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61 巻, 5 号
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John A. WILLIAMS1985 年 61 巻 5 号 p. 533-540
発行日: 1985/05/20
公開日: 2012/09/24
ジャーナル フリーBrain-gut peptide action has been best studied in certain target cells of the gastrointestinal tract such as isolated pancreatic acini. Cholecystokinin (CCK) activation of pancreatic digestive enzyme secretion is initiated by specific receptors present in the basolateral membrane of the acinar cell. These receptors are highly selective for CCK and readily dis criminate it from the homologous peptide, gastrin. Studies covalently crosslinking125I-CCK to its receptor have revealed a binding glycoprotein subunit of Mr= 76,000 attached by a disulfide bridge to a Mr=40,000 nonbinding subunit. Receptor occupancy leads to phosphotidylinositide breakdown and Ca2+ mobilization. Recent studies with the fluorescent chelate probe Quin-2 have shown that CCK increases cytosolic Ca2+ from a basal level of 100 nM to 500-1000 nM. The effects of Ca2+, and diacylglycerol produced by the breakdown of phosphoinositides, are believed mediated by activation of a group of protein kinases and phosphatases.
CCK in the brain is present in neurons and is released from nerve endings by depolarization. The cellular mechanism of action of CCK, however, is essentially unknown. CCK application excites certain neurons but attempts to demonstrate effects on ion fluxes, phospholipid metabolism and protein phosphorylation have been negative to date. A possible explanations is provided by the finding that the brain CCK receptor shows differences in binding specificity from peripheral CCK receptors. Moreover, crosslinking studies reveal a single binding protein of Mr= 51,000. Thus, CCK may act differently in the brain and pancreas.抄録全体を表示PDF形式でダウンロード (919K) -
坪井 久美子1985 年 61 巻 5 号 p. 541-553
発行日: 1985/05/20
公開日: 2012/09/24
ジャーナル フリーMonolayer cultures of human thyroid cells derived from thyroid adenoma were utilized for the assay of thyroid stimulating substances such as thyrotropin (TSH), cholera toxin and thyroid stimulating immunoglobulin (TSI) in patients with Graves' disease. Adenoma cells were treated with 0.1% collagenase or 2000 unit/ml dispase to thyrocytes. The cells were cultured in MEM containing 10% fetal calf serum under an atmosphere of 5% CO2 in air. Within 24 hours, the cells attached themselves to the plastic surface and formed a monolayer.
Cyclic AMP responses to TSH, cholera toxin or Graves' IgG were tested in a medium (PBS) containing 0.5 mM IBMX. The cyclic AMP responses to TSH were generally maximal on the 3rd day of culture and declined thereafter. The response was dose-dependent, and 10 μU/ml of TSH produced a significant increase of cellular cyclic AMP. The response by 1 mU/ml of TSH was 28-57 fold above the basal. The response was also a function of the incubation period. The maximal response was attained after 1 h incubation. When the cultures were washed after exposure to TSH, the cellular cyclic AMP levels rapidly declined, suggesting that removal of receptor-bound TSH results in a prompt cessation of cyclic AMP production.
The thyroid cells in monolayer also responded to cholera toxin. The response was dose-dependent, and cholera toxin as low as 1 ng/ml was able to increase cyclic AMP production. In contrast to the observations in TSH, the cyclic AMP responses induced by cholera toxin were hardly affected by washing the cultures after exposure to cholera toxin. Treatment of the cells with cholera toxin for only 3 min resulted in a continuous stimulation of cyclic AMP production for more than 4 hours.
Confirming recent observations by others, most of Graves' IgG stimulated cyclic AMP production in a dose-dependent manner, but some of them inhibited the response at high concentrations. IgG derived from normal subjects did not increase cellular cyclic AMP. The time course in the cyclic AMP responses induced by Graves' IgG was variable among the IgG preparations from different patients. In some patients, the maximal responses were attained after 4 hours of incubation. A significant difference was noted between TSH and Graves' IgG in the stimulation of cyclic AMP production after washing the cultures. When the cultures were treated with Graves' IgG for 30 min, washed and then incubated without Graves' IgG, cellular cyclic AMP levels remined at the levels which were almost equivalent to those observed in the continuous presence of the IgGs. This finding suggests that binding of Graves' IgG to TSH-receptor is less reversible compared to that of TSH. Alternatively, the mechanism by which Graves' IgG stimulates cyclic AMP production might not be identical to that postulated in TSH.
In the present system, approximately 72% of IgG preparations from untreated patients with Graves' disease stimulated cyclic AMP production significantly at a concentration of 1 mg/ml after incubation for 1 hour. The present assay systems are considered to be useful for detecting TSI present in the sera of patients, however, further studies are required to improve their sensitivity.抄録全体を表示PDF形式でダウンロード (1253K) -
貴田岡 博史, 桜田 俊郎, 深沢 洋, 鈴木 道子, 海瀬 信子, 海瀬 和郎, 吉田 克已, 山本 蒔子, 斉藤 慎太郎, 吉永 馨, ...1985 年 61 巻 5 号 p. 554-570
発行日: 1985/05/20
公開日: 2012/09/24
ジャーナル フリーIt is difficult to study subacute thyroiditis epidemiologically since it occurs sporadically and infrequently.
Information about 1,127 cases (108 males, 1,019 females, from 1967 to 1982) of subacute thyroiditis in northern Japan was obtained through a questionnaire.
It was found that the usual age for the disease was forty, that females predominated in a ratio of 10.6 : 1, and that the prevalent month was July.
In clinical features, the frequencies of the inflammatory symptoms were high in the acute phase of the disease, and the frequencies of hyperthyroid symptoms increased with the progress of the disease.
According to the course of the disease (days after the onset without treatment), the patients were divided into seven subgroups, such as 1-7 days, 8-14 days, 15-21 days, 22-28 days, 29-42 days, 43-56 days and over 57 days, respectively.
Compared with the 1-7 days group, the erythrocyte sedimentation rate, serum T4 and T3 concentrations in the 15-21 days group showed a significant increase from 64 ± 35 to 75 ± 30 mm/h (p<0.001), 14.6 ± 5.5 to 17.6 ± 5.6 μg/100 ml (p<0.001) and 218± 124 to 263 ± 109 ng/100 ml (p<0.05), respectively, but the BMR showed as insignificant increase from 20 15 to 24 ± 14%.
The 24-hr 131I-thyroid uptake and resin sponge uptake (RSU) in the 21-28 days group were 1.2 ± 1.5% and 35.1 ± 6.7%, respectively; the former was significantly lower (p<0.02) and the latter was insignificantly higher than the values (2.0 ± 2.6% and 33.9 ± 7.9%, respectively) in the 1-7 days group.
The recovery time in the steroid-treated group was 57.2 ± 47.6 days, which showed a statistically insignificant difference from 64.8 ± 50.5 days of the sodium salycylate-treated group.
But the recovery time of 78.2 ± 64.9 days in other anti-inflammatory drug-treated groups was significantly longer than that of the steroid and sodium salycylate-treated groups (p<0.001 and p<0.05).
Among 9 viral diseases, such as measles, varicella, erythema infectiosum, hand-foot and mouth disease, rubella, mumps, influenza, epidemic keratoconjunctivitis and acute hemorrhagic conjunctivitis observed in northern Japan and Miyagi prefecture in the past 4 years, mumps, hand-foot and mouth disease and epidemic keratoconjunctivitis were pr-valent in summer.
The monthly variation of mumps infection seemed to be fairly correlated with that of subacute thyroiditis. But there was no significant difference between the antiviral antibody titers against viruses, such as mumps, rebella and measles, measured at the first medical examination or one month later in the patients with subacute thyroiditis.
Therefore, more direct serological and virological studies are needed to make clear the etiology of the disease.抄録全体を表示PDF形式でダウンロード (1388K) -
水野 兼志, 後藤 光弘, 橋本 重厚, 小島 元子, 福地 総逸1985 年 61 巻 5 号 p. 571-580
発行日: 1985/05/20
公開日: 2012/09/24
ジャーナル フリーThe biochemical properties of renin, extracted from human pituitary specimens obtained at autopsy, were studied using a specific antirenin antibody raised against human kidney renin. The following results were obtained.
1) The molecular weight of pituitary renin was estimated to be about 37,000 daltons by gel filtration through Sephadex G-100.
2) The optimum pH of pituitary renin was between 6.0-7.0, while that of a renin-like substance which did not react with the antirenin antibody had an acidic pH of 4.0, with a pH comparable to that of the cathepsin D-like enzyme in the pituitary tissue.
3) The presence of two different isoelectric-point species of pituitary renin was revealed by isoelectric focusing, one with a point of pH 4.47 and the other with that of pH 5.77.
4) The Km value of pituitary renin was 37.9 piM for synthetic human renin substrate.
5) Affinity chromatography of the pituitary renin on a Concanavalin-Sepharose column showed that most (87.4%) of the pituitary renin did not contain glycoprotein residues.
6) Treatment with either trypsin or glandular kallikrein increased the renin activity, indicating the presence of an inactive form of renin in the pituitary tissue.
From these findings, it is concluded that specific renin exists in human pituitary tissue. It seems likely that the pituitary renin is of local origin rather than contamination of the circulating enzyme.抄録全体を表示PDF形式でダウンロード (886K) -
免疫組織化学的研究下瀬川 徹, 小針 瑞男, 山家 誠, 小泉 勝, 豊田 隆謙, 後藤 由夫, 小林 繁, 望月 徹, 矢内原 千鶴子, 矢内原 昇1985 年 61 巻 5 号 p. 581-591
発行日: 1985/05/20
公開日: 2012/09/24
ジャーナル フリーThe occurrence and localization of Met-enkephalin-Arg-Gly-Leu (Met-Enk-Arg-Gly-Leu) -like immunoreactivity in the lumbar paravertebral ganglion and the superior mesenteric ganglion in the rat were investigated by immunocytochemistry. Colchicine was employed as an axonal flow blocker to accumulate Met-Enk-Arg-Gly-Leu in the nerve cell bodies. The Met-Enk-Arg-Gly-Leu serum (R 0171) was produced by immunizing a mixed breed female rabbit with synthetic Met-Enk-Arg-Gly-Leu conjugated to ascaris protein by the glutaraldehyde method. Sections, 7μm in thickness, of Bouin-fixed and paraffin-embedded tissues were immunostained by the peroxidase-antiperoxidase (PAP) method.
Results obtained were summarized as follows :
1) Colchicine-untreated rats possessed no strongly-immunoreactive nerve cell bodies for Met-Enk-Arg-Gly-Leu in the lumbar paravertebral ganglion, though a few of them wereweakly immunopositive. Met-Enk-Arg-Gly-Leu-like immunoreactivity showing nerve fibers were occasionally seen in nerve fiber bundles of the lumbar paravertebral ganglion. In the superior mesenteric ganglion, a dense network of positively immunostained nerve fibers with a beaded appearance were seen around nerve cell bodies which were immunonegative for Met-Enk-Arg-Gly-Leu.
2) In colchicine-treated rats, 55 percent of nerve cell bodies of the lumbar paravertebral ganglion showed various degrees of positive immunoreactivities for Met-Enk-Arg-Gly-Leu. Many strongly immunostained nerve terminals were seen in the lumbar paravertebral ganglion of colchicine-treated rats. In the superior mesenteric ganglion, the immunoreactivity for Met-Enk-Arg-Gly-Leu in the beaded nerve fibers around nerve cell bodies was intensified by the colchicine treatment, whereas the nerve cell bodies themselves remained immnonegative for Met-Enk-Arg-Gly-Leu.抄録全体を表示PDF形式でダウンロード (2395K) -
若林 茂, 香川 昌平, 中尾 啓子, 松岡 瑛1985 年 61 巻 5 号 p. 592-604
発行日: 1985/05/20
公開日: 2012/09/24
ジャーナル フリーMonolayer islet cells prepared from neonatal rat pancreases were cultured in media with 5.5 mM glucose alone or supplemented with 1 mM 2-deoxy-2-fluoroglucose for a total of 7 days. The recovery of insulin in the cells and media, and the insulin secretory responses to four secretagogues were determined on several occasions.
Under culture conditions with a basal medium containing 5.5 mM glucose, the responses to insulin secretagogues tested were abolished after 7 days of culture. In contrast, the addition of 2-deoxy-2-fluoroglucose maintained the insulin secretory responses to glucose (2.8-33.4 mM), leucine (2.5-10 mM) and 2-ketoisocaproate (2.5-10 mM) at levels several times higher than at day 0. Moreover, in these monolayer islet cells the rates of 0.62 mM [U-14 C] glutamine oxidation were significantly increased by leucine or 2-ketoisocaproate at 10 mM. From these results, it is suggested that a series of metabolic adaptations in response to change in nutritional status (possibly attributable to the action of 2deoxy-2-fluoroglucose as an inhibitor of glycolysis) may facilitate the metabolism of amino acids in B cells. Such an activation may be associated with the survival and maturation of neonatal B cells in vitro.抄録全体を表示PDF形式でダウンロード (1399K) -
高橋 晃1985 年 61 巻 5 号 p. 605-618
発行日: 1985/05/20
公開日: 2012/09/24
ジャーナル フリーTo clarify the possible intervention of gonadal steroids on the secretion of bioactive LH from the pituitary, the levels of plasma LH were measured by in vitro bioassay as well as radioimmunoassay, and their changes in specific endocrine conditions were investigated.
The ratio of bioactivity to immunoactivity (B/I ratio) of LH in patients with hyper-gonadotropic hypogonadism and in postmenopausal women was significantly greater than that in women during the follicular phase of the menstrual cycle, and estradiol levels in the former groups were significantly lower than those of the latter group. In cases of gonadotropin-secreting pituitary tumor with high LH and normal estradiol levels, B/I ratio was found at a level similar to that during the follicular phase. The administration of combined pills decreased the high B/I ratio of oophorectomized women to levels comparable to those in the normal follicular phase.
Although bioactive LH responded in all groups to LH-RH with a similar pattern to that observed with immunoactive LH with a peak value 15-30 min. after the stimulation, followed by a gradual decrease thereafter, the B/I ratio of women during the follicular phase was the lowest at 15 min. and returned up to the initial value within 60 min. after the injection of LH-RH. In contrast, this drop of the B/I ratio did not occur in 7 out of 15 cases composed either of hypergonadotropic hypogonadism or postmenopausal women. The peak values of LH in patients without decrease in B/I ratios were higher than those of women showing decreased B/I ratios. In addition, circulating levels of gonadotropin a-subunit did not affect the B/I ratio. These results suggest that circulating levels of gonadal steroids regulate the secretion and synthesis of LH quantitatively as well as qualitatively.抄録全体を表示PDF形式でダウンロード (1240K) -
レニン・アンジオテンシン・アルドステロン系ならびにカリクレイン・キニン系との関連後藤 光弘, 水野 兼志, 橋本 重厚, 国井 伸泰, 福地 総逸1985 年 61 巻 5 号 p. 619-629
発行日: 1985/05/20
公開日: 2012/09/24
ジャーナル フリーThe acute antihypertensive effect of a new long-acting oral angiotensin I-converting enzyme (ACE) inhibitor, enalapril maleate, was assessed in 20 hypertensive patients, of whom 14 had essential hypertension, 4 had renovascular hypertension, one had hypertension associated with chronic renal failure, and one had primary aldosteronism.
Enalapril maleate significantly lowered the blood pressure in either low-renin or normal- and high-renin hypertensives. There was a significant correlation for all patients as a group between the pretreatment levels of serum ACE activity and the reduction in mean blood pressure (r=- 0.454, p<0.05, n=20) 2 h after drug administration.
The serum ACE activity decreased maximally 3 to 4 hours after drug administration and did not return to baseline levels within 24 h. There was a significant correlation between the reduction in mean blood pressure and changes in ACE activity 90 min and 2h after drug administration, respectively, for all patients as a group (r= 0.495, p<0.05, n=20, at 90 min; r=0.508, p<0.05, n=20, at 2h).
The plasma renin activity (PRA) significantly increased in normal- and high-renin hypertensives but not in low-renin hypertensives. There was a close correlation between the reduction in mean blood pressure and the PRA 8 h after drug administration in normaland high-renin patients (r=- 0.623, p<0.05, n=13), while no such relationship was observed in low-renin patients. The plasma aldosterone concentration (PAC) significantly decreasedwithin 3 h, the lowest values occurring at 8h after drug administration, and it returned to baseline levels within 24 h in all patients. No relationship was found between the reduction in mean blood pressure and changes in PAC after drug administration in either low-renin or normal- and high-renin hypertensives.
The plasma bradykinin concentration (PBC) increased within 1 h, the highest values occurring at 3h after drug administration, and returned to baseline levels within 24 h in low-renin hypertensives, while the PBC was significantly increased at 4 h and had not returned to baseline levels within 24 h in normal- and high-renin hypertensives. There was a significant correlation between percentage changes in mean blood pressure and those in PBC 90 min after drug administration in normal- and high-renin hypertensives (r=- 0.556, p<0.05, n=13), while no relationship was observed between them in low-renin hypertensives.
From these findings, it is suggested that the acute hypotensive effect of enalapril maleate is due mainly to the inhibition of angiotensin II formation and kinin accumulation in patients with normal- and high-renin-angiotensin activity. Conversely, in low-renin hypertension, its vasodepressor effect may be due to kinin accumulation.抄録全体を表示PDF形式でダウンロード (855K)
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