Pulmonary nociceptors are potentially connected with neuroepithelial bodies.
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Animals↗
Biomedical subjects
J Yu
Publications and source records attributed to J Yu.
Dorsal-ventral pattern of Delta trafficking is established by a Snail-Tom-Neuralized pathway.
The intracellular trafficking of the Notch ligand Delta plays an important role in the activation of the Notch pathway. We have addressed the snail-dependent regulation of Delta trafficking during the plasma membrane growth of the mesoderm in the Drosophila embryo. We show that Delta is retained in endocytic vesicles in the mesoderm but expressed on the surface of the adjacent ectoderm. This trafficking pattern requires Neuralized. We developed a protocol based on chromosomal deletion and microarray analysis that led to the identification of tom as the target of snail regulating Delta trafficking. Snail represses Tom expression in the mesoderm and thereby activates Delta trafficking. Overexpression of Tom abolishes Delta trafficking and signaling to the adjacent mesoectoderm. Loss of Tom produces mesoderm-type Delta trafficking in the entire blastoderm epithelium and an expansion of mesoectoderm gene expression. We propose that Tom antagonizes the activity of Neuralized and thus establishes a sharp mesoderm-mesoectoderm boundary of Notch signaling.
Animals↗
Long-term results of surgical treatment of tetralogy of Fallot in adults.
BACKGROUND: The long-term results of patients with tetralogy of Fallot surgically treated in adulthood were evaluated to define the real benefit of surgical correction. METHODS: Between August 1990 and February 2004, 57 patients older than 18 years of age with tetralogy of Fallot received total correction. Forty-two patients (73.7 %) required transannular patch. RESULTS: Hospital and late mortality were 7.0 % (n = 4) and 5.7 % (n = 3), respectively. One patient was reoperated on to close residual ventricular septal defect. Four patients were lost. Of the remaining 49 patients, the mean follow-up was 65 +/- 38 months (range 11 - 173 months). Actuarial survival was 97.4 +/- 2.5 %, 91 +/- 7 % and 72.8 +/- 17.1 % at 5, 10 and 14 years, respectively. At the latest follow-up, 35 (76.1 %) of the surviving patients presently have NYHA functional class I ( P < 0.01). CONCLUSION: The overall survival of surgically treated adult patients with tetralogy of Fallot is acceptable. The greatest benefit of total correction at this age is the functional improvement.
Adolescent↗
Proteomics in gastrointestinal cancer.
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Biomarkers, Tumor↗
Propofol inhibits phorbol 12, 13-dibutyrate-induced, protein kinase C-mediated contraction of rat aortic smooth muscle.
BACKGROUND: Propofol induces dose-dependent vasodilation and hypotension in the clinical situation, and protein kinase C (PKC)-mediated Ca2+ sensitization plays an important role in vascular smooth muscle contraction. This study is designed to examine the effects of propofol on the active phorbol ester (phorbol 12, 13-dibutyrate; PDBu)-induced, PKC-mediated contraction of rat aortic smooth muscle. METHODS: The PDBu-induced contraction of endothelium-denuded rat aortic rings was measured in the presence or absence of PKC inhibitor, bisindolylmaleimide I, or propofol, using isometric force transducers. The PDBu-induced PKC phosphorylation of endothelium-denuded rat aortic strips was detected in the presence or absence of bisindolylmaleimide I or propofol, using Western blotting. RESULTS: PDBu, but not the inactive phorbol ester, 4-alpha-phorbol 12-myristate-13-acetate, dose-dependently induced both a slowly developing sustained contraction and PKC phosphorylation of rat aortic smooth muscle, reaching the peak level at the concentration of 10(-6) M. The PDBu (10(-6) M)-induced contraction was dose-dependently inhibited by bisindolylmaleimide I with reductions of 6.8 +/- 1.8% (P > 0.05), 39.8 +/- 8.7% (P < 0.01) and 96.7 +/- 1.4% (P < 0.01) in response to concentrations of 5 x 10(-7) M, 10(-6)x M and 5 x 10(-6) M, respectively, and by propofol with decreases of 5.2 +/- 1. 6% (P > 0.05), 9.4 +/- 1.7% (P < 0.05), 65.3 +/- 9.2% (P < 0.01) and 96.2 +/- 1.6% (P < 0.01) in response to concentrations of 5 x 10(-7) M, 10(-6) M, 5 x 10(-6) M and 10(-5) M, respectively. Both bisindolylmaleimide I and propofol also inhibited the PDBu-induced increase in the density of the phosphorylated PKC bands in a dose-dependent manner, with decreases of 6.3 +/- 2.8% (P > 0.05), 42.9 +/- 3.2% (P < 0.01) and 96.6 +/- 3.4% (P < 0.01) in response to 5 x 10(-7) M, 10(-6) M or 5 x 10(-6) M bisindolylmaleimide I, respectively, and with decreases of 4.2 +/- 2.5% (P > 0.05), 13.5 +/- 1.7% (P < 0.05), 69.5 +/- 3.5% (P < 0.01) and 95.3 +/- 4.3% (P < 0.01) in response to 5 x 10(-7) M, 10(-6) M, 5 x 10(-6) M and 10(-5) M propofol, respectively. CONCLUSION: Propofol dose-dependently inhibits PDBu-induced, PKC-mediated contraction of rat aortic smooth muscle.
Anesthetics, Intravenous↗
Simultaneous combined interventional percutaneous left atrial auricle and atrial septal defect closure.
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Aged↗
Methacholine and adenosine 5'-monophosphate challenges in children with post-infectious bronchiolitis obliterans.
Airway hyperresponsiveness (AHR) is a characteristic feature of asthma, but is also frequently demonstrated by children and adults with chronic obstructive lung diseases. AHR is usually measured by bronchial challenges using direct or indirect stimuli. The aim of this study was to compare these two types of bronchial challenge in children with post-infectious bronchiolitis obliterans (BO). Methacholine and adenosine 5'-monophosphate (AMP) challenges were used as tools for the evaluation of AHR to direct and indirect stimuli, respectively, in children with post-infectious BO (n = 28). These results were compared with those of asthmatic (n = 30) and control children (n = 25). Altogether, twenty-two patients (78.6%) with post-infectious BO were hyperreactive to methacholine with a provocative concentration causing a 20% fall in forced expiratory volume in one second (PC20) of <16 mg x mL(-1), but only six (21.4%) were hyperreactive to AMP with a PC20 of <200 mg x mL(-1). All patients with asthma responded positively to methacholine, and most (28, 93.3%) also responded positively to AMP. The majority of controls were insensitive to both challenges. Airway hyperresponsiveness to methacholine is a frequent, but by no means universal, finding in children with post-infectious bronchiolitis obliterans, but is usually not accompanied by airway hyperresponsiveness to adenosine 5'-monophosphate. This finding suggests that airway hyperresponsiveness in patients with post-infectious bronchiolitis obliterans has characteristics that differ from those of asthmatic subjects.
Adenosine Monophosphate↗
Adenoviral vectors encoding tumor necrosis factor-alpha and FasL induce apoptosis of normal and tumoral anterior pituitary cells.
Our previous work showed that tumor necrosis factor (TNF)-alpha and FasL induce apoptosis of anterior pituitary cells. To further analyze the effect of these proapoptotic factors, we infected primary cultures from rat anterior pituitary, GH3 and AtT20 cells with first-generation adenoviral vectors encoding TNF-alpha, FasL or, as a control, beta-galactosidase (beta-Gal), under the control of the human cytomegalovirus promoter. Successful expression of the encoded transgenes was determined by immunocytochemistry. Although we observed basal expression of TNF-alpha and FasL in control cultures of anterior pituitary cells, fluorescence-activated cell sorting (FACS) cell cycle analysis showed that the overexpression of TNF-alpha or FasL increases the percentage of hypodiploid lactotropes and somatotropes. Nuclear morphology and TUNEL staining revealed that the cells undergo an apoptotic death process. We detected strong immunoreactivity for TNFR1 and Fas in the somatolactotrope cell line GH3. TNF-alpha, but not FasL, was expressed in control cultures of GH3 cells. The infection of GH3 cells with adenovirus encoding TNF-alpha or FasL increased the percentages of hypodiploid and TUNEL-positive cells. TNF-alpha or FasL immunoreactivity was not observed in the corticotrope cell line AtT20. However, adenovirus encoding TNF-alpha or FasL efficiently transduced these cells and increased the percentages of hypodiploid and TUNEL-positive cells. The expression of beta-Gal was detected in all these cultures but did not affect cell viability. In conclusion, these results suggest that death signaling cascades triggered by TNF receptor 1 (TNFR1) and Fas are present in both normal and tumoral pituitary cells. Therefore, overexpression of proapoptotic factors could be a useful tool in the therapy of pituitary adenomas.
Adenoviridae↗
Separation of THF and water by room temperature ionic liquids.
Liquid-liquid equilibrium data are presented for mixtures of 1-(2-hydroxyethyl)-3-methylimidazolium chloride or tetrafluoroborate + tetrahydrofuran(THF) + water at 293.15 K. The data presented provides a valuable insight into how the environmentally friendly ionic liquid solvent can have the separation power of THF-water azeotropic systems. The sloping of the tie lines towards the THF vertex is investigated for mixtures of 1-(2-hydroxyethyl)-3-methylimidazolium chloride (or tetrafluoroborate) + THF + water. Selectivity values, derived from the tie line data, indicate that these two ionic liquids are suitable solvents for the liquid-liquid extraction of water from THF.
Borates↗
Genetic determinants of cancer coagulopathy, angiogenesis and disease progression.
Progression of human malignancies is accompanied by vascular events, such as formation and remodeling of blood vessels and systemic coagulopathy. Though long appreciated as comorbidity of cancer (Trousseau syndrome), vascular involvement is increasingly recognized as a central pathogenetic mechanism of tumor growth, invasion and metastasis. The major outstanding question in relation to this role has been, whether vascular perturbations are simply a reaction to the conditions of the tumor microenvironment, or are linked to the known genetic lesions causal for the onset and progression of malignancy. In this regard, we have previously hypothesized, and recently demonstrated experimentally that deregulation of certain hemostatic mechanisms, namely upregulation of tissue factor (TF) and possibly other changes (e.g. expression of thrombin receptor - PAR-1) are controlled by cancer-associated oncogenic events, such as activation of K-ras, epidermal growth factor receptor (EGFR), or inactivation of the p53 tumor suppressor gene in various human cancer cells. It appears that these respective transforming alterations exert their impact on both, cell-associated and soluble/circulating (microvesicle- associated) TF, i.e. may cause a systemic hypercoagulable state. Other genes, which more recently emerged as regulators of cancer coagulopathy include: PML-RARalpha, PTEN, and MET. While the spectrum of procoagulant targets of these genes may vary somewhat it includes: TF, PAI-1, COX-2 and possibly other hemostatic proteins. It is noteworthy that these prothrombotic changes may impact the malignant process directly (e.g. stimulate angiogenesis, tumor growth or metastasis) as a consequence of both coagulation-dependent and -independent effects. The latter are mostly related to cellular signaling events and changes in gene expression which are now known to be induced by the TF/FVIIa/Xa complex, thrombin and PARs, expressed on the surface of cancer cells, as well as tumor-associated endothelium. Interestingly, certain anticoagulants possess antimetastatic and anticancer properties (e.g. LMWH), an observation that further suggests that hypercoagulability may act as an effector mechanism of genetically driven tumor progression. Conversely, we suggest that oncogene-directed (targeted) anticancer agents could, at least in some cases, ameliorate not only cellular transformation itself, but also some of the chronic components of the cancer-related coagulopathy, something that may be relevant to therapeutic efficacy of these drugs. We also postulate that since TF is the oncogene target, circulating TF (microparticles) could serve as surrogate marker of the biological activity oncogene-directed agents exert in vivo. Thus, both genetic and epigenetic factors appear to conspire to activate various components of the hemostatic system in cancer patients, both locally and systemically. These activities act as mediators of cancer coagulopathy, angiogenesis, metastasis and other events involved in disease progression and should be recognized in designing better anticancer therapies.
Animals↗
[Stable tachycardia with wide QRS complex in pre-hospital emergency medicine].
BACKGROUND: Sustained, stable wide QRS-complex tachycardia (WCT) remains a diagnostic challenge, because the treatment of supra-ventricular tachycardia (SVT) with aberrant conduction differs considerably from that of a ventricular tachycardia (VT). A usual recommendation for treating a case of a stable WCT is to manage it as if it were VT, in accordance with the consideration of "first do no harm". The aim of this study was to determine whether Board-certified emergency-physicians are able to differentiate VT from SVT with aberrant conduction in a high percentage of cases (> 90%), thus to assure more precise prehospital treatment." METHODS: Eight electrocardiograms with WCT (four with electrophysiologically proven VT or SVT, respectively) were evaluated in a blinded fashion by 64 Board-certified emergency-physicians (23 female, 41 male, mean age: 37,8 + 5,1 years). Initially, the diagnosis had to be made without any further information. Afterwards the same electrocardiograms were presented again, providing important additional information. RESULTS: 55% of the study population were able to establish the correct diagnosis merely by evaluating the electrocardiogram. Providing the above mentioned additional information, the number of correct diagnoses increased to 61%. These results were roughly similar in all subgroups, only the subgroup of cardiologists showed a trend to better results with correct diagnoses in 68% without and 73 % with additional information. None of the subgroups reached the pre-specified cut-off of > or = 90% correct diagnoses. Specialist status as well as experience in emergency medicine had no significant influence on the results, only the subgroup of emergency physicians with an experience of more than five years showed a trend towards a higher rate of correct diagnosis, compared with the subgroup with less than one year experience in emergency medicine. CONCLUSION: In cases of stable WCT the evaluation of the electrocardiogram without further information in prehospital emergency-medicine leads to unsatisfactory results. The correct diagnosis in WCT can be improved by using additional data but the diagnostic accuracy is still low. Therefore, the differential diagnosis of stable WCT in preclinical emergency-medicine cannot be recommended. Until proven otherwise, any stable WCT should be managed as if it were VT.
Adult↗
Double echo steady state magnetic resonance imaging of knee articular cartilage at 3 Tesla: a pilot study for the Osteoarthritis Initiative.
BACKGROUND: Quantitative magnetic resonance imaging (qMRI) may provide valuable measures of cartilage morphology in osteoarthritis (OA) but has been confined to sequences with relatively long acquisition times at 1.5 Tesla (T). OBJECTIVE: To test the accuracy and precision of knee cartilage qMRI with a fast double echo, steady state (DESS) sequence with water excitation (we) at 3 T. METHODS: As a pilot study for the Osteoarthritis Initiative, test-retest MR images were acquired in the knees of 19 participants with no OA to moderate degrees of clinical OA. Two double oblique coronal fast low angle shot (FLASHwe) sequences (1.5 mm slice thickness) were acquired at 3 T, and two sagittal DESSwe sequences (0.7 mm slice thickness). Double oblique coronal multiplanar reformats (MPR) were performed (1.5 mm slice thickness) from the sagittal DESSwe. Knee joint cartilage plates were quantified unpaired in random order with blinding to subject identification. RESULTS: In the femorotibial joint, precision errors (root mean square coefficient of variation in % for unpaired analysis) for cartilage volume and thickness were 3.0-6.4% with coronal FLASHwe, 2.4-6.2% with coronal MPR DESSwe, and 2.3-8.2% with sagittal DESSwe. Correlation coefficients between DESSwe and FLASHwe ranged from r = 0.88 to 1.0. In the femoropatellar joint, precision errors (sagittal DESSwe) were 3.4-8.5%. CONCLUSIONS: DESSwe permits accurate and precise analysis of cartilage morphology in the femorotibial joint at 3 T. Further studies are needed to examine the accuracy of DESSwe in the femoropatellar joint and its ability to characterise sensitivity to longitudinal changes in cartilage morphology.
Adult↗
Multifilamentation transmission through fog.
The influence of atmospheric aerosols on the filamentation patterns created by TW laser beams over 10 m propagation scales is investigated, both experimentally and numerically. From the experimental point of view, it is shown that dense fogs dissipate quasi-linearly the energy in the beam envelope and diminish the number of filaments in proportion. This number is strongly dependent on the power content of the beam. The power per filament is evaluated to about 5 critical powers for self-focusing in air. From the theoretical point of view, numerical computations confirm that a dense fog composed of micrometric droplets acts like a linear dissipator of the wave envelope. Beams subject to linear damping or to collisions with randomly-distributed opaque droplets are compared.
Journal Article↗
Cor triatriatum sinister in a 61-year-old patient.
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Angioplasty, Balloon, Coronary↗
Power of in silico QTL mapping from phenotypic, pedigree, and marker data in a hybrid breeding program.
Most quantitative trait locus (QTL) mapping studies in plants have used designed mapping populations. As an alternative to traditional QTL mapping, in silico mapping via a mixed-model approach simultaneously exploits phenotypic, genotypic, and pedigree data already available in breeding programs. The statistical power of this in silico mapping method, however, remains unknown. Our objective was to evaluate the power of in silico mapping via a mixed-model approach in hybrid crops. We used maize (Zea mays L.) as a model species to study, by computer simulation, the influence of number of QTLs (20 or 80), heritability (0.40 or 0.70), number of markers (200 or 400), and sample size (600 or 2,400 hybrids). We found that the average power to detect QTLs ranged from 0.11 to 0.59 for a significance level of alpha=0.01, and from 0.01 to 0.47 for alpha=0.0001. The false discovery rate ranged from 0.22 to 0.74 for alpha=0.01, and from 0.05 to 0.46 for alpha=0.0001. As with designed mapping experiments, a large sample size, high marker density, high heritability, and small number of QTLs led to the highest power for in silico mapping via a mixed-model approach. The power to detect QTLs with large effects was greater than the power to detect QTL with small effects. We conclude that gene discovery in hybrid crops can be initiated by in silico mapping. Finding an acceptable compromise, however, between the power to detect QTL and the proportion of false QTL would be necessary.
Breeding↗
Unfavourable expression of pharmacologic markers in mucinous colorectal cancer.
Patients with mucinous colorectal cancer generally have worse prognoses than those with the nonmucinous variety. The reason for this disparity is unclear, but may result from a differential response to adjuvant chemotherapy. We examined known molecular markers for response to common chemotherapy in these two histological subtypes. In all, 21 patients with mucinous and 30 with nonmucinous Dukes C colorectal cancer were reviewed for demographic data and outcome. Total RNA from the tumours and adjacent normal mucosa was isolated and reverse transcribed. Quantitative expression levels of drug pathway genes were determined using TaqMan RT-PCR (5-fluorouracil (5-FU): TYMS, DPYD, ECGF1; oxaliplatin: GSTP1 (glutathione S-transferase pi), ERCC1 and 2; irinotecan: ABCB1, ABCG2, CYP3A4, UGT1A1, CES2, TOP1). Mucinous tumours significantly overexpressed both TYMS and GSTP1 relative to nonmucinous tumours and patient-matched normal mucosa. No significant differences in expression of the remaining markers were found. Mean follow-up was 20 months; 17 patients had recurrent disease. Among patients receiving 5-FU, those with mucinous tumours experienced shorter disease-free survival (DFS) than those with nonmucinous tumours (median DFS 13.8 vs 46.5 months, P=0.053). Mucinous colorectal cancer overexpresses markers of resistance to 5-FU and oxaliplatin. Likewise, DFS may be decreased in patients with mucinous tumours who receive 5-FU. The presence of mucin should be carefully evaluated in developmental trials of new agents for treating colorectal cancer.
Adenocarcinoma, Mucinous↗
Supercontinuum emission and enhanced self-guiding of infrared femtosecond filaments sustained by third-harmonic generation in air.
The long-range propagation of two-colored femtosecond filaments produced by an infrared (IR) ultrashort pulse exciting third harmonics (TH) in the atmosphere is investigated, both theoretically and experimentally. First, it is shown that the coupling between the pump and TH components is responsible for a wide spectral broadening, extending from ultraviolet (UV) wavelengths (220 nm) to the mid-IR (4.5 microm). Supercontinuum generation takes place continuously as the laser beam propagates, while TH emission occurs with a conversion efficiency as high as 0.5%. Second, the TH pulse is proven to stabilize the IR filament like a saturable quintic nonlinearity through four-wave mixing and cross-phase modulation. Third, the filamentation is accompanied by a conical emission of the beam, which becomes enlarged at UV wavelengths. These properties are revealed by numerical simulations and direct experimental observations performed from the Teramobile laser facility.
Journal Article↗
Quantitative assessment of emphysema using hyperpolarized 3He magnetic resonance imaging.
In this experiment, Sprague-Dawley rats with elastase-induced emphysema were imaged using hyperpolarized (3)He MRI. Regional fractional ventilation r, the fraction of gas replaced with a single tidal breath, was calculated from a series of images in a wash-in study of hyperpolarized gas. We compared the regional fractional ventilation in these emphysematous rats to the regional fractional ventilations we calculated from a previous baseline study in healthy Sprague-Dawley rats. We found that there were differences in the maps of fractional ventilation and its associated frequency distribution between the healthy and emphysematous rat lungs. Fractional ventilation tended to be much lower in emphysematous rats than in normal rats. With this information, we can use data on fractional ventilation to regionally distinguish between healthy and emphysematous portions of the lung. The successful implementation of such a technique on a rat model could lead to work toward the future implementation of this technique in human patients.
Animals↗