Prenatal hypoxia affects scaling of blood pressure and arterial wall mechanics in the common snapping turtle, Chelydra serpentina

In reptiles, exposure to hypoxia during embryonic development affects several cardiovascular parameters. These modifications may impose different mechanical stress to the arterial system, and we speculated that the arterial wall of major outflow vessels would be modified accordingly. Since non-crocodilian reptiles possess a partially divided ventricle, ensuing similar systemic and pulmonary systolic pressures, we investigated how morphological and mechanical properties of segments from the left aortic arch (LAo) and the proximal and distal segments of the left pulmonary artery (LPAp and LPAd, respectively) change as body mass (M) increases. Eggs from common snapping turtles, Chelydra serpentina, were incubated under normoxia (21% O; N21) or hypoxia (10% O; H10), hatched and maintained in normoxia thereafter. Turtles (0.11-6.85 kg) were cannulated to measure arterial pressures, and an injection of adrenaline was used to increase pressures. Portions of the LAo, LPAp and LPAd were fixed under physiological hydrostatic pressures for histology and mechanical assessment. Arterial pressures increased with M for N21 but not for H10. Although mechanical and functional characteristics from the LPAp and LPAd were similar between N21 and H10, wall thickness from LAo did not change with M in the H10 group, thus wall stress increased in larger turtles. This indicates that larger H10 turtles probably experience an elevated probability of arterial wall rupture without concomitant changes in the cardiovascular system to prevent it. Finally, collagen content of the LPAp and LAo was smaller than in LPAd, suggesting a more distensible arterial wall could attenuate higher pressures from larger turtles

First Case Report of Catheter-Related Bacteremia Due to “Mycobacterium lacticola”

This is the first report of infection caused by “Mycobacterium lacticola,” a rapidly growing, scotochromogenic mycobacterium that was isolated from the blood of an immunosuppressed child. The organism was identified by sequence analysis of >1,400 bp of the 16S rRNA gene. The clinical relevance of this isolate, coupled with its unique 16S rRNA gene sequence, should prompt further investigation to establish this organism as a valid mycobacterial species

Comparison of diabetic nephropathy between male and female eNOS\u3csup\u3e−/−\u3c/sup\u3e \u3ci\u3edb\u3c/i\u3e/\u3ci\u3edb\u3c/i\u3e mice

Sex is an important biological variable that impacts diverse physiological and pathological processes, including the progression of diabetic nephropathy. Diabetic nephropathy is one of the most common complications of diabetes mellitus and is the leading cause of end-stage renal disease. The endothelial nitric oxide synthase-deficient (eNOS−/−) db/ db mouse is an appropriate and valuable model to study mechanisms in the development of diabetic nephropathy because of the similarities of the features of diabetic kidney disease in this model to those in humans. The aim of the present study was to determine whether there was a sex difference in renal injury in eNOS−/− db/ db mice. Both male and female eNOS−/− db/ db mice showed hyperglycemia, obesity, and renal hypertrophy. However, there was no significant difference in those variables between male and female mice. Furthermore, both male and female diabetic mice showed progressive albuminuria and significantly greater levels of serum creatinine and blood urea nitrogen compared with the same sex of wild-type mice (nondiabetic controls). Although all three variables in female eNOS−/− db/ db mice had a tendency to be greater than those in male eNOS−/− db/ db mice, those sex differences were not statistically significant. Moreover, both male and female eNOS−/− db/ db mice showed significant mesangial expansion, higher glomerular injury scores, profound renal fibrosis, and substantial accumulation of fibronectin and collagen type IV proteins. However, sex differences in those structural changes were not observed. Similarly, survival rates of male and female eNOS−/− db/ db mice were comparable. Taken together, the results from the present study suggest no sex difference in renal structural and functional damage in eNOS−/− db/ db mice

Myc Drives Chromosomal Gain in Acute Myeloid Leukemia

Acute Myeloid Leukemia (AML) is a disease characterized by diverse genetic pathogenesis, including both balanced and unbalanced chromosomal aberrations. Much is known regarding the pathogenic effects of balanced rearrangements in AML, whereas our understanding of how unbalanced aberrations contribute to leukemia is more limited. The balanced t(15;17) chromosomal rearrangement is a nearly constant feature of acute promyeloctyic leukemia (APL), a subtype AML. The translocation fuses the promyelocytic leukemia gene (PML) to the retinoic acid receptor gene (RARA). Trisomy 8 is the most common secondary karyotypic lesion observed in APL, and it has been speculated but not proven that the MYC gene contributes to this chromosomal gain. We previously reported that mouse chromosome 15, which contains the mouse Myc gene in a region syntenic to human chromosome 8q24, is commonly gained in the MRP8 PML-RARA mouse model of APL. We now report our work to assess the hypothesis that increased MYC cooperates with PML-RAR to accelerate disease and that gain of MYC/Myc drives +8 in humans and +15 in mice. Expressing MYC with a retroviral vector in PML-RARA bone marrow led to the rapid development of APL-like leukemias (3 months vs. 8.5 months with PML-RARA alone). Chromosome 15 was not gained in any of the leukemias, although 70% had other clonal karyotypic abnormalities. This finding suggests that when MYC is overexpressed, there is no selective pressure to gain chromosome 15, supporting our hypothesis that Myc is driving this gain. We also generated PML-RARA mice haploinsufficient for Myc to examine the effect of decreasing MYC levels. The median latency among leukemic animals was 258 days for mice with PML-RARA and two wild-type Myc alleles, whereas the latency was increased to 339 days for PML-RARA Myc haploinsufficient mice. Hence, lower MYC expression served as a check on leukemic transformation. Furthermore, the majority of the leukemias that arose in Myc haploinsufficient mice had gained wild-type Myc. These data demonstrate a selective pressure for Myc gain. Additional experiments showed that as MYC expression increases there is a decrease in both latency and genetic complexity of leukemias that arise, that MYC and PML-RAR interact to disrupt myeloid differentiation in vivo and that although MYC cooperates with PML-RAR to cause leukemia, additional events are required for completing transformation even at high levels of MYC. Altogether our studies of increased and decreased MYC expression in PML-RARA mice show a strong correlation between MYC dosage and leukemic transformation. Our results suggest that agents that target MYC might be useful for the treatment of AML