A Pin1/PML/P53 axis activated by retinoic acid in NPM-1c acute myeloid leukemia

Retinoic acid (RA) was proposed to increase survival of chemotherapy- treated patients with nucleophosmin-1 (NPM-1c)-mutated acute myeloid leukemia. We reported that, ex vivo, RA triggers NPM-1c degradation, P53 activation and growth arrest. PML organizes domains that control senescence or proteolysis. Here, we demonstrate that PML is required to initiate RA-driven NPM-1c degradation, P53 activation and cell death. Mechanistically, RA enhances PML basal expression through inhibition of activated Pin1, prior to NPM-1c degradation. Such PML induction drives P53 activation, favoring blast response to chemotherapy or arsenic in vivo. This RA/PML/P53 cascade could mechanistically explain RA-facilitated chemotherapy response in patients with NPM-1c mutated acute myeloid leukemia.     

Inherited thrombophilia in childhood arterial stroke: data from Lebanon

Pediatric ischemic stroke still represents a burden, and more than half of the survivors will experience cognitive or motor disabilities. The objective of this study was to investigate the role of thrombophilia in a cohort of children with arterial ischemic stroke. The records of infants and children with clinically and radiologically confirmed stroke were reviewed. Patients with venous or perinatal stroke were not included. Thirty-three patients were diagnosed with arterial ischemic stroke. The male/female ratio was 1.75:1. The median age was 4 years. The most frequent clinical manifestations were hemiparesis (54.5%) and seizures (33.3%). Genetic thrombophilia testing was available on 24 patients. Nine of the 24 patients (37.5%) were heterozygous for factor V Leiden. None of the patients carried the factor II G20210A variant. Ten patients (41.7%) were heterozygous and 3 (12.5%) were homozygous for methylenetetrahydrofolate reductase (MTHFR) C677T variant. Fifteen patients (62.5%) had one or more genetic polymorphism. Factor V Leiden was significantly associated with arterial ischemic stroke (P < 0.001). Stroke recurred in 2 children with multiple risk factors and MTHFR C677T mutation. Factor V Leiden is one of the major genetic risk factors for pediatric arterial ischemic stroke in Lebanon. MTHFR C677T was prevalent among patients with recurrent stroke.     

Hyperforin induces apoptosis of chronic lymphocytic leukemia cells through upregulation of the BH3-only protein Noxa

We previously reported that hyperforin, a phloroglucinol purified from Hypericum perforatum, induces the mitochondrial pathway of caspase-dependent apoptosis in chronic lymphocytic leukemia (CLL) cells ex vivo, and that this effect is associated with upregulation of Noxa, a BH3-only protein of the Bcl-2 family. Here, we investigated the role of this upregulation in the pro-apoptotic activity of hyperforin in the cells of CLL patients and MEC-1 cell line. We found that the increase in Noxa expression is a time- and concentration-dependent effect of hyperforin occurring without change in Noxa mRNA levels. A post-translational regulation is suggested by the capacity of hyperforin to inhibit proteasome activity in CLL cells. Noxa silencing by siRNA reduces partially hyperforin-elicited apoptosis. Furthermore, treatment with hyperforin, which has no effect on the expression of the prosurvival protein Mcl-1, induces the interaction of Noxa with Mcl-1 and the dissociation of Mcl-1/Bak complex, revealing that upregulated Noxa displaces the proapoptotic protein Bak from Mcl-1. This effect is accompanied with Bak activation, known to allow the release of apoptogenic factors from mitochondria. Our data indicate that Noxa upregulation is one of the mechanisms by which hyperforin triggers CLL cell apoptosis. They also favor that new agents capable of mimicking specifically the BH3-only protein Noxa should be developed for apoptosis-based therapeutic strategy in CLL.     

Percutaneous thoracic aortic aneurysm repair through transcaval aortic access

Transcaval aortic access has been used for deployment of transcatheter aortic valves in patients in whom conventional arterial approaches are not feasible. This access can be vital in other situation when large bore access is needed. We described a case of 65‐year‐old man who had large thoracic descending aortic aneurysm with diffuse bilateral iliac disease precluding the arterial access required for the procedure. The patient underwent successful transcaval access with placement of 22‐Fr balloon expandable sheath followed with successful deployments of 32 mm × 32 mm × 150 mm Valiant stent graft (Medtronic, Minneapolis, MN). The aorto‐vena cava tract was closed successfully using 12 × 10 PDA occluder device with no residual flow at the end of the case, which was confirmed on repeated CT next day.     

Sex identification from fingertip features in Egyptian population

Identification of an individual plays a vital part of any medico-legal investigation. Fingerprints are considered to be one of the most reliable methods of identification. The present study was conducted on 752 healthy adult Egyptian subjects (380 males and 372 females) with age ranged from 20 to 30 years. Consents were obtained from all participants and their 10 digits were photographed to determine the sexual dimorphism by some fingertip features (ridge count, square area, finger breadth and finally ridge density) in Egyptians. Statistical analysis was made using a multivariate logistic regression variation analyses. Results showed that females tend to have statistically significant shorter (narrower) finger breadth (right: male > 9.54 ≥ female, left: male > 9.38 ≥ female), smaller square area (right: male ≥ 16.1 > female, left: male > 15.1 ≥ female), more ridge count (right: female > 21.0 ≥ male, left: female > 21.2 ≥ male), and higher ridge density (right: female >1.35 ≥ male, left: female > 1.5 ≥ male) when compared with males. The ridge density of the left hand was the most single accurate parameter in correct sex determination. The best classification accuracy of 82% was generated upon combining ridge count, square area and ridge density. It was concluded that fingertip features of Egyptians can be used by medico-legal experts for accurate sex identification.     

The value of 16-slice multidetector computed tomographic angiography in preoperative appraisal of vascular anatomy in potential living renal donors

Background

Comprehensive preoperative appraisal of potential living renal donors is the key for selecting a proper donor and a suitable kidney.

Objective

To prospectively assess the diagnostic value of 16-slice multidetector computed tomography (MDCT) in preoperative appraisal of vascular anatomy in potential living renal donors.

Materials and methods

Preoperative angiography using a 16-slice MDCT scanner was performed in 68 consecutive potential living renal donors. The MDCT angiography included unenhanced and contrast-enhanced multiphasic scans. The MDCT images were reviewed for the number and branching pattern of the renal arteries and for the number and presence of major or minor variants of the renal veins. The results were compared with the actual anatomy at the open donor nephrectomy as the diagnostic standard of reference.

Results

The sensitivity and the specificity of MDCT angiography for the detection of various anatomic variants of renal arteries as well as renal venous anomalies were 100%. The anatomic variants of renal arteries included accessory arteries (n = 7) and early arterial branching (n = 10). Whereas, the detected venous anomalies were of major category of the circumaortic left renal vein anomaly (n = 2). No minor renal venous anomaly was identified in any subject.

Conclusion

16-Slice MDCT angiography is highly accurate for preoperative assessment of diverse anomalies of the renal vascular anatomy in potential living renal donors; in consequence, it markedly affects the surgical planning.     

Multimodal CT assessment of acute ischemic stroke

Aim of the work

To evaluate the role of multimodal CT [non-enhanced CT (NECT), CT perfusion (CTP), and CT angiography (CTA)] in selection of acute ischemic stroke patients for reperfusion therapy.

Patients and methods

This prospective study included 35 patients with evidence of acute stroke in the middle cerebral artery territory of less than 12 h duration. Patients underwent multimodal CT including: (1) NECT (2) CTP (3) CTA. Qualitative and quantitative interpretation of the CTP was done to differentiate penumbra and infarction. CTA was evaluated for arterial occlusion or stenosis and the presence of collaterals.

Results

The areas of infarction showed a significant decrease in CBF (p = 0.03) and CBV values (p = 0.01) compared to the corresponding area in the contralateral normal hemisphere. The areas of penumbra showed a significant decrease in CBF (p = 0.04) and insignificant difference in CBV (p = 0.2) compared to the corresponding area in the contralateral normal hemisphere. Cutoff values of 2.0 for the CBV and MTT > 130% of the contralateral normal hemisphere allowed the best differentiation of infarction and penumbra.

Conclusion

Multimodal CT imaging fulfills all the requirements for selection of patients for reperfusion therapy and so helps in stroke treatment decisions.