SPECT/CT-plethysmography – non-invasive quantitation of bone and soft tissue blood flow

Preserved blood flow to bone and soft tissue is essential for their normal function. To date only numerous methods are suitable for direct bone blood flow (BBF) measurement. Here, we introduce a novel quantitative method for bone and soft tissue blood flow (BBF and SBF, respectively) measurement. It involves a combination of SPECT/CT imaging for blood pool localization in a specific region of interest ("soft" and "hard" tissues composing a limb) with veno-occlusive plethysmography. Using it, we measured BBF and SBF in the four limbs of 10 healthy subjects. At steady state blood flow measurements in the four limbs were similar, ranging between 5.5 – 6.5 and 1.87–2.48 ml per 100 ml of tissue per minute for BBF and SBF, respectively. Our results are comparable to those in the literature. We concluded that SPECT/CT-plethysmography appears to be a readily available and easy to use method to measure BBF and SBF, and can be added to the armamentarium of methods for BBF measurements

Monosomal Karyotype at the Time of Diagnosis or Transplantation Predicts Outcomes of Allogeneic Hematopoietic Cell Transplantation in Myelodysplastic Syndrome

AbstractVarious cytogenetic risk scoring systems may determine prognosis for patients with myelodysplastic syndromes (MDS). We evaluated 4 different risk scoring systems in predicting outcome after allogeneic hematopoietic cell transplantation (alloHCT). We classified 124 patients with MDS using the International Prognostic Scoring System (IPSS), the revised International Prognostic Scoring System (R-IPSS), Armand's transplantation-specific cytogenetic grouping, and monosomal karyotype (MK) both at the time of diagnosis and at alloHCT. After adjusting for other important factors, MK at diagnosis (compared with no MK) was associated with poor 3-year disease-free survival (DFS) (27% [95% confidence interval, 12% to 42%] versus 39% [95% confidence interval, 28% to 50%], P = .02) and overall survival (OS) (29% [95% confidence interval, 14% to 44%] versus 47% [95% confidence interval, 36% to 59%], P = .02). OS but not DFS was affected by MK at alloHCT. MK frequency was uncommon in low-score R-IPPS and IPSS. Although IPSS and R-IPSS discriminated good/very good groups from poor/very poor groups, patients with intermediate-risk scores had the worst outcomes and, therefore, these scores did not show a progressive linear discriminating trend. Cytogenetic risk score change between diagnosis and alloHCT was uncommon and did not influence OS. MK cytogenetics in MDS are associated with poor survival, suggesting the need for alternative or intensified approaches to their treatment

p16(Ink4a) Interferes with Abelson Virus Transformation by Enhancing Apoptosis

Pre-B-cell transformation by Abelson virus (Ab-MLV) is a multistep process in which primary transformants are stimulated to proliferate but subsequently undergo crisis, a period of erratic growth marked by high levels of apoptosis. Inactivation of the p53 tumor suppressor pathway is an important step in this process and can be accomplished by mutation of p53 or down-modulation of p19(Arf), a p53 regulatory protein. Consistent with these data, pre-B cells from either p53 or Ink4a/Arf null mice bypass crisis. However, the Ink4a/Arf locus encodes both p19(Arf) and a second tumor suppressor, p16(Ink4a), that blocks cell cycle progression by inhibiting Cdk4/6. To determine if p16(Ink4a) plays a role in Ab-MLV transformation, primary transformants derived from Arf(−/−) and p16(Ink4a(−/−)) mice were compared. A fraction of those derived from Arf(−/−) animals underwent crisis, and even though all p16(Ink4a(−/−)) primary transformants experienced crisis, these cells became established more readily than cells derived from +/+ mice. Analyses of Ink4a/Arf(−/−) cells infected with a virus that expresses both v-Abl and p16(Ink4a) revealed that p16(Ink4a) expression does not alter cell cycle profiles but does increase the level of apoptosis in primary transformants. These results indicate that both products of the Ink4a/Arf locus influence Ab-MLV transformation and reveal that in addition to its well-recognized effects on the cell cycle, p16(Ink4a) can suppress transformation by inducing apoptosis