Upregulation of the oncoprotein SET determines poor clinical outcomes in hepatocellular carcinoma and shows therapeutic potential.

The SET protein is a potent inhibitor of protein phosphatase 2A (PP2A). Here, we report the oncogenic role of SET in hepatocarcinogenesis, clinical aggressiveness and anti-hepatocellular carcinoma (HCC) therapeutics. By analyzing samples obtained from 147 HCC patients, we found that SET overexpression was detected specifically in 30.6% HCC tumor samples, and was significantly associated with worse clinical features and high p-Akt expression in HCC tumors. Co-expression of SET and Akt predicted shorter post-operative recurrence-free survival in this cohort (P=0.045). Furthermore, SET was significantly associated with cell growth and hepatosphere formation. To elucidate the anti-HCC potential of targeting SET, we generated a novel SET antagonist, EMQA (N(4)-(3-ethynylphenyl)-6,7-dimethoxy-N(2)-(4-phenoxyphenyl) quinazoline-2,4-diamine). EMQA enhanced PP2A activity via disrupting SET-PP2Ac (catalytic domain of PP2A) binding in HCC cells, which restored PP2A-mediated p-Akt downregulation and promoted HCC cell death. In HCC cells or recombinant proteins expressing the N- and C- truncated forms of SET, only the C-terminal SET was required for EMQA targeting. Furthermore, combining sorafenib and EMQA showed good synergism in inhibiting HCC survival. Our findings suggested the oncogenic role of SET and the adverse prognostic value of SET overexpression in HCC. This alteration defines a subgroup of HCC patients who could benefit from SET antagonists, such as EMQA.

Improvements on a patient-specific dose estimation system in nuclear medicine examination.

The purpose of this paper is to develop a patient-specific dose estimation system in nuclear medicine examination. A dose deposition routine to store the deposited energy of the photons during their flights was embedded in the widely used SimSET Monte Carlo code and a user-friendly interface for reading PET and CT images was developed. Dose calculated on ORNL phantom was used to validate the accuracy of this system. The ratios of S value for (99m)Tc, (18)F and (131)I computed by this system to those obtained with OLINDA for various organs were ranged from 0.93 to 1.18, which were comparable to that obtained from MCNPX2.6 code (0.88-1.22). Our system developed provides opportunity for tumor dose estimation which cannot be known from the MIRD. The radiation dose can provide useful information in the amount of radioisotopes to be administered in radioimmunotherapy.

Characteristic length scale of electric transport properties of genomes.

A tight-binding model together with a statistical method are used to investigate the relation between the sequence-dependent electric transport properties and the sequences of protein-coding regions of complete genomes. A correlation parameter Omega is defined to analyze the relation. For some particular propagation length w max, the transport behaviors of the coding and noncoding sequences are very different and the correlation reaches its maximal value Omega max. w max and Omega max are characteristic values for each species. A possible reason for the difference between the features of transport properties in the coding and noncoding regions is the mechanism of DNA damage repair processes together with natural selection.

Enhancement of pairing correlation by t' in the two-dimensional extended t-J model.

We investigate the effects of the next-nearest-neighbor (t') and the third-nearest-neighbor (t") hopping terms on superconductivity correlation in the 2D hole-doped extended t-J model based on the variational Monte Carlo, mean-field calculation and exact diagonalization method. Despite the diversity of the methods employed, the results all point to a consistent conclusion: While the d-wave superconductivity correlation is slightly suppressed by t' and t" in underdoped regions, it is greatly enhanced in the optimal and overdoped regions. The optimal Tc is a result of the balance of these two opposite trends.

Geometric and statistical properties of the mean-field hydrophobic-polar model, the large-small model, and real protein sequences.

Lattice models, for their coarse-grained nature, are best suited for the study of the "designability problem," the phenomenon in which most of the about 16 000 proteins of known structure have their native conformations concentrated in a relatively small number of about 500 topological classes of conformations. Here it is shown that on a lattice the most highly designable simulated protein structures are those that have the largest number of surface-core switchbacks. A combination of physical, mathematical, and biological reasons that causes the phenomenon is given. By comparing the most foldable model peptides with protein sequences in the Protein Data Bank, it is shown that whereas different models may yield similar designabilities, predicted foldable peptides will simulate natural proteins only when the model incorporates the correct physics and biology, in this case if the main folding force arises from the differing hydrophobicity of the residues, but does not originate, say, from the steric hindrance effect caused by the differing sizes of the residues.

Mean-field HP model, designability and alpha-helices in protein structures.

Analysis of the geometric properties of a mean-field HP model on a square lattice for protein structure shows that structures with a large number of switchbacks between surface and core sites are chosen favorably by peptides as unique ground states. Global comparison of model (binary) peptide sequences with concatenated (binary) protein sequences listed in the Protein Data Bank and the Dali Domain Dictionary indicates that the highest correlation occurs between model peptides choosing the favored structures and those portions of protein sequences containing alpha helices.

Transorbital penetrating injury of the paranasal sinuses.

Penetrating injuries of the paranasal sinuses due to foreign bodies are rare, especially as a result of a traffic accident. Here we report a patient with a ballpoint pen lodged in his left eye following a traffic accident. The pen extended from the medial aspect of the left orbit, through the left ethmoid sinus and the nasal septum, to the right sphenoid sinus. We removed the pen uneventfully using endoscopic sinus surgery. There are no similar reports in the English literature and we therefore present this case because of its rarity.

Early results of the advanced coronary endarterectomy combined with CABG in the treatment of coronary artery occlusive disease.

BACKGROUND: Coronary Endarterectomy is a controversial but effective procedure for diffuse coronary artherosclerosis. Between April 1991 and January 1993, 57 patients in VGH-Taipei who had their diffuse coronary artery disease treated with combined endarterectomy and coronary artery bypass grafting (CABG). METHODS: One hundred and thirty-eight endarterectomies were performed, including 6 on the left main coronary artery system, 77 on the left anterior descending coronary artery system, 15 on left circumflex coronary artery system and 40 on the right coronary artery system (an average of 2.42 endarterectomies/patient). For graft conduit, great saphenous vein was used in 149 anastomoses, left internal mammary artery in 21, right internal mammary artery in 6 and right gastroepiploic artery in 4. The mean number of distal graft anastomoses was 3.15 per patient. Additional procedures were performed in 8 patients (14%): two patients required aortic valve replacement, one patient had mitral valve replacement, one had mitral annuloplasty, one had VSD repair and three had left ventricle aneurysm plications. The mean aortic clamp time was 108.8 +/- 30.5 minutes. RESULTS: The early mortality rate was 5.3%. The late mortality rate was 3.5%. During follow-up of mean 17.5 months, 98% of survivors were asymptomatic or in improved condition. CONCLUSIONS: Although endarterectomy is still a debatable procedure, it is valuable especially for the diffusely diseased arteries.

Early detection of the tip position and complication of the intra-aortic balloon pump catheter by perioperative transesophageal echocardiography.

BACKGROUND: Intraoperative verification of the precise balloon position of intra-aortic balloon pump(IABP) is necessary and important. We introduced transesophageal echocardiogram (TEE) as one of our routine intraoperative image monitor to accomplish this identification fluently, conveniently and also precisely. METHODS: 56 patients who needed the hemodynamic support when weaning the cardiopulmonary bypass were introduced to receive IABP and the balloon position was verified by TEE. To confirm the accurate location, the position of balloon tip was rechecked with postoperative portable chest x-ray. RESULTS: The balloon tip was attempted to locate in the proximal descending aorta, which was verified via TEE to be successful in 98.1% of patients by postoperative chest x-ray. Five (8.9%) patients failed to pass the balloon catheter at the first time due to high arterial resistance. One iatrogenic aortic dissection (1.8%) and one case in the wrong lumen (1.8%) were detected by TEE. No early death was contributed to IABP insertion. CONCLUSIONS: The application of TEE in the perioperative period helps not only detect IABP complication early but also verify of balloon catheter position quickly. It can replace the conventional role of fluorography.

Right gastroepiploic artery: an alternative arterial conduit for coronary artery bypass.

From September 1990 to February 1991, 15 cases of myocardial revascularization with the right gastroepiploic artery (RGEA) combined with arterial or venous grafts were performed at VGH-Taipei. All were males, ranging in age from 49 to 64 years (mean age 61.2 +/- 4.6 years). The mean number of distal anastmoses including vein grafts was 3.6 +/- 0.7 and the mean number of graft was 3.1 +/- 0.3 per patient. The mean aortic clamp time was 123.6 +/- 24.0 minutes and the mean cardiopulmonary bypass time was 176 +/- 35 minutes. There was one mortality (6.7%). The other 14 patients are alive without angina. Studied within 3 postoperative months, graft early patency was 100% (6/6) in GEA graft. GEA graft should be a third available arterial conduit for coronary artery bypass.

Pseudoaneurysm of the profundus femoris artery resulting from chronic injury of internal fixation screw.

We present an unusual case of pseudoaneurysm of profundus femoris artery which formed after injury from internal fixation screw for intertrochanteric fracture 8 years before. The main clinical manifestation was progressively enlarged pulsating mass and mild intermittent claudication. We resected the pseudoaneurysm after ligating the vessel proximal and distal to the pseudoaneurysm and cut off the excessive tip of the screw. After operation, the recovery was uneventful and no problem of the limb viability was noted.

Successful management of perforating injury of right atrium by chest tube.

Tube thoracostomy is an invasive procedure caring about 1% complication rate. Most confronted complications include diaphragm or lung laceration [1-3], damage to intrabdominal organ, intercostal artery bleeding and unilateral pulmonary edema. Here we present another rare complication of perforation of the right atrium which occurred in a patient with rheumatic heart disease (RHD) who had received mitral valve replacement (MVR) and tricuspid annuloplasty. Severe tricuspid regurgitation (TR) with huge right atrium was noted. Chest tube was inserted for pleural effusion drainage. The lesion was proved to be in the right atrium by echocardiography and computerized tomography three days later. The penetrated hole was repaired with bovine pericardium patch with minimal blood loss. This case attests to the extreme caution warranted when performing tube thoracostomy in patient with huge cardiomegaly.

Formulas for fetal weight estimation by ultrasound measurements based on neonatal specific gravities and volumes.

To improve the accuracy of fetal weight estimation by ultrasound measurement, especially in low birth weight infants, including those with intrauterine growth retardation, two new formulas were developed from a new point of view. The formulas were established by (1) actual measurements of the volumes of the neonatal head and trunk with limbs, (2) analysis of the relationship between the sizes of the parts of the fetal body measured by ultrasound examination before birth and the volumes of the parts of the neonatal body, and (3) calculation of the specific gravities of the parts of the neonatal body. The prospective study showed a high correlation between estimated weights and actual birth weights with a small range of error in infants weighing between 450 and 4800 gm.

Translation of encephalomyocarditis virus RNA in reticulocyte lysates: kinetic analysis of the formation of virion proteins and a protein required for processing.

In cell-free extracts derived from rabbit reticulocytes, encephalomyocarditis RNA can be translated completely, and the products can be processed extensively to give encephalomyocarditis virion proteins and several nonvirion proteins, including a genome-coded protein required for processing. The latter is probably a protease. Translation is very efficient. Under typical conditions, each EMC RNA is translated approximately eight times during a 3-h period. Kinetic analyses (time-course experiments, pulse-chase experiments, and pulse-stop experiments) have been used to determine the time of appearance of major products, and these times have been correlated with map positions. The gene for the putative protease is located near the middle of the genome downstream from the virion protein genes. Ribosomes can travel the length of encephalomycarditis RNA within 30 min, but there is a delay in their progress along the RNA at some point soon after they traverse the region coding for virion protein precursors. This delay results in the accumulation of precursors for a period of about 10 min before the putative protease is made and virion proteins (epsilon, alpha, and gamma) are released by proteolysis.

Cell-free synthesis and processing of the proteins of poliovirus.

Poliovirus RNA can be translated completely and accurately in rabbit reticulocyte lysates; the nascent poly-protein is processed to give primary products 1a, X, and 1b indistinguishable from those made in poliovirus-infected HeLa cells. The capsid precursor protein 1a is processed to form the capsid proteins VP0, VP1, and VP3, while the noncapsid precursor 1b is processed to form protein 2.