Development of Eosinophilic Airway Inflammation and Airway Hyperresponsiveness in Mast Cell–deficient Mice

Mast cells are the main effector cells of immediate hypersensitivity and anaphylaxis. Their role in the development of allergen-induced airway hyperresponsiveness (AHR) is controversial and based on indirect evidence. To address these issues, mast cell–deficient mice (W/W  v) and their congenic littermates were sensitized to ovalbumin (OVA) by intraperitoneal injection and subsequently challenged with OVA via the airways. Comparison of OVA-specific immunoglobulin E (IgE) levels in the serum and numbers of eosinophils in bronchoalveolar lavage fluid or lung digests showed no differences between the two groups of mice. Further, measurements of airway resistance and dynamic compliance at baseline and after inhalation of methacholine were similar. These data indicate that mast cells or IgE–mast cell activation is not required for the development of eosinophilic inflammation and AHR in mice sensitized to allergen via the intraperitoneal route and challenged via the airways

Decay of the metastable phase in d=1 and d=2 Ising models

We calculate perturbatively the tunneling decay rate $\Gamma$ of the metastable phase in the quantum d=1 Ising model in a skew magnetic field near the coexistence line $0<h_{x}<1, h_{z}\to -0$ at T=0. It is shown that $\Gamma$ oscillates in the magnetic field $h_{z}$ due to discreteness of the excitation energy spectrum. After mapping of the obtained results onto the extreme anisotropic d=2 Ising model at $T<T_c$, we verify in the latter model the droplet theory predictions for the free energy analytically continued to the metastable phase. We find also evidence for the discrete-lattice corrections in this metastable phase free energy.Comment: 4 pages, REVTe

HEALTHCARE PROCESS OF THE PATIENT WITH ACUTE PANCREATITIS

Akutni pankreatitis je nagla upala gušterače koja se može javiti u blagom ili teškom obliku. Ova nagla upala se u gotovo 80% prijema u bolnicu pripisuje postojanju žučnih kamenaca ili konzumaciji alkohola. Žučni kamenci kao uzrok budu 1,5 puta češći kod žena, dok se alkohol kao uzrok u muškaraca pojavljuje šest puta više nego kod žena. Žučni kamenci najčešće začepe otvor pankreatičnog voda ili se na neko vrijeme zaustave u Oddijevu sfinkteru uzrokujući time upalu dok svakodnevna konzumacija alkohola također može dovesti do začepljenja malih vodova. Jaki bolovi se javljaju najčešće naglo nakon konzumacije prekomjerne količine obroka ili alkohola u gornjem srednjem dijelu abdomena. Osim što je bol nagla, pacijenti je opisuju kao probadajuću bol koja se širi u leđa. Može se javiti mučnina kao i nagon na povraćanje, u većini slučajeva popratnu uz temperaturu. Bolesnik se javlja u hitni trakt radi jakih bolova koji se ne smanjuju te se podvrgava daljnjoj dijagnostici. Laboratorijskim pretragama ne može se potvrditi dijagnoza akutnog pankreatitisa ali povišenom razinom enzima gušterače tu dijagnozu možemo potkrijepiti. Daljnjim radiološkim pretragama (rendgen abdomena, kompjutorizirana tomografija) dokazuje se mogućnost postojanja žučnih kamenaca kao i promjene u veličini i strukturi gušterače. Sa utvrđenom dijagnozom akutnog pankreatitisa, osoba se zaprima na odjel gdje se prekida daljnji unos hrane i pića kako bi se smanjila daljnja proizvodnja enzima u gušterači. Svu potrebnu tekućinu i ostale hranjive tvari nadoknađuju se intravenskim putem. U cijelom procesu liječenja ključna je i medicinska sestra koja najprije može uočiti eventualne promjene koje se mogu javiti kod pacijenta, kao što su primjerice smanjeno mokrenje, otežano disanje te stagniranje ili pogoršavanje intenziteta boli unatoč primijenjenoj analgetskoj terapiji.Acute pancreatitis is a sudden pancreatic inflammation occurring in mild or severe form. This sudden inflammation in almost 80% of admission to the hospital is attributed to the existence of gallstones or drinking alcohol. The gallstones as a cause of Acute pancreatitis are 1.5 times more common in women, while alcohol as a cause is present men appears six times more than in women. Gallstones usually close the pancreatic opening or stop for a while in Oddies sphincter causing it to inflate ,while daily alcohol consumption also leads to clogging of small lines. Strong pain usually are occurring suddnely after eating excessive meals or presence of alcohol in the upper mid-section of the abdomen. Apart pain is acute, patients are describeing as a stabbing kind of pain that is spreading in their back. There can be nausea and vomiting, in most cases accompanied by temperature. The patient is coming to an emergency with severe pain that does not diminish and undergoes further diagnosis. Laboratory examinations can not confirm the diagnosis of acute pancreatitis but elevated pancreatic enzyme levels can be supported by this diagnosis. Further radiological examinations (X-ray abdomena, computerized tomography) are proveing the possibility of gallstones as well as changes in the size and structure of the pancreas. With established diagnosis of acute pancreatitis, a person is hospitalized in intensice care where further food and drink intake is discontinued in order to reduce further enzyme production in the pancreas. All the necessary fluid and other nutrients are compensated by the intravenous. Throughout the process of treatment, role of nurse is also crucial to notice possible changes that may occur in the patient, such as decreased urination, difficulty breathing and stagnation or aggravation of pain intensity despite analgesic therapy

A novel patient-derived tumorgraft model with TRAF1-ALK anaplastic large-cell lymphoma translocation.

Although anaplastic large-cell lymphomas (ALCL) carrying anaplastic lymphoma kinase (ALK) have a relatively good prognosis, aggressive forms exist. We have identified a novel translocation, causing the fusion of the TRAF1 and ALK genes, in one patient who presented with a leukemic ALK+ ALCL (ALCL-11). To uncover the mechanisms leading to high-grade ALCL, we developed a human patient-derived tumorgraft (hPDT) line. Molecular characterization of primary and PDT cells demonstrated the activation of ALK and nuclear factor kB (NFkB) pathways. Genomic studies of ALCL-11 showed the TP53 loss and the in vivo subclonal expansion of lymphoma cells, lacking PRDM1/Blimp1 and carrying c-MYC gene amplification. The treatment with proteasome inhibitors of TRAF1-ALK cells led to the downregulation of p50/p52 and lymphoma growth inhibition. Moreover, a NFkB gene set classifier stratified ALCL in distinct subsets with different clinical outcome. Although a selective ALK inhibitor (CEP28122) resulted in a significant clinical response of hPDT mice, nevertheless the disease could not be eradicated. These data indicate that the activation of NFkB signaling contributes to the neoplastic phenotype of TRAF1-ALK ALCL. ALCL hPDTs are invaluable tools to validate the role of druggable molecules, predict therapeutic responses and implement patient specific therapies

Ex vivo fucosylation improves human cord blood engraftment in NOD-SCID IL-2Rγ null mice

Delayed engraftment remains a major hurdle after cord blood (CB) transplantation. It may be due, at least in part, to low fucosylation of cell surface molecules important for homing to the bone marrow microenvironment. Because fucosylation of specific cell surface ligands is required before effective interaction with selectins expressed by the bone marrow microvasculature can occur, a simple 30-minute ex vivo incubation of CB hematopoietic progenitor cells with fucosyltransferase-VI and its substrate (GDP-fucose) was performed to increase levels of fucosylation. The physiologic impact of CB hematopoietic progenitor cell hypofucosylation was investigated in vivo in NOD-SCID interleukin (IL)-2Rγ null (NSG) mice. By isolating fucosylated and nonfucosylated CD34 + cells from CB, we showed that only fucosylated CD34 + cells are responsible for engraftment in NSG mice. In addition, because the proportion of CD34 + cells that are fucosylated in CB is significantly less than in bone marrow and peripheral blood, we hypothesize that these combined observations might explain, at least in part, the delayed engraftment observed after CB transplantation. Because engraftment appears to be correlated with the fucosylation of CD34 + cells, we hypothesized that increasing the proportion of CD34 + cells that are fucosylated would improve CB engraftment. Ex vivo treatment with fucosyltransferase-VI significantly increases the levels of CD34 + fucosylation and, as hypothesized, this was associated with improved engraftment. Ex vivo fucosylation did not alter the biodistribution of engrafting cells or pattern of long-term, multilineage, multi-tissue engraftment. We propose that ex vivo fucosylation will similarly improve the rate and magnitude of engraftment for CB transplant recipients in a clinical setting