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标记免疫分析与临床 1999年第1期6卷 21-25页

作者：刘道平黄兆坚汪寅章解放军总医院内分泌科100853

建立血清胰岛素样生长因子Ⅰ(IGF-Ⅰ)的放射免疫分析(RIA)方法并初步将其应用于临床。采用血标本通过酸性乙醇提取冷冻再沉淀法,提取率达91.5%±4.4%;用乳过氧化酶法以碘-125标记IGF-Ⅰ,RIA反应液中含提取液(或标准液)50μL,抗体200... 详细信息

建立血清胰岛素样生长因子Ⅰ(IGF-Ⅰ)的放射免疫分析(RIA)方法并初步将其应用于临床。采用血标本通过酸性乙醇提取冷冻再沉淀法,提取率达91.5%±4.4%;用乳过氧化酶法以碘-125标记IGF-Ⅰ,RIA反应液中含提取液(或标准液)50μL,抗体200μL(最终滴度1:10000),125I-IGF-Ⅰ200μL(约13000cpm),4℃反应过夜,双抗分离。RIA回收率为98.1%-105.0%,批内变异系数5.4%-7.5%,批间变异系数9.1%-10.7%,灵敏度达0.01nmol/L。用此法测得垂体性侏儒患者血清IGF-Ⅰ的浓度为5.4±1.7nmol/L,它明显低于同龄正常组(49.3±26.6nmol/L)的IGF-Ⅰ浓度(P<0.001);测得肢端肥大症患者血清IGF-Ⅰ的浓度为107.7±25.6nmol/L,它明显高于同龄正常组(26.3±12.2nmol/L)的IGF-Ⅰ浓度(P<0.001)。RIA测定血清IGF-Ⅰ,灵敏度高,准确可靠,对垂体性侏儒及肢端肥大症的诊断有重要参考价值。

关键词：化学沉淀放射免疫测定胰岛素样生长因子ⅰ/分析肢端肥大症/诊断侏儒症/诊断人类

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非糖尿病巨大儿胰岛素样生长因子1与胰岛素样生长因子结合蛋白3水平探讨

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中国误诊学杂志 2008年第21期8卷 5102-5103页

作者：梁慧付敏吴庆荣赵玉环邓巧玲李红国江苏省徐州市妇幼保健院 221009

目的:探讨胰岛素样生长因子1(IGF-1)及胰岛素样生长因子结合蛋白3(IGFBP-3)与非糖尿病巨大儿发病的相关性。方法:选取分娩巨大儿的正常孕妇(非GDM-MS)38例,分娩巨大儿的糖尿病孕妇20例(GDM-MS)、分娩正常体重儿正常孕妇(N)50例,分娩后... 详细信息

目的:探讨胰岛素样生长因子1(IGF-1)及胰岛素样生长因子结合蛋白3(IGFBP-3)与非糖尿病巨大儿发病的相关性。方法:选取分娩巨大儿的正常孕妇(非GDM-MS)38例,分娩巨大儿的糖尿病孕妇20例(GDM-MS)、分娩正常体重儿正常孕妇(N)50例,分娩后即抽母血及脐血,分离血清,采用放免法测定。结果:三组母血IGF-1与新生儿体重呈正相关(P<0.01);非GDM-MS组及GDM-MS组脐血IGF-1高于正常组(P<0.01);3组母血IGFBP-3、IGF-1水平皆高于脐血(P<0.01)。结论:非糖尿病巨大儿可通过测定母血IGF-1进行预测。

关键词：巨大胎儿/胚胎学/诊断胰岛素样生长因子ⅰ/分析胰岛素样生长因子结合蛋白质3/血液人类

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重组人生长激素对生长激素缺乏症儿童骨代谢的影响

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浙江大学学报（医学版） 2005年第4期34卷 312-315页

作者：李筠陈黎勤梁黎浙江大学医学院附属儿童医院浙江杭州310003

目的:研究生长激素缺乏症(GHD)儿童用生长激素治疗前后的骨代谢指标和骨量的改变.方法:测定37例完全性生长激素缺乏症(CGHD)、31例部分性生长激素缺乏症(PGHD)和31例年龄、性别匹配的正常健康儿童的血清骨代谢指标、类胰岛素生长因子1(I... 详细信息

目的:研究生长激素缺乏症(GHD)儿童用生长激素治疗前后的骨代谢指标和骨量的改变.方法:测定37例完全性生长激素缺乏症(CGHD)、31例部分性生长激素缺乏症(PGHD)和31例年龄、性别匹配的正常健康儿童的血清骨代谢指标、类胰岛素生长因子1(IGF1)和桡骨远端超声传播速度(SOS),比较各组差异;同时对29例接受重组人生长激素(rhGH)治疗的GHD儿童3～6月定期复查.结果: CGHD组血清骨碱性磷酸酶(BAP)、Ⅰ型胶原交联羧基末端肽(ICTP)、IGF1显著低于正常对照组(P<0.05),ICTP与IGF1呈正相关(r=0.32,P=0.01);PGHD组IGF1低于正常对照组(P<0.05),其余各项指标与正常对照组比较无显著差异.GH治疗3月后BA P、ICTP、骨钙素(OC)和IGF1均显著高于基线值(P<0.05);ICTP和IGF1随治疗时间延长逐步增高.桡骨远端SOS SDS有增加趋势,但与基线值比较差异无显著性(P>0.05). 结论:CGHD儿童体内骨转换水平明显降低,桡骨远端骨量改变不明显;GH替代治疗半年后,骨形成和骨吸收指标明显增高,同时伴有骨量增加趋势.

关键词：促生长素/缺乏生长激素/治疗应用胰岛素样生长因子ⅰ/分析骨代谢骨量

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GH substitution does not alter the pulsatile pattern of LH in amenorrhoeic growth hormone deficient women

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CLINICAL ENDOCRINOLOGY 1999年第4期51卷 479-485页

作者： de Boer, JAM van der Veen, EA Schoemaker, J VU Med Ctr Inst Endocrinol Reprod & Metab Div Reprod Endcrinol & FertilDept Obstet & Gynae Amsterdam Netherlands VU Med Ctr Div Endocrinol Dept Internal Med Amsterdam Netherlands

OBJECTIVE GH substitution in GH-deficient (GHD) children promotes pubertal development. In some GHD women, secondary amenorrhoea occurs after discontinuation of GH treatment. This study was designed to investigate whether GH substitution directly influences the GnRH pulse generator. For this reason, the pulsatile release of LH was studied in amenorrhoeic GHD women before and during GH substitution. DESIGN GH deficiency was confirmed by an insulin tolerance test. During a 24-h period, blood samples were drawn every 10 min for determination of LH, FSH and GH levels. Oestradiol and IGF-1 were determined at 1000 h and 2200 h. After the first test day, patients started with GH substitution, 0.25 IU/kg/week. During month 6 of GH treatment, the 24 h blood sampling was repeated. SUBJECTS Ten amenorrhoeic GH-deficient women participated in the trial. All were diagnosed as GH deficient during childhood or adolescence. Eight of them had been treated with GH during childhood. Seven women suffered from primary amenorrhoea and three from secondary amenorrhoea. Six women were started with GH substitution after the first test day (according to randomization in a larger study). MEASUREMENTS LH and GH were determined every 10 min and FSH every 60 min. LH pulse detection was conducted using a validated statistical method. RESULTS Prior to GH treatment, the LH pulse interval did not show a diurnal pattern as found during normal pubertal development. During GH treatment, IGF-1 levels rose significantly. No differences were found in mean LH, LH pulse amplitude and LH pulse interval before and during GH treatment. Oestradiol levels did not change either. CONCLUSIONS GH substitution in amenorrhoeic GH-deficient women does not alter the pulsatile pattern of LH, This may suggest that GH treatment does not influence central nervous system control of gonadotropin secretion in GHD patients.

关键词：闭经/病理生理学雌二醇/血液卵泡刺激素/血液生长激素/血液生长激素/缺乏激素替代疗法人生长激素/治疗应用胰岛素样生长因子ⅰ/分析促黄体激素/血液促黄体激素/代谢分泌率统计学非参数成年人女(雌)性人类

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mRNA of insulin-like growth factor (IGF) quantification and presence of IGF binding proteins, and receptors for growth hormone, IGF-I and insulin, determined by reverse transcribed polymerase chain reaction, in the liver of growing and mature male cattle

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DOMESTIC ANIMAL ENDOCRINOLOGY 2000年第3期19卷 191-208页

作者： Cordano, P Hammon, HM Morel, C Zurbriggen, A Blum, JW Univ Bern Fac Med Vet Div Nutr Pathol CH-3012 Bern Switzerland Univ Bern Fac Med Vet Inst Anim Nuerol CH-3012 Bern Switzerland

Plasma insulin-like growth factor-I (IGF-I) concentrations were related to hepatic levels of IGF-I mRNA measured by competitive reverse transcription polymerase chain reaction (PCR) (RT-PCR) in neonatal (8 d old) calves, veal calves, fattened castrated bulls and mature intact bulls. Furthermore, the presence of mRNAs of IGF-II and of receptors for IGF-I (ICF-IR), growth hormone (GHR) and insulin (IR), as well as mRNAs of IGF binding proteins (IGFBP-1, -2 and -3) were assessed by RT-PCR. Hepatic ICF-I mRNA levels and plasma IGF-I concentrations in veal calves, fattened castrated bulls and in intact bulls were 4 to 8 times higher than in 8-d old calves and were 2 to 3 times higher in calves fed colostrum than in calves fed only milk replacer. Hepatic IGF-I mRNA concentrations were closely correlated (r = 0.92) with plasma IGF-I concentrations, suggesting that hepatic IGF-I production largely determines plasma IGF-I levels. The presence of ICF II, IGF-IR, GHR, IR and IGFBP-1, -2 and -3 mRNA was confirmed in the liver of 8-d old calves and older cattle as well, and among newborn calves their presence was independent of differences in nutrition. In conclusion, the major hepatic components of the GH-IGF axis were present in neonatal calves, but the IGF-I expression and therefore also plasma IGF-I levels were relatively low. (C) 2000 Elsevier Science Inc. All rights reserved.

关键词：氨基酸序列动物新生碱基序列牛/遗传学牛/生长和发育牛/生理学初乳/生理学 DNA/化学 DNA引物/化学电泳琼脂凝胶/兽医学胰岛素样生长因子结合蛋白质类/分析胰岛素样生长因子结合蛋白质类/遗传学胰岛素样生长因子ⅰ/分析胰岛素样生长因子Ⅰ/遗传学胰岛素样生长因子Ⅰ/分泌胰岛素样生长因子Ⅱ/分析胰岛素样生长因子Ⅱ/遗传学肝/化学肝/生理学分子序列数据 RNA 信使/分析 RNA 信使/化学放射免疫测定/兽医学受体胰岛素/分析受体胰岛素/遗传学受体生长调节素/分析受体生长调节素/遗传学受体促生长素/分析受体促生长素/遗传学逆转录聚合酶链反应/兽医学动物女(雌)性男(雄)性妊娠

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Effect of recombinant human growth hormone in elderly osteoporotic women

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CLINICAL ENDOCRINOLOGY 1999年第6期51卷 715-724页

作者： Sugimoto, T Nakaoka, D Nasu, M Kanzawa, M Sugishita, T Chihara, K Kobe Univ Sch Med Dept Med Div 3Chuo Ku Kobe Hyogo 6500017 Japan

OBJECTIVE Bone mineral density and growth hormone (GH) secretion rate both decline during normal human ageing, We evaluated the effects of recombinant human GH on markers of body composition and bone turnover in an open study in 8 elderly osteoporotic women aged 68-75 years (mean age 71 years). DESIGN Subjects were treated with GH as a single daily subcutaneous injection (0.125 IU/kg/week for the first 4 weeks and subsequently 0.25 IU/kg/week) for 48 weeks. RESULTS GH treatment caused a rapid (within 2 weeks) increase in serum levels of IGF-I and IGF-binding protein-3 (IGFBP-3) which was sustained throughout the study, Markers of bone formation and resorption were both gradually increased up to 24 weeks of GH treatment, The bone formation markers, osteocalcin (OC) and bone alkaline phosphatase, remained high during GH treatment, while the bone resorption marker, deoxypyridinoline (D-Pyr), tended to return to baseline levels after 24 weeks of GH therapy. GH treatment for 48 weeks caused a significant increase in hand grip and a decrease in waist/hip ratio. The mean percentage changes in bone mineral density (BMD) of mid-radius and lumbar spine were + 2.1% and + 1.2%, respectively, although they were not statistically significant, GH treatment was well tolerated and no major side-effects except mild oedema and joint pain were found. Since GH treatment produced durable increases in bone formation markers, BMD continued to be monitored after discontinuation of GH treatment for another 48 weeks, during which significant increases in radial and lumbar BMD (8.1 +/- 2.1 and 3.8 +/- 1.4% above pretreatment values, respectively) were recorded. CONCLUSION These results indicate that GH attenuates the decrease in muscle strength and bone mass as well as the gain of abdominal fat with ageing in elderly women. The present data provide useful information about the application of GH treatment in elderly women.

关键词：碱性磷酸酶/血液氨基酸类/血液体质骨密度/药物作用生长激素/治疗应用握力人生长激素/治疗应用胰岛素样生长因子结合蛋白质3/血液胰岛素样生长因子ⅰ/分析骨钙素/血液骨质疏松绝经后/血液骨质疏松绝经后/药物疗法统计学非参数老年人女(雌)性人类

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Influences on quality of life in GH deficient adults and their effect on response to treatment

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CLINICAL ENDOCRINOLOGY 1999年第5期51卷 565-573页

作者： Murray, RD Skillicorn, CJ Howell, SJ Lissett, CA Rahim, A Smethurst, LE Shalet, SM Christie Hosp NHS Trust Dept Endocrinol Manchester M20 4BX Lancs England

OBJECTIVE Studies of the effect of GH on quality of life (QOL) in growth hormone deficient (GHD) adults have reported conflicting results. Recently, however, we have demonstrated that by selecting only those patients with impaired QOL the efficacy of GH replacement on QOL can be greatly improved. The improvement in QOL was observed to correlate significantly with that recorded before commencing GH therapy. This study aims to assess if demographic variables affect QOL in untreated GHD adults or the improvement in QOL following GH therapy. DESIGN An open study of GH replacement, initiating treatment with a dose of 0.8 IU/day and titrating the dose by 0.4 IU increments to normalize the IGF-1 SDS between -2.0 and +2.0 SD of the age related normal range. PATIENTS 65 severely GHD patients (peak GH < 9 mU/l to provocative testing), mean age 38.7 (range 17-72) years. Inclusion criterion was that of subjectively poor quality of life on clinical interview. MEASUREMENTS Blood was taken for insulin-like growth factor 1 (IGF-1). The Psychological General Well-Being Schedule (PGWB) and Adult Growth Hormone Deficiency Assessment (AGHDA) self-rating questionnaires were used to assess quality of life at baseline, three and eight months after commencing GH. RESULTS The patients were subgrouped on the basis of gender, age of onset of GHD, pathology and presence of additional pituitary hormone deficits. The cohort consisted of 40 females and 25 males, 45 of adult-onset (AO) and 20 of childhood-onset (CO). GH deficiency resulted from a hypothalamo-pituitary pathology, or treatment thereof, in 36 patients and as a result of cranial irradiation for a primary brain tumour or prophylaxis in acute lymphoblastic leukaemia in 29 patients. Isolated GH deficiency (IGHD) was present in 25 patients, and 32 patients were demonstrated to have at least two additional pituitary hormone deficits (MPHD). No significant difference was detected between baseline PGWB scores of the subgroups. Multiple linea

关键词：生长激素/缺乏人生长激素/治疗应用垂体功能减退症/药物疗法垂体功能减退症/心理学胰岛素样生长因子ⅰ/分析线性模型精神病状态评定量表生活质量统计学非参数时间因素青少年成年人老年人女(雌)性人类男(雄)性中年人

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Osteoporosis and fractures in Turner syndrome - importance of growth promoting and oestrogen therapy

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CLINICAL ENDOCRINOLOGY 1999年第4期51卷 497-502页

作者： Landin-Wilhelmsen, K Brymant, I Windh, M Wilhelmsens, L Sahlgrens Univ Hosp Res Ctr Endocrinol & Metab S-41345 Gothenburg Sweden Sahlgrens Univ Hosp Dept Gynaecol S-41345 Gothenburg Sweden Sahlgrens Univ Hosp Sect Prevent Cardiol S-41345 Gothenburg Sweden

OBJECTIVE Turner syndrome (TS) is a chromosomal aberration (45,X) characterized by endogenous oestrogen deficiency and short stature. The aim was to study body composition, bone mineral density, fracture frequency, social and life style factors and biochemical bone markers, as well as hormones, in adults with TS in comparison with a female random population sample. PATIENTS Seventy women with TS responded to questionnaires. They underwent physical examination, bone mineral density measurement with Dual Energy X-ray Absorptiometry (DEXA) and blood sampling. Mean age was 31 +/- 12 (range 16-71) years. A random population sample of women from the WHO MONICA Project, Goteborg (25-64 years) served as controls (n = 740). RESULTS Women with TS were shorter than the controls and had lower body weight and lean body mass (P < 0.0001). Body mass index and waist/hip circumference ratio were higher in TS (P < 0.0001). Osteoporosis was present in seven TS women, six above 45 years of age. None of these had received oestrogen substitution continuously. Fractures tall types) were reported by 11 (16%) TS women (six (50%) above 45 years) compared with 5% in the population sample (P < 0.001). Four TS women with fractures had osteoporosis, all above 45 years of age. Osteoporosis and fractures did not differ between women with the 45,X karyotype and those with mosaicism. Impaired hearing was reported by 40%, and 73% wore glasses. Six percent among TS were smokers compared with 25% in the population (P < 0.001). TS women reported a lower degree of leisure time physical activity than controls (P < 0.001). Parathyroid hormone and osteocalcin were higher among TS (P < 0.02 and 0.001). Insulin-like growth factor-1 was similar. Ninety-one percent of all TS had oestrogen substitution and 98% of TS below 25 years of age had received growth hormone treatment. CONCLUSION Osteoporosis and fractures were common above, but not below, 45 years of age in Turner syndrome. It is probable that modern the

关键词：身体成分身高人体质量指数体重骨密度病例对照研究雌激素替代疗法骨折/血液骨折/病因学骨折/病理生理学生长激素/治疗应用听力障碍/血液听力障碍/并发症听力障碍/病理生理学胰岛素样生长因子ⅰ/分析骨钙素/血液骨质疏松/血液骨质疏松/并发症骨质疏松/病理生理学甲状旁腺素/血液特纳综合征/血液特纳综合征/并发症特纳综合征/病理生理学青少年成年人老年人女(雌)性人类中年人

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Correlation of preoperative plasma IGF-I levels with pathologic parameters and progression in patients undergoing radical prostatectomy

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UROLOGY 2000年第3期56卷 423-429页

作者： Shariat, SF Bergamaschi, F Adler, HL Nguyen, C Kattan, MW Wheeler, TM Slawin, KM Baylor Coll Med Scott Dept Urol Houston TX 77030 USA Baylor Coll Med Matsunaga Conte Prostate Canc Res Ctr Houston TX 77030 USA Baylor Coll Med Dept Pathol Houston TX 77030 USA Methodist Hosp Houston TX 77030 USA Mem Sloan Kettering Canc Ctr Dept Urol New York NY 10021 USA Mem Sloan Kettering Canc Ctr Dept Biostat New York NY 10021 USA

Objectives. To test whether preoperative insulin-like growth factor (IGF)-I levels could predict pathologic stage and prognosis of prostate cancer in patients undergoing radical prostatectomy. Methods. The study group consisted of 120 consecutive patients who underwent radical prostatectomy for clinically localized prostate cancer. Preoperative plasma IGF-I levels were measured using the DSL-IGF-I Elisa assay. Surgically removed prostate specimens were analyzed pathologically, using a whole-mount step-section technique. Preoperative plasma IGF-I levels were compared with final pathologic parameters and with prostate-specific antigen (PSA) progression-free survival. Preoperative IGF-I levels in this cohort were also compared with IGF-I levels measured in 20 healthy men without any cancer and in 10 men with untreated, metastatic prostate cancer. Results. Plasma IGF-I levels predicted neither organ-confined disease (P = 0.5611) nor the risk of PSA progression (P = 0.8125) at a median follow-up of 48.6 months after prostatectomy. Furthermore, IGF-I levels did not correlate with preoperative PSA level (P = 0.2811) or final Gleason score (P = 0.4906). IGF-I levels in radical prostatectomy patients were not significantly higher than those in healthy subjects or in patients with metastatic disease (mean 156.7 +/- 66 ng/mL, 148.6 +/- 49 ng/mL, and 148.6 +/- 93 ng/mL, respectively;P = 0.8442). Conclusions. Circulating IGF-I levels may predict the future risk of developing prostate cancer, but our study found no association with other established markers of biologically aggressive disease or with disease progression in patients with clinically localized prostate cancer. UROLOGY 56: 423-429, 2000. (C) 2000, Elsevier Science Inc.

关键词：腺癌/血液腺癌/病理学腺癌/外科学方差分析疾病恶化无病生存随访研究胰岛素样生长因子ⅰ/分析 Logistic模型肿瘤蛋白质类/血液肿瘤分期前列腺/病理学前列腺切除术前列腺肿瘤/血液前列腺肿瘤/病理学前列腺肿瘤/外科学标本制备老年人人类男(雄)性中年人

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Initial characterization of the GH-IGF axis and nutritional status of the Ati Negritos of the Philippines

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CLINICAL ENDOCRINOLOGY 1999年第6期51卷 741-747页

作者： Clavano-Harding, AB Ambler, GR Cowell, CT Garnett, SP Al-Toumah, B Coakley, JC Ho, KKY Baxter, RC Royal Alexandra Hosp Children Growth Res Ctr Ray Williams Inst Endocrinol Diabet & Metab Westmead NSW 2145 Australia Royal Alexandra Hosp Children Dept Biochem Westmead NSW 2145 Australia St Vincent Hosp Garvan Inst Med Res Darlinghurst NSW Australia Royal N Shore Hosp Kolling Inst Med Res St Leonards NSW Australia

BACKGROUND AND OBJECTIVE The Ati Negritos are a Pygmy-like aboriginal population from the Philippines with physical characteristics of short stature, dark skin and woolly, kinked hair. Their final height, components of their GH-IGF axis and various nutritional markers are described. SUBJECTS, DESIGN AND MEASUREMENTS Auxological data and sera for the components of the GH-IGF axis and nutritional parameters were collected from 9 adult Ati Negritos in their native environment and 10 Filipinos in Sydney. RESULTS The height SDS (-3.66 +/- 1.1 vs. -1.01 +/- 1.2), weight SDS (-2.30 +/- 1.6 vs. 0.10 +/- 0.7), and BMI SDS (-1.4 +/- 1.8 vs. -0.2 +/- 0.5) between the two groups were significantly different (P <0.01). The mean height of the 6 male Ati Negritos was 149 +/- 7 and 144 +/- 3 cm for the females and are comparable with the African Pygmies and the Mountain Ok people of Papua New Guinea. The Ati Negritos showed lower growth hormone binding protein (GHBP), insulin-like growth factor I(IGF-I), insulin-like growth factor binding protein 3 (IGFBP-3), acid labile subunit (ALS), zinc, albumin, ferritin, iron, iron saturation and much higher insulin-like growth factor binding protein 2 (IGFBP-2) and plasma transferrin concentrations. No differences were noted in random growth hormone (GH), plasma insulin-like growth factor II (IGF-II), nor in their plasma concentrations of prealbumin, thyroid stimulating hormone (TSH) and free thyroxine (T-4). CONCLUSION Perturbations of both the GH-IGF-I axis and nutritional markers exist in the Ati Negritos, These findings may be determinants of their stature;however, the aetiology of these changes remains to be fully elucidated.

关键词：身高/生理学人体质量指数载体蛋白质类/血液病例对照研究大陆人口群铁蛋白质类/血液糖蛋白类/血液生长激素/血液胰岛素样生长因子结合蛋白质2/血液胰岛素样生长因子结合蛋白质3/血液胰岛素样生长因子ⅰ/分析铁/血液营养状况大洋洲世系人群菲律宾/人种学血清白蛋白/分析统计学非参数转铁蛋白/分析锌/血液成年人女(雌)性人类男(雄)性中年人

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