bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mesophyll conductance to CO2: current knowledge and future prospects
Authors: FLEXAS JAUME , RIBAS‐CARBÓ MIQUEL , DIAZ‐ESPEJO ANTONIO , GALMÉS JERONI , MEDRANO HIPÓLITO 
Published: March 2008

ABSTRACTDuring photosynthesis, CO2 moves from the atmosphere (Ca) surrounding the leaf to the sub‐stomatal internal cavities (Ci) through stomata, and from there to the site of carboxylation inside the chloroplast stroma (Cc) through the leaf mesophyll. The latter CO2 diffusion component is called mesophyll conductance (gm), and can be divided in at least three components, that is, conductance through intercellular air spaces (gias), through cell wall (gw) and through the liquid phase inside cells (gliq). A large body of evidence has accumulated in the past two decades indicating that gm is sufficiently small as to significantly decrease Cc relative to Ci, therefore limiting photosynthesis. Moreover, gm is not constant, and it changes among species and in response to environmental factors. In addition, there is now evidence that gliq and, in some cases, gw, are the main determinants of gm. Mesophyll conductance is very dynamic, changing in response to environmental variables as rapid or even faster than stomatal conductance (i.e. within seconds to minutes). A revision of current knowledge on gm is presented. Firstly, a historical perspective is given, highlighting the founding works and methods, followed by a re‐examination of the range of variation of gm among plant species and functional groups, and a revision of the responses of gm to different external (biotic and abiotic) and internal (developmental, structural and metabolic) factors. The possible physiological bases for gm, including aquaporins and carbonic anhydrases, are discussed. Possible ecological implications for variable gm are indicated, and the errors induced by neglecting gm when interpreting photosynthesis and carbon isotope discrimination models are highlighted. Finally, a series of research priorities for the near future are proposed.
Platelet‐rich plasma and platelet gel preparation using Plateltex®
Authors: Mazzucco L. , Balbo V. , Cattana E. , Borzini P. 
Published: March 2008

Background  The platelet gel is made by embedding concentrate platelets within a semisolid (gel) network of polymerized fibrin. It is believed that this blood component will be used more and more in the treatment of several clinical conditions and as an adjunctive material in tissue engineering. Several systems are available to produce platelet‐rich plasma (PRP) for topical therapy. Recently, a new system became commercially available, Plateltex®. Here we report the technical performance of this system in comparison with the performance of other commercially available systems: PRGF®, PRP‐Landesber, Curasan®, PCCS®, Harvest®, Vivostat®, Regen® and Fibrinet®.Material and Methods  Both the PRP and the gel were prepared according to the manufacturer's directions. The blood samples of 20 donors were used. The yield, the efficiency, and the amount of platelet‐derived growth factor AB (PDGF‐AB), transforming growth factor β, vascular endothelial growth factor and fibroblast growth factor were measured in the resulting PRP. The feature of the batroxobin‐induced gelation was evaluated.Results  The yield, the collection efficiency and the growth factor content of Plateltex® were comparable to those of most of the other available systems. The gelation time was not dependent on the fibrinogen concentration; however, it was strongly influenced by the contact surface area of the container where the clotting reaction took place (P < 0·0001).Conclusions  Plateltex® provided platelet recovery, collection efficiency and PDGF‐AB availability close to those provided by other systems marketed with the same intended use. Batroxobin, the enzyme provided to induce gelation, acts differently from thrombin, which is used by most other systems. Platelets treated with thrombin become activated; they release their growth factors quickly. Furthermore, thrombin–platelet interaction is a physiological mechanism that hastens the clot‐retraction rate. On the contrary, platelets treated with batroxobin do not become activated; they are passively entrapped within the fibrin network, and their growth factor release occurs slowly. In these conditions, the clot retraction takes longer to occur. According to these differences between thrombin and batroxobin, it is expected that batroxobin‐induced PRP activation will tailor slow release of the platelet content, thus, providing longer in loco availability of trophic factors. In selected clinical conditions, this durable anabolic factor availability might be preferable to quick thrombin‐induced growth factor release.
Cholesterol and sphingolipids in alcohol‐induced liver injury
Authors: Fernández Anna , Colell Anna , Garcia‐Ruiz Carmen , Fernandez‐Checa José C 
Published: March 2008

AbstractThe pathogenesis of alcohol‐induced liver disease (ALD) is still poorly understood. One of the clues to its progression relates to the alcohol‐mediated susceptibility of hepatocytes to cell death by reactive oxygen species (ROS) and inflammatory cytokines. Tumor necrosis factor α (TNF) has been considered a key ALD mediator with acidic sphingomyelinase (ASMase)‐mediated ceramide generation playing a critical role. TNF receptor 1 and 2 knock‐out mice or ASMase−/− mice exhibit resistance to alcohol‐mediated fatty liver and cell death. Furthermore, alcohol feeding has been shown to sensitize hepatocytes to TNF due to the limitation of mitochondrial glutathione (mGSH) through impaired import of GSH from the cytosol due to altered membrane order parameter caused by mitochondrial cholesterol increase. Selective pharmacological depletion of mGSH sensitizes hepatocytes to TNF‐mediated cell death, which reproduces the observations found with alcohol feeding. TNF signaling analyses in hepatocytes with or without mGSH depletion indicate that mGSH prevents cardiolipin peroxidation (CLOOH) formation by TNF‐induced ROS via ASMase and that CLOOH cooperates with oligomerized Bax to cause mitochondrial outer membrane permeabilization through destabilization of the lipid bilayer via increased bilayer‐to‐inverted hexagonal phase transitions. Thus, activation of ASMase and cholesterol‐mediated mGSH depletion both collaborate to promote alcohol‐induced TNF‐mediated hepatocellular damage, suggesting novel therapeutic opportunities in ALD.
Protein kinase C in the pancreatic acinar cell
Authors: Gorelick Fred , Pandol Stephen , Thrower Edwin 
Published: March 2008

AbstractPathological activation of selective signaling molecules within the pancreatic acinar cell mediates the development of acute pancreatitis. Some of the key early acinar cell events include activation of proteases, inhibition of apical secretion, and elaboration of inflammatory mediators. Previous studies have shown that supraphysiological concentrations of cholecystokinin (CCK) that can cause pancreatitis in vivo, also initiate these pathological responses in dispersed groups of acinar cells (acini). Protein kinase C (PKC) regulates many cellular events and a role for this family of signaling molecules has been described in some of the pathological responses of pancreatitis. Notably, ethanol can activate specific PKC isoforms and sensitize the acinar cells to the pathological effects of CCK. Our preliminary studies in isolated pancreatic acini and a cell‐free reconstitution system suggest that PKC can mediate protease activation in the acinar cell. These findings may be relevant to the pathogenesis of pancreatitis from alcohol and other etiologies.
S‐Adenosylmethionine in cell growth, apoptosis and liver cancer
Authors: Lu Shelly C , Mato José M 
Published: March 2008

Abstract S‐Adenosylmethionine (SAMe), the principal biological methyl donor, is synthesized from methionine and ATP in a reaction catalyzed by methionine adenosyltransferase (MAT). In mammals, two genes (MAT1A and MAT2A), encode for two homologous MAT catalytic subunits, while a third gene MAT2β, encodes for the β‐subunit that regulates MAT2A‐encoded isoenzyme. Normal liver expresses MAT1A, whereas extrahepatic tissues express MAT2A. MAT2A and MAT2β are induced in human hepatocellular carcinoma (HCC), which facilitate cancer cell growth. Patients with cirrhosis of various etiologies, including alcohol, have decreased hepatic MAT activity and SAMe biosynthesis. Consequences of hepatic SAMe deficiency as illustrated by the Mat1a knock‐out mouse model include increased susceptibility to steatosis and oxidative liver injury, spontaneous development of steatohepatitis and HCC. Predisposition to HCC can be partly explained by the effect of SAMe on growth. Thus, SAMe inhibits the mitogenic effect of growth factors such as hepatocyte growth factor and, following partial hepatectomy, a fall in SAMe level is required for the liver to regenerate. During liver regeneration, the fall in hepatic SAMe is transient. If the fall were to persist, it would favor a proliferative phenotype and, ultimately, development of HCC. Not only does SAMe control liver growth, it also regulates apoptosis. Interestingly, SAMe is anti‐apoptotic in normal hepatocytes but pro‐apoptotic in liver cancer cells. In liver cancer cells but not in normal human hepatocytes, SAMe can selectively induce Bcl‐xS, an alternatively spliced isoform of Bcl‐xL that promotes apoptosis. This should make SAMe an attractive agent for both chemoprevention and treatment of HCC.
Epigenetic regulation of hepatic stellate cell activation
Authors: Mann Derek A , Mann Jelena 
Published: March 2008

AbstractActivation of hepatic stellate cells (HSC) to a myofibroblast‐like phenotype is the pivotal event in liver fibrosis. In uninjured liver, HSC are quiescent and non‐dividing, but upon liver injury these cells undergo a dramatic change in phenotype which generates activated myofibroblast‐like HSC. The change in phenotype is underpinned by a global change in gene expression with hundreds of genes being up‐ or downregulated. Molecular events that orchestrate changes in gene expression take place at the level of chromatin packaging which is altered through three main processes: histone modifications, DNA methylation, and silencing by non‐coding RNAs. The present review focuses on the epigenetic regulation of HSC activation.
Transforming growth factor‐β and hepatocyte transdifferentiation in liver fibrogenesis
Authors: Meindl‐Beinker Nadja M , Dooley Steven 
Published: March 2008

AbstractCurrently, hepatic stellate cells (HSC) are thought to be the major fibrotic precursor cells that transdifferentiate to fibrogenic, extracellular matrix producing myofibroblasts in inflammatory liver tissue upon transforming growth factor‐β (TGF‐β) signaling, whereas hepatocytes are thought to respond with apoptosis to this cytokine. Starting out from in vitro experiments with primary hepatocyte cultures and immortalized AML‐12 cells, TGF‐β signaling in this cell type was assessed and apoptosis was found to be only a minor effect. Instead, hepatocytes undergo epithelial mesenchymal transition (EMT), a physiological process in embryogenesis and of relevance for cancerous cell transformation. In injured liver, however, this process contributes to the promotion of fibrosis. Already after a few days of culture, hepatocytes lose their epithelial honeycomb‐like shape towards a fibroblast‐like phenotype. We could demonstrate by microarray analysis that stimulation of hepatocytes with TGF‐β regulates the expression of genes involved in EMT and fibrosis. Among these were, for example, Snail, a known mediator of EMT, and connective tissue growth factor (CTGF), a strong inducer of fibrosis. In a mouse model, hepatocyte‐specific overexpression of Smad7 was able to blunt a fibrogenic response after CCl4 intoxication. These results emphasize the dynamic nature of liver fibrosis, challenge the paradigm of HSC as a crucial source of liver myofibroblasts and hint towards a prominent role for hepatocytes in liver fibrogenesis.
Quantifying the risk for alcohol‐use and alcohol‐attributable health disorders: Present findings and future research needs
Authors: Li Ting‐Kai 
Published: March 2008

AbstractThe aim of the present review was to: (i) highlight epidemiological and other studies that have generated important data on the harmful patterns of drinking that increase the risk for chronic diseases, including alcohol dependence, and on the mechanisms by which alcohol produces and, in some instances, may protect against damage; and (ii) discuss a conceptual basis for quantifying risk criteria for alcohol‐induced chronic disease based on the quantity, frequency, and pattern of drinking. The relationship between heavy drinking and risk for adverse health conditions such as alcoholic liver disease (ALD), dementia, and alcohol dependence is well known. However, not everyone who drinks chronically develops ALD or dementia, and the major risk factors for disease development and the mechanisms by which this occurs have remained unclear. Large‐scale, general population‐based studies have provided the evidence by which quantifying the frequency of a pattern of high‐risk drinking can be related directly to risk and the severity of alcohol dependence. Cellular and molecular biology studies have identified the major pathways of alcohol metabolism and how genetics and the environment can interact in some individuals to further increase the risk of organ damage. Extant databases should allow scientists and clinicians jointly to develop the framework for quantifying the drinking patterns that increase the risk of alcohol‐induced organ pathologies, to develop clinical practice guidelines, such as those used to diagnose other common complex diseases (e.g. diabetes and hypertension), and to propose future studies for refining such guidelines. Attention must be paid to comorbid conditions such as hepatitis B and C infections, HIV, obesity, and environmental exposures other than alcohol. Developing trait and state biomarkers is critical to the process of discovery and to fulfilling the promise of personalized medicine.
The prognostic role of the pathological T2 subclassification for prostate cancer in the 2002 Tumour‐Nodes‐Metastasis staging system
Authors: Van Oort Inge M. , Witjes J. Alfred , Kok Dieuwertje E.G. , Kiemeney Lambertus A.L.M. , Hulsbergen‐Van De Kaa Christina A. 
Published: March 2008

OBJECTIVETo evaluate the prognostic role of the 2002 Tumour‐Nodes‐Metastasis (TNM) pT2 subclassification for biochemical recurrence (BCR) after radical prostatectomy (RP) for prostate cancer.PATIENTS AND METHODSThe 1997 TNM staging system is based on one subdivision for organ‐confined prostate tumours (T2a, unilateral; T2b, bilateral involvement). The 2002 TNM staging system subdivides unilateral involvement into T2a (half of one lobe or less) and T2b (more than one half of one lobe), while bilateral involvement is classified as T2c. In all, 542 patients were treated with RP at our institute; the RP specimens were completely embedded and histopathologically evaluated for Gleason grade, tumour volume and anatomical extent, and were staged according to the 2002 TNM staging criteria. Patients were followed for a median of 39.5 months. BCR was defined as two subsequent increasing prostate‐specific antigen (PSA) levels of >0.10 ng/mL. Kaplan‐Meier and proportional hazards regression analyses were used to evaluate the univariable and multivariable prognostic effect of tumour stage.RESULTSAccording to the 2002 TNM staging system, 360 specimens were found to have pT2 tumours; 79 (22%) of the RP specimens were staged as pT2a and 281 (78%) as pT2c; no pT2b specimens were identified. Patients with unilateral involvement (pT2a) had a 5‐year risk of BCR of 13%, while those with bilateral involvement (pT2c) had a risk of 23% (log rank test, P = 0.056). Patients with pT2c disease were more likely to have a larger tumour volume (Mann–Whitney U‐test P < 0.001) and positive surgical margins (Fishers’ exact test, P = 0.001)than those with pT2a tumours. Mann–Whitney U‐tests showed no differences between the groups for preoperative PSA levels (P = 0.167). Also, the RP Gleason score was no different between groups (Pearson chi‐square, P = 0.807). In the multivariable analyses, positive surgical margins appeared to increase the risk of BCR (hazard ratio 4.4, 95% confidence interval 2.5–7.9); pT2c vs pT2a had only a marginally (insignificant) additional effect (1.3, 0.6–2.7).CONCLUSIONThe absence of a true unilateral pathological T2b tumour in a series of 360 pT2 RP specimens questions the relevance of substaging unilateral disease. The limited differences in BCR and in pathological features of unilateral vs bilateral pT2 prostate cancer justify modifying the TNM staging system to one with no subclassification of pT2 disease, or at most as only one subdivision into unilateral (T2a) and bilateral (T2b) disease, combining the T2b and T2c substages.
Renal cell carcinoma metastatic to the stomach: single‐centre experience and literature review
Authors: Pollheimer Marion J. , Hinterleitner Thomas A. , Pollheimer Verena S. , Schlemmer Andrea , Langner Cord 
Published: March 2008

OBJECTIVESTo investigate the incidence, clinical presentation and therapy of gastric metastases, an uncommon finding, in a large group of patients with renal cell carcinoma (RCC).PATIENTS AND METHODSWe systematically searched the computerized RCC database of our institute, covering 2082 patients (1180 men and 902 women) who had surgery between January 1984 and September 2005, to identify those with a synchronous and/or metachronous diagnosis of cancer in gastric biopsies or resection specimens. The histopathological slides of both renal and gastric cancer probes, and the clinical presentation, treatment and outcome of affected patients, were reassessed.RESULTSTwelve patients with primary gastric cancer, one with local RCC recurrence affecting the antrum and five with clear cell RCC (three men and two women; mean age 73 years, range 65–83) with haematogenous cancer spread to the stomach were detected. The mean (range) time to gastric metastasis was 6.9 (1.7–13.1) years. There were metastases to other organs, most often the lung, in all patients. Three patients presented with symptoms of gastrointestinal bleeding, which was successfully controlled by local endoscopic therapy. Four patients died from disease at 3–19 months after diagnosis. One patient is still alive with disease after ≈2 years.CONCLUSIONSGastric metastasis in patients with RCC appears to be a late event in the course of the disease. Most patients show concomitant tumour spread to other organs, and the outcome is generally poor. The use of targeted drugs might offer a new perspective for affected patients.
IT STICKS IN MY THROAT
Authors: RADFORD COLIN 
Published: March 2008

In challenging the implications of my putative counter‐example to Wittgenstein's claim that “It's on the tip of my tongue” (TT) is not the expression of an experience (cf. Philosophical Investigations, p.219)1, Professor Slater writes2… the obvious way in which to meet the threat to the adequacy of (b1) [which is that the speaker should believe that he may be able to produce the missing word (fairly soon)] is to claim that the utterer of “It's on the tip of my tongue” must not merely believe that he may recall the word fairly soon, he must also believe, i.e., not rule out the possibility that, he may do so without any treatment, i.e., without being prompted by an external source such as cues, pills, or shock, (p.51)
THE U.S. MULTINATIONAL ENTERPRISE AND THE NATION‐STATE
Authors: Keohane Robert O. 
Published: March 2008

National Interests and the Multinational Enterprise: Tensions Among the North Atlantic Countries. Jack N. Behrman (Englewood Cliffs, N.J.: Prentice‐Hall, 1970), 198 pp. The International Corporation: A Symposium. Charles P. Kindleberger, ed., (Cambridge, Mass.: M.I.T. Press, 1970), vii + 415 pp. Silent Surrender: The Multinational Corporation in Canada. Kari Levitt (Toronto: Macmillan Company of Canada Limited), 1970. Preface by Mel Watkins. xxi + 185 pp. The Emergence of Multinational Enterprise,: American Business Abroad from the Colonial Era to 1914. Mira Wilkins (Cambridge, Mass.: Harvard University Press), 1970. xiv + 310 pp. Sovereignty at Bay: The Multinational Spread of US Enterprises. Raymond Vernon (New York: Basic Books, 1971), x+326 pp.
WEST EUROPEAN STUDIES AT THE NEW UNIVERSITY OF ULSTER, COLERAINE
Authors: Edwards Gwyneth E. 
Published: March 2008

SUMMARYBy their very nature, area studies are not easy to devise or to carry out in practice. They are still experimental and developing and the need the full support of the institution where they are taught and that of the subjects which contribute to the programme. West European Studies in Coleraine has been fortunate in many respects. The university appointed staff specifically for the core units and encouraged them to experiment. The staff appointed, although themselves products of language and literary courses, were eager to extend their range of interest into history and the social sciences and to experiment with new teaching methods. All subjects contributing options have made at least one staff appointment who has a strong interest in Western Europe and wishes to contribute to the programme. A number of those appointed have a good knowledge of French or German and have spent long periods in Western Europe. The staff from the optional and the core units are working closely together and some joint seminars and lectures are given so that there can be cross‐fertilization between the disciplines and, in particular, through this the West European staff can seriously learn the techniques of the social sciences and history. This latter aspect is further strengthened by staff from different disciplines working together on common research projects. Staff involved in West European Studies, whether in the core or the options, seem to feel increasingly that they represent a new ‘discipline’, albeit one which is not yet ready for formal definition, but which is as real to them as a social science, history or literature discipline. Similarly, the students identify strongly with West European Studies rather than with its individual components.Some of the most positive aspects are the enthusiasm expressed by the students for the programme, the high level of linguistic attainment achieved, even in the second language, and the high standards attained in the history, economics and social science options where the students are in direct competition with students whose main studies are in those disciplines. The flexibility given by the student having eight optional units allows him to plan a coherent, integrated course which meets his individual interests and needs. Finally, the experiences of the first four years of graduates show that the West Euroan Studies degree is a good qualification for posts in industry and commerce, the Civil Service, the social services, teaching and post‐graduate research work.
Book Reviews
Authors: Harrison R. 
Published: March 2008

Book reviewed in this article:The State in Capitalist EuropeCompetition and Industrial Policy in the European CommunityEurope's Industries: Public and Private Strategies for ChangePoverty and Dependence in the European CommunityRegional Development and the European CommunityThe European Community Transport PolicyPlanning in Europe: Urban and Regional Planning in the EECSterling in Decline. The Devaluations of 1931, 1949 and 1967The Red Market: Industrial Co‐operation and Specialisation in ComeconEconomies of Scale, Competitiveness and Trade Patterns within the European CommunicyStrategies and Policies of the European Economic Communig to Improve the Competitiveness of European IndustryIn Search of a Common Fisheries PolicyStrikes in Europe and the United States, Measurement and IncidenceOfficial Publicatiotrc of Western Europe. Volume I: Denmark, Finland, France, Ireland, Italy, Luxembourg, Netherlands, Spain and TurkeyThe Pilkington Library, Loughborough University of Technology Grants for Europe: How to Get Money and lnfuence Policy