Aglossia-adactylia syndrome (special emphasis on the inheritance pattern)

Three cases, one with aglossia-adactylia and two with aglossia, are presented, all of whom were born to consanguineous families. Although none of the cases had similarly affected sibs, the possibility of the autosomal recessive mode of inheritance might be taken into account in this syndrome. The dermatoglyphic findings in one previously reported patient showed great similarity to those of one of our cases.     

Temporal endothelin dynamics of the myocardial interstitium and systemic circulation in cardiopulmonary bypass

OBJECTIVE: Increased systemic levels of the bioactive peptide endothelin 1 during and after cardioplegic arrest and cardiopulmonary bypass have been well documented. However, endothelin 1 is synthesized locally, and therefore myocardial endothelin 1 production during and after cardiopulmonary bypass remains unknown. METHODS: Pigs (n = 11) were instrumented for cardiopulmonary bypass, and cardioplegic arrest was initiated. Myocardial interstitial and systemic arterial levels of endothelin 1 were measured before cardiopulmonary bypass, throughout bypass and cardioplegic arrest (90 minutes), and up to 90 minutes after separation from bypass. Myocardial interstitial endothelin 1 was determined by microdialysis and radioimmunoassay. RESULTS: Baseline myocardial endothelin 1 levels were higher than systemic endothelin 1 levels (25.6 +/- 6.7 vs 8.3 +/- 1.1 fmol/mL, P <.05). With the onset of bypass, myocardial endothelin 1 increased by 327% +/- 92% from baseline (P <.05), which preceded the increase in systemic endothelin 1 levels. CONCLUSION: Myocardial compartmentalization of endothelin 1 exists in vivo. Cardiopulmonary bypass and cardioplegic arrest induce temporal differences in endothelin 1 levels within the myocardial interstitium and systemic circulation, which, in turn, may influence left ventricular function in the postbypass period.     

CYP1A1 gene polymorphism and polycystic ovary syndrome

The aim of this study was to assess the rates of variant alleles of cytochrome P4501A1 (CYP1A1) in patients with polycystic ovary syndrome (PCOS). It was designed as a case-control study in Hacettepe University, Faculty of Medicine, Department of Obstetrics and Gynecology and Genetics. Forty-eight patients with PCOS served as the study group. Ninety-six regularly cycling women with no clinical and biochemical evidence of hyperandrogenism and polycystic ovary appearance served as the controls. The CYP1A1 variant alleles of all patients were determined via polymerase chain reaction. The rate of the CYP1A1 isoleucine (Ile)/valine (Val) allele was significantly higher in patients with PCOS than in the controls (OR: 7.8, 95% CI: 3.45-17.52, P < 0.001). However, there was no statistically significant difference in the distribution of Val/Val genotype (OR: 4.0, 95% CI: 0.60-26.73). The rate of any Val genotype (Ile/Val or Val/Val) was significantly higher in patients with PCOS compared with the control group (OR: 7.4, 95% CI: 3.33-16.46, P < 0.001). In conclusion, the patients with PCOS had a 7.8-fold higher frequency of CYP1A1 Ile/Val genotype and a 7.4-fold higher frequency of CYP1A1 of any Val genotype (Ile/Val or Val/Val).     

The Akt inhibitor,triciribine, ameliorates chronic hypoxia-induced vascular pruning and TGFβ-induced pulmonary fibrosis

Background and Purpose

Interstitial lung disease accounts for a group of chronic and progressive disorders associated with severe pulmonary vascular remodelling, peripheral vascular rarefaction and fibrosis, thus limiting lung function. We have previously shown that Akt is necessary for myofibroblast differentiation, a critical event in organ fibrosis. However, the contributory role of the Akt-mTOR pathway in interstitial lung disease and the therapeutic benefits of targeting Akt and mTOR remain unclear.

Experimental Approach

We investigated the role of the Akt-mTOR pathway and its downstream molecular mechanisms in chronic hypoxia- and TGFβ-induced pulmonary vascular pruning and fibrosis in mice. We also determined the therapeutic benefits of the Akt inhibitor triciribine and the mTOR inhibitor rapamycin for the treatment of pulmonary fibrosis in mice.

Key Results

Akt1^−/− mice were protected from chronic hypoxia-induced peripheral vascular pruning. In contrast, hyperactivation of Akt1 induced focal fibrosis similar to TGFβ-induced fibrosis. Pharmacological inhibition of Akt, but not the Akt substrate mTOR, inhibited hypoxia- and TGFβ-induced pulmonary vascular rarefaction and fibrosis. Mechanistically, we found that Akt1 modulates pulmonary remodelling via regulation of thrombospondin1 (TSP1) expression. Hypoxic Akt1^−/− mice lungs expressed less TSP1. Moreover, TSP1^−/− mice were resistant to adMyrAkt1-induced pulmonary fibrosis.

Conclusions and Implications

Our study identified Akt1 as a novel target for the treatment of interstitial lung disease and provides preclinical data on the potential benefits of the Akt inhibitor triciribine for the treatment of interstitial lung disease.     

Higher expression of the novel gene upregulated gene 4 in two acute lymphoblastic leukemia patients with poor prednisolone response

Elucidation of the molecular mechanisms of leukemogenesis is important for a better understanding of the prognosis of acute lymphoblastic leukemia (ALL). Studies have shown that the expression of upregulated gene 4 (URG4), which promotes cell growth and survival, is increased in different types of carcinomas including hepatocellular carcinoma, gastric cancer and osteosarcoma. Similarly, higher expression of URG4 and cyclin D1 gene might promote proliferation of the blast cells by causing escape from the G1 checkpoint and entry into the S phase. This study reports the high expression level of URG4 in 2 high-risk ALL patients for the first time in the literature. In conclusion, the higher expression of URG4 in our 2 patients suggests that URG4 might be involved in leukemogenesis. Future studies with a large number of high-risk ALL patients and cell culture studies are needed to demonstrate the exact role of URG4 in leukemogenesis.     

Aortic cusp ablation for premature ventricular contractions and ventricular tachycardia in children: a 5-year single-center experience

Journal of Interventional Cardiac Electrophysiology - Aortic cusps might be the source of supraventricular or ventricular arrhythmias. For many years, aortic cusp ablation has been widely used to...