Post-translational processing of thyrotropin-releasing hormone precursor in rat brain: identification of 3 novel peptides derived from pro TRH

The sequence of rat hypothalamic pro-thyrotropin releasing hormone, deduced by sequencing of cDNA, in addition to 5 TRH progenitor genitor sequences contains leader, trailer and 4 intervening sequences separated by paired basic amino acid sequences. We have developed radioimmunoassays to synthetic peptides corresponding to portions of these cryptic proTRH sequences and have used these assays to identify and partially characterize proTRH peptides, distinct from TRH, in extracts of rat brain. Two of these peptides correspond closely in size to one intervening sequence and the car☐y-terminal sequence of proTRH. Three other peptides correspond to the intact amino-terminal leader sequence and two peptides formed by a further cleavage of the leader sequence at an internal paired basic amino acid sequence.     

Natural history of parathyroid function and calcium metabolism after kidney transplantation: a single-centre study.

BACKGROUND: The natural history of parathyroid function after successful renal transplantation (RT) and the factors predisposing to persistent hyperparathyroidism (HPT) are not well established. A better knowledge of these data may be helpful in the development of algorithms for optimal surveillance and treatment of HPT after successful RT. Our aim was to evaluate the post-transplant natural history of parathyroid function and calcium metabolism in patients with a functional renal graft and to identify risk factors for persistent HPT. METHODS: Charts of 1165 allograft kidney recipients transplanted between 1989 and 2000 were reviewed. Patients with an intact parathyroid hormone (iPTH) level available at the time of transplantation were identified. The charts of the latter patients were checked for a variety of demographic and clinical data, and all determinations of the iPTH concentration available since transplantation were recorded. Serum levels of calcium, phosphorus, alkaline phosphatases and creatinine, concurrently determined, were also registered. RESULTS: After an initial fall, iPTH levels showed a slow but steady decline towards the upper normal limit. The prevalence of persistent HPT, defined as an iPTH level > or =2.5 times the upper normal limit or the need for parathyroidectomy following transplantation, remained stable at approximately 17% up to 4 years after transplantation. Patients with persistent HPT had significantly elevated serum levels of iPTH, calcium and phosphorus at the time of RT, and had spent a longer time on dialysis. Post-transplant iPTH levels correlated significantly with transplant kidney function. CONCLUSION: Kidney transplant recipients with a high iPTH and calcium x phosphate product at the time of transplantation are at risk for persistent HPT especially when renal function is suboptimal. Therapy for persistent HPT, if considered, should be initiated 3 months post-transplantation since further spontaneous improvement of parathyroid function thereafter is limited.     

Retrospective study on stage B prostate cancer in the Hokuriku District, Japan

BACKGROUND: The present study was conducted to investigate how patients with clinically localized prostate cancer were treated in the Hokuriku District, Japan. METHODS: Medical records of 536 patients with stage B prostate cancer were retrospectively reviewed. The patients were diagnosed and treated at four university hospitals and 32 collaborating hospitals in the Hokuriku District. RESULTS: Because their medical records were incomplete and/or they not available for follow up, 79 cases were excluded from this study. Conservative treatment with hormone therapy was used for 248 cases. Radical prostatectomy was performed in 199 cases, only 27 of whom underwent surgical monotherapy. There was no significant difference in disease-specific survival rates between the hormone (69.0%) and surgery group (83.2%) after 110 months. Results of the analysis of disease-specific survival rates according to histologic grade showed that patients with poorly differentiated cancers treated with hormone therapy were the only subset with significant differences when compared against the other patients. CONCLUSION: The value of prostatectomy alone or added was marginal in terms of survival. Only patients with poorly differentiated cancer might benefit from prostatectomy.     

重组人生长激素在肝硬变围手术期应用的临床研究

目的探讨重组人生长激素（rhGH）对肝硬变门静脉高压症患者术后肝功能和营养代谢的影响。方法将2003年2月至2004年1月期间我院收治的48例肝硬变患者随机均分为rhGH组和对照组，2组患者分别于术后第2d给予rhGH或生理盐水，共7d，检测2组患者的白蛋白水平、肝功能及血糖水平。结果rhGH组治疗后第7d起，血浆白蛋白水平明显高于对照组相应时相（P〈0．05）；血ALT、AST明显低于对照组相应时相（P〈0．05）；2组血糖含量随治疗时间延长逐渐降低，治疗后第14d恢复正常，但2组血糖治疗前、后相应时相比较差异无统计学意义（P〉0．05）；2组血浆胆红素水平于治疗前、后相应时相比较差异无统计学意义（P〉0．05）。结论rhGH可促进肝硬变门静脉高压症患者术后蛋白质的合成，纠正低蛋白血症，改善肝功能。     

Ghrelin does not stimulate gastrointestinal motility and gastric emptying: an experimental study of conscious dogs

Ghrelin is a peptide that was discovered in endocrine cells of the stomach. However, its action in regulating the fasted and fed motor activity of the digestive tract is not fully understood. In the present study, we examined the effects of an intravenous (i.v.) injection of canine ghrelin on the physiological fasted and fed motor activities in the stomach, duodenum, jejunum and colon of freely moving conscious dogs. An i.v. injection of canine ghrelin released growth hormone in a dose-dependent manner; however, it did not stimulate the motor activity of the digestive tract in either the fasted or the fed state. Moreover, an i.v. injection of high-dose canine ghrelin significantly reduced the motility index in the gastric body in the fasted state. Ghrelin did not accelerate gastric emptying, either. These results differ from previous reports dealing with rodents. It is significant that such results were obtained in research with dogs, which are larger animals.     

Comparison of the growth hormone, IGF-1 and insulin in cerebrospinal fluid and serum between patients with motor neuron disease and healthy controls

Neurotrophic effects of the growth hormone (GH), insulin-like growth factor-1 (IGF-1) and insulin on the central nervous system have become more apparent in the past decade. In this study, we measured serum and cerebrospinal fluid (CSF) concentrations of GH, IGF-1 and insulin in 35 patients with motor neuron disease (MND) [24 patients with definite amyotrophic lateral sclerosis (ALS) and 11 patients with progressive bulbar palsy] and in 40 healthy controls. Levels of serum concentrations of GH and IGF-1 did not significantly differ between the MND patient group and the healthy controls, while the level of insulin was significantly decreased ( P  = 0.0033) in the MND patient group. However, levels of all three examined parameters in CSF were significantly lower in the MND group than in the healthy controls with the statistical significance for IGF-1 and insulin of P  < 0.001. This finding has not been reported previously, and further investigations into its association with ALS should establish whether it can be used as an early marker of the disease, or whether it merely represents a consequence of ALS development.     

重组生长激素对腹部大手术患者血浆蛋白的影响

目的研究重组人生长激素（rhGH）对腹部大手术患者术后代谢、免疫功能和术后并发症的影响。方法回顾性分析腹部大手术患者79人，其中37人为治疗组，42人为对照组。治疗组手术后第2天开始，每天皮下注射思真（重组人生长激素，瑞士雪兰诺公司生产）8U，对照组给予安慰剂（生理盐水），共用7d；分别在治疗前，治疗后3、7、10、14d检测血浆白蛋白、前白蛋白及转铁蛋白水平。记录切口愈合情况及术后并发症情况。结果（1）治疗前，两组白蛋白、前白蛋白及转铁蛋白水平差异无统计学意义（P〉0．05）；治疗后3d，两组白蛋白水平差异无统计学意义（P〉0．05），且均低于治疗前；治疗组前白蛋白、转铁蛋白均高于对照组（P〈0．05）；治疗后7d，治疗组3项指标均高于对照组。（2）治疗组切口愈合情况明显优于对照组（P〈0.05）。（3）治疗组术后并发症发生率明显低于对照组（P〈0．05）。结论腹部大手术患者术后应用重组人生长激素可以提高免疫功能，促进切口愈合，减少术后并发症的发生。     

部分创面外用抗菌药物与成纤维细胞生长因子2、表皮生长因子、重组人生长激素对成纤维细胞生物学特性影响的实验研究

目的观察部分创面外用抗菌药物与成纤维细胞生长因子(FGF)2、表皮生长因子 (EGF)、重组人生长激素(rhGH)对成纤维细胞生物学特性的影响。方法体外培养成纤维细胞, 按所加药物不同分为对照组(常规培养)、丁胺卡那霉素(0．021、0．210、2．100 mg/L)组、庆大霉素(5、 50、500 mg/L)组、氯霉素(0．01、0．10、1．00 mg/L)组、磺胺米隆(5、10 g/L)组、FGF2(2 400 U/ml)组、 EGF(2 000 U/ml)组及rhGH(0．016、0．160、1．600 g/L)组。用噻唑蓝(MTT)法测定各组成纤维细胞增殖活性[吸光度(A)值],用流式细胞仪检测细胞周期,并于显微镜下观察细胞形态的变化。结果 (1)MTT法检测:与对照组A值0．455 3±0．021 7比较,各种剂量丁胺卡那霉素组、庆大霉素组、氯霉素组、磺胺米隆组成纤维细胞A值均明显降低(P<0．05或0．01),其中磺胺米隆(5、10 g/L)组降低最明显,分别为0．101 3±0．001 1、0．095 0±0．004 1(P<0．01)。FGF2组及0．016 g/L rhGH 组细胞A值明显高于对照组(P<0．05),而EGF组及0.160、1．600 g/L rhGH组A值与对照组接近 (P>0．05)。(2)细胞周期检测:对照组细胞增殖指数(PI)为(9．63±0．45)％,与之比较,0．210 mg/L丁胺卡那霉素组细胞PI值无明显变化(P>0．05),FGF2组、EGF组及0．016 g/L rhGH组PI值均明显升高,分别为(46．76±2．33)％、(42．30±1．41)％、(13．29±0．47)％(P<0．05或0．01)。 (3)形态学观察:对照组、EGF组及0．160、1．600 g/L rhGH组成纤维细胞数目较多,呈长条形或梭形, 轮廓不清,透明度高;丁胺卡那霉素组、庆大霉素组、氯霉素组、磺胺米隆组细胞数目较少,形态不规则,轮廓清晰,透明度低,细胞内多有颗粒样物质及空泡;FGF2组、0．016 g/L rhGH组细胞分布均匀、密集,呈长条形或梭形,核分裂相多见,轮廓不清,透明度高。结论不同创面外用药物对成纤维细胞生物学特性的影响各异,在创面修复过程中应选择合适的创面外用药物,以促进愈合并抑制瘢痕增生。     

Calorie restriction increases serum parathyroid hormone and decreases serum calcitonin levels in patients with maturity onset diabetes mellitus

Calorie restriction is important in managing patients with maturity onset diabetes mellitus (NIDDM). The effect of such restriction on calcium metabolism is not known. The objective of this study was to determine whether patients on calorie restricted diets would show any modification of parathyroid hormone (PTH) and calcitonin (CTN). The serum levels of PTH and CTN were measured by radioimmunoassays in 269 patients with NIDDM. The patients were divided into two groups depending on the intake of calorie, and PTH and CTN were monitored for 2 years. Plasma levels of vitamin D were measured by competitive protein binding assays before and after each program. The level of PTH (520.8±266.0 pg/ml) (mean±S.D.) was significantly (P<0.01) higher in 109 diabetic patients whose calorie intake was restricted for 2 years (diet (D) group) as compared with that (256.6±103.8 pg/ml) of 160 diabetic patients whose calorie intake was not restricted (non-diet (ND) group). The daily oral calcium intake of the two groups did not differ significantly. We found no significant difference in the serum PTH level in the ND groupVS. normal control subjects (248.8±98.4, N=78). The serum calcium concentration and the amount of calcium excreted in urine were slightly but significantly (P<0.01) lower in the D than in the ND group. The rate of tubular reabsorption of phosphate (% TRP) was significantly lower in the D group than that in the ND group (P<0.01). The serum CTN level was significantly (P<0.01) lower in the D group (33.9±11.3 pg/ml) than in the ND group (64.9±21.2 pg/ml) 2 years after each treatment. The plasma 1,25-(OH)₂-vitamin D level was significantly (P<0.01) lower in the D group (22.2±6.6 pg/ml) than in the ND group (50.6±4.2 pg/ml). When the restriction of calorie intake in the D group was canceled, their PTH levels decreased, which was accompanied by increase in the 1,25-(OH)₂-vitamin D levels, whereas their CTN levels were unchanged. These observations suggested that a restricted calorie intake is a risk factor for secondary hyperparathyroidism as well as for a low serum level of CTN in patients with NIDDM.