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1.
2.
David R. Powell Frances Liu Bonita K. Baker Phillip D. K. Lee Raymond L. Hintz 《Pediatric nephrology (Berlin, Germany)》1996,10(3):343-347
Children with chronic renal failure (CRF) often fail to attain an adult height consistent with their genetic potential. The growth hormone (GH)/insulin-like growth factor (IGF)/growth plate chondrocyte axis has been intensively studied in these children to determine the basis for this growth failure. Evidence suggests that hepatic GH resistance results in deficient expression of IGF-I. However, serum IGF-I levels are usually normal and it is IGF-I action on target tissues which is inhibited, possibly by the presence of excess high-affinity IGF binding proteins (IGFBPs) in CRF serum. In this paper we evaluate the roles of IGFBP-1, -2, and -3 as growth inhibitors in CRF children. The data support a role for each of these IGFBPs as growth inhibitors. Currently, IGFBP-1 meets most criteria expected of a growth inhibitor, but IGFBP-2 and -3 will likely also meet these criteria and may well be important contributors to the growth failure of CRF. Ultimately, many or all of the six IGFBPs may be found to contribute to the excess high-affinity IGF binding sites which are a hallmark of CRF serum and are possible contributors to the growth failure of CRF children. 相似文献
3.
Dae-Yeol Lee Pinchas Cohen Alan M. Krensky Ron G. Rosenfeld Peter D. Yorgin 《Pediatric nephrology (Berlin, Germany)》1993,7(4):416-423
The insulin-like growth factors, IGF-1 and IGF-II, are polypeptides that potentiate cellular growth. In addition to binding to specific cell surface receptors, the IGFs bind with high affinity to a family of proteins, the insulin-like growth factor binding proteins (IGFBPs). Serum and urine IGFBP patterns are altered in individuals with chronic renal failure (CRF). We recently reported that the urinary IGFBP pattern of CRF patients is unique for increased insulin-like growth factor binding protein-1 (U-IGFBP-1) levels. In this study, we used western ligand blotting (WLB), western immunoblotting (WIB), and radioimmunoassay (RIA) to further evaluate serum and urine IGFBP profiles of children with CRF (n=14). Five patients with CRF displayed decreased serum IGFBP-3 profiles by WLB. Serum IGFBP-3 WIB profiles were remarkable for 30- and 20-kDa fragments of IGFBP-3 not seen in control serum. Serum IGFBP-3 levels, as determined by RIA, were slightly elevated. Serum levels of IGFBP-2 also were increased, although not at a level reaching statistical significance. WLB of CRF urine revealed a large increase in U-IGFBP-1 and a complete absence of urinary IGFBP-3. Recent studies of serum from pregnant women and seminal plasma have demonstrated a similar absence of intact IGFBP-3, due to the presence of a specific IGFBP-3 protease. To evaluate whether an IGFBP-3 protease accounts for the absence of intact U-IGFBP-3 in children with CRF, urine and serum samples from individuals with CRF and controls were tested. An IGFBP-3 protease assay using concentrated urine revealed the presence of two distinct proteases found only in the CRF urines. Serum IGFBP-3 protease activity was no greater in patients with CRF than in controls. We conclude that the decrease in intact urinary IGFBP-3 is due to proteolysis by an IGFBP-3 protease. 相似文献
4.
Growth hormone/insulin-like growth factor system in children with chronic renal failure 总被引:4,自引:3,他引:1
Disturbances of the somatotropic hormone axis play an important pathogenic role in growth retardation and catabolism in children with chronic renal failure (CRF). The apparent discrepancy between normal or elevated growth hormone (GH) levels and diminished longitudinal growth in CRF has led to the concept of GH insensitivity, which is caused by multiple alterations in the distal components of the somatotropic hormone axis. Serum levels of IGF-I and IGF-II are normal in preterminal CRF, while in end-stage renal disease (ESRD) IGF-I levels are slightly decreased and IGF-II levels slightly increased. In view of the prevailing elevated GH levels in ESRD, these serum IGF-I levels appear inadequately low. Indeed, there is both clinical and experimental evidence for decreased hepatic production of IGF-I in CRF. This hepatic insensitivity to the action of GH may be partly the consequence of reduced GH receptor expression in liver tissue and partly a consequence of disturbed GH receptor signaling. The actions and metabolism of IGFs are modulated by specific high-affinity IGFBPs. CRF serum has an IGF-binding capacity that is increased by seven- to tenfold, leading to decreased IGF bioactivity of CRF serum despite normal total IGF levels. Serum levels of intact IGFBP-1, -2, -4, -6 and low molecular weight fragments of IGFBP-3 are elevated in CRF serum in relation to the degree of renal dysfunction, whereas serum levels of intact IGFBP-3 are normal. Levels of immunoreactive IGFBP-5 are not altered in CRF serum, but the majority of IGFBP-5 is fragmented. Decreased renal filtration and increased hepatic production of IGFBP-1 and -2 both contribute to high levels of serum IGFBP. Experimental and clinical evidence suggests that these excessive high-affinity IGFBPs in CRF serum inhibit IGF action in growth plate chondrocytes by competition with the type 1 IGF receptor for IGF binding. These data indicate that growth failure in CRF is mainly due to functional IGF deficiency. Combined therapy with rhGH and rhIGF-I is therefore a logical approach.This work was presented in part at the IPNA Seventh Symposium on Growth and Development in Children with Chronic Kidney Disease: The Molecular Basis of Skeletal Growth, 1–3 April 2004, Heidelberg, Germany 相似文献
5.
Ulinski T Mohan S Kiepe D Blum WF Wingen AM Mehls O Tönshoff B 《Pediatric nephrology (Berlin, Germany)》2000,14(7):589-597
Growth retardation in children with chronic renal failure (CRF) is partly due to an inhibition of insulin-like growth factor
(IGF) activity by an excess of high-affinity IGF-binding proteins (IGFBPs). The aim of this study was to analyze the serum
levels and forms of IGFBP-4 and IGFBP-5 in CRF patients using specific, recently developed radioimmunoassays (RIAs) and immunoblot
analysis. We examined 89 children [age 11.5 (2.8–19.0) years] with CRF [glomerular filtration rate 26.6 (7.0–67.4) ml/min
per 1.73 m2], nine of them with end-stage renal disease undergoing peritoneal dialysis. Serum-immunoreactive IGFBP-4 levels were fourfold
increased in CRF (prepubertal 1080±268 ng/ml; pubertal 989±299 ng/ml) compared to healthy prepubertal controls (265±73 ng/ml).
In contrast, serum IGFBP-5 levels were not significantly increased neither in prepubertal (361±120 ng/ml vs 282±75 ng/ml in
controls) nor pubertal CRF children (478±165 ng/ml vs 491±80 ng/ml in controls). Immunoblot analysis showed the presence of
intact as well as fragmented IGFBP-4 and IGFBP-5. Serum IGFBP-4, but not IGFBP-5, levels were inversely correlated with GFR
(r=–0.39, P<0.001). In prepuber- tal children, IGFBP-4 levels were inversely correlated with standardized height (r=–0.40; P<0.005). In contrast, IGFBP-5 levels were positively correlated both with standardized height (r=0.32, P<0.02) and baseline height velocity (r=0.45, P<0.005). A 3-month therapy with rhGH stimulated serum IGFBP-5 levels by 43% (P<0.01); there was no consistent effect on IGFBP-4 levels. There was a positive correlation between IGFBP-4 and IGFBP-2 (r=0.46, P<0.001); IGFBP-5 was positively correlated with IGF-I (r=0.59, P<0.001), IGF-II (r=0.42, P<0.001) and IGFBP-3 (r=0.47, P<0.001) and inversely correlated with IGFBP-1 (r=–0.41, P<0.001). In summary, serum IGFBP-4 is fourfold elevated in children with CRF in relation to the degree of renal dysfunction
and contributes to the marked increase in IGF-binding capacity in CRF serum. The inverse correlation of serum IGFBP-4 with
standardized height is consistent with its role as another inhibitor of the biological action of the IGFs on growth plate
cartilage. In contrast, serum IGFBP-5 is not elevated in CRF serum and circulates mainly as proteolysed fragments. The positive
correlation of serum IGFBP-5 with growth and its increase during GH therapy indicate that IGFBP-5 is a stimulatory IGFBP in
patients with CRF, either by enhancing IGF activity through better presentation of IGF to its receptor or by an IGF-independent
effect through activation of a specific, recently described putative IGFBP-5-receptor.
Received: 24 September 1999 / Revised: 6 January 2000 / Accepted: 13 January 2000 / Accepted: 13 January 2000 相似文献
6.
Chronic renal failure (CRF) results in complex metabolic and hormonal derangements, particularly in the GH-IGF-IGFBP axis,
which can be manifest in children as growth retardation. The decreased glomerular filtration rate (GFR) in CRF is associated
with increased plasma IGFBP levels, which may have an important role in inhibiting the bioavailability of IGF-I. There is
a large literature from both animal and human studies showing that the administration of IGF-I can affect structure and function
of normal and compromised kidneys. We propose an alternative therapeutic approach: activating bound IGF by administering molecules
that bind to the IGFBPs. In initial animal studies we used a mutant IGF, an IGF displacer, that binds to IGFBPs but not to
IGF receptors. In the rat this molecule activated the IGF system and produced IGF-like effects in vivo, such as increased
kidney size, reduced serum creatinine, increased bone growth and increased body weight. Novel synthetic peptides have also
been discovered which bind to specific IGFBPs, and we believe such molecules hold promise as therapeutic agents in renal disease.
Received: 12 April 1999 / Revised: 21 December 1999 / Accepted: 27 December 1999 相似文献
7.
Growth hormone resistance and inhibition of somatomedin activity by excess of insulin-like growth factor binding protein in uraemia 总被引:1,自引:1,他引:0
Werner F. Blum Michael B. Ranke Klaus Kietzmann Burkhardt Tönshoff Otto Mehls 《Pediatric nephrology (Berlin, Germany)》1991,5(4):539-544
Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) were studied in children with end-stage renal failure (ESRF,n=31) and chronic renal failure (n=11) with residual glomerular filtration. Somatomedin bioactivity in patient sera was found to be decreased while IGF-I and IGF-II levels by radio-immunoassay (RIA) were normal. In contrast, IGFBP-1 and IGFBP-3 levels (measured by RIA) were markedly increased in uraemia. Excess IGFBP was shown to be able to bind IGF by determination of the free IGF binding capacity. Using high-performance liquid chromatography a shift of the IGFBP-3 profile to low molecular weight components could be demonstrated in ESRF. Affinity crosslinking experiments showed that these low molecular weight IGFBP-3 immunoreactive forms are biologically active. In normal urine only IGFBP-3 forms smaller than 60 kDa were detected with a major peak at 12–20 kDa. Removal of excessive IGFBP from patient sera by affinity chromatography on an IGF-II Sepharose column resulted in a significant increase in somatomedin bioactivity. Model calculations on the interaction of IGF and IGFBP using empirical data suggested a reduction of IGF secretion in uraemia by an order of magnitude. It is concluded: (1) that renal failure causes an accumulation of low molecular weight IGFBP, (2) that the resulting excess of IGFBP acts as a somatomedin inhibitor, and (3) that in uraemia there is a relative growth hormone resistance with respect to IGF production. 相似文献
8.
The insulin-like growth factor (IGF) system is an important regulator of bone formation. The IGFs (IGF-I and IGF-II) are the most abundant growth factors produced by bone, and are regulated by their six high affinity binding proteins (IGFBPs). The IGFBPs are produced by osteoblasts and are responsible for transporting the IGFs and extending their half-lives. In general, IGFBP-1, -2, -4, and -6 inhibit and IGFBP-3 and –5 stimulate osteoblast function. IGFBP-4 and -5 are the most abundant IGFBPs produced by osteoblasts, and therefore they are the primary focus of this review. IGFBP-5 is an important stimulator of bone formation and may also function independently of IGFs. IGFBP-4 inhibits osteoblast function by sequestering IGF and preventing it from binding to its receptor. This review focuses on the specific IGF-dependent and IGF-independent roles of the IGFBPs in bone formation, as well as their potential mechanisms of action. In addition, discussion of the regulation of the IGFBPs by post-translational modification (i.e., proteolysis) has been included. Studies on the regulation of production and actions of IGFBPs suggest that the IGFBP system in bone is pleiotropic and capable of serving multiple effector inputs from systemic and local sources.This work was presented in part at the IPNA Seventh Symposium on Growth and Development in Children with Chronic Kidney Disease: The Molecular Basis of Skeletal Growth, 1–3 April 2004, Heidelberg, Germany 相似文献
9.
目的探讨血清胰岛素、胰岛素样生长因子(IGF-1)、IGF结合蛋白(IGFBPs)体质量指数(BMI)、腰臀围比(WHR)的变化及与结直肠癌发生、发展的关系。方法检测对象为2006年6月至2007年10月间住院收治和门诊复查的结直肠癌患者615例(术前检测244例,术后371例)和健康对照者150例。采用酶联免疫吸附法检测血清胰岛素、IGF-1和IGFBPS水平。结果结直肠癌患者术前血清胰岛素、IGF-1水平和IGF-I/IGFBP-3比值与健康对照组、术后患者比较,均明显升高,IGFBP-3水平明显降低,差异均有统计学意义(P〈0.05,P〈0.01)。结直肠癌术后未发生转移者与有肝或腹腔远处转移者胰岛素、IGF-1、IGFBP-1、IGFBP-3、IGF-1/IGFBP-3比较,差异均无统计学意义(P〉0.05)。结直肠癌患者WHR明显高于健康对照组(P〈0.01和P〈0.05);而BMI与健康对照组比较,差异无统计学意义(P〉0.05)。结肠癌患者WHR、BMI与胰岛素水平、IGF-1/IGFBP-3比值呈正相关(P〈0.01,P〈0.05),与IGFBP-3呈负相关(P〈0.01,P〈0.05);直肠癌患者WHR与血清瘦素、胰岛素水平及BMI与血清IGFBP-1水平均呈正相关(P〈0.05),与其他无相关性(P〉0.05)。结论胰岛素、IGF-1水平和IGF-I/IGFBP-3比值升高及IGFBP-3水平降低,可能与结直肠癌的发生有关,但与肿瘤转移与否无关,中心性肥胖是结肠癌发生的危险因素之一。 相似文献
10.
Schebek-Fürstenberg V Ständker L Oppermann M Müller-Wiefel DE Hahn W Blum WF Braulke T Kübler B 《Pediatric nephrology (Berlin, Germany)》2004,19(12):1418-1425
The insulin-like growth factors (IGF) -I and -II promote cellular growth and differentiation of various organs. Their growth-stimulating effects are modulated by a family of six IGF-binding proteins (IGFBPs). Altered patterns of intact and fragmented IGFBPs have been reported in serum and urine of children with chronic renal failure (CRF), and it has been suggested that this may contribute to the growth failure observed in these patients. In the present study, a rapid and comprehensive method is presented to analyze IGFBPs and IGFBP fragments in the plasma of a child with acute renal failure (ARF) who had undergone plasmapheresis. The plasma IGF-I and IGFBP-3 levels were drastically reduced. Plasmapheresis filtrate (3 l) was fractionated by cation-exchange chromatography and reversed-phase high-performance liquid chromatography. The fractions obtained were tested by ligand and immunoblotting. In addition to IGFBP-1 and -4 fragments, the majority of IGF-binding polypeptides were IGFBP-3 immunoreactive. N-terminal sequence analysis of a 17-kDa polypeptide revealed the isolation of a C-terminal fragment of IGFBP-3 starting with Lys 160. The IGF-II-binding polypeptide pattern in the ARF plasma resembles the pattern in hemofiltrate from CRF patients, suggesting that similar or identical proteases are involved in IGFBP-3 fragmentation and common mechanisms may lead to the accumulation of the fragments in both diseases. 相似文献
11.
Burkhard Tönshoff Werner F. Blum Otto Mehls 《Pediatric nephrology (Berlin, Germany)》1996,10(3):269-274
Serum levels of insulin-like growth factor-I (IGF-I), IGF-II, and IGF binding protein-1 (IGFBP-1), IGFBP-2, and IGFBP-3 were measured in 54 children with end-stage renal disease (ESRD). The results were compared with their respective age-dependent normal ranges. IGFs and IGFBPs were quantified by specific radioimmunoassay. Serum IGF-I in children with ESRD tended to cluster in the low-normal range. Mean age-related serum IGF-I levels were slightly, but significantly decreased (–1.08±0.17 SDS). In view of the prevailing elevated growth hormone levels in ESRD, these serum, IGF-I levels must be interpreted as inadequately low. In contrast to IGF-I, individual serum IGF-II levels were either in the uppernormal range or clearly elevated. Mean age-related IGF-II (1.09±0.15 SDS) was lightly, but significantly elevated. Mean age-related IGFBP-1 serum levels (2.20±0.10 SDS) were moderately increased, while mean age-related serum IGFBP-2 (5.65±0.36) and IGFBP-3 levels (3.60±0.19) were markedly elevated. Affinity cross-linking of125iodine-IGF-II to sera from patients with ESRD and immunoprecipitation with a specific antiserum showed that low molecular weight IGFBP-3 fragments in ESRD serum are capable of binding IGF. In patients with ESRD, a rapid and persistent decline of immunoreactive IGFBP-3 in response to restoration of renal function by renal transplantation was observed. This finding indicates that renal dysfunction contributes to high immunoreactive, IGFBP-3 levels in ESRD. In conclusion, the imbalance between normal total IGF levels and the excess of IGFBPs in ESRD is likely to play a role in growth failure in these children. 相似文献
12.
Yamaguchi T Kanatani M Yamauchi M Kaji H Sugishita T Baylink DJ Mohan S Chihara K Sugimoto T 《Calcified tissue international》2006,78(1):18-24
We previously found that serum levels of insulin-like growth factor I (IGF-I) and IGF-binding protein (IGFBP)-3, but not IFGBP-2,
were associated with bone mineral density (BMD) and the risk of vertebral fractures. The aim of the present study was to investigate
the roles of IGFBP-4 and -5 in age-dependent bone loss and vertebral fracture risk in postmenopausal Japanese women and to
compare them with those of IGF-I and IGFBP-3. One hundred and ninety-three Japanese women aged 46–88 years (mean 62.5) were
enrolled in the cross-sectional study. BMD was measured at the lumbar spine, femoral neck, ultradistal radius (UDR), and total
body by dual-energy X-ray absorptiometry. Serum levels of IGFBP-4 and -5 as well as IGF-I and IGFBP-3 were measured by radioimmunoassay.
Serum levels of IGF-I, IGFBP-3, and IGFBP-5 declined with age, while serum IGFBP-4 increased with age. Multiple regression
analysis was performed between BMD at each skeletal site and serum levels of IGF-I and IGFBPs adjusted for age, body weight,
height, and serum creatinine. BMD at the UDR was significantly and positively correlated with all serum levels of IGF-I and
IGFBPs measured (P < 0.01), while BMD at the femoral neck was correlated with none of them. Serum IGF-I level was significantly and positively
correlated with BMD at all sites except the femoral neck (P < 0.01), while serum IGFBP-3 and -4 levels were significantly and positively correlated with only radial BMD (P < 0.01). Serum IGFBP-5 level was positively correlated with UDR BMD (P < 0.001) and negatively correlated with total BMD (P < 0.05). Serum IGF-I, IGFBP-3, and IFGBP-5 levels were significantly lower in women with vertebral fractures than in those
without fractures (mean ± SD: 97.1 ± 32.1 vs. 143.9 ± 40.9 ng/dl, P < 0.0001; 2.18 ± 1.02 vs. 3.23 ± 1.07 μg/ml, P < 0.0001; 223.6 ± 63.3 vs. 246.5 ± 71.5 ng/ml, P = 0.0330, respectively). When multivariate logistic regression analysis was performed with the presence of vertebral fractures
as a dependent variable and serum levels of IGF-I and IGFBPs adjusted for age, body weight, height, serum creatinine, and
serum alubumin as independent variables, IGF-I and IGFBP-3 were selected as indices affecting the presence of vertebral fractures
[odds ratio (OR) = 0.29, 95% confidential interval (CI) 0.15–0.57 per SD increase, P = 0.0003 and OR = 0.31, 95% CI 0.16–0.61 per SD increase, P = 0.0007, respectively]. To compare the significance values, IGF-I, IGFBP-3, and age were simultaneously added as independent
variables in the analysis. IGFBP-3 was more strongly associated with the presence of vertebral fractures than IGF-I and age
(P = 0.0006, P = 0.0148, and P = 0.0013, respectively). Thus, after comprehensive measurements of serum levels of IGF-I and IGFBPs, it seems that serum
IGF-I level is most efficiently associated with bone mass and that serum IGFBP-3 level is most strongly associated with the
presence of vertebral fractures in postmenopausal women among the IGF system components examined. 相似文献
13.
Jorge R. Ferraris Patricia Pennisi Titania Pasqualini Hector Jasper 《Pediatric nephrology (Berlin, Germany)》1997,11(3):322-324
Deflazacort is an oxazoline compound derived from prednisolone. We studied changes in kidney function, growth velocity, weight/height
ratio, insulin-like growth factor (IGF-I), and IGF binding proteins before and after substitution of deflazacort for methylprednisone
in 27 transplanted patients aged 3.1 – 20 years. Methylprednisone (mean±SEM 0.17±0.01 mg/kg per day) was replaced by deflazacort
(0.29±0.01 mg/kg per day) for a period of 1 – 5 years. Calculated creatinine clearance did not change significantly during
deflazacort treatment. Growth velocity increased from 2.6±0.5 cm/year to 5.2±0.7 cm/year (1st year) in 14 prepubertal patients.
After 4 years of deflazacort treatment, height standard deviation score for chronological age did not change in 7 prepubertal
patients. Mean weight/height ratio decreased by 50% (1st year) and remained reduced during follow-up. Serum IGF-I, IGF binding
protein -3 (IGFBP3), IGF/IGFBP3 molar ratio, and IGF-I and -II binding capacities showed no significant change; however in
5 of 6 patients IGFBP2 decreased during deflazacort therapy. Our findings suggest that immunosuppressive treatment with deflazacort
is as effective as methylprednisone and may lead to an improvement in the growth prognosis of children with renal transplantation.
Received May 13, 1996; received in revised form and accepted November 20, 1996 相似文献
14.
Gamze Bereket Jen Jar Lin Abdullah Bereket Charles H. Lang Frederick J. Kaskel 《Pediatric nephrology (Berlin, Germany)》1998,12(7):581-588
The kinetics of peritoneal transport of insulin-like growth factor (IGF) system-related proteins during dialysis is not well
characterized. We studied temporal changes in dialysate and serum concentrations of IGF-I and IGF-II as well as IGF binding
protein (BP)-1, -2, and -3 in ten children with end-stage renal disease (ESRD) undergoing continuous cycling peritoneal dialysis
(CCPD) during a 4-h peritoneal equilibration test (PET). Dialysate concentrations of IGF-I, IGF-II, and all three IGFBPs demonstrated
a time-dependent increase during PET. Despite their transport, the serum concentrations of these proteins did not change significantly
during the PET. Dialysate/serum ratios for IGF-I, IGF-II, and IGFBP-1, -2, and -3 were significantly increased at 2 h and
increased further at 4 h, at which time values averaged 1.3±0.2%, 3.1±0.5%, 6.2±1.0%, 2.4±0.2%, and 1.3±0.2% of serum levels,
respectively. The transperitoneal clearance (μl/min per 1.73 m2) of the three IGFBPs was inversely related to both their molecular weight and plasma concentration. However, peritoneal clearance
of IGF-I and -II was similar to that of the larger and more-abundant IGFBP-3. Mass transfer rates (μg/h per 1.73 m2) for the IGFs and their binding proteins were directly proportional to their prevailing plasma concentration. Based on estimates
of mass transfer, only a small molar excess of IGFBPs was removed from the circulation relative to the combined molar concentration
of IGF-I and IGF-II. Hence, it seems unlikely that any beneficial effect of CCPD on growth in children with ESRD is mediated
via a preferential loss of IGFBPs into the dialysate fluid.
Received August 15, 1997; received in revised form January 7, 1998; accepted January 9, 1998 相似文献
15.
Margaret J. van Renen Sabine Harrer Ken F. Jureidini Anne A. Martin 《Pediatric nephrology (Berlin, Germany)》1996,10(4):483-487
A
bstract. Three short children with severe chronic renal failure were treated with recombinant human growth hormone (rhGH) for 2 years.
Each received a transplant in the 2nd year. Serum collected before and during rhGH therapy was analysed retrospectively by
Western ligand blot and immunoblotting techniques. In addition, radioimmunoassays for insulin-like growth factor-I (IGF-I),
IGF binding protein-3 (IGFBP-3), acid-labile subunit (ALS) and IGFBP-1 were performed. IGFBPs in serum, detected by Western
ligand blot, were identified as IGFBP-3, -2, -1 and -4 by immunoblot. The serum concentration of IGF-I in each child rose
approximately fourfold with rhGH before transplantation and subsequently remained elevated. IGFBP-3 levels rose to double
the pretreatment value, but dropped to normal levels following transplantation, while ALS rose with rhGH treatment and remained
increased after transplantation. IGFBP-1 levels changed little with rhGH but fell following transplantation. A low molecular
weight form of IGFBP-3 was noted at 30 kilodaltons on immunoblot which was not clearly seen on the ligand blot. IGFBP-2 was
present as a distinct band on Western ligand blot before transplantation and appeared decreased in intensity subsequently.
IGFBP-1, seen on immunoblot clearly before transplant, disappeared after the transplant. rhGH successfully improved growth
in these children, in association with a fourfold increase in IGF-I levels, which was maintained following transplantation.
The reduction in IGFBPs following transplantation suggests correction of impaired clearance by the diseased kidney.
Received September 5, 1994; received in revised form November 8, 1995; accepted November 21, 1995 相似文献
16.
目的 探讨血清胰岛素、胰岛素样生长因子(IGF-1)、IGF结合蛋白(IGFBPs)及体质量指数(BMI)、腰臀围比(WHR)的变化及与结直肠癌发生、发展的关系.方法 检测对象为2006年6月至2007年10月间住院收治和门诊复查的结直肠癌患者615例(术前检测244例,术后371例)和健康对照者150例.采用酶联免疫吸附法检测血清胰岛素、IGF-1和IGFBPS水平.结果 结直肠癌患者术前血清胰岛素、IGF-1水平和IGF-Ⅰ/IGFBP-3比值与健康对照组、术后患者比较,均明显升高,IGFBP-3水平明显降低,差异均有统计学意义(P<0.05,P<0.01).结直肠癌术后未发生转移者与有肝或腹腔远处转移者胰岛素、IGF-1、IGFBP-1、IGFBP-3、IGF-1/IGFBP-3比较.差异均无统计学意义(P>0.05).结直肠癌患者WHR明显高于健康对照组(P<0.01和P<0.05):而BMI与健康对照组比较,差异无统计学意义(P>0.05).结肠癌患者WHR、BMI与胰岛素水平、IGF-1/IGFBP-3比值呈正相关(P<0.01,P<0.05),与IGFBP-3呈负相关(P<0.01,P<0.05);直肠癌患者WHR与血清瘦素、胰岛素水平及BMI与血清IGFBP-1水平均呈正相关(P<0.05),与其他无相关性(P>0.05).结论 胰岛素、IGF-1水平和IGF-Ⅰ/IGFBP-3比值升高及IGFBP-3水平降低,可能与结直肠癌的发生有关,但与肿瘤转移与否无关,中心性肥胖是结肠癌发生的危险因素之一. 相似文献
17.
目的 探讨血清胰岛素、胰岛素样生长因子(IGF-1)、IGF结合蛋白(IGFBPs)及体质量指数(BMI)、腰臀围比(WHR)的变化及与结直肠癌发生、发展的关系.方法 检测对象为2006年6月至2007年10月间住院收治和门诊复查的结直肠癌患者615例(术前检测244例,术后371例)和健康对照者150例.采用酶联免疫吸附法检测血清胰岛素、IGF-1和IGFBPS水平.结果 结直肠癌患者术前血清胰岛素、IGF-1水平和IGF-Ⅰ/IGFBP-3比值与健康对照组、术后患者比较,均明显升高,IGFBP-3水平明显降低,差异均有统计学意义(P<0.05,P<0.01).结直肠癌术后未发生转移者与有肝或腹腔远处转移者胰岛素、IGF-1、IGFBP-1、IGFBP-3、IGF-1/IGFBP-3比较.差异均无统计学意义(P>0.05).结直肠癌患者WHR明显高于健康对照组(P<0.01和P<0.05):而BMI与健康对照组比较,差异无统计学意义(P>0.05).结肠癌患者WHR、BMI与胰岛素水平、IGF-1/IGFBP-3比值呈正相关(P<0.01,P<0.05),与IGFBP-3呈负相关(P<0.01,P<0.05);直肠癌患者WHR与血清瘦素、胰岛素水平及BMI与血清IGFBP-1水平均呈正相关(P<0.05),与其他无相关性(P>0.05).结论 胰岛素、IGF-1水平和IGF-Ⅰ/IGFBP-3比值升高及IGFBP-3水平降低,可能与结直肠癌的发生有关,但与肿瘤转移与否无关,中心性肥胖是结肠癌发生的危险因素之一. 相似文献
18.
目的 探讨血清胰岛素、胰岛素样生长因子(IGF-1)、IGF结合蛋白(IGFBPs)及体质量指数(BMI)、腰臀围比(WHR)的变化及与结直肠癌发生、发展的关系.方法 检测对象为2006年6月至2007年10月间住院收治和门诊复查的结直肠癌患者615例(术前检测244例,术后371例)和健康对照者150例.采用酶联免疫吸附法检测血清胰岛素、IGF-1和IGFBPS水平.结果 结直肠癌患者术前血清胰岛素、IGF-1水平和IGF-Ⅰ/IGFBP-3比值与健康对照组、术后患者比较,均明显升高,IGFBP-3水平明显降低,差异均有统计学意义(P<0.05,P<0.01).结直肠癌术后未发生转移者与有肝或腹腔远处转移者胰岛素、IGF-1、IGFBP-1、IGFBP-3、IGF-1/IGFBP-3比较.差异均无统计学意义(P>0.05).结直肠癌患者WHR明显高于健康对照组(P<0.01和P<0.05):而BMI与健康对照组比较,差异无统计学意义(P>0.05).结肠癌患者WHR、BMI与胰岛素水平、IGF-1/IGFBP-3比值呈正相关(P<0.01,P<0.05),与IGFBP-3呈负相关(P<0.01,P<0.05);直肠癌患者WHR与血清瘦素、胰岛素水平及BMI与血清IGFBP-1水平均呈正相关(P<0.05),与其他无相关性(P>0.05).结论 胰岛素、IGF-1水平和IGF-Ⅰ/IGFBP-3比值升高及IGFBP-3水平降低,可能与结直肠癌的发生有关,但与肿瘤转移与否无关,中心性肥胖是结肠癌发生的危险因素之一. 相似文献
19.
目的 探讨血清胰岛素、胰岛素样生长因子(IGF-1)、IGF结合蛋白(IGFBPs)及体质量指数(BMI)、腰臀围比(WHR)的变化及与结直肠癌发生、发展的关系.方法 检测对象为2006年6月至2007年10月间住院收治和门诊复查的结直肠癌患者615例(术前检测244例,术后371例)和健康对照者150例.采用酶联免疫吸附法检测血清胰岛素、IGF-1和IGFBPS水平.结果 结直肠癌患者术前血清胰岛素、IGF-1水平和IGF-Ⅰ/IGFBP-3比值与健康对照组、术后患者比较,均明显升高,IGFBP-3水平明显降低,差异均有统计学意义(P<0.05,P<0.01).结直肠癌术后未发生转移者与有肝或腹腔远处转移者胰岛素、IGF-1、IGFBP-1、IGFBP-3、IGF-1/IGFBP-3比较.差异均无统计学意义(P>0.05).结直肠癌患者WHR明显高于健康对照组(P<0.01和P<0.05):而BMI与健康对照组比较,差异无统计学意义(P>0.05).结肠癌患者WHR、BMI与胰岛素水平、IGF-1/IGFBP-3比值呈正相关(P<0.01,P<0.05),与IGFBP-3呈负相关(P<0.01,P<0.05);直肠癌患者WHR与血清瘦素、胰岛素水平及BMI与血清IGFBP-1水平均呈正相关(P<0.05),与其他无相关性(P>0.05).结论 胰岛素、IGF-1水平和IGF-Ⅰ/IGFBP-3比值升高及IGFBP-3水平降低,可能与结直肠癌的发生有关,但与肿瘤转移与否无关,中心性肥胖是结肠癌发生的危险因素之一. 相似文献
20.
目的 探讨血清胰岛素、胰岛素样生长因子(IGF-1)、IGF结合蛋白(IGFBPs)及体质量指数(BMI)、腰臀围比(WHR)的变化及与结直肠癌发生、发展的关系.方法 检测对象为2006年6月至2007年10月间住院收治和门诊复查的结直肠癌患者615例(术前检测244例,术后371例)和健康对照者150例.采用酶联免疫吸附法检测血清胰岛素、IGF-1和IGFBPS水平.结果 结直肠癌患者术前血清胰岛素、IGF-1水平和IGF-Ⅰ/IGFBP-3比值与健康对照组、术后患者比较,均明显升高,IGFBP-3水平明显降低,差异均有统计学意义(P<0.05,P<0.01).结直肠癌术后未发生转移者与有肝或腹腔远处转移者胰岛素、IGF-1、IGFBP-1、IGFBP-3、IGF-1/IGFBP-3比较.差异均无统计学意义(P>0.05).结直肠癌患者WHR明显高于健康对照组(P<0.01和P<0.05):而BMI与健康对照组比较,差异无统计学意义(P>0.05).结肠癌患者WHR、BMI与胰岛素水平、IGF-1/IGFBP-3比值呈正相关(P<0.01,P<0.05),与IGFBP-3呈负相关(P<0.01,P<0.05);直肠癌患者WHR与血清瘦素、胰岛素水平及BMI与血清IGFBP-1水平均呈正相关(P<0.05),与其他无相关性(P>0.05).结论 胰岛素、IGF-1水平和IGF-Ⅰ/IGFBP-3比值升高及IGFBP-3水平降低,可能与结直肠癌的发生有关,但与肿瘤转移与否无关,中心性肥胖是结肠癌发生的危险因素之一. 相似文献