Association of IGF-I gene polymorphisms with milk yield and body size in Chinese dairy goats

The association of IGF-I gene polymorphisms with certain traits in 708 individuals of two Chinese dairy-goat breeds (Guanzhong and Xinong Saanen) was investigated. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing methods were employed in screening for genetic variation. Two novel mutations were detected in the 5'-flanking region and in intron 4 of IGF-I gene, viz., g.1617 G > A and g.5752 G > C (accession D26119.2), respectively. The associations of the g.1617 G > A mutation with milk yield and the body size were not significant (p > 0.05). However, in the case of g.5752 G > C, Xinong Saanen dairy goats with the CG genotype presented longer bodies (p < 0.05). Chest circumference (p < 0.05) was larger in Guanzhong goats with the GG genotype. In Xinong Saanen dairy goats with the CC genotype, milk yields were significantly higher during the first and second lactations (p < 0.05). Hence, the g.5752 G > C mutation could facilitate association analysis and serve as a genetic marker for Chinese dairy-goat breeding and genetics

Severe paraneoplastic hypoglycemia in a patient with a gastrointestinal stromal tumor with an exon 9 mutation: a case report

BACKGROUND: Non-islet cell tumor induced hypoglycemia (NICTH) is a very rare phenomenon, but even more so in gastrointestinal stromal tumors. It tends to present in large or metastatic tumors, and can appear at any time in the progression of the disease. We present herein a case of NICTH in a GIST tumor and report an exon 9 mutation associated to it. CASE PRESENTATION: A thirty nine year-old man with a recurrent, metastatic gastrointestinal stromal tumor presented to the hospital with nausea, dizziness, loss of consciousness, and profound hypoglycemia (20 mg/dL). There was no evidence of factitious hypoglycemia. He was stabilized with a continuous glucose infusion and following selective vascular embolization, the patient underwent debulking of a multicentric 40 cm × 25 cm × 10 cm gastrointestinal stromal tumor. After resection, the patient became euglycemic and returned to his normal activities. Tumor analysis confirmed excessive production of insulin-like growth factor II m-RNA and the precursor protein, "big" insulin-like growth factor II. Mutational analysis also identified a rare, 6 bp tandem repeat insert (gcctat) at position 1530 in exon 9 of KIT. CONCLUSION: Optimal management of gastrointestinal stromal tumor-induced hypoglycemia requires a multidisciplinary approach, and surgical debulking is the treatment of choice to obtain immediate symptom relief. Imatinib or combinations of glucocorticoids and growth hormone are alternative palliative strategies for symptomatic hypoglycemia. In addition, mutations in exon 9 of the tyrosine kinase receptor KIT occur in 11–20% of GIST and are often associated with poor patient outcomes. The association of this KIT mutation with non-islet cell tumor induced hypoglycemia has yet to be established

Growth hormone axis in chronic kidney disease

Chronic kidney disease (CKD) in children is associated with dramatic changes in the growth hormone (GH) and insulin-like growth factor (IGF-1) axis, resulting in growth retardation. Moderate-to-severe growth retardation in CKD is associated with increased morbidity and mortality. Renal failure is a state of GH resistance and not GH deficiency. Some mechanisms of GH resistance are: reduced density of GH receptors in target organs, impaired GH-activated post-receptor Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling, and reduced levels of free IGF-1 due to increased inhibitory IGF-binding proteins (IGFBPs). Treatment with recombinant human growth hormone (rhGH) has been proven to be safe and efficacious in children with CKD. Even though rhGH has been shown to improve catch-up growth and to allow the child to achieve normal adult height, the final adult height is still significantly below the genetic target. Growth retardation may persist after renal transplantation due to multiple factors, such as steroid use, decreased renal function and an abnormal GH–IGF1 axis. Those below age 6 years are the ones to benefit most from transplantation in demonstrating acceleration in linear growth. Newer treatment modalities targeting the GH resistance with recombinant human IGF-1 (rhIGF-1), recombinant human IGFBP3 (rhIGFBP3) and IGFBP displacers are under investigation and may prove to be more effective in treating growth failure in CKD

Body weight and risk of soft-tissue sarcoma

The relation between body mass (BMI) and soft-tissue sarcoma (STS) risk was evaluated in a case–control study from Northern Italy based on 217 incident STS and 1297 hospital controls. The risk of STS rose with BMI, with multivariate odds ratios of 3.49 (95% confidence interval (CI) 1.06–11.55) among men and 3.26 (95% CI 1.27–8.35) among women with a BMI >30 kg m–2 compared to those with BMI ≤ 20 kg m–2. © 1999 Cancer Research Campaig

Alterations in the insulin-like growth factor system during treatment with diethylstilboestrol in patients with metastatic breast cancer

Alterations in the insulin-like growth factor (IGF)-system were evaluated in 16 patients treated with diethylstilboestrol 5 mg 3 times daily. Fasting blood samples were obtained before treatment and after 2 weeks, 1 month and/or 2–3 months on therapy. Insulin-like growth factor (IGF)-I, IGF-II, free IGF-I, IGF-binding protein (IGFBP)-1, IGFBP-2 and IGFBP-3 were measured by radioimmuno-/immunoradiometric-assays. All samples were subjected to Western ligand blotting as well as immunoblotting for IGFBP-3. We observed a significant decrease (percentage of pretreatment levels with 95 confidence intervals of the mean) in IGF-I [2 weeks 63% (49–79); 1 month 56% (44–73); 2–3 months 66% (53–82)], IGF-II [2 weeks 67% (56–80); 1 month 60% (52–68); 2–3 months 64% (55–75)], free IGF-I [2 weeks 29% (19–42); 1 month 25% (18–36); 2–3 months 31% (21–46)], IGFBP-2 [2 weeks 53% (18–156); 1 month 69% (61–78); 2–3 months 66% (57–78)], IGFBP-3 [2 weeks 74% (63–85); 1 month 69% (62–76); 2–3 months 71% (63–80)], as well as IGFBP-3 protease activity [2 weeks 71% (54–95); 1 month 78% (64–94); 2–3 months 71% (54–93)]. Contrary, the plasma levels (percentage of pretreatment levels with 95 confidence intervals of the mean) of IGFBP-1 [2 weeks 250% (127–495); 1 month 173% (138–542); 2–3 months 273% (146–510)] and IGFBP-4 [2 weeks 146% (112–192); 1 month 140% (116–169); 2–3 months 150% (114–198)] increased significantly. While this study confirms previous observations during treatment with oral oestrogens in substitution doses, the reduction in plasma IGF-II, free IGF-I, IGFBP-2 and -3 are all novel findings. A profound decrease in free IGF-I suggests a reduced bioavailability of IGFs from plasma to the tissues. These observations may be of significance to understand the mechanisms of the antitumour effect of diethylstilboestrol in pharmacological doses. © 2001 Cancer Research Campaign http://www.bjcancer.co