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Sexual dimorphism in circulating monomeric and dimeric inhibins in normal boys and girls from birth to puberty

CLINICAL ENDOCRINOLOGY 1999年第4期51卷 455-460页

作者： Bergadá, I Rojas, G Ropelato, G Ayuso, S Bergadá, C Campo, S Hosp Ninos Dr Ricardo Gutierrez Ctr Invest Endocrinol RA-1425 Buenos Aires DF Argentina

BACKGROUND AND OBJECTIVE Inhibins are peptides, mainly of gonadal origin, that suppress FSH production. Dimeric forms of inhibin (A and B) have been proposed as peripheral markers of Sertoli and granulosa cell function, The aim of this study was to establish the relationship between circulating dimeric and monomeric inhibins, and gonadotrophins and sex steroids, in normal boys and girls from birth to puberty. SUBJECTS One hundred and forty-six normal children (females: 57;males: 89) were studied. MEASUREMENTS Serum LH and FSH were measured by an immunofluorometric assay. Serum oestradiol and testosterone were measured by radioimmunoassay. Serum inhibin A and B, and Pro-alpha C, were measured by specific two-site enzyme-linked immunosorbent assays. RESULTS In boys from birth to 6 months of age, the mean serum inhibin a concentration was as high (477 +/- 53.7 ng/l) as that found at puberty (400 +/- 70.2 ng/l). After the first year, inhibin B gradually decreased to reach its lowest concentration (153 +/- 23.6ng/l) at age 4-6 years. At approximately age 10, it rose progressively to reach pubertal concentrations, Pro-alpha C showed a similar pattern but at lower concentrations. Inhibin A was not detected at any age, In girls from birth to 6 months, inhibin B levels (83.0 +/- 18.3 ng/l) were approximately 50% lower than those found at puberty (181 +/- 25.7 ng/l). After 6 months of age, these levels dropped (17.5 +/- 1.6 ng/ I) and remained low until the prepubertal years, Thereafter, they increased to pubertal concentrations, The serum inhibin A concentration after birth (29.9 +/- 8.7 ng/l) was similar to that found at puberty (18.3 +/- 5.7 ng/l);after 6 months, it fell to undetectable levels until the prepubertal years. CONCLUSION The sex difference in serum levels of gonadotrophins is associated with sex differences in the levels and proportions of circulating dimeric and monomeric inhibins.

关键词：方差分析酶联免疫吸附测定雌二醇/血液卵泡刺激素/血液抑制素类/血液促黄体激素/血液肽类/血液前列腺分泌蛋白质类蛋白质亚型/血液蛋白质前体/血液性征睾酮/血液青少年成年人儿童儿童学龄前女(雌)性人类婴儿婴儿新生男(雄)性

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Lipoprotein(a) levels and isoforms and fibrinolytic activity in postmenopause -: Influence of hormone replacement therapy

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THROMBOSIS AND HAEMOSTASIS 1999年第1期81卷 104-110页

作者： Estellés, A Cano, A Falcó, C España, F Gilabert, J Grancha, S Aznar, J Univ Valencia Hosp La Fe Ctr Invest Valencia 46009 Spain Univ Valencia Hosp La Fe Dept Obstet & Gynecol Valencia 46009 Spain Univ Valencia Hosp La Fe Dept Clin Pathol Valencia 46009 Spain Univ Valencia Sch Med Dept Obstet & Gynecol Valencia Spain

Epidemiological studies suggest that hormone replacement therapy (HRT) decreases the risk of cardiovascular disease in postmenopausal women via several mechanisms, including modifications in the fibrinolytic system and lipoprotein(a) [Lp(a)] levels. The aim of this study was to examine the influence of the levels and isoforms of Lp(a) on fibrinolytic activity in 91 postmenopausal women in comparison with premenopause and analyze the effect of HRT on those parameters. In postmenopause, an increase in plasma Lp(a) and plasminogen activator inhibitor-1 (PAI-1) levels was found. A significant inverse correlation was observed between Lp(a) or PAI-I levels and plasmin generation. Plasma samples with low molecular weight (MW) apo(a) isoforms showed higher plasmin inhibition than plasmas with high MW apo(a) isoforms and similar levels of total Lp(a) and PAI-1. HRT induced a significant decrease in Lp(a) and PAI-I levels and an increase in estradiol levels, as well as an increase in fibrinolytic activity. A significant correlation was found between the percentages of variation in Lp(a) levels and in plasmin generation and between the percentages of variation in PAI-1 levels and in the euglobulin lysis time under HRT. In conclusion, the increase in fibrinolytic activity observed in women under HRT could be explained by two independent mechanisms: (a) the decrease in PAI-1 and (b) the decrease in the inhibition of plasmin generation due to the decrease in Lp(a) levels.

关键词：心血管疾病/血液心血管疾病/预防和控制纤维蛋白溶解激素替代疗法脂蛋白(A)/血液绝经后期/血液蛋白质亚型/血液成年人老年人女(雌)性人类中年人

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Tropomyosin isoform 5b is expressed in human erythrocytes: implications of tropomodulin-TM5 or tropomodulin-TM5b complexes in the protofilament and hexagonal organization of membrane skeletons

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BLOOD 2000年第4期95卷 1473-1480页

作者： Sung, LA Gao, KM Yee, LJ Temm-Grove, CJ Helfman, DM Lin, JJC Mehrpouryan, M Univ Calif San Diego Dept Bioengn La Jolla CA 92093 USA Univ Calif San Diego Ctr Genet Mol La Jolla CA 92093 USA Univ Arizona Dept Nutr Sci Tucson AZ 85721 USA Cold Spring Harbor Lab Cold Spring Harbor NY 11724 USA Univ Iowa Dept Biol Sci Iowa City IA 52242 USA

The human erythrocyte membrane skeleton consists of hexagonal lattices with junctional complexes containing F-actin protofilaments of approximately 33-37 nm in length. We hypothesize that complexes formed by tropomodulin, a globular capping protein at the pointed end of actin filaments, and tropomyosin (TM), a rod-like molecule of approximately 33-35 nm, may contribute to the formation of protofilaments, We have previously cloned the human tropomodulin complementary DNA and identified human TM isoform 5 (hTM5), a product of the gamma-TM gene, as one of the major TM isoforms in erythrocytes, We now identify TM5b, a product of the alpha-TM gene, to-be the second major TM isoform, TM5a, the alternatively spliced isoform of the (U-TM gene, which differs by 1 exon and has a weaker actin-binding affinity, however, is not present. TM4, encoded by the delta-TM gene, is not present either. In sodium dodecyl sulfate-polyacrylamide gel electrophoresis, hTM5 comigrated with the slower TM major species in erythrocyte membranes, and hTM5b comigrated with the faster TM major species. TM5b, like TM5, binds strongly to tropomodulin, more so than other TM isoforms, The 2 major TM isoforms, therefore, share several common features: They have 248 residues, are approximately 33-35 nm long, and have high affinities toward F-actin and tropomodulin. These common features may be the key to the mechanism by which protofilaments are formed. Tropomodulin-TM5 or tropomodulin-TM5b complexes may stabilize F-actin in segments of approximately 33-37 nm during erythroid terminal differentiation and may, therefore, function as a molecular ruler. TM5 and TM5b further define the hexagonal geometry of the skeletal network and allow actin-regulatory functions of TMs to be modulated by tropomodulin, (C) 2000 by The American Society of Hematology.

关键词：氨基酸序列载体蛋白质类/血液载体蛋白质类/化学克隆分子细胞骨架/超微结构红细胞膜/超微结构红细胞/代谢红系祖细胞/代谢红系祖细胞/超微结构微丝蛋白质类/血液微丝蛋白质类/化学分子序列数据蛋白质亚型/血液蛋白质亚型/化学蛋白质亚型/遗传学重组蛋白质类/化学重组蛋白质类/代谢序列比对序列同源性氨基酸原肌球调节蛋白质原肌球蛋白/血液原肌球蛋白/化学原肌球蛋白/遗传学动物人类大鼠

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Circulating GH isoforms and GH bioactivity in preterm neonates

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PEDIATRIC RESEARCH 2000年第2期48卷 244-247页

作者： Radetti, G Bozzola, M Pagani, S Avanzini, MA Messner, H Belloni, C Hayakawa, M Reg Hosp Bolzano Dept Paediat I-39100 Bolzano Italy Univ Pavia Policlin San Matteo IRCCS Dept Paediat I-27100 Pavia Italy Mitsui Pharmaceut Inc Clin Dev Dept Chuo Ku Tokyo 1030027 Japan

Among the molecular variants of human GH, the monomeric 22-kD is the predominant isoform, whereas the 20-kD is the second most abundant isoform. Because Little is known on the pattern of human GH isoforms in the early postnatal period, we evaluated serum levels of 22-kD GH by an immunofluorometric assay and of 20-kD GH by an ELISA using an anti-20-kD antibody, and measured GH bioactivity with the Nb, cell bioassay in 19 preterm neonates (gestational age, 32 +/- 0.5 wk;mean +/- SEM) on the fourth and 15th days of life. As control subjects, we studied 19 full-term neonates (gestational age, 39 +/- 0.3 wk) on the fourth day of life and 20 healthy adults, aged 20 +/- 0.3 y. Four-day-old preterm neonates showed significantly higher serum values of 20-kD GH (0.99 +/- 0.14 ng/mL) than full-term neonates (0.33 +/- 0.07 ng/mL;p < 0.001) and adults (0.09 +/- 0.02;p < 0.0001). Likewise, 22-kD GH and GH levels by Nb-2 cell bioassay were also significantly higher (p < 0.001) in preterm than in full-term neonates and young adults. A significant decrease (p < 0.01) in 20-kD, 22-kD, and Nb-2-determined GH was observed in preterm neonates on the 15th day of life The percentage of the 20-kD isoform was similar in the preterm infants at the fourth and 15th day, in full-term infants, and in adults (2.7%, 2.7%, 2.8%, and 3.16%, respectively). Our results indicate that 20-kD GH serum levels change throughout life as regards total amount, but not as regards percentage.

关键词：衰老/血液酶联免疫吸附测定荧光抗体技术人生长激素/血液婴儿出生时低体重/血液婴儿新生/血液婴儿早产/血液蛋白质亚型/血液参考值回归分析成年人女(雌)性人类男(雄)性

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Serum vascular endothelial growth factor in epithelial ovarian neoplasms: Correlation with patient survival

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GYNECOLOGIC ONCOLOGY 1999年第2期74卷 235-240页

作者： Chen, CA Cheng, WF Lee, CN Chen, TM Kung, CCS Hsieh, FJ Hsieh, CY Natl Taiwan Univ Coll Med Dept Obstet & Gynecol Taipei 10018 Taiwan

Objective. To investigate the relationship between serum vascular endothelial growth factor (VEGF) and clinicopathological factors and to determine whether VEGF is an independent prognostic factor of ovarian cancer patients. Methods. Fifty-six women with International Federation of Gynecology and Obstetrics stages I to IV epithelial ovarian cancer undergoing surgery were enrolled. Clinical and pathologic items were recorded. Pretreatment VEGF serum samples of the 56 women were measured by an enzyme-linked immunosorbent assay. The results were correlated to clinical data. The histopathologic items and serum VEGF influencing clinical outcome were evaluated comparatively. Results. The median VEGF serum level in ovarian cancer patients was 458.7 pg/mL. The 75% quatile was defined as the cutoff level. Elevated vascular endothelial growth factor serum levels before therapy correlated significantly with poorer disease-free survival (DFS) (log rank test, P = 0.001) and overall survival (OS) (log rank test, P < 0.001) on all of the 56 patients. Besides, significantly reduced DFS (log rank test, P = 0.001) and OR (log rank test, P = 0.006) were also observed on 40 patients with residual disease less than 2 cm. High histologic grade (RR = 2.24 for DFS;RR = 2.38 for OS) and elevated serum VEGF levels (RR = 3.34 for DFS;RR = 4.47 for OS) are the prognostic factors on the 56 ovarian carcinoma patients by multivariate analyses. The advanced surgical staging (RR = 3.28 for DFS;RR = 3.84 for OS), high histologic grade (RR = 2.55 for DFS;RR = 2.44 for OS), and elevated serum VEGF levels (RR = 5.62 for DFS;RR = 5.37 for OS) are the prognostic factors for 40 ovarian carcinoma patients with residual disease less than 2 cm by multivariate analyses. Conclusions. Pretreatment VEGF serum levels might be regarded as an additional factor in predicting the outcome of ovarian cancer patients. It also could provide prognostic information in clinically relevant subsets, such as those of residual

关键词：内皮生长因子/血液淋巴因子/血液卵巢肿瘤/血液卵巢肿瘤/死亡率卵巢肿瘤/病理学预后蛋白质亚型/血液存活率血管内皮生长因子A 血管内皮生长因子类成年人老年人老年人 80以上女(雌)性人类中年人

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Cofactor dependence and isotype distribution of anticardiolipin antibodies in viral infections

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ANNALS OF THE RHEUMATIC DISEASES 2001年第5期60卷 500-504页

作者： Guglielmone, H Vitozzi, S Elbarcha, O Fernandez, E Lab Anal Clin Especializados RA-5000 Cordoba Argentina Univ Nacl Cordoba Fac Ciencias Quim Dept Bioquim Clin RA-5000 Cordoba Argentina

Background-Antibodies to cardiolipin (aCLs) are often detected in patients with autoimmune disorders or infectious diseases. Objective-To investigate the distribution of aCL isotypes and requirement of protein cofactor in viral infections in order to establish the importance, if any, of these antibodies in these infectious diseases. Patients and methods-The isotype distribution of aCLs in the sera from 160 patients with infection caused by HIV-1 (n=40), hepatitis A virus (n=40), hepatitis B virus (n=40), or hepatitis C virus (n=40) was studied by standardised enzyme linked immunosorbent assay (ELISA) in the presence and absence of protein cofactor (mainly beta2-glycoprotein I). Serum samples from healthy volunteers and patients with syphilis and antiphospholipid syndrome were also included and served as negative and positive control groups respectively. Results-The prevalence of one or more aCL isotypes in serum of patients with HIV-1, hepatitis A virus, hepatitis B virus, or hepatitis C virus infection was 47%, 92%, 42%, and 17% respectively (principally IgM and/or IgA). Most of these antibodies were mainly cofactor independent. Conclusions-The presence of aCLs in viral infections is principally cofactor independent, suggesting that cofactor dependence of the aCLs should be assessed to distinguish subjects most likely to suffer from clinical symptoms observed in the presence of these antibodies.

关键词：抗体抗心脂/分析抗磷脂综合征/免疫学病例对照研究酶联免疫吸附测定糖蛋白类/代谢 HIV感染/免疫学 HIV-1 甲型肝炎/免疫学乙型肝炎/免疫学丙型肝炎/免疫学蛋白质亚型/血液梅毒/免疫学病毒性疾病/免疫学 β2糖蛋白Ⅰ 女(雌)性人类男(雄)性

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Distribution and characterization of immunoreactive prolactin-releasing peptide (PrRP) in rat tissue and plasma

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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 1999年第2期257卷 264-268页

作者： Matsumoto, H Murakami, Y Horikoshi, Y Noguchi, J Habata, Y Kitada, C Hinuma, S Onda, H Fujino, M Takeda Chem Ind Ltd Div Pharmaceut Discovery Discovery Res Labs 1 Ibaraki Osaka 3004293 Japan

We established a sensitive and specific two-site enzyme immunoassay (EIA) for prolactin-releasing peptide (PrRP) using two region-specific monoclonal antibodies. We investigated the tissue distribution and the plasma concentration of immunoreactive (ir-) PrRP in rats using this assay. Ir-PrRP was widely distributed in the central nervous system and pituitary gland. The highest concentration of ir-PrRP was found in the hypothalamus. In peripheral tissues, appreciable levels of ir-PrRP were found only in the adrenal gland. The mean plasma concentration of ir-PrRP was 0.13 +/- 0.01 fmol/ml (mean +/- SEM). In reverse-phase and gel-filtration high performance liquid chromatography, hypothalamic ir-PrRP eluted at a position identical to that of PrRP31 and PrRP20. On the other hand, ir-PrRP from the adrenal gland and plasma eluted only at the position of synthetic PrRP31, indicating that molecular forms of ir-PrRP in vivo differed among tissues. (C) 1999 Academic Press.

关键词：肾上腺/代谢抗体单克隆/免疫学抗体特异性中枢神经系统/代谢色谱法高压液相下丘脑激素类/血液下丘脑激素类/免疫学下丘脑激素类/代谢免疫酶技术神经肽类/血液神经肽类/免疫学神经肽类/代谢肽碎片/血液肽碎片/免疫学肽碎片/代谢垂体/代谢蛋白质亚型/血液蛋白质亚型/免疫学蛋白质亚型/代谢大鼠 Wistar 敏感性与特异性动物女(雌)性男(雄)性大鼠

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Major surgery increases serum levels of vascular endothelial growth factor only temporarily

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AMERICAN JOURNAL OF SURGERY 2000年第1期179卷 57-59页

作者： Bondestam, J Salven, P Jääskelä-Saari, H Ikonen, T Lepäntalo, M Mattila, S Joensuu, H Univ Helsinki Cent Hosp Dept Oncol HYKS FIN-00029 Helsinki Finland Univ Helsinki Cent Hosp Dept Otorhinolaryngol FIN-00029 Helsinki Finland Univ Helsinki Cent Hosp Dept Surg FIN-00029 Helsinki Finland

BACKGROUND: Vascular endothelial growth factor (VEGF) is a hypoxia-induced endothelial cell-specific mitogen, which is angiogenic in vivo and up-regulated in several malignancies. VEGF can be used as a prognostic marker, but the effect of surgical trauma on serum VEGF (S-VEGF) concentrations is unknown and might reduce the value of VEGF as a serum marker. METHODS: We monitored S-VEGF levels by enzyme-linked immunosorbent assay in patients undergoing surgery. RESULTS: Eighteen patients with major surgery had slightly elevated S-VEGF compared with the preoperative level (median 9.5 pg/mL) on the first (median 35 pg/mL;P = 0.0002) and third (median 19 pg/mL;P = 0.004) postoperative day, but not in later samples. The levels measured in 8 patients after minor surgery did not differ from the preoperative levels (P = 0.14). CONCLUSIONS: Even major surgery is associated only with a slight and transient increase in S-VEGF levels, and, therefore, is unlikely to interfere markedly with the use of VEGF as a prognostic marker. (C) 2000 by Excerpta Medica, Inc.

关键词：内皮生长因子/血液酶联免疫吸附测定淋巴因子/血液预后蛋白质亚型/血液外科手术时间因素血管内皮生长因子A 血管内皮生长因子类女(雌)性人类男(雄)性中年人

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Is soluble CD44 variant isoform 5 useful as a predicting factor and a parameter for long term observation in rheumatoid arthritis?

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ANNALS OF THE RHEUMATIC DISEASES 2002年第11期61卷 1036-1037页

作者： Skoumal, M Kolarz, G Haberhauer, G Feyertag, J Wottawa, A Donau Univ Krems Inst Rheumatol A-2500 Baden Austria Wilhelminenspital Stadt Wien Dept Internal Med Rheumatol 5 A-1160 Vienna Austria

Table 1 Clinical data of 81 patients (57 female, 24 male) at the first visit Mean SD Minimum Maximum Age at onset (years) 48.6 18.0 72.0 Disease duration (years) 11.6 0.9 58.0 Observation period (years) 6.7 2.7 10.0 ESR (mm/1st h) 35.2 22.3 4.0 108.0 sCD44v5 (ng/ml) 41.7 27.6 6.3 160.8 CRP (mg/l) 29.8 27.8 0.0 120.0 DAS 3.9 1.1 0.8 7.1 PIP 1.8 3.0 0.0 10.0 RF (U/ml) 272.8 764.6 0.0 6634.0 Ritchie index 14.1 10.2 0.0 41.0 Steinbrocker stage 2.3 0.8 1.0 4.0 Stoke 6.4 3.4 1.0 17.0 28JC 17.2 11.9 0.0 55.0 30SJC 8.4 6.6 0.0 28.0 Larsen score 50.8 43.9 0.0 178.0 ESR, erythrocyte sedimentation rate; sCD44v5, soluble CD44 variant isoform 5; CRP, C reactive protein; DAS, disease activity score; PIP, proximal interphalangeal score; RF, rheumatoid factor; 28JC, 28 joint count; 30SJC, 30 swollen joint count.

关键词：关节炎类风湿/免疫学随访研究蛋白质亚型/血液成年人人类中年人

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Inverse relationship between serum inhibin B and FSH levels in prepubertal boys with cryptorchidism

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PEDIATRIC RESEARCH 1999年第5期46卷 496-500页

作者： Raivio, T Dunkel, L Univ Helsinki Hosp Children & Adolescents Helsinki 00029 Finland

To investigate the gonadal control of FSH secretion in prepuberty, we studied the relationship between circulating inhibin B and FSH levels in 16 prepubertal boys with cryptorchidism (age range, 1-8 y). The effect of Leydig cell stimulation on the secretion of inhibin B, sex steroids, and FSH was investigated in nine boys who were given human chorionic gonadotropin (hCG) treatment. In these boys, serum inhibin B, testosterone, estradiol, and gonadotropin levels were measured before and on the fourth day of the last (third) hCG injection, given at l-wk intervals. Except for one boy with both high inhibin B and FSH concentrations, basal serum levels of these hormones correlated negatively (r(S) = -0.79, it = 15,p < 0.005). This inverse relationship remained significant in the subgroup of boys younger than 2 y of age (r(S) = -0.84, n = 11, p = 0.008) who also had greater variance of serum FSH concentrations than 14 control boys of similar age with normally located testes (p < 0.01). hCG stimulation increased serum testosterone and suppressed serum FSH concentrations in each boy (n = 9,p < 0.005). In the four oldest subjects, the serum inhibin B level increased from the mean of 91 to 135 pg/mL (p < 0.05), These findings suggest that inhibin B regulates FSH secretion in early childhood. Moreover, the hCG-induced suppression of FSH secretion was probably mediated by sex steroids rather than by inhibin B. Finally, the increase in serum inhibin B concentration during the hCG treatment was likely to be indirect via Leydig cell-Sertoli cell or Sertoli cell-germ cell interaction(s).

关键词：绒毛膜促性腺激素/治疗应用隐睾/血液隐睾/病理学卵泡刺激素/血液抑制素类/血液莱迪希细胞/药物作用蛋白质亚型/血液青春期/血液塞尔托利细胞/病理学刺激化学性睾丸/生理学儿童儿童学龄前人类婴儿男(雄)性

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