechanism of this enhancing effect of IFN. The present study was undertaken to investigate the effect of IFN on LPS-induced NO synthesis and iNOS mRNA expression in VSM and the possibility of nuclear factor kB (NFkB) involvement in the effect of IFN. LPS-induced NO synthesis is markedly potentiated by IFN in VSM. Expression of iNOS mRNA in VSM costimulated with IFN and LPS was greatly increased compared to that induced by LPS alone. IFN did not alter the lifetime of iNOS mRNA. LPS stimulated translocation into the nuclei of NFkB which is believed to play an important role in the induction of iNOS, but IFN did not enhance NFkB activation by LPS. These results suggest that the enhancing effect of IFN is due to the increased transcription of the iNOS gene rather than a decreased degradation of iNOS mRNA and that the NFkB activation pathway is not involved in this effect of IFN.