Induction of PUMA-α and down-regulation of PUMA-β expression is associated with benzo(a)pyrene-induced apoptosis in MCF-7 cells

Benzo(a)pyrene (BP) forms benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE)-DNA adducts in human breast adenocarcinoma MCF-7 cells, leading to p53 protein induction and phosphorylation. Although BP-induced apoptosis in rodent cells is known, it is still unclear in human cells. Here we have analyzed the effects of BP on p53 related apoptotic proteins, cell cycle and cell death in MCF-7 cells. PUMA-protein (p53 up-regulated modulator of apoptosis) levels were changed after BP exposure so that PUMA-α protein was statistically significantly increased whereas PUMA-β protein was statistically significantly decreased. PUMA-protein levels were also investigated in ZR-75-1 cells, where PUMA-α protein was statistically significantly increased. Cytochrome c, which is released from mitochondria during apoptosis to form the apoptosome, was increased in cytoplasmic fraction after BP exposure in MCF-7 cells. Increased apoptosis was also seen after 48 and 72 h BP exposure (2.5 and 5 μM). In addition, BP decreased dose dependently cell viability (2.5 and 5 μM) and increased ROS formation (1 and 10 μM). Our results suggest that PUMA-α protein is involved in BP-induced cell death most likely through a p53 dependent apoptotic pathway.     

The red cell LW blood group protein is an intercellular adhesion molecule which binds to CD11/CD18 leukocyte integrins

Leukocyte adhesion involves the leukocyte-specific integrins CD11a/CD18, CD11b/CD18 and CD11c/CD18, which bind to intercellular adhesion molecules (ICAM). Three ICAM have been described, and are expressed on leukocytes and various other cells, but are absent from red cells. Here, we show that the red cell Landsteiner-Wiener (LW) blood group glycoprotein is an ICAM which binds to the leukocyte-specific integrins. This finding has important implications in red cell physiology.     

Clustering of Serratia marcescens infections in a neonatal intensive care unit.

OBJECTIVES: To study clusters of infections caused by Serratia marcescens in a neonatal intensive care unit (NICU) and to determine risk factors for S. marcescens infection or colonization. DESIGN: Genotyping of S. marcescens isolates was performed by pulsed-field gel electrophoresis (PFGE). A retrospective case-control study was conducted. SETTING: A tertiary-care pediatric hospital with a 16-bed NICU. PATIENTS: All neonates with at least one culture positive for S. marcescens in the NICU during December 1999 to July 2002. Case-patients (n = 11) treated in the NICU during December 1999 to February 2000 were included in the case-control study. Neonates treated in the NICU for at least 72 hours during the same period with cultures negative for S. marcescens were used as control-patients (n = 27). RESULTS: S. marcescens was cultured from 19 neonates; 9 were infected and 10 were colonized. PFGE analysis identified three epidemic strains; each cluster consisted of identical isolates, except one isolate in the first cluster that was different. The risk factors identified were low birth weight, prematurity, prolonged respiratory therapy, prolonged use of antibiotics, and maternal infection prior to delivery. Overcrowding and understaffing were recorded simultaneously with the clusters. CONCLUSIONS: PFGE analysis showed three independent clusters. Several factors contributed to spread of the epidemic strains: (1) there were many severely premature and susceptible neonates, (2) the NICU was overcrowded during the clusters, and (3) transmission was likely to occur via the hands of staff. Cohorting and improvement of routine infection control measures led to the cessation of each cluster.     

Up-regulation of Bcl-2 during adipogenesis mediates apoptosis resistance in human adipocytes

Targeting apoptotic pathways in adipocytes has been suggested as a pharmacological approach to treat obesity. However, adipocyte apoptosis was identified as a cause for macrophage infiltration into adipose tissue. Previous studies suggest that mature adipocytes are less sensitive to apoptotic stimuli as compared to preadipocytes. Here, we aimed to identify proteins mediating apoptosis resistance in adipocytes.     

Improved detection of localized prostate cancer using co-registered MRI and (11)C-acetate PET/CT

Objectives

We aimed to study the ability of contrast enhanced MRI at 1.5 T and ¹¹C-acetate PET/CT, both individually and using fused data, to detect localized prostate cancer.

Methods

Thirty-six men with untreated prostate cancer and negative for metastatic disease on pelvic CT and bone scan were prospectively enrolled. A pelvic ¹¹C-acetate PET/CT scan was performed in all patients, and a contrast enhanced MRI scan in 33 patients (6 examinations using both endorectal coil and surface coils, and 27 examinations using surface coils only). After the imaging studies 10 patients underwent prostatectomy and 26 were treated by image guided external beam radiation treatment. Image fusion of co-registered PET and MRI data was performed based on anatomical landmarks visible on CT and MRI using an advanced in-house developed software package. PET/CT, MRI and fused PET/MRI data were evaluated visually and compared with biopsy findings on a lobar level, while a sextant approach was used for patients undergoing prostatectomy.

Results

When using biopsy samples as method of reference, the sensitivity, specificity and accuracy for visual detection of prostate cancer on a lobar level by contrast enhanced MRI was 85%, 37%, 73% and that of ¹¹C-acetate PET/CT 88%, 41%, 74%, respectively. Fusion of PET with MRI data increased sensitivity, specificity and accuracy to 90%, 72% and 85%, respectively.

Conclusions

Fusion of sequentially obtained PET/CT and MRI data for the localization of prostate cancer is feasible and superior to the performance of each individual modality alone.     

Effects of High‐Impact Training on Bone and Articular Cartilage: 12‐Month Randomized Controlled Quantitative MRI Study

Osteoarthritis and osteoporosis often coexist in postmenopausal women. The simultaneous effect of bone‐favorable high‐impact training on these diseases is not well understood and is a topic of controversy. We evaluated the effects of high‐impact exercise on bone mineral content (BMC) and the estimated biochemical composition of knee cartilage in postmenopausal women with mild knee osteoarthritis. Eighty women aged 50 to 66 years with mild knee osteoarthritis were randomly assigned to undergo supervised progressive exercise three times a week for 12 months (n = 40) or to a nonintervention control group (n = 40). BMC of the femoral neck, trochanter, and lumbar spine was measured by dual‐energy X‐ray absorptiometry (DXA). The biochemical composition of cartilage was estimated using delayed gadolinium‐enhanced magnetic resonance imaging (MRI) cartilage (dGEMRIC), sensitive to cartilage glycosaminoglycan content, and transverse relaxation time (T2) mapping that is sensitive to the properties of the collagen network. In addition, we evaluated clinically important symptoms and physical performance–related risk factors of falling: cardiorespiratory fitness, dynamic balance, maximal isometric knee extension and flexion forces, and leg power. Thirty‐six trainees and 40 controls completed the study. The mean gain in femoral neck BMC in the exercise group was 0.6% (95% CI, –0.2% to 1.4%) and the mean loss in the control group was –1.2% (95% CI, –2.1% to –0.4%). The change in baseline, body mass, and adjusted body mass change in BMC between the groups was significant (p = 0.005), whereas no changes occurred in the biochemical composition of the cartilage, as investigated by MRI. Balance, muscle force, and cardiorespiratory fitness improved significantly more (3% to 11%) in the exercise group than in the control group. Progressively implemented high‐impact training, which increased bone mass, did not affect the biochemical composition of cartilage and may be feasible in the prevention of osteoporosis and physical performance–related risk factors of falling in postmenopausal women. © 2014 American Society for Bone and Mineral Research.     

In vivo transport of Gd-DTPA(2-) in human knee cartilage assessed by depth-wise dGEMRIC analysis

Purpose:

To investigate the transport of Gd‐DTPA^2? in different layers of femoral knee cartilage in vivo.

Materials and Methods:

T₁ measurements (1.5 Tesla) were performed in femoral knee cartilage of 23 healthy volunteers. The weight‐bearing central cartilage was analyzed before contrast and at eight time points after an intravenous injection of Gd‐DTPA^2?: 12–60 min (4 volunteers) and 1–4 h (19 volunteers). Three regions of interest were segmented manually: deep, middle, and superficial.

Results:

Before contrast injection, a depth‐wise variation of T₁ was observed with 50% higher values in the superficial region compared with the deep region. In the deep region, the uptake of Gd‐DTPA^2? was not detected until 36 min and the concentration increased until 240 min, whereas in the superficial region, the uptake was seen already at 12 min and the concentration decreased after 180 min (P < 0.01). There was a difference between medial and lateral compartment regarding bulk, but not superficial Gd‐DTPA^2? concentration. The bulk gadolinium concentration was negatively related to the cartilage thickness (r = ?0.68; P < 0.01).

Conclusion:

The depth‐wise and thickness dependent variations in Gd‐DTPA² transport influence the interpretation of bulk dGEMRIC analysis in vivo. In thick cartilage, incomplete penetration of Gd‐DTPA² will yield a falsely too long T₁. J. Magn. Reson. Imaging 2011;. © 2011 Wiley Periodicals, Inc.