Insulin-like growth factor (IGF)-I and IGF binding protein-3 concentrations in fluid from human stimulated follicles

Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP- 3) play an important role in regulating follicle growth and maturation. We have evaluated whether responsiveness to gonadotrophins during an in- vitro fertilization (IVF) treatment is related to follicular fluid IGF- I and IGFBP-3 concentrations. We also investigated if a difference is present in IGF-I and IGFBP-3 concentrations between patients treated with human menopausal gonadotrophin (HMG) and patients treated with highly purified follicle stimulating hormone (FSH). We have measured IGF-I and IGFBP-3 in follicular fluid from pre-ovulatory follicles in an IVF programme. All 70 patients were stimulated after being down- regulated with a gonadotrophin-releasing hormone (GnRH) analogue. IGF-I concentrations in follicular fluid were significantly inversely correlated with the number of ampoules FSH administered and number of days of FSH administration, and significantly correlated with the number of follicles aspirated. IGFBP-3 concentrations were not correlated with any other parameter measured nor were IGF-I and IGFBP-3 concentrations correlated. IGFBP-3 concentrations were significantly higher in patients receiving highly purified FSH compared with patients receiving HMG (P < 0.005). These results are new evidence that IGF-I concentration in follicular fluid is higher in women who respond better to follicular stimulation, i.e. women who grow many follicles, women who need a shorter duration of stimulation and women who need fewer ampoules FSH before oocyte retrieval.      

Immunosuppressive activities in the seminal plasma of infertile men: relationship to sperm antibodies and autoimmunity

Semen samples from infertile men were assessed for sperm autoimmunity by direct immunobead assay for immunoglobulin (Ig)A and IgG sperm antibodies and mucus penetration test. Immunosuppressive activity in seminal plasma was measured by an in-vitro bioassay employing dose- dependent inhibition of phytohaemagglutinin-induced activation of rat thymocytes, in the presence or absence of hydroxylamine (0.1 mM), an inhibitor of polyamine oxidation. All seminal plasma samples, regardless of autoimmune status, caused inhibition of T-lymphocyte activation, and hydroxylamine reduced this bioactivity by appproximately 50%. Dialysis (<3500 molecular weight) also significantly reduced seminal plasma bioactivity, both in the presence and absence of hydroxylamine. In the presence of hydroxylamine, there was a negative correlation between IgA, but not IgG, antibody concentrations and lymphosuppressive activity in seminal plasma. Antibody-positive samples displaying impaired sperm function, as indicated by the mucus penetration test, had reduced activity compared with other samples. In contrast, there was no relationship between sperm autoimmunity and lymphosuppressive activity assayed in the absence of hydroxylamine. The data indicate that T-lymphocyte inhibition by human seminal plasma is due to multiple factors, and reduced amounts of these factors may contribute to the development and/or persistence of sperm autoimmunity in infertile men; however, differences in polyamine substrates available for oxidation in semen do not appear to be a major contributing factor.      

肝炎后高胆红素血症18例分析

0　引言　肝炎后高胆红素血症 ,极易与肝炎伴发高胆红素血症相混淆 .该病是肝炎后遗症之一 ,临床上并不少见 .患者常以间歇性黄疸或隐性黄疸前来就诊 ,但并无先天性黄疸、肝炎、肝硬化及肝内外胆管结石的临床证据 ,多数既往有肝炎病史 ,肝炎已达治愈标准 ,虽增加活动量亦无复发 ,临床预后良好 .现将我院 1995 - 10 / 1999- 0 9肝炎后高胆红素血症 18例作一小结 .1　临床资料　男 12例 ,女 6例 ,年龄 2 2～ 5 8(平均 40岁 ) .门诊 11例 ,住院 7例 .其中 11例曾患急性病毒性乙型肝炎 ,1例曾患中毒性肝炎 ,1例曾患药物性肝炎 ,5例无明确肝炎病…     

Change in obesity‐related metabolic abnormalities associated with body mass index improvement through life‐style intervention: A meta‐regression

The reduction in body mass index standard deviation score (BMI‐SDS) associated with improvement in biomarkers relating to metabolic health in obese children is unknown. We aimed to establish the change in BMI‐SDS associated with improved inflammation, liver function, and insulin resistance to inform clinical guidelines for pediatric weight management interventions and to assess the efficacy of future trials. A large‐scale systematic review was conducted to identify relevant studies. Studies of children with a diagnosis of obesity according to defined BMI thresholds, participating in lifestyle interventions to reduce obesity, were included. Studies must have reported baseline (pre‐) and postintervention (or change of) BMI‐SDS and either fasting glucose, homeostatic model of insulin resistance (HOMA‐IR), alanine aminotransferase (ALT), C‐reactive protein (CRP), or interleukin‐6 (IL‐6). A series of meta‐regressions were conducted to establish links between BMI‐SDS change scores and change in metabolic markers of health. Sixty‐eight articles were identified. From the meta‐regression analyses, across all study subsets, greater mean falls in all four parameters, (HOMA‐IR, Glucose, ALT, and CRP) were observed with greater mean loss of BMI‐SDS, but the trends were only statistically significant for HOMA‐IR and CRP (P = .003; P = .021). However, we could not find minimum changes in BMI‐SDS that would ensure a fall in these outcomes. At this time, we are unable to recommend a definitive value of BMI‐SDS reduction needed to improve the markers of metabolic health. Future trials should aim to report additional indices of derived BMI values, which may better reflect changes in actual adiposity.     

De novo microduplications at 1q41, 2q37.3, and 8q24.3 in patients with VATER/VACTERL association

The acronym VATER/VACTERL association describes the combination of at least three of the following congenital anomalies: vertebral defects (V), anorectal malformations (A), cardiac defects (C), tracheoesophageal fistula with or without esophageal atresia (TE), renal malformations (R), and limb defects (L). We aimed to identify highly penetrant de novo copy number variations (CNVs) that contribute to VATER/VACTERL association. Array-based molecular karyotyping was performed in a cohort of 41 patients with VATER/VACTERL association and 6 patients with VATER/VACTERL-like phenotype including all of the patients'' parents. Three de novo CNVs were identified involving chromosomal regions 1q41, 2q37.3, and 8q24.3 comprising one (SPATA17), two (CAPN10, GPR35), and three (EPPK1, PLEC, PARP10) genes, respectively. Pre-existing data from the literature prompted us to choose GPR35 and EPPK1 for mouse expression studies. Based on these studies, we prioritized GPR35 for sequencing analysis in an extended cohort of 192 patients with VATER/VACTERL association and VATER/VACTERL-like phenotype. Although no disease-causing mutation was identified, our mouse expression studies suggest GPR35 to be involved in the development of the VATER/VACTERL phenotype. Follow-up of GPR35 and the other genes comprising the identified duplications is warranted.     

Catalog of intravascular contrast media

The ionic intravascular contrast media formulations now commercially available are presented, along with those new formulations, nonionic and ionic, that have a significant reduced osmolality compared with those previously available.     

Overexpression of the MDM2 gene by childhood acute lymphoblastic leukemia cells expressing the wild-type p53 gene

The wild-type (wt) p53 tumor suppressor gene is commonly inactivated in human malignancies, either by mutations or by loss of expression. An additional proposed mechanism for inactivation of wt-p53 is amplification of the murine double minute 2 (MDM2) gene and overexpression of the MDM2 protein, which binds to p53 and eliminates its tumor suppressor function. To investigate a potential role for MDM2 in the inactivation of wt-p53 in pediatric acute lymphoblastic leukemia (ALL), we examined the expression of MDM2 and p53, as well as the occurrence of p53 mutations and possible amplification of the MDM2 gene, in 19 pediatric ALL cell lines and one pediatric acute myelogenous leukemia (AML) line. Although we did not find significant amplification of the MDM2 gene in any of the leukemic lines, we detected overexpression of MDM2 in all 10 lines that expressed wt-p53. Of the 10 lines without overexpression of the MDM2 gene, six (including the AML line) did not express p53, and four expressed mutant p53 with single point mutations in exons 7 and 8. To determine whether primary leukemic cells showed a similar correlation, we analyzed the original cryopreserved leukemic bone marrow cells from seven patients from whom cell lines were established. We obtained similar results from both the primary leukemic cells and the corresponding cell lines: overexpression of MDM2 was present in primary cells that expressed wt-p53 but not in cells that lacked expression of wt-p53. These findings suggest an important role for MDM2 in the pathogenesis of pediatric ALL in which leukemic cells express wt-p53.     

Immunologic aspect of ovarian cancer and p53 as tumor antigen

Ovarian cancer represents the fifth leading cause of death from all cancers for women. During the last decades overall survival has improved due to the use of new chemotherapy schedules. Still, the majority of patients die of this disease. Research reveals that ovarian cancer patients exhibit significant immune responses against their tumor. In this review the knowledge obtained thus far on the interaction of ovarian cancer tumor cells and the immune system is discussed. Furthermore the role of p53 as tumor antigen and its potential role as target antigen in ovarian cancer is summarized. Based on the increased knowledge on the role of the immune system in ovarian cancer major improvements are to be expected of immunotherapy based treatment of this disease.