Colocalization of the tetraspanins, CO-029 and CD151, with integrins in human pancreatic adenocarcinoma: impact on cell motility.

PURPOSE: Patients with pancreatic adenocarcinoma have a poor prognosis due to the extraordinary high invasive capacity of this tumor. Altered integrin and tetraspanin expression is suggested to be an important factor. We recently reported that after protein kinase C activation, colocalization of alpha6beta4 with the tetraspanin CO-029 strongly supports migration of a rat pancreatic adenocarcinoma. The finding led us to explore whether and which integrin-tetraspanin complexes influence the motility of human pancreatic tumors. EXPERIMENTAL DESIGN: Integrin and tetraspanin expression of pancreatic and colorectal adenocarcinoma was evaluated with emphasis on colocalization and the impact of integrin-tetraspanin associations on tumor cell motility. RESULTS: The majority of pancreatic and colorectal tumors expressed the alpha2, alpha3, alpha6, beta1, and beta4 integrins and the tetraspanins CD9, CD63, CD81, CD151, and CO-029. Expression of alpha6beta4 and CO-029 was restricted to tumor cells, whereas alpha1, alpha2, alpha3, alpha6, beta1, and CD9, CD81, CD151 were also expressed by the surrounding stroma. CD63, CD81, and beta1 expression was observed at comparably high levels in healthy pancreatic tissue. alpha3beta1 frequently colocalized and coimmunoprecipitated with CD9, CD81, and CD151, whereas alpha6beta4 colocalized and coimmunoprecipitated mostly with CD151 and CO-029. Notably, protein kinase C activation strengthened only the colocalization of CD151 and CO-029 with beta4 and was accompanied by internalization of the integrin-tetraspanin complex, decreased laminin 5 adhesion, and increased cell migration. CONCLUSION: alpha6beta4 is selectively up-regulated in pancreatic and colorectal cancer. The association of alpha6beta4 with CD151 and CO-029 correlates with increased tumor cell motility.     

Qualitative proof of liquid dispersion and penetration-involved granule formation in a high shear mixer.

The origination of granules in the early seconds is an important aspect of high shear granulation. To elucidate these mechanisms, a substandard amount (1.5% w/w) of an aqueous hydroxypropyl cellulose solution was added to four different lactose mixtures: (1) lactose 100 M (d(4,3) approximately 170 microm), (2) lactose 200 M (d(4,3) approximately 50 microm), and (3, 4) 10% magnesium stearate/lactose 100 or 200 M. Between 1 and 15 s after binder addition samples were taken, which were immediately frozen in liquid nitrogen. The frozen sample was sieved into granular (> 280 microm) and non-granular-material (< 280 microm). The binder distribution in these fractions was determined. The observed binder distribution behaviour revealed that three different nucleation mechanisms can occur: (I) For lactose 100 M holds that all the binder is initially located in the granules. These granules are subsequently broken again. (II) The lactose 200 M granules also contain 100% of the added binder liquid. Contrary to lactose 100 M the lactose 200 M granules remain intact during the process. It is argued that in both cases liquid penetration is responsible for the accumulation of all liquid in the granules. A theoretical evaluation also confirmed that liquid penetration leads to the formation of the primary granules (III) No liquid penetration is possible in the hydrophobic magnesium stearate/lactose mixtures and the binder is completely dispersed in the non-granular material.     

Deformation-Induced Martensitic Transformation in Laser Cladded 304 Stainless Steel Coatings

There are only a few cost-effective solutions for coating applications in combined mechanical loading and corrosive environments. Stainless steel AISI 304 has the potential to fill this niche, showing excellent corrosion resistance while utilizing the deformation-induced phase transformation from γ-austenite to α’-martensite, which results in an increase in strength. However, it is not known whether this can occur in laser cladded material. Therefore, laser cladded AISI 304 coatings in as-cladded condition and after heat treatment at 1100 °C for 60 min were investigated before and after bending deformation, by means of light microscopy, energy-dispersive X-ray spectroscopy and electron backscatter diffraction. It was shown that due to the dendritic microstructure accompanied by an inhomogeneous distribution of the main alloying elements (Cr and Ni), no deformation-induced phase transformation occurred in the as-cladded coating. The applied approach with subsequent solution heat treatment at 1100 °C for 60 min resulted in a homogeneous γ-austenite microstructure, so that a deformation-induced martensitic transformation (DIMT) could occur in the coatings. However, the volume fraction of martensite that had been formed locally at individual shear bands was rather low, which can be possibly attributed to the high Ni content of the feedstock, stabilizing the γ-austenite microstructure. This study shows the possibility of exploiting the DIMT mechanism in heat-treated laser-cladded AISI 304 coatings.     

Das Pankreaskarzinom

Zum Thema In jüngster Zeit konnte mit Hilfe der Molekularbiologie Licht in die Pathogenese des Pankreaskarzinoms und seiner Vorl?uferl?sionen, der duktalen pankreatischen intraepithelialen Neoplasien gebracht werden. Die Detektion des K-ras-Onkogens, z. B. hat zu einer deutlichen Erh?hung der Sensitivit?t der Diagnostik in Kombination mit den etablierten Verfahren geführt. Interessanterweise lassen sich bei der famili?ren Pankreatitis und beim Pankreaskarzinom spezifische Gendefekte finden. Daher ist bereits abzusehen, dass auf der Grundlage tumorbiologischer Erkenntnisse neue Therapiestrategien für das Pankreaskarzinom entwickelt werden.     

Toxoplasmosis in hairy-cell leukaemia

Toxoplasma serology was performed in 28 patients with hairy-cell leukaemia and was positive in eight patients (29%). In two patients (7%) reactivated toxoplasmosis was proven by either isolation of Toxoplasma gondii or by significant antibody titre rise with generation of specific IgM-antibodies. In four patients (14%), a clinical diagnosis of active toxoplasmosis was based on signs and symptoms, serologic tests, and response to specific treatment. The high proportion of patients in which active toxoplasmosis was proven or probable (six; 21%) may be related to the presence of severe monocytopenia. In patients with hairy-cell leukaemia developing fever of unknown origin and myositis, toxoplasma serology should be performed, particularly because treatment of active toxoplasmosis usually is successful.     

Combinations of self‐reported rhinitis,conjunctivitis, and asthma predicts IgE sensitization in more than 25,000 Danes

BackgroundAllergic rhinitis (AR), allergic conjunctivitis (AC), and asthma composing multiple phenotypes and improved understanding of these phenotypes and their respective risk factors are needed.ObjectivesThe objective of this study was to define the prevalence of AR, AC, and asthma and their association with allergen‐specific immunoglobulin E (sIgE) sensitization in a large cohort of blood donors and identify risk factors.MethodsFrom the nationwide population‐based Danish Blood Donor Study, 52,976 participants completed an electronic questionnaire including AR, AC, asthma, allergic predisposition, and childhood residence. Of these, 25,257 were additionally tested for sIgE to inhalation allergens (Phadiatop).ResultsThe prevalence of sIgE sensitization, AR, AC, and asthma was 30%, 19%, 15%, and 9%, respectively. The youngest birth cohorts had the highest prevalence of sIgE sensitization and symptoms of asthma, AR, and AC, and for asthma, they apparently experienced symptoms at an earlier age. The sIgE sensitization was positively associated with male sex. The sIgE seroprevalence was higher in participants with both AR and AC (ARC) than in participants with either AR or AC. Allergic predisposition and sIgE sensitization increased the risk of the diseases, while farm upbringing was associated with reduced prevalence of ARC, however, only in sIgE sensitized participants.ConclusionBirth year, childhood residence, sIgE sensitization, and allergic predisposition were associated with asthma, AR, and AC prevalence. Individuals with self‐reported ARC represent a primarily sIgE‐positive phenotype, while those with either AR or AC represent more diverse phenotypes.