Because the potency and selectivity of compounds for a given receptor in an in vivo setting can be dissimilar to that observed in an in vitro system, we developed an in vivo assay to simultaneously determine the absolute potency and selectivity of muscarinic receptor antagonists at M-2 and M-3 receptors using the pithed rat. Methacholine (MCh)-induced bradycardia and depressor responses were used as surrogate functional endpoints for M-2 and M-3 receptor activation, respectively. The influence

of the muscarinic antagonists, tolterodine, oxybutynin, darifenacin, Ro 320-6206, solifenacin, or tiotropium on the MCh-induced responses Dinaciclib cost were studied. The estimated DR10 values (dose producing a tenfold shift in the MCh curve) of tolterodine, oxybutynin, darifenacin, Ro 320-6206, solifenacin, and tiotropium for the M-2 muscarinic receptor-mediated bradycardia were 0.22, 1.18, similar to 2.6, 0.025, 0.40, and 0.0026 mg/kg, respectively, and 0.14, 0.18, 0.11, 3.0, 0.18, and 0.0017 mg/kg, respectively, for the M-3 muscarinic FDA approved Drug Library datasheet receptor-mediated depressor response. In a separate set of experiments, a single intravenous dose of tiotropium was administered before a MCh curve at 1, 3, 6, or 9 h to determine if tiotropium exhibited time-dependent selectivity for the M-3 receptor as has been reported from in vitro

studies. The results indicate a slight preference of tiotropium for the M-3 receptor at later time points. The pithed rat assay may serve useful for elucidating the functional contribution of M-2 and M-3 receptors to the in vivo pharmacological effects of antagonists in disease www.selleckchem.com/products/ferrostatin-1-fer-1.html animal models.”
“We used a central composite rotatable experimental design and response surface methodology to evaluate the effects of temperature (18-37 degrees C), salinity (0-20 parts per thousand), and their interaction on specific growth rate (SGR), feed efficiency (FE), plasma osmolality, and gill Na+, K+-ATPase activity in GIFT tilapia juveniles. The linear and quadratic effects of temperature and salinity on SGR, plasma osmolality, and gill Na+, K+-ATPase

activity were statistically significant (P < 0.05). The interactive effects of temperature and salinity on plasma osmolality were significant (P < 0.05). In contrast, the interaction term was not significant for SGR, FE, and gill Na+, K+-ATPase activity (()p > 0.05). The regression equations for SGR, FE, plasma osmolality, and gill Na+, K+-ATPase activity against the two factors of interest had coefficients of determination of 0.944, 0.984, 0.966, and 0.960, respectively (P < 0.01). The optimal temperature/salinity combination was 28.9 degrees C/7.8 parts per thousand at which SGR (2.26% d(1)) and FE (0.82) were highest. These values correspond to the optimal temperature/salinity combination (29.1 degrees C/7.5 parts per thousand) and the lowest plasma osmolality (348.38 mOsmol kg(-1)) and gill Na+, K+-ATPase activity (1.31 mu mol Pi.

03; 95% CI 0.84 to 1.27) and no evidence of effect on clinical pregnancy rate, ongoing pregnancy rate, multiple pregnancy rate, miscarriage rate or ectopic pregnancy rate.\n\nAuthors’ conclusions\n\nThe use of a medium dose of long-acting FSH is a safe treatment option and equally effective compared to daily FSH. Further research is needed to determine if long-acting FSH is safe and effective for use in hyper- or poor responders and in women with all causes of subfertility.”
“Previous PET and fMRI brain imaging studies targeting neural networks processing itch sensation have used histamine as the sole itch inducer. In contrast with histamine, cowhage-induced itch is

mediated via proteinase activated receptors PAR2 and is transmitted through a separate spinothalamic pathway, therefore imaging the brain activation evoked

by cowhage could provide further insight into central processing of itch. We report for the first time a functional HDAC inhibitor MRI Arterial Spin Labeling (ASL) study of neuronal processing of itch induced by cowhage, analyzed in contrast with histamine-induced itch. We also explored the brain responses induced by histamine and cowhage combined in a tight sequence. The results of our analyses obtained in a group of 15 healthy volunteers suggested that cowhage and histamine co-activated a core group of brain structures, while also revealing notable differences. Core areas activated by both stimuli were found in the thalamus, primary and secondary somatosensory cortices, posterior AG-120 in vivo parietal cortex, superior and middle temporal cortices, PCC. ACC, precuneus and cuneus. Cowhage induced a notably distinct and more extensive GSK1838705A chemical structure involvement of the insular cortex, claustrum, basal ganglia, putamen, thalamic nuclei and pulvinar. The differences observed between these two itch modalities were investigated to determine the impact of quantitative versus qualitative factors, and correlations between itch intensity and the patterns in brain activation were explored. Our analysis revealed that the most significant differences between cowhage and histamine itch were not affected by stimulus intensity, although a subset of regions displayed

activations which were intensity-dependent. The combined application of cowhage and histamine highlighted the role of insula and claustrum in the processing of both itch modalities in the same time. The present results suggest the existence of overlapping but also distinct neuronal networks processing these two different types of itch. (C) 2011 Elsevier Inc. All rights reserved.”
“Background\n\nThe association between hypertriglyceridemia and pancreatitis remains obscure in dogs. A possible role of hypertriglyceridemia as a cause of pancreatitis in Miniature Schnauzers has been suspected.\n\nHypothesis/Objectives\n\nTo compare serum triglyceride concentrations between Miniature Schnauzers with and without a recent history of pancreatitis.

When 1-ascorbic acid was used as the reducing agent, conformal overgrowth of Au on the Pd nanocubes led to the formation of Pd-Au nanocrystals with a core-shell structure. On the contrary, localized overgrowth of Au was observed when citric acid was used as the reducing agent, producing Pd-Au bimetallic dimers. Through this Morphological control, we were able to tune the localized surface plasmon resonance peaks of Pd-Au bimetallic nanostructures GDC-0994 in the visible region.”
“Background Intestinal ischemia and reperfusion (I/R) injury leads to abnormalities

in motility, namely delay of transit, caused by damage to myenteric neurons. Alterations of the nitrergic transmission may occur in these conditions. This study investigated whether an in vitro I/R injury may affect nitric oxide (NO) production from the myenteric plexus of the guinea pig ileum and which NO synthase (NOS) isoform is involved. Methods The distribution of the neuronal (n) and inducible (i) NOS was determined by immunohistochemistry

during 60 min of glucose/oxygen deprivation (in vitro ischemia) followed by 60 min of reperfusion. The protein and mRNA levels of nNOS and iNOS were investigated by Western-immunoblotting and real time RT-PCR, selleck chemicals respectively. NO levels were quantified as nitrite/nitrate. Key Results After in vitro I/R the proportion of nNOS-expressing neurons and protein levels remained unchanged. nNOS mRNA levels increased 60 min after inducing ischemia and in the following 5 min of reperfusion. iNOS-immunoreactive neurons, protein and mRNA levels were up-regulated during the whole I/R period. A significant increase of nitrite/nitrate levels was observed in the first 5 min after inducing I/R and was significantly reduced by N-omega-propyl-L-arginine and 1400 W, selective inhibitors of nNOS and iNOS, respectively. Conclusions & Inferences Our data demonstrate that both iNOS and nNOS represent sources for NO overproduction selleck inhibitor in ileal myenteric plexus during I/R, although iNOS undergoes more consistent changes suggesting a more

relevant role for this isoform in the alterations occurring in myenteric neurons following I/R.”
“Background: The newly identified metastasis-associated in colon cancer-1 (MACC1) gene is involved in angiogenesis, epithelial-to-mesenchymal transition (EMT), invasiveness, and metastasis in a variety of malignancies. Overexpression of MACC1 gene is a prognostic marker for poor outcome of hepatocellular carcinoma (HCC) patients. However, the association between genetic polymorphisms of MACC1 gene and poor outcome in HCC has been not been performed. We therefore investigated the correlation of MACC1 single nucleotide polymorphisms (SNPs) with tumor recurrence and overall survival in HCC patients undergoing liver transplantation (LT). Methods: The study included 187 HCC patients treated with LT.

However, several adult worms of the dose-limiting species C. oncophora demonstrably survived the IVM treatment.”
“Acquired long QT syndrome (LQTS) is a disorder of cardiac repolarization most often due to specific drugs, hypokalemia, or hypomagnesemia that may precipitate torsade de pointes and cause sudden cardiac death. Common presentations of the LQTS are palpitations, presyncope, syncope, cardiac arrest, and seizures. An abnormal 12-lead electrocardiogram learn more obtained while the patient

is at rest is the key to diagnosis. The occurrence of drug-induced LQTS is unpredictable in any given individual, but a common observation is that most patients have at least 1 identifiable risk factor in addition to drug exposure. The cornerstone of the management of acquired LQTS includes the identification and discontinuation of any precipitating drug and the correction of metabolic abnormalities, such NVP-HSP990 molecular weight as hypokalemia or hypomagnesemia. Most of the episodes of torsade de pointes are short-lived and terminate spontaneously. We propose a management protocol that could be useful for the daily practice in the emergency pediatric department to reduce the risk of acquired QT prolongation.”
“We are currently

in the midst of a revolution in ageing research, with several dietary, genetic and pharmacological interventions now known to modulate ageing in model organisms. Excitingly, these interventions also appear to have beneficial effects on late-life health. For example, dietary restriction (DR) has been shown to slow the incidence of age-associated cardiovascular disease, metabolic disease, cancer and brain ageing in non-human primates and has been shown to improve a range of health indices in humans. While the idea that DR’s ability to extend lifespan is often thought of as being universal, studies in a range of organisms, including yeast, mice and monkeys, suggest that

this may not actually be the case. The precise reasons see more underlying these differential effects of DR on lifespan are currently unclear, but genetic background may be an important factor in how an individual responds to DR. Similarly, recent findings also suggest that the responsiveness of mice to specific genetic or pharmacological interventions that modulate ageing may again be influenced by genetic background. Consequently, while there is a clear driver to develop interventions to improve late-life health and vitality, understanding precisely how these act in response to particular genotypes is critical if we are to translate these findings to humans. We will consider of the role of genetic background in the efficacy of various lifespan interventions and discuss potential routes of utilising genetic heterogeneity to further understand how particular interventions modulate lifespan and healthspan.”
“OBJECTIVE.

The ability of noninvasive stress tests to predict coronary vasomotor

dysfunction in patients with nonobstructive coronary artery disease is unknown.\n\nMethods and Results – All patients with nonobstructive coronary artery disease who had invasive coronary vasomotor assessment and a noninvasive stress test (exercise ECG, stress echocardiography, or stress nuclear imaging) within 6 months of the cardiac catheterization with provocation at our institution were identified (n = 376). Coronary vasomotor dysfunction was defined as a percentage increase in coronary blood flow of <= 50% to intracoronary acetylcholine (endothelium-dependent dysfunction) and/or a coronary flow reserve ratio of <= 2.5 to intracoronary R406 ic50 adenosine (endothelium-independent dysfunction). We determined the sensitivity and specificity of various noninvasive stress tests to predict coronary vasomotor dysfunction in these patients. On invasive testing, THZ1 in vitro 233 patients (63%) had coronary vasomotor dysfunction, of which 187 patients (51%) had endothelium-dependent dysfunction, 109 patients (29%) had endothelium-independent dysfunction, and 63 patients (17%) had both. On noninvasive stress testing, 157 (42%) had a positive imaging study and 56 (15%) a positive ECG stress test. The noninvasive stress tests had limited diagnostic

accuracy for predicting coronary vasomotor dysfunction (41% sensitivity [95% CI, 34 to 47] and 57% specificity [95% CI, 49 to 66]), endothelium-dependent dysfunction (41% sensitivity [95% CI, 34 to 49] and 58% specificity Galardin [95% CI, 50 to 65]), or endothelium-independent dysfunction (46% sensitivity [95% CI, 37 to 56] and 61% specificity [95% CI, 54 to 67]). The exercise ECG test was more specific but less sensitive than the imaging tests.\n\nConclusion – This study suggests that a negative noninvasive stress test does not rule out

coronary vasomotor dysfunction in symptomatic patients with nonobstructive coronary artery disease. This underscores the need for invasive assessment or novel more sensitive noninvasive imaging for these patients. (Circ Cardiovasc Intervent. 2009;2:237-244.)”
“A melt-mixing process based on convergent-divergent flow has been used to prepare PP/MWCNT composites with a self-built convergent-divergent die (C-D die) composed of different numbers of convergent plates. Dynamic extensional deformation was generated in the C-D die, which improved the mixing effect and mixing efficiency of the composites during extrusion. The C-D die acted as a mixer for composites when mounted onto a capillary rheometer. The residence time of PP/MWCNTs melt in the extensional flow field is adjusted by changing the numbers of convergent plates and the velocity of the ram. The intensity of extensional flow field is controlled by the structure of the convergent plate and the ram velocity.

“
“Objective: This study examined the relationships between affect consciousness (AC) and symptom distress, interpersonal problems, low self-esteem, and the number of PD traits in patients with avoidant personality disorder (APD) and borderline BKM120 personality disorder (BPD).\n\nMethod: Within the setting of a treatment trial, 52 patients with APD or BPD were examined with structured interviews and self-report questionnaires before treatment and at 3-year follow-up. The evaluations included the Affect Consciousness

Interview, the SCID-II interview, the Symptom Checklist 90-R, the Circumplex of Interpersonal Problems, and the Index of Self-esteem. A low global level of AC was expected to be associated with the severity of psychopathology; a low AC for interest, joy, and tenderness was expected to be associated with social detachment; and a low AC for anger, contempt, and disgust was expected to be associated with nonassertiveness.\n\nResults: A low AC was associated with interpersonal problems and low self-esteem, but not symptom distress or the number of fulfilled SCID-II criteria. Despite a significant reduction in the psychopathology based on most clinical variables, the associations measured at baseline were maintained after 3 years. Examination of specific affect categories showed a pattern of convergent and

discriminative relationships with different types of interpersonal problems. A low AC for pleasant affects

was specifically related to communion problems, like this website cold, detached behavior, both at baseline and follow-up. In contrast, a low AC for self-boundary affects was specifically related to agency problems, like non-assertiveness, at follow-up.\n\nConclusion: Our results showed that a low AC was associated with central domains of psychopathology in patients with PDs. This suggested that AC would be an important focus for treatment and further research in PDs. Future studies are needed to examine how AC is related to various forms of personality pathology. (C) 2013 Elsevier Inc. All rights reserved.”
“To evaluate whether a short follicular phase of ovarian stimulation compromises the chance of pregnancy, BMS-777607 datasheet subjects from a double-blind, randomized trial treated with a single dose of corifollitropin alfa (n = 756) or daily recombinant FSH (n = 750) were categorized as early responders if three follicles bigger than = 17 mm were reached and human chorionic gonadotrophin (HCG) was administered prior to or on stimulation day 8, and as normal responders if three follicles bigger than = 17 mm were reached and HCG was administered after stimulation day 8. In the corifollitropin alfa and recombinant FSH groups, 23.2% and 29.1%, respectively, were early responders (P = 0.01).

Over time, reporting of cost-effectiveness has generally improved; however, there is still room for improvement, and authors C59 Stem Cells & Wnt inhibitor need to use the recommended checklists for economic evaluations.”
“BACKGROUND: New oncology drugs are being developed in conjunction with companion diagnostics with approval restricting their use to certain biomarker-positive subgroups. We examined the impact of different predictive biomarker

screening techniques and population enrichment criteria on the cost-effectiveness of targeted drugs in lung cancer, using ALK and crizotinib to build the initial model.\n\nMETHODS: Health economic modeling of cost per Quality Adjusted Life Year was based on literature review and expert opinion. The modeled population represented advanced non-small cell lung cancer (NSCLC), eligible for predictive biomarker screening with prescribing restricted to biomarker-positive patients.\n\nRESULTS: For assays costing $1400 per person, cost per quality-adjusted life year (QALY) gained for ALK screening all advanced NSCLC, excluding treatment cost, is $106 707. This falls to $4756 when Staurosporine only a highly enriched population is screened (increasing biomarker frequency from 1.6 to 35.9%). However, the same enrichment involves

missing 56% patients who segregate within the unscreened group. Cheaper screening tests that miss some true positives can be more cost-effective if proportional reductions in cost exceed proportion of subjects missed. Generic modeling of idealised screening assays, including treatment cost, reveals a dominant effect of screening cost per person at low biomarker frequencies. Cost-effectiveness of <$100 000 per QALY gained is not achievable at biomarker frequencies <5% (with drug costs $1-5000 per month and screening costs $600-1400 per person).\n\nINTERPRETATION:

Cost-effectiveness of oncology drugs whose prescribing is restricted to biomarker-positive subgroups should address the cost of detecting marker-positive patients. The cost of screening dominates at low frequencies and strategies to improve cost-effectiveness based on the assay cost, drug cost and the group screened should be considered in these scenarios. British Journal this website of Cancer (2012) 106, 1100-1106. doi:10.1038/bjc.2012.60 www.bjcancer.com Published online 28 February 2012 (C) 2012 Cancer Research UK”
“To better understand the effects of pubertal maturation on the contractile properties of skeletal muscle in vivo, the present study investigated whether there are any differences in the specific tension of the quadriceps muscle in 20 adults and 20 prepubertal children of both sexes. Specific tension was calculated as the ratio between the quadriceps tendon force and the sum of the physiological cross-sectional area (PCSA) multiplied by the cosine of the angle of pennation of each head within the quadriceps muscle.

\n\nResults. – Based on RT-PCR of 13 AQPs examined, AQP1, 3, 4, 5 and 11 were expressed in human gastric cancers

or normal gastric tissues, and AQP3, 4 and 5 exhibited differential expression between human gastric carcinomas and corresponding normal tissues, which was confirmed by Western blot analyses. lmmunohistochemical assay showed that AQP4 protein was expressed mainly in the membrane ON-01910 in vivo of parietal cell and chief cell in the normal gastric mucosa, and absent in carcinoma tissues. AQP3 and AQP5 were detected remarkably stronger in the carcinoma tissues than that in normal mucosa by immunofluorescence. AQP3 expression in cases with undifferentiated tumor was more than that in cases with well-differentiated tumor. Both AQP3 and AQP5 expression were associated with lymph node AZD2171 concentration metastasis and lymphovascular invasion in patients.\n\nConclusions. – These findings of differential expressions of AQPs and their correlation with clinicopathologic characteristics implicated AQPs

might play a role in human gastric carcinogenesis. (C) 2009 Elsevier Masson SAS. All rights reserved.”
“Reproductive functions can be modulated by both stimulatory and inhibitory primer pheromones released by conspecifics. Many stimulatory primer pheromones have been documented, but relatively few inhibitory primer pheromones have been reported in vertebrates. The sea lamprey male sex pheromone system presents an advantageous model to explore the stimulatory and inhibitory primer pheromone functions in vertebrates since several pheromone components have been identified. We hypothesized that a candidate sex pheromone component, 7 alpha, 12 alpha-dihydroxy-5a-cholan-3-one-24-oic acid (3 keto-allocholic acid or 3kACA), exerts priming effects through the hypothalamic-pituitary-gonadal (HPG) axis. To test this hypothesis, we measured the peptide concentrations and gene expressions of lamprey gonadotropin releasing hormones (lGnRH) and the HPG output in immature male sea lamprey exposed to waterborne 3kACA. Exposure to waterborne 3kACA altered neuronal activation

https://www.selleckchem.com/products/sn-38.html markers such as jun and jun N-terminal kinase (JNK), and lGnRH mRNA levels in the brain. Waterborne 3kACA also increased lGnRH-III, but not lGnRH-I or -II, in the forebrain. In the plasma, 3kACA exposure decreased all three lGnRH peptide concentrations after 1 h exposure. After 2 h exposure, 3kACA increased lGnRH-I and -III, but decreased lGnRH-II peptide concentrations in the plasma. Plasma lGnRH peptide concentrations showed differential phasic patterns. Group housing condition appeared to increase the averaged plasma lGnRH levels in male sea lamprey compared to isolated males. Interestingly, 15 alpha-hydroxyprogesterone (15 alpha-P) concentrations decreased after prolonged 3kACA exposure (at least 24 h). To our knowledge, this is the only known synthetic vertebrate pheromone component that inhibits steroidogenesis in males.

Visual grading IPI145 using multiplanar reformations (MPR), thick slab maximum intensity projections (MIP) and quantitative vessel analysis (QVA) of stenoses was performed prior and after DE bone removal. Results were evaluated for the detection of relevant stenoses (vessel area reduction >70%). Vessel segmentation errors were analyzed.\n\nResults: Segmentation errors

occurred in 19% of all vessel segments. Nevertheless, most post-bone removal artifacts could be recognized using the MPR technique for reading. Compared to MPR reading prior to bone removal, sensitivity, specificity, positive and negative predictive values after bone removal were 100%, 98%, 88% and 100% for MPR reading and 100%, 91%, 63% and 100% for exclusive MIP reading, respectively. There was a good agreement between the QVA results prior and post-DE plaque removal (r(2) = 0.8858).\n\nConclusion: DE bone and plaque removal for head and neck angiography is feasible and offers a rapid and highly sensitive overview over vascular head and neck studies. Due to a slightly limited specificity

of the MIP technique due to segmentation errors, AG-881 molecular weight possible stenoses should be verified and graded using MPR techniques. (C) 2009 Elsevier Ireland Ltd. All rights reserved.”
“Background: The effectiveness of recommended measures, such as “cover your mouth when coughing”, in disrupting the chain of transmission of infectious respiratory diseases (IRD) has been questioned. The objective of the current study was to determine the effectiveness of simple primary respiratory hygiene/cough etiquette maneuvers in blocking droplets expelled as aerosol during coughing.\n\nMethod: In this study, 31 healthy non-smokers performed cough etiquette maneuvers in an effort to cover their voluntarily elicited best effort coughs in an open bench format. A laser diffraction system was used to obtain accurate, non-invasive, quantitative, real time measurements of the size and number of droplets emitted during the assessed cough etiquette maneuvers.\n\nResults: Recommended cough etiquette maneuvers did not block the release and dispersion

of a variety of different diameter droplets to the surrounding environment. Droplets smaller than one-micron size dominate BAY 73-4506 ic50 the total number of droplets leaked when practicing assessed maneuvers.\n\nConclusions: All the assessed cough etiquette maneuvers, performed as recommended, do not block droplets expelled as aerosol when coughing. This aerosol can penetrate profound levels of the respiratory system. Practicing these assessed primary respiratory hygiene/cough etiquette maneuvers would still permit direct, indirect, and/or airborne transmission and spread of IRD, such as influenza and Tuberculosis. All the assessed cough etiquette maneuvers, as recommended, do not fully interrupt the chain of transmission of IRD.

The Sciex API 5000 mass spectrometer was operated in multiple-reaction monitoring (MRM) and electrospray positive ionization mode. An MS/MS transition of 780 -> 216 was used to monitor the analyte DM4 and 635 -> 547 for the internal standard (IS) ansamitocin P-3. A liquid-liquid extraction was utilized for sample pre-treatment with a volume of 100 mu L plasma. A Thermo Hypersil Gold PFP column was used for chromatographic separation with a 2.0 min HPLC gradient. The quantitation

range of the method was 0.500-100 ng/mL with a lower limit of quantitation of 0.500 ng/mL. The method was validated in monkey S63845 clinical trial and rat plasma according to FDA guidance on Bioanalytical Method Validation (2001). The intra- and inter-day precision and accuracy were found to be within the FDA recommended acceptance criteria. The validated method was employed to monitor the free DM4 levels in plasma in the IND-enabling toxicology studies of antitumor agent DM4 conjugated hu-anti-Cripto this website MAb B3F6 (B3F6-DM4). (C) 2011 Elsevier B.V. All rights reserved.”
“In order to improve the robustness against the array

steering vector mismatch, the norm constraint on the weight vector is used. By the complete investigation on the Capon beamformer under norm inequality constraint (NICCB), the existence of its solution is analyzed in detail, the choice of the norm inequality constraint

parameter for NICCB is analyzed and the selecting range is given. In this paper, the Capon beamformer under norm equality constraint (NECCB) is also proposed and is solved effectively. At the end, numerical examples attest the correctness of the theory, and show that when the norm constraint parameter is selected in the allowable range, the performances of the optimal NICCB and NECCB vary unobvious, but for the same given norm constraint parameter, NECCB has the better performance than NICCB, namely the optimal negative loading that has the preferable robustness. (C) 2009 Elsevier B.V. All rights reserved.”
“Gastric FK228 purchase carcinoma is the second leading cause of cancer-related deaths in the world, accounting for more than 700,000 deaths each year. Recent studies have revealed that infection with cagA-positive Helicobacter pylori plays an essential role in the development of gastric carcinoma. The cagA-encoded CagA protein is delivered into gastric epithelial cells via the bacterial type IV secretion system, where it undergoes tyrosine phosphorylation by Src and Abl kinases. Tyrosine-phosphorylated CagA then acquires the ability to interact with and deregulate SHP-2 phosphatase, a bona-fide oncoprotein, deregulation of which is involved in a variety of human malignancies.