The anticancer gene ORCTL3 targets stearoyl-CoA desaturase-1 for tumour-specific apoptosis.

ORCTL3 is a member of a group of genes, the so-called anticancer genes, that cause tumour-specific cell death. We show that this activity is triggered in isogenic renal cells upon their transformation independently of the cells' proliferation status. For its cell death effect ORCTL3 targets the enzyme stearoyl-CoA desaturase-1 (SCD1) in fatty acid metabolism. This is caused by transmembrane domains 3 and 4, which are more efficacious in vitro than a low molecular weight drug against SCD1, and critically depend on their expression level. SCD1 is found upregulated upon renal cell transformation indicating that its activity, while not impacting proliferation, represents a critical bottleneck for tumourigenesis. An adenovirus expressing ORCTL3 leads to growth inhibition of renal tumours in vivo and to substantial destruction of patients' kidney tumour cells ex vivo. Our results indicate fatty acid metabolism as a target for tumour-specific apoptosis in renal tumours and suggest ORCTL3 as a means to accomplish this.

Estimated long-term dietary exposure to lead, cadmium, and mercury in young Korean children.

BACKGROUND: Controlling for day-to-day variation is a key issue in estimating long-term dietary exposure to heavy metals using 24-hour recall (24HR) data from a relatively small number of days. OBJECTIVES: This study was conducted to estimate long-term dietary exposure to lead, cadmium and mercury among Korean children using the Iowa State University (ISU) method and to assess the contributions of different food groups to heavy metal intake. METHODS: We analyzed 2 days of 24HR data from 457 children between 0 and 6 years of age in 2010. Using bootstrapped concentration data for 118 representative foods, 93.5% of total intake was included in the exposure estimates in this study. Using the 2-day exposure data, we estimated long-term exposure by controlling for within-individual variation using the ISU method. RESULTS: The long-term dietary exposure estimates (mean±standard deviation) for lead, cadmium, and mercury were 0.47±0.14, 0.38±0.20, and 0.22±0.08 µg/kg bw/day, respectively. For lead and cadmium, the percentages of children whose exposure was greater than the reference value were 35 and 42%, respectively. Fruits were an important source of lead exposure, and cereal and fish and shellfish made the greatest contributions to the total cadmium and mercury exposure. CONCLUSIONS: Our findings also suggest that the long-term exposure to lead and cadmium was somewhat greater than the reference values, whereas mercury exposure was well below than the reference value in this population. Further studies may be necessary to evaluate the food items contributing to heavy metal exposure, and continuous monitoring is needed to ensure the safety of food intake and dietary patterns among vulnerable groups in Korea.

Mitochondrial Ca(2+) influx targets cardiolipin to disintegrate respiratory chain complex II for cell death induction.

Massive Ca(2+) influx into mitochondria is critically involved in cell death induction but it is unknown how this activates the organelle for cell destruction. Using multiple approaches including subcellular fractionation, FRET in intact cells, and in vitro reconstitutions, we show that mitochondrial Ca(2+) influx prompts complex II of the respiratory chain to disintegrate, thereby releasing an enzymatically competent sub-complex that generates excessive reactive oxygen species (ROS) for cell death induction. This Ca(2+)-dependent dissociation of complex II is also observed in model membrane systems, but not when cardiolipin is replaced with a lipid devoid of Ca(2+) binding. Cardiolipin is known to associate with complex II and upon Ca(2+) binding coalesces into separate homotypic clusters. When complex II is deprived of this lipid, it disintegrates for ROS formation and cell death. Our results reveal Ca(2+) binding to cardiolipin for complex II disintegration as a pivotal step for oxidative stress and cell death induction.

A NOVEL INTRINSIC UNSCENTED KALMAN FILTER FOR TRACTOGRAPHY FROM HARDI*

The unscented Kalman filter (UKF) was recently introduced in literature for simultaneous multi-tensor estimation and tractography. This UKF however was not intrinsic to the space of diffusion tensors. Lack of this key property leads to inaccuracies in the multi-tensor estimation as well as in tractography. In this paper, we propose an novel intrinsic unscented Kalman filter (IUKF) in the space of symmetric positive definite matrices, which can be used for simultaneous recursive estimation of multi-tensors and tractography from diffusion weighted MR data. In addition to being more accurate, IUKF retains all the advantages of UKF for instance, multi-tensor estimation is only performed in the places where it is needed for tractography, which would be much more efficient than the two stage process involved in methods that do tracking post diffusion tensor estimation. The accuracy and effectiveness of the proposed method is demonstrated via real data experiments.

Iatrogenic cardiovocal syndrome caused by transcatheter coil closure of patent ductus arteriosus.

UNLABELLED: Two infants developed hoarseness unexpectedly the day after transcatheter coil closure of a slender patent ductus arteriosus (PDA). The pathogenesis of this complication appears to be similar to that of the classic cardiovocal syndrome. During the intervention, the inappropriately implanted coil might have distorted the slender PDA, thereby causing angulation of the pliable PDA itself and precipitating impingement on the left recurrent laryngeal nerve. Fortunately, both infants recovered spontaneously from the hoarseness within several weeks. At present, the definite underlying neuropathology of this complication is unknown as we have not yet confirmed recovery of the left vocal cord movement by follow-up fibreoptic bronchoscopy. CONCLUSION: Iatrogenic cardiovocal syndrome could occur in infants after transcatheter coil closure of a slender PDA, using the currently popular 0.038-inch coil. A coil with a smaller diameter might prevent the occurrence of this syndrome.

Inhibition of c-erbB-2 expression an activity in human ovarian carcinoma cells by hypericin.

The c-erbB-2 oncogene encodes a tyrosine kinase that constitutes the internal and transmembrane part of the epidermal growth factor receptor (EGFR). ErbB-2 overexpression has been reported in 20% to 30% of human adenocarcinomas of the breast and ovary, and has been linked to an unfavorable prognosis in patients. Hypericin is a protein tyrosine kinase inhibitor that has been exploited in models for anti-tumor and anti-viral activity. In this study, we investigated the effects of hypericin on the activity of the c-erbB-2 oncoprotein and its downstream kinases. We also investigated the effect of hypericin on metastasis. We used ovarian SK-OV-3 cells as a model to determine whether hypericin-induced cell death was associated with inhibition of c-erbB-2 expression and activation. The IC50 of hypericin after 72 hrs exposure was 7.5 microM as determined by the MTT assay. Apoptosis, which was assessed by morphological changes and a flow cytometric assay, was observed at 24 h after continuous exposure to 5 microM hypericin. Inhibition of expression of the c-erbB-2 protein was detected, using a monoclonal anti-erbB-2 antibody after 12-48 hrs of exposure to hypericin. Hypericin was found to inhibit autophosphorylation of the erbB-2 protein and downstream kinases such as MEK and ERK1/2. We also found up-regulation of p21WAF1 expression and down-regulation of Bcl-2 in hypericin treated cells. An invasion assay showed that hypericin inhibited the movement of SK-OV-3 cells into the Matrigel. However, gelatin zymography showed that hypericin had no effect on the secretion of matrix metalloproteinases (MMPs) in SK-OV-3 cells. From these results, we conclude that hypericin inhibits the growth of SK-OV-3 ovarian cancer cells, inhibits the autophosphorylation of c-erbB-2, induces apoptosis, and may inhibit invasion.

Effect of head rotation on lateral cephalometric radiographs.

The purpose of this study was to identify the potential projection errors of lateral cephalometric radiographs due to head rotation in the vertical Z-axis. For this investigation, 17 human dry skull samples with permanent dentition were collected from the Department of Anatomy in the College of Medicine, Chosun University. They had no gross asymmetry and were well preserved. Each dry skull was rotated from 0 degrees to +/- 15 degrees at 1 degrees intervals. A vertical axis, the Z-axis, was used as a rotational axis to have 527 lateral cephalometric radiographs exposed. The findings were that: (1) angular measurements have fewer projection errors than linear measurements; (2) the greater the number of landmarks on the midsagittal plane that are included in angular measurements, the fewer the projection errors occurring; (3) horizontal linear measurements decrease gradually in length as the rotational angle toward the film increases, whereas a small increase and then decrease of the length occurs as the rotational angle toward the focal spot increases; (4) horizontal linear measurements have more projection errors than vertical linear measurements according to head rotation; and (5) projection errors of vertical linear measurements increase as the distance from the rotational axis increases. In summary, angular measurements of lateral cephalometric radiographs are more useful than linear measurements in minimizing the projection errors associated with head rotation on a vertical axis.

The structural and functional organization of the yeast mediator complex.

The Mediator complex of Saccharomyces cerevisiae is required for diverse aspects of transcription by RNA polymerase II (pol II). Mediator is composed of two functionally distinct subcomplexes, Rgr1 and Srb4. To identify the structures and functions of each subcomplex, we expressed recombinant proteins for each subunit and assayed their interactions with each other and with basal transcription proteins. The Rgr1 subcomplex is composed of the Gal11 module, which binds activators, and the Med9/10 module. The Med9/10 module is required for both transcriptional activation and repression, and these activities appear to be carried out by two submodules. Proteins in the Med9 submodule interact physically and genetically with Srb10/11, suggesting that the Med9 submodule mediates the repression of pol II. Purified recombinant Srb4 subcomplex stimulated basal transcription of pol II but had little effect on activated transcription and phosphorylation of the C-terminal domain of the Rpb1 subunit of pol II. Both subcomplexes of Mediator interacted with a distinct set of basal transcription factors and pol II. The modular organization of Mediator and the associated functions suggest that the Mediator complex may recruit and/or stabilize the preinitiation complex through several points of contact with transcriptional regulators and basal transcription factors.

A remote password authentication scheme for multiserver architecture using neural networks.

Conventional remote password authentication schemes allow a serviceable server to authenticate the legitimacy of a remote login user. However, these schemes are not used for multiserver architecture environments. We present a remote password authentication scheme for multiserver environments. The password authentication system is a pattern classification system based on an artificial neural network. In this scheme, the users only remember user identity and password numbers to log in to various servers. Users can freely choose their password. Furthermore, the system is not required to maintain a verification table and can withstand the replay attack.

In vivo requirement of activator-specific binding targets of mediator.

There has been no unequivocal demonstration that the activator binding targets identified in vitro play a key role in transcriptional activation in vivo. To examine whether activator-Mediator interactions are required for gene transcription under physiological conditions, we performed functional analyses with Mediator components that interact specifically with natural yeast activators. Different activators interact with Mediator via distinct binding targets. Deletion of a distinct activator binding region of Mediator completely compromised gene activation in vivo by some, but not all, transcriptional activators. These demonstrate that the activator-specific targets in Mediator are essential for transcriptional activation in living cells, but their requirement was affected by the nature of the activator-DNA interaction and the existence of a postrecruitment activation process.

Clinical features and risk factors of pulmonary oedema after enterovirus-71-related hand, foot, and mouth disease.

BACKGROUND: In Taiwan, from April to July, 1998, an epidemic of hand, foot, and mouth disease associated with enterovirus 71 (EV71) occurred with fatal complications. We did a clinical study of EV71-related diseases in Taiwan. METHODS: We studied 154 children with virus-culture confirmed EV71 infection. Children were divided into three groups: 11 patients with pulmonary oedema; 38 patients with central nervous system (CNS) involvement and no pulmonary oedema; and 105 children without complications. We compared the clinical features, laboratory findings, risk factors, and outcome among these three groups. FINDINGS: Nine children with pulmonary oedema had hand, foot, and mouth disease, one had herpangina, and one had febrile illness with eight children with limb weakness and one with limb hypesthesia. All children had had sudden onset of tachycardia, tachypnoea, and cyanosis 1-3 days after onset of the disease. Nine of 11 children died within 12 h of intubation; one child was braindead within 15 h and died 17 days after intubation; one child was in deep coma and died 3 months later. In children with CNS complication and no pulmonary oedema, one child died of pneumonia after 4 months of ventilator support and four children had sequelae. All 105 children without complications recovered. There was a significant association between CNS involvement and pulmonary oedema (odds ratio 12.4 [95% CI 2.6-60.1], p=0.001). Risk factors for pulmonary oedema after CNS involvement were hyperglycaemia, leucocytosis, and limb weakness. Hyperglycaemia was the most significant prognostic factor for pulmonary oedema (odds ratio 21.5 [3-159], p=0.003). INTERPRETATION: EV71 can cause hand, foot, and mouth disease, CNS involvement with severe sequelae, and fatal pulmonary oedema. Hyperglycaemia is the most important prognostic factor.

Guillain-Barré syndrome: MR imaging findings of the spine in eight patients.

PURPOSE: To evaluate magnetic resonance (MR) imaging findings of the spine in patients with Guillain-Barré syndrome. MATERIALS AND METHODS: MR imaging findings in eight patients (three male, five female; age range, 2-47 years) with Guillain-Barré syndrome were retrospectively reviewed. Guillain-Barré syndrome was diagnosed mainly on the basis of symptoms and also on the basis of supportive ancillary data, such as the results cerebrospinal fluid analysis and electrophysiologic evaluation. In addition, follow-up MR imaging was performed in three patients, who had slight clinical improvement. RESULTS: All patients had thickening of the intrathecal spinal nerve roots and cauda equina, with varying degrees of enhancement on gadolinium-enhanced axial T1-weighted images. Two enhancement patterns were noted. One was enhancement of both the anterior and posterior spinal nerve roots (n = 2); the other was enhancement of the anterior spinal nerve roots only (n = 6). Follow-up MR imaging in the three patients with slight improvement of symptoms revealed that the thickening and the degree of enhancement of the spinal nerve roots were diminished. CONCLUSION: Although the enhancement of the intrathecal spinal nerve roots is not specific to Guillain-Barré syndrome and can be seen in neoplasia and other inflammatory processes, the enhancement of only the anterior spinal nerve roots is strongly suggestive of Guillain-Barré syndrome.

A virtual image cryptosystem based upon vector quantization.

We propose a new image cryptosystem to protect image data. It encrypts the original image into another virtual image. Since both original and virtual images are significant, our new cryptosystem can confuse illegal users. Besides the camouflage, this new cryptosystem has three other benefits. First, our cryptosystem is secure even if the illegal users know that our virtual image is a camouflage. Second, this cryptosystem can compress image data. Finally, our method is more efficient than a method that encrypts the entire image directly.

Selective inhibition of the effects of phorbol ester on doxorubicin resistance and P-glycoprotein by the protein kinase C inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7) in multidrug-resistant MCF-7/Dox human breast carcinoma cells.

The possible regulation of the multidrug-resistant (MDR) phenotype and P-glycoprotein by protein kinase C (PKC) was investigated in the doxorubicin (Dox)-resistant MCF-7 cell line (MCF-7/Dox). In a clonogenic assay, cells exposed to 100 nM phorbol 12-myristate 13-acetate (PMA) for 1 hr were about 3-fold more resistant to Dox than were cells exposed to Dox alone. The PKC inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7, 30 microM) completely blocked the PMA-induced effect, but did not reverse the MDR phenotype. Complete down-regulation of PKC from MCF-7/Dox cells by 24-hr preincubation with PMA did not alter the degree of Dox resistance. Intracellular accumulation of [14C]Dox decreased from a baseline of 28 pmol/10(6) cells to 15 pmol/10(6) cells in the presence of 100 nM PMA. The reduced Dox accumulation in the presence of PMA was not blocked by pretreatment of cells with H7. Following a 24-hr pretreatment with PMA, the cells accumulated almost equal amounts of [14C]Dox in the absence or presence of PMA. Cells from PMA-treated colonies showed significantly higher levels of expression of P-glycoprotein when compared with those from control colonies. H7 did not affect the basal level of P-glycoprotein in cells from control colonies or PMA-induced overexpression of P-glycoprotein in cells from PMA-treated colonies. Upon stimulation with PMA (100 nM), PKC alpha and beta translocated to the cell membrane and nucleus and PKC delta and epsilon to the perinuclear membrane and the nucleus, respectively. H7 (30 microM) completely inhibited PMA-induced translocations of PKC delta and epsilon, whereas it only partially blocked the translocations of PKC alpha and beta. These results suggest that PMA appears to alter Dox resistance and intracellular Dox accumulation in a PKC-dependent manner and to induce increased expression of P-glycoprotein in MCF-7/Dox cells. Differential effects of H7 on the PMA-induced changes suggest that different isoforms of PKC may be involved in cell growth and drug accumulation processes as well as P-glycoprotein expression.

Non-hyperventilation respiratory therapy of persistent pulmonary hypertension of the newborn.

Persistent pulmonary hypertension of the newborn (PPHN) is one of the most challenging situations in the neonatal intensive care nursery and it is associated with a high mortality rate. Hyperventilation therapy has been recommended as the primary ventilator management during recent decades. The associations of pulmonary barotrauma, chronic lung disease and hearing impairment raised the questions of significant pulmonary and neurological complications with this therapeutic modality. From July 1990 to April 1993, 14 cases of neonatal persistent pulmonary hypertension were treated with nonhyperventilation respiratory therapy at the Chang Gung Memorial Hospital. The goals of this therapy were to attain a pH level between 7.40 and 7.50, a PaO2 level between 60 and 90 mmHg and a PaCO2 level between 30 and 50 mmHg. High peak inflating pressure (> 35 cmH2O) and high ventilator rates (> 60/min) were avoided. The average duration on a ventilator was 6.8 +/- 2.9 days. Four patients had pulmonary barotrauma (29%); three of which were pulmonary interstitial emphysema and one pneumothorax. Three patients died (21%). Only one patient had neurological sequelae. No one had developed chronic lung disease. The non-hyperventilation approach for PPHN may be considered as an alternative ventilator management before starting a more aggressive hyperventilation therapy.

Neonatal meningococcal meningitis: report of two cases.

Two neonates with meningococcal meningitis and meningococcemia are reported. The two, aged 28 and 16 days, respectively, presented similar symptoms of fever, poor appetite and poor activity. Both blood and cerebrospinal fluid cultures of each patient grew Neisseria meningitidis. The isolated bacteria were sensitive to penicillin, and both patients recovered completely after penicillin treatment for 22 and 15 days, respectively. In the antibiotic era, only 22 cases of neonatal meningococcal meningitis have been reported in the English literature. Among these reports, at least 7 patients survived without sequelae; 6 of those were treated with different combinations of antibiotics, including penicillin, for variable durations of 7-14 days. Therefore, effective antibiotic therapy for 14 days should be adequate in the treatment of uncomplicated neonatal meningococcal meningitis and meningococcemia.

[Pulmonary nocardiosis with cerebral abscess successfully treated by medication alone--a case report].

Nocardiosis is an illness caused by members of the genus Nocardia. Although it is usually an opportunistic infection in immunocompromised hosts, it can also occur in patients without a definable predisposing condition. Three species are recognized as being responsible for what most frequently seen. The primary site of infection is overwhelmingly the lungs. Brain abscess is by far the most common site for nocardial metastasis from pulmonary lesion. Although surgical intervention must always be considered in the treatment of nocardial brain abscess, it can clearly be cured by medical therapy alone. We report this case and also review the literature.

[Acute pneumonitis caused by inhalation of mercury vapor--report of a case].

Two characteristics, volatility and biotransformation, make mercury somewhat unique as environmental toxicant, and make mercury poisoning as one of occupational diseases in the industry. Acute mercury vapor poisoning is a rare event. It often occurs during industrial accident or ignorant experiment. We report a case, a 28-year-old male waterworks technician, who developed dyspnea, cough, chest pain, metallic taste and ache in the whole body three hours after heating approximately 30 ml of liquid mercury during an experiment. Diarrhea with tarry stool occurred the next day. Chest roentgenogram revealed diffuse pulmonary infiltrates similar to pulmonary edema in both lungs, and was complicated by pneumomediastinum and subcutaneous emphysema later. The concentration of mercury in the plasma was over the toxic level. The urinary excretion of mercury greatly exceeded normal value. During hospitalization, the patient's liver and renal function tests were both normal. He was treated with penicillamine, 300 mg every six hours orally for 10 days in addition to a support treatment and oxygen therapy. He was discharged on the 15th hospital day with partial resolution of pulmonary infiltrates and was free of symptom.