Immunological characterization of chromogranins A and B and secretogranin II in the bovine pancreatic islet

Antisera against chromogranin A and B and secretogranin II were used for analysing the bovine pancreas by immunoblotting and immunohistochemistry. All three antigens were found in extracts of fetal pancreas by one dimensional immunoblotting. A comparison with the soluble proteins of chromaffin granules revealed that in adrenal medulla and in pancreas antigens which migrated identically in electrophoresis were present. In immunohistochemistry, chromogranin A was found in all pancreatic endocrine cell types with the exception of most pancreatic polypeptide-(PP-) producing cells. For chromogranin B, only a faint immunostaining was obtained. For secretorgranin II, A-and B-cells were faintly positive, whereas the majority of PP-cells exhibited a strong immunostaining for this antigen. These results establish that chromogranins A and B and secretogranin II are present in the endocrine pancreas, but that they exhibit a distinct cellular localization

PDGF-Rα gene expression predicts proliferation, but PDGF-A suppresses transdifferentiation of neonatal mouse lung myofibroblasts

<p>Abstract</p> <p>Background</p> <p>Platelet-derived growth factor A (PDGF-A) signals solely through PDGF-Rα, and is required for fibroblast proliferation and transdifferentiation (fibroblast to myofibroblast conversion) during alveolar development, because <it>pdgfa</it>-null mice lack both myofibroblasts and alveoli. However, these PDGF-A-mediated mechanisms remain incompletely defined. At postnatal days 4 and 12 (P4 and P12), using mouse lung fibroblasts, we examined (a) how PDGF-Rα correlates with ki67 (proliferation marker) or alpha-smooth muscle actin (αSMA, myofibroblast marker) expression, and (b) whether PDGF-A directly affects αSMA or modifies stimulation by transforming growth factor beta (TGFβ).</p> <p>Methods</p> <p>Using flow cytometry we examined PDGF-Rα, αSMA and Ki67 in mice which express green fluorescent protein (GFP) as a marker for PDGF-Rα expression. Using real-time RT-PCR we quantified αSMA mRNA in cultured Mlg neonatal mouse lung fibroblasts after treatment with PDGF-A, and/or TGFβ.</p> <p>Results</p> <p>The intensity of GFP-fluorescence enabled us to distinguish three groups of fibroblasts which exhibited absent, lower, or higher levels of PDGF-Rα. At P4, more of the higher than lower PDGF-Rα + fibroblasts contained Ki67 (Ki67+), and Ki67+ fibroblasts predominated in the αSMA + but not the αSMA- population. By P12, Ki67+ fibroblasts comprised a minority in both the PDGF-Rα + and αSMA+ populations. At P4, most Ki67+ fibroblasts were PDGF-Rα + and αSMA- whereas at P12, most Ki67+ fibroblasts were PDGF-Rα- and αSMA-. More of the PDGF-Rα + than - fibroblasts contained αSMA at both P4 and P12. In the lung, proximate αSMA was more abundant around nuclei in cells expressing high than low levels of PDGF-Rα at both P4 and P12. Nuclear SMAD 2/3 declined from P4 to P12 in PDGF-Rα-, but not in PDGF-Rα + cells. In Mlg fibroblasts, αSMA mRNA increased after exposure to TGFβ, but declined after treatment with PDGF-A.</p> <p>Conclusion</p> <p>During both septal eruption (P4) and elongation (P12), alveolar PDGF-Rα may enhance the propensity of fibroblasts to transdifferentiate rather than directly stimulate αSMA, which preferentially localizes to non-proliferating fibroblasts. In accordance, PDGF-Rα more dominantly influences fibroblast proliferation at P4 than at P12. In the lung, TGFβ may overshadow the antagonistic effects of PDGF-A/PDGF-Rα signaling, enhancing αSMA-abundance in PDGF-Rα-expressing fibroblasts.</p

Rapid Transition towards the Division of Labor via Evolution of Developmental Plasticity

A crucial step in several major evolutionary transitions is the division of labor between components of the emerging higher-level evolutionary unit. Examples include the separation of germ and soma in simple multicellular organisms, appearance of multiple cell types and organs in more complex organisms, and emergence of casts in eusocial insects. How the division of labor was achieved in the face of selfishness of lower-level units is controversial. I present a simple mathematical model describing the evolutionary emergence of the division of labor via developmental plasticity starting with a colony of undifferentiated cells and ending with completely differentiated multicellular organisms. I explore how the plausibility and the dynamics of the division of labor depend on its fitness advantage, mutation rate, costs of developmental plasticity, and the colony size. The model shows that the transition to differentiated multicellularity, which has happened many times in the history of life, can be achieved relatively easily. My approach is expandable in a number of directions including the emergence of multiple cell types, complex organs, or casts of eusocial insects

Methodological aspects of a GIS-based environmental health inspection program used in the Athens 2004 Olympic and Para Olympic Games

BACKGROUND: The use of geographical information system (GIS) technologies in public health surveillance is gradually gaining momentum around the world and many applications have already been reported in the literature. In this study, GIS technology was used to help county departments of Public Health to implement environmental health surveillance for the Athens 2004 Olympic and Para Olympic Games. METHODS: In order to assess the workload in each Olympic county, 19 registry forms and 17 standardized inspection forms were developed to register and inspect environmental health items requiring inspection (Hotels, restaurants, swimming pools, water supply system etc), respectively. Furthermore, related databases were created using Epi Info 2002 and a geographical information system (GIS) were used to implement an integrated Environmental Health inspection program. The project was conducted in Athens by the Olympic Planning Unit (OPU) of the National School of Public Health, in close cooperation with the Ministry of Health and Social Solidarity and the corresponding departments of Public Health in all municipalities that were scheduled to host events during the Athens 2004 Olympic and Para Olympic games. RESULTS: A total of 44,741 premises of environmental health interest were geocoded into GIS databases and several electronic maps were developed. Using such maps in association with specific criteria, we first identified the maximum workload required to execute environmental health inspections in all premises within the eleven Olympic County Departments of Public Health. Six different scenarios were created for each county, based on devised algorithms in order to design the most effective and realistic inspection program using the available inspectors from each municipality. Furthermore, GIS applications were used to organize the daily inspection program for the Olympic games, provide coloured displays of the inspection results and link those results with the public health surveillance of specific cases or outbreak investigation. CONCLUSION: Our computerised program exhibited significant efficiency in facilitating the prudent use of public health resources in implementing environmental health inspections in densely populated urban areas as well as in rural counties. Furthermore, the application of simple algorithms in integrating human and other resources provided tailored and cost-effective applications to different public health agencies

Global lung function initiative 2012 reference values for spirometry in Asian Americans

Background Spirometry reference values specifically designed for Asian Americans are currently unavailable. The performance of Global Lung Function Initiative 2012 (GLI-2012) equations on assessing spirometry in Asian Americans has not been evaluated. This study aimed to assess the fitness of relevant GLI-2012 equations for spirometry in Asian Americans. Methods Asian subjects who never smoked and had qualified spirometry data were extracted from the National Health and Nutrition Examination Survey (NHANES) 2011–2012. Z-scores of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and FEV1/FVC were separately constructed with GLI-2012 equations for North East (NE) Asians, South East (SE) Asians, and individuals of mixed ethnic origin (Mixed). In addition, Proportions of subjects with observed spirometry data below the lower limit of normal (LLN) were also evaluated on each GLI-2012 equation of interest. Results This study included 567 subjects (250 men and 317 women) aged 6–79 years. Spirometry z-scores (z-FEV1, z-FVC, and z-FEV1/FVC) based on GLI-2012 Mixed equations had mean values close to zero (− 0.278 to − 0.057) and standard deviations close to one (1.001 to 1.128); additionally, 6.0% (95% confidence interval (CI) 3.1–8.9%) and 6.4% (95% CI 3.7–9.1%) of subjects were with observed data below LLN for FEV1/FVC in men and women, respectively. In contrast, for NE Asian equations, all mean values of z-FEV1 and z-FVC were smaller than − 0.5; for SE Asian equations, mean values of z-FEV1/FVC were significantly smaller than zero in men (− 0.333) and women (− 0.440). Conclusions GLI-2012 equations for individuals of mixed ethnic origin adequately fitted spirometry data in this sample of Asian Americans. Future studies with larger sample sizes are needed to confirm these findings

Organic Geochemical Studies. I. Molecular Criteria for Hydrocarbon Genesis

In recent years the search for life-forms at the earliest periods of geological time has been continued not only at the morphological level but also at the molecular level. This has been possible as a result of the increase in the biochemical knowledge and with the advent of analytical techniques that are capable of describing the intimate molecular architecture of individual molecules in acute detail. The fundamental premises upon which this organic geochemical approach rest are the following: that certain molecules, possessing a characteristic structural skeleton, show a reasonable stability to degradation over long periods of geological time; that their structural specificity can be understood in terms of known biosynthetic sequences; and that their formation by any non-biological means is of negligible probability. In this manuscript it is proposed to critically re-examine these premises and to establish criteria whereby one can differentiate molecules derived from biological systems from those that have their origin in non-biological processes. The importance of establishing such criteria lies in the significance these criteria have in determining whether life exists, or has existed, on other planets. Within the very near future it may be possible to provide an initial answer to this question when the first lunar samples are returned to the earth for analysis

Air pollution from traffic and cancer incidence: a Danish cohort study

<p>Abstract</p> <p>Background</p> <p>Vehicle engine exhaust includes ultrafine particles with a large surface area and containing absorbed polycyclic aromatic hydrocarbons, transition metals and other substances. Ultrafine particles and soluble chemicals can be transported from the airways to other organs, such as the liver, kidneys, and brain. Our aim was to investigate whether air pollution from traffic is associated with risk for other cancers than lung cancer.</p> <p>Methods</p> <p>We followed up 54,304 participants in the Danish Diet Cancer and Health cohort for 20 selected cancers in the Danish Cancer Registry, from enrolment in 1993-1997 until 2006, and traced their residential addresses from 1971 onwards in the Central Population Registry. We used modeled concentration of nitrogen oxides (NO_x) and amount of traffic at the residence as indicators of traffic-related air pollution and used Cox models to estimate incidence rate ratios (IRRs) after adjustment for potential confounders.</p> <p>Results</p> <p>NO_xat the residence was significantly associated with risks for cervical cancer (IRR, 2.45; 95% confidence interval [CI], 1.01;5.93, per 100 μg/m³NO_x) and brain cancer (IRR, 2.28; 95% CI, 1.25;4.19, per 100 μg/m³NO_x).</p> <p>Conclusions</p> <p>This hypothesis-generating study indicates that traffic-related air pollution might increase the risks for cervical and brain cancer, which should be tested in future studies.</p

The Whereabouts of 2D Gels in Quantitative Proteomics

Two-dimensional gel electrophoresis has been instrumental in the development of proteomics. Although it is no longer the exclusive scheme used for proteomics, its unique features make it a still highly valuable tool, especially when multiple quantitative comparisons of samples must be made, and even for large samples series. However, quantitative proteomics using 2D gels is critically dependent on the performances of the protein detection methods used after the electrophoretic separations. This chapter therefore examines critically the various detection methods (radioactivity, dyes, fluorescence, and silver) as well as the data analysis issues that must be taken into account when quantitative comparative analysis of 2D gels is performed

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.