Showing papers by "University of Naples Federico II published in 2002"

Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases.

Abstract: The goal of this review is to place the exciting advances that have occurred in our understanding of the molecular biology of the types 1, 2, and 3 (D1, D2, and D3, respectively) iodothyronine deiodinases into a biochemical and physiological context. We review new data regarding the mechanism of selenoprotein synthesis, the molecular and cellular biological properties of the individual deiodinases, including gene structure, mRNA and protein characteristics, tissue distribution, subcellular localization and topology, enzymatic properties, structure-activity relationships, and regulation of synthesis, inactivation, and degradation. These provide the background for a discussion of their role in thyroid physiology in humans and other vertebrates, including evidence that D2 plays a significant role in human plasma T3 production. We discuss the pathological role of D3 overexpression causing “consumptive hypothyroidism” as well as our current understanding of the pathophysiology of iodothyronine deiodination during illness and amiodarone therapy. Finally, we review the new insights from analysis of mice with targeted disruption of the Dio2 gene and overexpression of D2 in the myocardium. (Endocrine Reviews 23: 38–89, 2002)

Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency

Abstract: The wide range of phenotypic abnormalities seen in the leptin-deficient ob/ob mouse and their reversibility by leptin administration provide compelling evidence for the existence of multiple physiological functions of this hormone in rodents. In contrast, information regarding the roles of this hormone in humans is limited. Three morbidly obese children, who were congenitally deficient in leptin, were treated with daily subcutaneous injections of recombinant human leptin for up to 4 years with sustained, beneficial effects on appetite, fat mass, hyperinsulinemia, and hyperlipidemia. Leptin therapy resulted in a rapid and sustained increase in plasma thyroid hormone levels and, through its age-dependent effects on gonadotropin secretion, facilitated appropriately timed pubertal development. Leptin deficiency was associated with reduced numbers of circulating CD4+ T cells and impaired T cell proliferation and cytokine release, all of which were reversed by recombinant human leptin administration. The subcutaneous administration of recombinant human leptin has major and sustained beneficial effects on the multiple phenotypic abnormalities associated with congenital human leptin deficiency.

Fiber-Reinforced Polymer Composites for Construction—State-of-the-Art Review

Abstract: A concise state-of-the-art survey of fiber-reinforced polymer (also known as fiber-reinforced plastic) composites for construction applications in civil engineering is presented. The paper is organized into separate sections on structural shapes, bridge decks, internal reinforcements, externally bonded reinforcements, and standards and codes. Each section includes a historical review, the current state of the art, and future challenges.

Recovering traceability links between code and documentation

Abstract: Software system documentation is almost always expressed informally in natural language and free text. Examples include requirement specifications, design documents, manual pages, system development journals, error logs, and related maintenance reports. We propose a method based on information retrieval to recover traceability links between source code and free text documents. A premise of our work is that programmers use meaningful names for program items, such as functions, variables, types, classes, and methods. We believe that the application-domain knowledge that programmers process when writing the code is often captured by the mnemonics for identifiers; therefore, the analysis of these mnemonics can help to associate high-level concepts with program concepts and vice-versa. We apply both a probabilistic and a vector space information retrieval model in two case studies to trace C++ source code onto manual pages and Java code to functional requirements. We compare the results of applying the two models, discuss the benefits and limitations, and describe directions for improvements.

The supramolecular structure of humic substances: A novel understanding of humus chemistry and implications in soil science

Abstract: The scientific understanding of the molecular structure of humic substances is critically reviewed here. The traditional view that humic substances are polymers in soil is not substantiated by any direct evidence but only assumed on the basis of laboratory experiments with model molecules and unwarranted results by incorrectly applying either analytical procedures or mathematical treatments developed for purified and undisputed biopolymers. A large body of evidence instead shows an alternative understanding of the conformational nature of humic substances which should be regarded as supramolecular associations of self-assembling heterogeneous and relatively small molecules deriving from the degradation and decomposition of dead biological material. A major aspect of the humic supramolecular structure is that it is predominantly stabilized by weak dispersive forces instead of covalent linkages. Hydrophobic (van der Waals, π-π, CH-π) and hydrogen bonds are responsible for the apparent large molecular size of humic substances, the former becoming more important with the increase of pH. Such novel description of humic substances structure better accounts for their essential role in providing and maintaining soil physical and chemical quality and their reactivity towards pesticides and other environmental soil contaminants. This innovative understanding of the nature of humic substances implies a further development of the science and technology for the control of the chemistry and dynamics of natural organic matter in the soil and the environment.

Thermogravimetric Analysis and Devolatilization Kinetics of Wood

Abstract: Thermogravimetric curves have been measured at a heating rate of 5 K/min for several hardwoods (beech, alder, birch, and oak) and softwoods (Douglas fir, two pine species, redwood, and spruce), whose chemical composition varies within the usual standards. The analysis of the devolatilization characteristics is based on the introduction of several reaction temperatures. A comparison between hardwoods and softwoods shows that, in the latter case, the decomposition starts at lower temperatures, the hemicellulose shoulder is more delayed, and both the hemicellulose and cellulose zones are wider. Furthermore, the yields of char are higher. However, a devolatilization mechanism, consisting of three parallel reactions and the same set of activation energies for hemicellulose, cellulose, and lignin (100, 236, and 46 kJ/mol), can describe the high-temperature (>553 K) degradation behavior of all of the woods with a good accuracy. Modifications for the extension of the mechanism at lower temperatures are required o...

Solution structure of the Alzheimer amyloid beta-peptide (1-42) in an apolar microenvironment. Similarity with a virus fusion domain.

Abstract: The major components of neuritic plaques found in Alzheimer disease (AD) are peptides known as amyloid beta-peptides (Abeta), which derive from the proteolitic cleavage of the amyloid precursor proteins. In vitro Abeta may undergo a conformational transition from a soluble form to aggregated, fibrillary beta-sheet structures, which seem to be neurotoxic. Alternatively, it has been suggested that an alpha-helical form can be involved in a process of membrane poration, which would then trigger cellular death. Conformational studies on these peptides in aqueous solution are complicated by their tendency to aggregate, and only recently NMR structures of Abeta-(1-40) and Abeta-(1-42) have been determined in aqueous trifluoroethanol or in SDS micelles. All these studies hint to the presence of two helical regions, connected through a flexible kink, but it proved difficult to determine the length and position of the helical stretches with accuracy and, most of all, to ascertain whether the kink region has a preferred conformation. In the search for a medium which could allow a more accurate structure determination, we performed an exhaustive solvent scan that showed a high propensity of Abeta-(1-42) to adopt helical conformations in aqueous solutions of fluorinated alcohols. The 3D NMR structure of Abeta-(1-42) shows two helical regions encompassing residues 8-25 and 28-38, connected by a regular type I beta-turn. The surprising similarity of this structure, as well as the sequence of the C-terminal moiety, with those of the fusion domain of influenza hemagglutinin suggests a direct mechanism of neurotoxicity.

Akt induces enhanced myocardial contractility and cell size in vivo in transgenic mice.

Abstract: The serine-threonine kinase Akt seems to be central in mediating stimuli from different classes of receptors. In fact, both IGF-1 and IL6-like cytokines induce hypertrophic and antiapoptotic signals in cardiomyocytes through PI3K-dependent Akt activation. More recently, it was shown that Akt is involved also in the hypertrophic and antiapoptotic effects of β-adrenergic stimulation. Thus, to determine the effects of Akt on cardiac function in vivo, we generated a model of cardiac-specific Akt overexpression in mice. Transgenic mice were generated by using the E40K, constitutively active mutant of Akt linked to the rat α-myosin heavy chain promoter. The effects of cardiac-selective Akt overexpression were studied by echocardiography, cardiac catheterization, histological and biochemical techniques. We found that Akt overexpression produced cardiac hypertrophy at the molecular and histological levels, with a significant increase in cardiomyocyte cell size and concentric LV hypertrophy. Akt-transgenic mice also showed a remarkable increase in cardiac contractility compared with wild-type controls as demonstrated by the analysis of left ventricular (dP/dtmax) in an invasive hemodynamic study, although with graded dobutamine infusion, the maximum response was not different from that in controls. Diastolic function, evaluated by left ventricular dP/dtmin, was not affected at rest but was impaired during graded dobutamine infusion. Isoproterenol-induced cAMP levels, β-adrenergic receptor (β-AR) density, and β-AR affinity were not altered compared with control mice. Moreover, studies on signaling pathway activation from myocardial extracts demonstrated that glycogen synthase kinase3-β is phosphorylated, whereas p42/44 mitogen-activated protein kinases is not, indicating that Akt induces hypertrophy in vivo by activating the glycogen synthase kinase3-β/GATA 4 pathway. In summary, our results not only demonstrate that Akt regulates cardiomyocyte cell size in vivo, but, importantly, show that Akt modulates cardiac contractility in vivo without directly affecting β-AR signaling capacity.

Expression of Epidermal Growth Factor Receptor Correlates with Disease Relapse and Progression to Androgen-independence in Human Prostate Cancer

Abstract: Purpose: The transforming growth factor α-epidermal growth factor receptor (EGFR) autocrine pathway has been implicated in prostate cancer cell growth. Amplification and/or overexpression of c-erbB-2, a receptor closely related to the EGFR, has been recently involved in prostate cancer progression. We investigated EGFR and c-erbB-2 expression in primary androgen-dependent and in advanced androgen-independent prostate cancer and their potential role as markers of disease progression. Experimental Design: EGFR and c-erbB-2 expression were evaluated by immunohistochemistry in a consecutive series of 74 prostate cancer patients with the following characteristics: 29 patients (group 1) treated with radical prostatectomy; 29 patients (group 2) treated with luteinizing hormone-releasing hormone analogues and antiandrogen therapy followed by radical prostatectomy; and 16 patients with hormone-refractory metastatic disease. In all patients we evaluated: association between EGFR and/or c-erbB-2 expression and clinicopathological parameters; and disease-free survival according to EGFR and c-erbB-2 expression in univariate analysis (Kaplan-Meier product-limit method) and in multivariate analysis (Cox proportional hazards regression model). Results: EGFR expression was found in 12 of 29 (41.4%) group 1 patients, in 22 of 29 (75.9%) group 2 patients (P Conclusions: EGFR expression increases during the natural history of prostate cancer. Correlation with disease progression and hormone-refractory disease suggests that EGFR-targeted drugs could be of therapeutic relevance in prostate cancer.

Effects of subclinical thyroid dysfunction on the heart.

Abstract: Because the heart responds to the minimal but persistent changes in circulating thyroid hormone levels, subclinical thyroid dysfunction is not simply a compensated biochemical change. Physicians sh...

The first large population based twin study of coeliac disease

Abstract: Background and aims: The genetic load in coeliac disease has hitherto been inferred from case series or anecdotally referred twin pairs. We have evaluated the genetic component in coeliac disease by estimating the concordance rate for the disease among twin pairs in a large population based study. Methods: The Italian Twin Registry was matched with the membership lists of a patient support group. Forty seven twin pairs were recruited and screened for antiendomysial (EMA) and antihuman-tissue transglutaminase (anti-tTG) antibodies; zygosity was verified by DNA fingerprinting and twins were typed for HLA class II DRB1 and DQB1 molecules. Results: Concordance rates for coeliac disease differ significantly between monozygotic (MZ) (0.86 probandwise and 0.75 pairwise) and dizygotic (DZ) (0.20 probandwise and 0.11 pairwise) twins. This is the highest concordance so far reported for a multifactorial disease. A logistic regression model, adjusted for age, sex, number of shared HLA haplotypes, and zygosity, showed that genotypes DQA1*0501/DQB1*0201 and DQA1*0301/DQB1*0302 (encoding for heterodimers DQ2 and DQ8, respectively) conferred to the non-index twin a risk of contracting the disease of 3.3 and 1.4, respectively. The risk of being concordant for coeliac disease estimated for the non-index twin of MZ pairs was 17 (95% confidence interval 2.1–134), independent of the DQ at risk genotype. Conclusion: This study provides substantial evidence for a very strong genetic component in coeliac disease, which is only partially due to the HLA region.

H1‐antihistamines: inverse agonism, anti‐inflammatory actions and cardiac effects

Abstract: This review addresses novel concepts of histamine H1-receptor function and attempts to relate them to the anti-inflammatory effects of H1-antihistamines. Furthermore, the molecular mechanisms underlying the cardiotoxic effects of H1-antihistamines are discussed. H1-receptors are G-protein-coupled-receptors (GPCRs), the inactive and active conformations of which coexist in equilibrium. The degree receptor activation in the absence of histamine is its 'constitutive activity'. In this two-state model, histamine acts as an agonist by combining with and stabilizing the activated conformation of the H1-receptor to shift the equilibrium towards the activated state. Drugs classified previously as antagonists act as either inverse agonists or neutral antagonists. Inverse agonists combine with and stabilize the inactive conformation of the receptor to shift the equilibrium towards the inactive state. Thus, they may down-regulate constitutive receptor activity, even in the absence of histamine. Neutral antagonists combine equally with both conformations of the receptor, do not affect basal receptor activity but do interfere with agonist binding. All H1-antihistamines examined to date are inverse agonists. As the term 'H1-receptor antagonists' is obviously erroneous, we suggest that it be replaced by 'H1-antihistamines'. The observations that H1-receptors modulate NF-kappaB activation and that there are complex interactions between GPCRs, has allowed us to postulate receptor dependent-mechanisms for some anti-inflammatory effects of H1-antihistamines, e.g. inhibition of ICAM-1 expression and the effects of bradykinin. Finally, the finding that blockade of HERG1 K+ channels is the mechanism by which some H1-antihistamines may cause cardiac arrhythmias has allowed the development of preclinical tests to predict such activity.

Ligands of the peroxisome proliferator-activated receptors (PPAR-gamma and PPAR-alpha) reduce myocardial infarct size.

Abstract: This study was designed to investigate the effects of various chemically distinct activators of PPAR-gamma and PPAR-alpha in a rat model of acute myocardial infarction. Using Northern blot analysis and RT-PCR in samples of rat heart, we document the expression of the mRNA for PPAR-gamma (isoform 1 but not isoform 2) as well as PPAR-beta and PPAR-alpha in freshly isolated cardiac myocytes and cardiac fibroblasts and in the left and right ventricles of the heart. Using a rat model of regional myocardial ischemia and reperfusion (in vivo), we have discovered that various chemically distinct ligands of PPAR-gamma (including the TZDs rosiglitazone, ciglitazone, and pioglitazone, as well as the cyclopentanone prostaglandins 15D-PGJ2 and PGA1) cause a substantial reduction of myocardial infarct size in the rat. We demonstrate that two distinct ligands of PPAR-alpha (including clofibrate and WY 14643) also cause a substantial reduction of myocardial infarct size in the rat. The most pronounced reduction in infarct size was observed with the endogenous PPAR-gamma ligand, 15-deoxyDelta12,14-prostagalndin J2 (15D-PGJ2). The mechanisms of the cardioprotective effects of 15D-PGJ2 may include 1) activation of PPAR-alpha, 2) activation of PPAR-gamma, 3) expression of HO-1, and 4) inhibition of the activation of NF-kappaB in the ischemic-reperfused heart. Inhibition by 15D-PGJ2 of the activation of NF-kappaB in turn results in a reduction of the 1) expression of inducible nitric oxide synthase and the nitration of proteins by peroxynitrite, 2) formation of the chemokine MCP-1, and 3) expression of the adhesion molecule ICAM-1. We speculate that ligands of PPAR-gamma and PPAR-alpha may be useful in the therapy of conditions associated with ischemia-reperfusion of the heart and other organs. Our findings also imply that TZDs and fibrates may help protect the heart against ischemia-reperfusion injury. This beneficial effect of 15D-PGJ2 was associated with a reduction in the expression of the 1) adhesion molecules ICAM-1 and P-selectin, 2) chemokine macrophage chemotactic protein 1, and 3) inducible isoform of nitric oxide synthase. 15D-PGJ2 reduced the nitration of proteins (immunohistological analysis of nitrotyrosine formation) caused by ischemia-reperfusion, likely due to the generation of peroxynitrite. Not all of the effects of 15D-PGJ2, however, are due to the activation of PPAR-gamma. For instance, exposure of rat cardiac myocytes to 15D-PGJ2, but not to rosiglitazone, results in an up-regulation of the expression of the mRNA for heme-oxygenase-1 (HO-1). Taken together, these results provide convincing evidence that several, chemically distinct ligands of PPAR-gamma reduce the tissue necrosis associated with acute myocardial infarction.

Risk of Non-Hodgkin Lymphoma in Celiac Disease

Abstract: ContextCeliac disease is one of the most common lifelong disorders. Non-Hodgkin lymphoma is a possible complication of celiac disease and may lead to a large portion of lymphoma cases.ObjectiveTo quantify the risk for developing non-Hodgkin lymphoma of any primary site associated with celiac disease.Design and SettingMulticenter, case-control study conducted between January 1996 and December 1999 throughout Italy.PatientsCases were older than 20 years (median, 57; range, 20-92 years) with non-Hodgkin lymphoma of any primary site and histological type and were recruited at the time of the diagnosis. Controls were healthy adults (2739 men and 2981 women) from the general population.Main Outcome MeasurePositive test result for class A serum antiendomysial antibody.ResultsCeliac disease was diagnosed in 6 (0.92%) of 653 patients with lymphoma. Of the 6 cases, 3 were of B-cell and 3 were of T-cell origin. Four of 6 cases had lymphoma primarily located in the gut. In the control group, 24 (0.42%) had celiac disease. The odds ratio (adjusted for age and sex) for non-Hodgkin lymphoma of any primary site associated with celiac disease was 3.1 (95% confidence interval [CI], 1.3-7.6), 16.9 (95% CI, 7.4-38.7) for gut lymphoma, and 19.2 (95% CI, 7.9-46.6) for T-cell lymphoma, respectively. The risk for non-Hodgkin lymphoma for the overall population, which was adjusted for age and sex, was 0.63% (95% CI, − 0.12% to 1.37%).ConclusionCeliac disease is associated with an increased risk for non-Hodgkin lymphoma, especially of T-cell type and primarily localized in the gut. However, the association does not represent a great enough risk to justify early mass screening for celiac disease.

Spastin, the protein mutated in autosomal dominant hereditary spastic paraplegia, is involved in microtubule dynamics

Abstract: Hereditary spastic paraplegia (HSP) is characterized by progressive weakness and spasticity of the lower limbs, caused by the specific degeneration of the corticospinal tracts, the longest axons in humans Most cases of the autosomal dominant form of the disease are due to mutations in the SPG4 gene, which encodes spastin, an ATPase belonging to the AAA family The cellular pathways in which spastin operates and its role in causing degeneration of motor axons are currently unknown By expressing wild-type or ATPase-defective spastin in several cell types, we now show that spastin interacts dynamically with microtubules Spastin association with the microtubule cytoskeleton is mediated by the N-terminal region of the protein, and is regulated through the ATPase activity of the AAA domain Expression of all the missense mutations into the AAA domain, which were previously identified in patients, leads to constitutive binding to microtubules in transfected cells and induces the disappearance of the aster and the formation of thick perinuclear bundles, suggesting a role of spastin in microtubule dynamics Consistently, wild-type spastin promotes microtubule disassembly in transfected cells These data suggest that spastin may be involved in microtubule dynamics similarly to the highly homologous microtubule-severing protein, katanin Impairment of fine regulation of the microtubule cytoskeleton in long axons, due to spastin mutations, may underlie pathogenesis of HSP

The single, ancient origin of chromist plastids.

Abstract: Algae include a diverse array of photosynthetic eukaryotes excluding land plants Explaining the origin of algal plastids continues to be a major challenge in evolutionary biology Current knowledge suggests that plastid primary endosymbiosis, in which a single-celled protist engulfs and “enslaves” a cyanobacterium, likely occurred once and resulted in the primordial alga This eukaryote then gave rise through vertical evolution to the red, green, and glaucophyte algae However, some modern algal lineages have a more complicated evolutionary history involving a secondary endosymbiotic event, in which a protist engulfed an existing eukaryotic alga (rather than a cyanobacterium), which was then reduced to a secondary plastid Secondary endosymbiosis explains the majority of algal biodiversity, yet the number and timing of these events is unresolved Here we analyzed a five-gene plastid data set to show that a taxonomically diverse group of chlorophyll c2-containing protists comprising cryptophyte, haptophyte, and stramenopiles algae (Chromista) share a common plastid that most likely arose from a single, ancient (≈1,260 million years ago) secondary endosymbiosis involving a red alga This finding is consistent with Chromista monophyly and implicates secondary endosymbiosis as an important force in generating eukaryotic biodiversity

Recursive estimation of the covariance matrix of a compound-Gaussian process and its application to adaptive CFAR detection

Abstract: Adaptive detection of signals embedded in Gaussian or non-Gaussian noise is a problem of primary concern among radar engineers. We propose a recursive algorithm to estimate the structure of the covariance matrix of either a set of Gaussian vectors that share the spectral properties up to a multiplicative factor or a set of spherically invariant random vectors (SIRVs) with the same covariance matrix and possibly correlated texture components. We also assess the performance of an adaptive implementation of the normalized matched filter (NMF), relying on the newly introduced estimate, in the presence of compound-Gaussian, clutter-dominated, disturbance. In particular, it is shown that a proper initialization of the recursive procedure leads to an adaptive NMF with the constant false alarm rate (CFAR) property and that it is very effective to operate in heterogeneous environments of relevant practical interest.

Nutritional value of cherry tomatoes (Lycopersicon esculentum Cv. Naomi F1) harvested at different ripening stages.

Abstract: The average content of some classes of antioxidants is generally higher in cherry tomatoes than in normal-sized berries. The aim of this work was to assess the nutritional value of cherry tomato (c...

Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia.

Abstract: Schimke immuno-osseous dysplasia (SIOD, MIM 242900) is an autosomal-recessive pleiotropic disorder with the diagnostic features of spondyloepiphyseal dysplasia, renal dysfunction and T-cell immunodeficiency. Using genome-wide linkage mapping and a positional candidate approach, we determined that mutations in SMARCAL1 (SWI/SNF2-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1), are responsible for SIOD. Through analysis of data from persons with SIOD in 26 unrelated families, we observed that affected individuals from 13 of 23 families with severe disease had two alleles with nonsense, frameshift or splicing mutations, whereas affected individuals from 3 of 3 families with milder disease had a missense mutation on each allele. These observations indicate that some missense mutations allow retention of partial SMARCAL1 function and thus cause milder disease.

Endoscopic transsphenoidal approach: adaptability of the procedure to different sellar lesions.

Abstract: OBJECTIVE: To demonstrate the flexibility of the endoscopic transsphenoidal approach, with respect to nasal and paranasal anatomic features and the extension of different sellar lesions, for customization of the procedure for specific conditions. METHODS: In 16 of 170 consecutive endoscopic transsphenoidal operations, some modifications of the standard approach were adopted to optimize surgical removal of different lesions. These modifications consisted of a hemisphenoidotomy, a partial ethmoidectomy, extended sellar floor opening toward the planum sphenoidale or the clivus, enlarged opening of the sphenoid ostium area with ipsilateral removal of the superior turbinate, and a bilateral approach. RESULTS: The endoscopic endonasal procedure is easily adaptable to different specific conditions, with slight changes in the standard approach (more or less invasive). Therefore, this surgical procedure is satisfactory for different lesion locations and for the nasal and paranasal sinus anatomic features of individual patients. CONCLUSION: The endoscopic surgical route should be tailored to different sellar lesions, and some modifications of the procedure are recommended in selected cases.

Variability of fish consumption within the 10 European countries participating in the European Investigation into Cancer and Nutrition (EPIC) study

Abstract: OBJECTIVE: To describe and compare the consumption of total fish (marine foods) and the fish sub-groups - white fish, fatty fish, very fatty fish, fish products and crustacea, in participants from the European Investigation into Cancer and Nutrition (EPIC) study. DESIGN: Cross-sectional analysis of dietary intake using a computerised standardised 24-hour recall interview. Crude means, means and standard errors adjusted by age, season and day of the week were calculated, stratified by centre and gender. SETTING: Twenty-seven redefined centres in the 10 European countries participating in the EPIC study. SUBJECTS: In total, 35 955 subjects (13 031 men and 22 924 women), aged 35-74 years, selected from the main EPIC cohort. RESULTS: A six- to sevenfold variation in total fish consumption exists in women and men, between the lowest consumption in Germany and the highest in Spain. Overall, white fish represented 49% and 45% of the intake of total fish in women and men, respectively, with the greatest consumption in centres in Spain and Greece and the least in the German and Dutch centres. Consumption of fatty fish reflected that of total fish. However, the greatest intake of very fatty fish was in the coastal areas of northern Europe (Denmark, Sweden and Norway) and in Germany. Consumption of fish products was greater in northern than in southern Europe, with white fish products predominating in centres in France, Italy, Spain, The Netherlands and Norway. Intake of roe and roe products was low. The highest consumption of crustacea was found in the French, Spanish and Italian centres. The number of fish types consumed was greater in southern than in northern Europe. The greatest variability in consumption by day of the week was found in the countries with the lowest fish intake. CONCLUSIONS: Throughout Europe, substantial geographic variation exists in total fish intake, fish sub-groups and the number of types consumed. Day-to-day variability in consumption is also high.

Crystal structure of the collagen triple helix model [(Pro-Pro-Gly)(10)](3).

Abstract: The first report of the full-length structure of the collagen-like polypeptide [(Pro-Pro-Gly)(10)](3) is given. This structure was obtained from crystals grown in a microgravity environment, which diffracted up to 1.3 A, using synchrotron radiation. The final model, which was refined to an R(factor) of 0.18, is the highest-resolution description of a collagen triple helix reported to date. This structure provides clues regarding a series of aspects related to collagen triple helix structure and assembly. The strict dependence of proline puckering on the position inside the Pro-Pro-Gly triplets and the correlation between backbone and side chain dihedral angles support the propensity-based mechanism of triple helix stabilization/destabilization induced by hydroxyproline. Furthermore, the analysis of [(Pro-Pro-Gly)(10)](3) packing, which is governed by electrostatic interactions, suggests that charges may act as locking features in the axial organization of triple helices in the collagen fibrils.

The fetal origins of atherosclerosis: maternal hypercholesterolemia, and cholesterol-lowering or antioxidant treatment during pregnancy influence in utero programming and postnatal susceptibility to atherogenesis

Abstract: It has long been postulated that pathogenic events during fetal development influence atherosclerosis-related diseases later in life, but the mechanisms involved are unknown. This review focuses on the evidence indicating that maternal hypercholesterolemia during pregnancy is responsible for one cascade of pathogenic events. Maternal hypercholesterolemia is associated with greatly increased fatty streak formation in human fetal arteries and accelerated progression of atherosclerosis during childhood. Recent experiments in genetically more homogeneous rabbits established that temporary diet-induced maternal hypercholesterolemia is sufficient to enhance fetal lesion formation. More important, maternal hypercholesterolemia or ensuing pathogenic events in the fetus increase postnatal atherogenesis in response to hypercholesterolemia. Maternal treatment with cholesterol-lowering agents or antioxidants greatly reduces fetal and postnatal atherogenesis, indicating a pathogenic role of lipid peroxidation and a potential involvement of oxidation-sensitive signaling pathways. Experiments in a murine model showed that differences in arterial gene expression between offspring of normo- and hypercholesterolemic mothers persist long after birth, supporting the assumption that fetal lesion formation is associated with genetic programming, which may in turn affect postnatal atherogenesis. A better understanding of pathogenic programming events in utero may lead to the identification of genes determining the susceptibility to atherosclerosis and define novel preventive approaches.

Enhancement of antitumor activity of ionizing radiation by combined treatment with the selective epidermal growth factor receptor-tyrosine kinase inhibitor ZD1839 (Iressa)

Abstract: Purpose: The epidermal growth factor receptor (EGFR) is expressed in the majority of human epithelial cancers and has been implicated in the development of cancer cell resistance to cyotoxic drugs and to ionizing radiation. Experimental Design: We used ZD1839, a selective small molecule EGFR tyrosine kinase inhibitor currently in clinical development. We tested the antiproliferative and the proapoptotic activity of ZD1839 in combination with ionizing radiation in human colon (GEO), ovarian (OVCAR-3), non-small cell lung (A549 and Calu-6), and breast (MCF-7 ADR) cancer cell lines. The antitumor activity of this combination was also tested in nude mice bearing established GEO colon cancer xenografts. Results: With ionizing radiation or ZD1839, a dose-dependent growth inhibition was observed in all of the cancer cell lines growing in soft agar. A cooperative antiproliferative and proapoptotic effect was obtained when cancer cells were treated with ionizing radiation followed by ZD1839. This effect was accompanied by inhibition in the expression of the antiapoptotic proteins bcl-xL and bcl-2, and by a suppression of the activated (phosphorylated) form of akt protein. Treatment of mice bearing established human GEO colon cancer xenografts with radiotherapy (RT) resulted in a dose-dependent tumor growth inhibition that was reversible upon treatment cessation. Long term GEO tumor growth regressions were obtained after RT in combination with ZD1839. This resulted in a significant improvement in survival of these mice as compared with the control group ( P P P Conclusion: This study provides a rationale for evaluating in cancer patients the combination of ionizing radiation and selective EGFR tyrosine kinase inhibitors such as ZD1839.

Introduction to Methodology

Abstract: This chapter explores various apparently unrelated problems and formulating them in the simplest form such that in most cases an analytical solution to the governing equations can be obtained. Lessons of general applicability are extracted from the solutions of the problems considered. The concept that the subjects of transport phenomena and of thermodynamics are strongly intertwined is strictly emphasized. All problems in engineering science are formulated on the basis of two types of equations: balance and constitutive. A balance equation can be written either for a quantity for which a general principle of conservation exists, or for a quantity for which no such principle exists provided its rate of generation is included in the balance equation. A constitutive equation is one that assigns the value of F ( X , t )—the flux of the quantity considered—in terms of C ( X , t )—the amount of the quantity considered per unit volume—so that the problem becomes a mathematically well posed one. The two types of equations are discussed by illustrating several classic problems such as the plug flow reactor with diffusion, shock waves in gases, and stefan problem.