The p53-targeting human phosphatase hCdc14A interacts with the Cdk1/cyclin B complex and is differentially expressed in human cancers

Background  

The evolutionary conserved cyclin-dependent kinase phosphatase hCdc14A has been shown to play potential roles in the regulation of mitotic exit and in the centrosome duplication cycle. We have recently shown that hCdc14A also can interact with the tumor suppressor p53 both in vitro and in vivo and specifically dephosphorylates the ser315 site of p53 in vitro. In this study we developed antibodies against hCdc14A to investigate the expression and regulation of hCdc14A in human tissues and cancer cells.     

The 3' conserved segment of integrons contains a gene associated with multidrug resistance to antiseptics and disinfectants.

Nucleotide sequence analysis of ORF1 from the integron on the broad-host-range plasmid R751 revealed that the first 94 of 110 codons of ORF1 from R751 are identical to ORF4, an open reading frame from the 3' conserved segment of other integrons found in gram-negative bacteria, after which point they diverged completely. The predicted products of both ORF1 and ORF4 share homology with the multidrug exporter QacC. Phenotypic analysis revealed that ORF1 specifies a resistance profile to antiseptics and disinfectants almost identical to that of qacC, whereas ORF4 specifies much lower levels of resistance to these compounds. ORF4, whose product lacks the C-terminal 16 amino acids of the ORF1 protein, may have evolved by the interruption of ORF1 from the insertion of a DNA segment carrying a sulI sulfonamide resistance determinant. Hence, ORF1 was designated qacE, and its partially functional deletion derivative, ORF4, was designated qacE delta 1. Fluorimetric experiments indicated that the mechanism of resistance mediated by QacE, the protein specified by qacE, is active export energized by proton motive force. Amino acid sequence comparisons revealed that QacE is related to a family of small multidrug export proteins with four transmembrane segments.     

Selective heparanase localization in malignant melanoma

Heparanase (HPSE-1) is an endo-beta-D-glucuronidase that cleaves heparan sulfate proteoglycans (HSPG), and its expression has been associated with increased growth, metastasis, and angiogenesis of tumors. Since metastatic melanoma cells express high levels of HSPG and because melanoma tumors grow highly vascularized, we analyzed melanoma tissue specimens for HPSE-1 expression from experimental animals as well as from patients. Laser capture microdissection microscopy was used to extract melanoma cell populations and to isolate them from adjacent tissue. In experimental animals, a 29-fold upregulation of HPSE-1 expression was detected by real-time PCR in metastatic melanoma compared to normal lung tissue. Additionally, immunohistochemistry (IHC) revealed selective HPSE-1 staining in human metastatic melanoma when compared to primary melanoma tumors from the same patient. IHC also showed a marked staining for the enzyme around blood vessels and in vascularized regions. Our results provide evidence demonstrating that HPSE-1 likely plays important roles in regulating the in vivo growth and progression of melanoma. These results further emphasize the importance that therapies designed to block HPSE-1 activity may aid in controlling this type of cancer.     

Imbalanced chordal force distribution causes acute ischemic mitral regurgitation: mechanistic insights from chordae tendineae force measurements in pigs

BACKGROUND: Ischemic mitral regurgitation is caused by an imbalance of the entire mitral-ventricular complex. This interaction is mediated through the chordae tendineae force distribution, which may perturb several elements of the mitral valve apparatus. Our objective was to investigate the association between the mitral valvular 3-dimensional geometric perturbations and chordae tendineae force redistribution in a porcine model of acute ischemic mitral regurgitation. METHODS: In 9 pigs, acute ischemic mitral regurgitation was induced by repeated microembolization of the left circumflex coronary artery. Mitral leaflet coaptation geometry was determined by 2-dimensional echocardiography and reconstructed 3-dimensionally. Leading edge chordal forces were measured by dedicated miniature force transducers at control and during ischemic mitral regurgitation. RESULTS: During acute ischemic mitral regurgitation, there was a decreased tension of the primary chorda from the ischemic posterior left ventricular wall to the anterior leaflet (0.295 +/- 0.063 N vs 0.336 +/- 0.071 N [control]; P < .05). The tension of the chorda from the nonischemic anterior left ventricular wall to the anterior leaflet increased (0.375 +/- 0.066 N vs 0.333 +/- 0.071 N [control]; P < .05). In accordance, relative leaflet prolapse was observed at the ischemic commissural side, whereas there was an increase in the leaflet surface area at the nonischemic commissural side, indicating localized leaflet tethering. CONCLUSIONS: Acute ischemic mitral regurgitation due to posterior left ventricular wall ischemia was associated with focal chordal and leaflet tethering at the nonischemic commissural portion of the mitral valve and a paradoxical decrease of the chordal forces and relative prolapse at the ischemic site of the anterior mitral valve leaflet.     

Secondary endoscopic forehead lift in patients with previous coronal brow lifts

INTRODUCTION: The development of endoscopic surgical techniques has allowed an evolution from the standard coronal forehead lift to a minimally invasive one. Endoscopy avoids many of the undesirable results of the coronal approach while it remains very efficacious. The purpose of this study is to evaluate the effectiveness and safety of endoscopic forehead lift in patients who have previously undergone coronal brow lift. MATERIALS AND METHODS: A retrospective review was performed on the medical records of 726 consecutive patients who had undergone endoscopic forehead lift between 1994 and 2004. Sixty-three patients were identified who had undergone prior coronal incision brow lift and then required subsequent elevation of the forehead using endoscopy. Those who had persistent low eyebrows and forehead wrinkles underwent the standard minimal incision endoscopic approach. Patients with severe brow ptosis and excessive height of the forehead underwent a biplanar endoscopic forehead lift. RESULTS: Of the 63 endoscopic forehead lifts performed, 49 used the minimal access technique, while 14 employed the biplanar approach. The subject population consisted of 58 female and 5 male patients whose average age was 57 years (range of 42 to 80 years). Eighty-seven percent of these brow lifts also had concomitant rhytidectomy, and 4% had blepharoplasty. Average follow-up was 21 months (range 1 to 7 years). Following the endoscopic procedure, none of the patients had frontal nerve injury, alopecia, or persistent glabellar wrinkle lines. Complications included 1 forehead dysesthesia, 1 forehead irregularity, 1 eyebrow malposition, 1 persistent horizontal forehead wrinkling, and 2 hematomas. Operative management was not required for any of these complications. CONCLUSION: The secondary endoscopic forehead lift is effective in rejuvenating the upper face in the patient who has had a previous coronal forehead lift. It elevates the eyebrows and reduces both transverse and vertical wrinkles while avoiding further displacement of the hairline. The low rate of complications is comparable to that of primary endoscopic forehead lifts. Finally, serial follow-up indicates that the results are effective at correcting brow ptosis and are long lasting.     

A kinetic model for dynamic [18F]-Fmiso PET data to analyse tumour hypoxia

A method is presented to identify and quantify hypoxia in human head-and-neck tumours based on dynamic [18F]-Fmiso PET patient data, using a model for the tracer transport. A compartmental model was developed, inspired by recent immunohistochemical investigations with the tracer pimonidazole. In order to take the trapping of the tracer and the diffusion in interstitial space into account, the kinetic model consists of two compartments and a specific input function. This voxel-based data analysis allows us to decompose the time-activity curves (TACs) into their perfusion, diffusion and hypoxia-induced retention components. This characterization ranges from well perfused tumours over diffusion limited hypoxia to strong hypoxia and necrosis. The overall shape of the TAC and the model parameters may point at the structural architecture of the tissue sample. The model addresses the two main problems associated with hypoxia imaging with PET. Firstly, the hypoxic areas are spatially separated from well perfused vessels, causing long diffusion times of the tracer. Secondly, tracer uptake occurs only in viable hypoxic cells, which constitute only a small subpopulation in the presence of necrosis. The resulting parameters such as the concentration of hypoxic cells and the perfusion are displayed in parameter plots ('hypoxia map'). Quantification of hypoxia performed with the presented kinetic model is more reliable than a criterion based on static standardized uptake values (SUV) at an early timepoint, because severely hypoxic/necrotic tissues show low uptake and are thus overlooked by SUV threshold identification. The derived independent measures for perfusion and hypoxia may provide a basis for individually adapted treatment planning.     

Design and implementation of a high frequency electrical impedance tomography system

Electrical impedance tomography is an imaging modality being investigated for use in detection of breast cancer. Use of higher frequencies than have typically been employed may benefit the detection processes. In this current work we discuss the design and initial implementation of a system having a bandwidth of 10 MHz. Previous investigations into high frequency designs have proven more difficult than anticipated and shown that careful selection of systems architecture is critical to achieving broadband performance above 1 MHz. The design for this new system is based on a digital signal processor (DSP) which is used for control, signal generation and signal processing. Signal generation and detection, software design and preliminary system specifications are discussed.