Imaging apolipoprotein AI in vivo

Coronary disease risk increases inversely with high-density lipoprotein (HDL) level. The measurement of the biodistribution and clearance of HDL in vivo, however, has posed a technical challenge. This study presents an approach to the development of a lipoprotein MRI agent by linking gadolinium methanethiosulfonate (Gd[MTS-ADO3A]) to a selective cysteine mutation in position 55 of apo AI, the major protein of HDL. The contrast agent targets both liver and kidney, the sites of HDL catabolism, whereas the standard MRI contrast agent, gadolinium-diethylenetriaminepentaacetic acid-bismethylamide (GdDTPA-BMA, gadodiamide), enhances only the kidney image. Using a modified apolipoprotein AI to create an HDL contrast agent provides a new approach to investigate HDL biodistribution, metabolism and regulation in vivo.     

Habitual cocaine use is associated with high defibrillation threshold during ICD implantation

Background: Habitual cocaine use can lead to dilated cardiomyopathy (DCM) and sudden cardiac death. Based on prior clinical observations, we hypothesized that prior habitual cocaine use is a strong predictor of high defibrillation threshold (DFT) during implantable cardioverter-defibrillator (ICD) implant.
Methods: We reviewed the medical records of 130 consecutive patients undergoing initial ICD implantation or revision at Parkland Hospital and the Dallas VA Hospital, Dallas, TX, from January 2002 to November 2005. Patient characteristics and DFT data were collected retrospectively.
Results: The study group includes 11 patients (8.46%) who were identified as having a history of prior habitual cocaine use as demonstrated by history and urine toxicology; the rest (119 patients) form the control group. Cocaine-using patients tended to be younger (48.2 ± 10 vs 60.1 ± 12.3 years; P = 0.0026), were less likely to have coronary disease (36.3% vs 72.2%; P = 0.032), and had less comorbidity. The average DFT was 27.9 ± 7.8 J for all cocaine-using patients and 14.5 ± 4.1 J for noncocaine-using patients (P = 0.00018). In the cocaine-using group, three out of 11 patients required a subcutaneous array compared to none in the control group.
Conclusions: Our results suggest that patients with a history of habitual cocaine use may be at increased risk to have a high DFT during ICD implantation. This is the first study to demonstrate such association. ICD implantation in patients with this history should be planned with these findings in mind, as larger output generators or subcutaneous arrays might be required.     

Bifid direct aortic arch origin of left vertebral artery: a unique vascular variant

The present report describes an unusual case of a duplicated origin of the left vertebral artery from the aorta discovered incidentally in a young patient. Computed tomographic angiography followed by conventional angiography demonstrated this anomaly. Angiographic findings and vertebral artery embryogenesis and anomalies are discussed.     

Bone marrow renin-angiotensin system expression in polycythemia vera and essential thrombocythemia depends on JAK2 mutational status

Recent observations raise possibility for constitutively active, mutated JAK2 to modulate expression of RAS genes in CMPD. We analyzed the expression of AGT, renin, AT2R1 and ACE genes in normal and bone marrows of PV and ET patients with the respect to the presence of V617F JAK2 mutation. PV and ET had different expression patterns of major RAS components compared to normal BM which was primarily associated with the JAK2V617F mutation and less with PV or ET disease phenotype. However, AT2R1 was exclusively markedly upregulated only in PV, while ET showed moderate expression irrespective of the JAK2 mutational status.     

Fine mapping and candidate gene analyses of pulmonary adenoma resistance 1, a major genetic determinant of mouse lung adenoma resistance

Pulmonary adenoma resistance 1 (Par1) is a major genetic determinant of mouse lung adenoma resistance. Although Par1 was previously mapped to mouse chromosome 11 by conventional linkage analyses, its candidate region was broad and undefined. In our present study, we generated Par1 congenic mice using two mouse strains A/J (Par1/-) and Mus spretus (Par1/+). Analyzing these congenic mice enabled us to fine map the Par1 quantitative trait loci (QTL) into a 2.0-cM (2.2 Mb) chromosomal region between genetic marker D11Mit70 and the gene Hoxb9. We then conducted systematic candidate gene screening through nucleotide polymorphism and expression analyses. Genes showing differential lung tissue expression or carrying nonsynonymous single nucleotide polymorphisms were identified and discussed. In particular, we evaluated tumor suppressor gene Tob1 for its Par1 candidacy. Our findings have narrowed the Par1 QTL region and will greatly facilitate the identification of the major genetic determinant of mouse lung adenoma resistance.