Citations

PurposeTo examine the outcomes of patients with chemotherapy-sensitive mantle-cell lymphoma (MCL) following a first hematopoietic stem-cell transplantation (HCT), comparing outcomes with autologous (auto) versus reduced-intensity conditioning allogeneic (RIC allo) HCT and with transplantation applied at different times in the disease course.Patients and MethodsIn all, 519 patients who received transplantations between 1996 and 2007 and were reported to the Center for International Blood and Marrow Transplant Research were analyzed. The early transplantation cohort was defined as those patients in first partial or complete remission with no more than two lines of chemotherapy. The late transplantation cohort was defined as all the remaining patients.ResultsAuto-HCT and RIC allo-HCT resulted in similar overall survival from transplantation for both the early (at 5 years: 61% auto-HCT v 62% RIC allo-HCT; P = .951) and late cohorts (at 5 years: 44% auto-HCT v 31% RIC allo-HCT; P = .202). In both early and late transplantation cohorts, progression/relapse was lower and nonrelapse mortality was higher in the allo-HCT group. Overall survival and progression-free survival were highest in patients who underwent auto-HCT in first complete response. Multivariate analysis of survival from diagnosis identified a survival benefit favoring early HCT for both auto-HCT and RIC allo-HCT.ConclusionFor patients with chemotherapy-sensitive MCL, the optimal timing for HCT is early in the disease course. Outcomes are particularly favorable for patients undergoing auto-HCT in first complete remission. For those unable to achieve complete remission after two lines of chemotherapy or those with relapsed disease, either auto-HCT or RIC allo-HCT may be effective, although the chance for long-term remission and survival is lower.

SummaryThe MRI technique diffusion tensor imaging (DTI) is reviewed along with microstructural changes associated with prodromal Alzheimer's disease (AD) as a potential biomarker for clinical applications. The prodromal stage of AD is characterized by mild cognitive impairment (MCI), representing a transitional state between normal aging and AD. Microstructural abnormalities on DTI are promising in vivo biomarkers of gray and white matter changes associated with the progression of AD pathology. Elevated mean diffusivity and decreased fractional anisotropy are consistently found in prodromal AD, and even in cognitively normal elderly who progress to MCI. However, quality of parameter maps may be affected by artifacts of motion, susceptibility, and eddy current‐induced distortions. The DTI maps are typically analyzed by region‐of‐interest or voxel‐based analytic techniques such as tract‐based spatial statistics. DTI‐based index of diffusivity is complementary to macrostructural gray matter changes in the hippocampus in detecting prodromal AD. Breakdown of structural connectivity measured with DTI may impact cognitive performance during early AD. Furthermore, assessment of hippocampal connections may help in understanding the cerebral organization and remodeling associated with treatment response.

Key Points STAT5 is constitutively phosphorylated in malignant B cells obtained from patients with Waldenström's macroglobulinemia. Inhibition of STAT5 signaling significantly decreases IgM production and may be useful therapeutically for patients with high IgM levels.

Key PointsMGUS patients have significantly increased cortical bone porosity and reduced bone strength relative to matched controls.

Recent biochemical and cell-based studies identified G0/G1 switch gene 2 (G0S2) as an inhibitor of adipose triglyceride lipase (ATGL), a key mediator of intracellular triacylglycerol (TG) mobilization. Here, we show that upon fasting, G0S2 protein expression exhibits an increase in liver and a decrease in adipose tissue. Global knockout of G0S2 in mice enhanced adipose lipolysis and attenuated gain of body weight and adiposity. More strikingly, G0S2 knockout mice displayed a drastic decrease in hepatic TG content and were resistant to high-fat diet (HFD)-induced liver steatosis, both of which were reproduced by liver-specific G0S2 knockdown. Mice with hepatic G0S2 knockdown also showed increased ketogenesis, accelerated gluconeogenesis, and decelerated glycogenolysis. Conversely, overexpression of G0S2 inhibited fatty acid oxidation in mouse primary hepatocytes and caused sustained steatosis in liver accompanied by deficient TG clearance during the fasting-refeeding transition. In response to HFD, there was a profound increase in hepatic G0S2 expression in the fed state. Global and hepatic ablation of G0S2 both led to improved insulin sensitivity in HFD-fed mice. Our findings implicate a physiological role for G0S2 in the control of adaptive energy response to fasting and as a contributor to obesity-associated liver steatosis.

The mechanical response of tissues to external forces has gained considerable interest in medical diagnosis. One approach of imaging the tissue elastic properties is to apply an external force on the surface of the body. Another approach is to generate a localized force inside the tissue with the radiation force of ultrasound. In this paper, a noninvasive method for imaging the vibration mode of an object is investigated. The radiation force of ultrasound is used to scan the object at a resonant frequency of the object. The vibration of the object is measured by laser and the resulting acoustic emission from the object is measured by a hydrophone. Experimental studies are carried out on a mechanical heart valve and arterial phantoms. The mode images on the valve are made by the hydrophone measurement and confirmed by FEM simulations. Compared with conventional B-scan imaging on arterial phantoms, the mode imaging can show not only the interface of the artery and the gelatin, but also the vibration modes of the artery. The images taken on the phantom surface suggest that an image of an interior artery can be made by vibration measurements on the surface of the body.

Increased stiffness of arteries has recently gained acceptance as an independent risk factor for cardiovascular and many other diseases. Pulse wave velocity (PWV) is widely used for estimating the stiffness of an artery. However, PWV is an average indicator of artery stiffness between the two measuring points, and therefore does not identify local stiffness. In addition, the thickness of the artery is needed to calculate artery elastic modulus. We have discovered that there is a series of ring resonant frequency in arteries that can be used for estimating local arterial elastic modulus. These resonances can be excited by remote palpation with selectively placed ultrasonic radiation force. Experiments on ring resonance were carried out on an excised artery as well as a rubber tube. This family of resonances occurs at relatively low frequency, around 356 Hz for the artery. Estimation of the Young’s modulus is 135 kPa by the ring frequency 356 Hz without the requirement of the arterial thickness. The estimated modulus is very consistent with the other ring resonant frequency measurements. The theory of ring resonance is developed and verified with the rubber tube experiments.

We have proposed generating a bending wave in the arterial wall using ultrasound radiation force and measuring the wave velocity along the arterial wall [Zhang et al., IEEE Trans. Ultrason. Ferroelectr. Freq. Control 52, 642–652 (2005)]. Here, we report the results of in vivo studies on pigs. The pig was anesthetized, and a micromanometer tip catheter was inserted into the femoral artery to measure luminal pressure. A water bath was created on the animal’s groin to allow unimpeded access of the ultrasound beams to the femoral artery. The femoral artery was first located using a 13-MHz linear-array transducer. Then, a vibro-acoustography image was obtained to ensure precise positioning of the excitation force relative to the artery. The artery was excited by the force transducer and the resulting vibration of the arterial wall was measured by a sensing Doppler transceiver. Measured wave velocity was 3.1 m/s at 300 Hz. With this new method wave velocity over a distance of 5 mm, and therefore stiffness of arteries, can be measured locally and non-invasively. Measurement time is short in a few tens of milliseconds, which allows pressure dependence and pharmacological effect on the wall properties to be measured at different cardiac times.

Abstract Ovarian cancer is a clinically and molecularly heterogeneous disease. The driving forces behind this variability are unknown. Here, we report wide variation in the expression of the DNA cytosine deaminase APOBEC3B, with elevated expression in the majority of ovarian cancer cell lines (three SDs above the mean of normal ovarian surface epithelial cells) and high-grade primary ovarian cancers. APOBEC3B is active in the nucleus of several ovarian cancer cell lines and elicits a biochemical preference for deamination of cytosines in 5′-TC dinucleotides. Importantly, examination of whole-genome sequence from 16 ovarian cancers reveals that APOBEC3B expression correlates with total mutation load as well as elevated levels of transversion mutations. In particular, high APOBEC3B expression correlates with C-to-A and C-to-G transversion mutations within 5′-TC dinucleotide motifs in early-stage high-grade serous ovarian cancer genomes, suggesting that APOBEC3B-catalyzed genomic uracil lesions are further processed by downstream DNA "repair" enzymes including error-prone translesion polymerases. These data identify a potential role for APOBEC3B in serous ovarian cancer genomic instability. Cancer Res; 73(24); 7222–31. ©2013 AACR.