bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multistage carcinogenesis and the incidence of human cancer
Authors: Moolgavkar Suresh H. , Luebeck E. Georg 
Published: October 2003

AbstractWe consider the implications of multistage carcinogenesis for the incidence of cancer in human populations. When clonal expansion of partially altered cells is properly accounted for, we find it unnecessary to invoke genomic instability as an early event in malignant transformation. Environmental agents that increase the rate of clonal expansion of partially altered cells are efficient carcinogens. As a corollary, intervention strategies that decrease this rate are to be preferred to strategies that decrease the rate of early mutational events in carcinogenesis. © 2003 Wiley‐Liss, Inc.
Search for unknown tumor‐antagonizing genes
Authors: Imreh Stephan , Klein George , Zabarovsky Eugene R. 
Published: October 2003

AbstractFollowing the ingenious prediction of Alfred Knudson in 1971, the first tumor suppressor gene, RB1, has been isolated. Its product, the RB1 protein, was found to play a major role in the control of the cell cycle. The loss of heterozygosity (LOH) technique, introduced by Cavenee and colleagues, was an important milestone toward the confirmation of Knudson's hypothesis and the identification of the gene. Subsequently, the LOH technique has provided important clues that have led to the discovery of other tumor suppressor genes. Most of them play important roles in the regulation of the cell cycle and/or of apoptosis. Circumstantial evidence suggests that still other and perhaps many unknown genes may participate in the protection of the organism against malignant growth. The numerous genome losses in tumors, detected by LOH, comparative genomic hybridization, and by cytogenetic techniques, support this possibility. The early work of one of us (G.K.), together with Henry Harris and Francis Wiener, had shown that the malignant phenotype can be suppressed by hybridizing malignant with low‐ or non‐tumorigenic cells. However, analysis of this phenomenon failed to assign the inhibition of tumorigenicity to any particular gene. We have pursued the search for new tumor‐antagonizing genes with two unconventional approaches, focusing on human chromosomal subband 3p21.3, a region frequently targeted by cytogenetically detectable deletions. We have detected four clusters of candidate tumor suppressor genes at 3p21.3 by a combination of deletion mapping and the “elimination test.” These findings raise the question whether the number and variety of genes that may contribute to the defense against uncontrolled proliferation may have been underestimated. © 2003 Wiley‐Liss, Inc.
Differential expression and localization of the phosphorylated and nonphosphorylated neurofilaments during the early postnatal development of rat hippocampus
Authors: Lopez‐Picon F.R. , Uusi‐Oukari M. , Holopainen I.E. 
Published: October 2003

AbstractNeurofilament (NF) proteins are expressed in most mature neurons in the central nervous system. Although they play a crucial role in neuronal growth, organization, shape, and plasticity, their expression pattern and cellular distribution in the developing hippocampus remain unknown. In the present study, we have used Western blotting and immunocytochemistry to study the low‐ (NF‐L), medium‐ (NF‐M), and high‐ (NF‐H) molecular‐weight NF proteins; phosphorylated epitopes of NF‐M and NF‐H; and a nonphosphorylated epitope of NF‐H in the early postnatal (through P1–P21) development of the rat hippocampus. During the first postnatal week, NF‐M was the most abundantly expressed NF, followed by NF‐L, whereas the expression of NF‐H was very low. Through P7–P14, the expression of NF‐H increased dramatically and later began to plateau, as also occurred in the expression of NF‐M and NF‐L. At P1, no NF‐M immunopositive cell bodies were detected, but cell processes in the CA1‐CA3 fields were faintly immunopositive for NF‐M and for the phosphorylated epitopes of NF‐M and NF‐H. At P7, CA3 pyramidal neurons were strongly immunopositive for NF‐L and NF‐H, but not for NF‐M. The axons of granule cells, the mossy fibers (MFs), were NF‐L and NF‐M positive through P7–P21 but were NF‐H immunonegative at all ages. Although they stained strongly for the phosphorylated NF‐M and NF‐H at P7, the staining intensity sharply decreased at P14 and remained so at P21. The cell bodies of CA1 pyramidal neurons and granule cells remained immunonegative against all five antibodies in all age groups. Our results show a different time course in the expression and differential cell type and cellular localization of the NF proteins in the developing hippocampus. These developmental changes could be of importance in determining the reactivity of hippocampal neurons in pathological conditions in the immature hippocampus. © 2003 Wiley‐Liss, Inc.
Impaired interleukin‐1 signaling is associated with deficits in hippocampal memory processes and neural plasticity
Authors: Avital Avi , Goshen Inbal , Kamsler Ariel , Segal Menahem , Iverfeldt Kerstin , Richter‐Levin Gal , Yirmiya Raz 
Published: October 2003

AbstractThe cytokine interleukin‐1 (IL‐1) is produced by peripheral immune cells as well as glia and neurons within the brain; it plays a major role in immune to brain communication and in modulation of neural, neuroendocrine, and behavioral systems during illness. Although previous studies demonstrated that excess levels of IL‐1 impaired memory processes and neural plasticity, it has been suggested that physiological levels of IL‐1 are involved in hippocampal‐dependent memory and long‐term potentiation (LTP). To examine this hypothesis, we studied IL‐1 receptor type I knockout (IL‐1rKO) mice in several paradigms of memory function and hippocampal plasticity. In the spatial version of the water maze test, IL‐1rKO mice displayed significantly longer latency to reach a hidden platform, compared with wild‐type controls. Furthermore, IL‐1rKO exhibited diminished contextual fear conditioning. In contrast, IL‐1rKO mice were similar to control animals in hippocampal‐independent memory tasks; i.e., their performance in the visually guided task of the water maze and the auditory‐cued fear conditioning was normal. Electrophysiologically, anesthetized IL‐1rKO mice exhibited enhanced paired‐pulse inhibition in response to perforant path stimulation and no LTP in the dentate gyrus. In vitro, decreased paired‐pulse responses, as well as a complete absence of LTP, were observed in the CA1 region of hippocampal slices taken from IL‐1rKO mice compared with WT controls. These results suggest that IL‐1 contributes to the regulation of memory processes as well as short‐ and long‐term plasticity within the hippocampus. These findings have important implications to several conditions in humans, which are associated with long‐term defects in IL‐1 signaling, such as mutations in the IL‐1 receptor accessory protein‐like gene, which are involved in a frequent form of X‐linked mental retardation. © 2003 Wiley‐Liss, Inc.
Loss of FHIT protein expression is a marker of adverse evolution in good prognosis localized breast cancer
Authors: Ginestier Christophe , Bardou Valérie‐Jeanne , Popovici Cornel , Charafe‐Jauffret Emmanuelle , Bertucci François , Geneix Jeannine , Adélaïde José , Chaffanet Max , Hassoun Jacques , Viens Patrice , Jacquemier Jocelyne , Birnbaum Daniel 
Published: October 2003

AbstractTheFHITtumor suppressor gene, which encompasses the fragile siteFRA3Bat 3p14.2, is altered frequently in many types of human cancers. To determine its importance as a prognostic marker in breast cancer, the expression of the FHIT protein was studied in a series of 452 breast carcinomas by using immunohistochemistry on sections of tissue microarrays. Three distinct levels of FHIT expression were observed: in 154 cases (34.1%) expression was unchanged as compared to normal level; in 78 (17.2%) no expression was found; in the remaining 220 cases (48.7%), expression was intermediate. Overall, two‐thirds of the cases had abnormal levels of the protein. Absence of FHIT was significantly associated with a higher grade (p< 0.01) and absence of hormone receptors (p< 0.001). The patients were separated into Group I (153 node‐negative good prognosis patients who did not receive adjuvant chemotherapy) and Group II (226 high‐risk patients treated by adjuvant chemotherapy) according to the St.‐Gallen conference consensus. The median follow‐up was 48 months. Among Group I but not Group II patients, a multivariate analysis showed that FHIT expression was significantly associated with disease‐free survival. The relative risk of recurrence for FHIT‐negative Group I patients was 2.37 (1.21–4.64;p= 0.03). Thus, among the patients who present with tumors of apparent good prognosis, FHIT is an independent prognostic factor that distinguishes a subgroup of patients who could benefit from adjuvant treatment. © 2003 Wiley‐Liss, Inc.
Comparison of age at first full‐term pregnancy between women with breast cancer and women with benign breast diseases
Authors: Lagiou Areti , Lagiou Pagona , Vassilarou Dorothy‐Stamatia , Stoikidou Melpomeni , Trichopoulos Dimitrios 
Published: October 2003

AbstractBenign breast diseases have a broadly similar risk profile to that of breast cancer, possibly reflecting a similar underlying endocrine milieu. We have hypothesized that a crucial distinction between breast cancer and benign breast diseases is that mammary gland terminal differentiation has not been successfully accomplished among women who tend to develop breast cancer. From October 2001 to December 2002, information concerning breast cancer risk factors and sociodemographic characteristics was collected from 174 women with breast cancer and 116 women with benign breast diseases, all 30 years old or older, who were histologically diagnosed at a major prevention center in Athens, Greece. Among the examined breast cancer risk factors, only age at first full‐term pregnancy was significantly associated with the odds of having breast cancer rather than benign breast disease, and the association was evident among premenopausal [odds ratio (OR) per 5 years = 1.76, 95% confidence interval (CI) 1.10–2.93] and postmenopausal (OR = 2.10, 95% CI 1.16–3.71) women, as well as among all women (OR = 1.93, 95% CI 1.34–2.70). There was no evidence that any of the remaining breast cancer risk factors could discriminate between breast cancer and benign breast diseases. We conclude that early age at first pregnancy may convey substantial protection against breast cancer risk among women with benign breast diseases, probably operating through induction of terminal differentiation of mammary gland cells. The finding is accentuated by the fact that women with benign breast diseases are already at a relatively high risk for breast cancer. © 2003 Wiley‐Liss, Inc.
Use of AFM to probe the adsorption strength and time‐dependent changes of albumin on self‐assembled monolayers
Authors: Dupont‐Gillain Ch. C. , Fauroux C. M. J. , Gardner D. C. J. , Leggett G. J. 
Published: October 2003

AbstractThe adsorption kinetics of human serum albumin (HSA) on CH3‐ and COOH‐terminated self‐assembled monolayers (SAMs) has been investigated using radioassays and atomic force microscopy (AFM). On both surfaces, the amount of HSA adsorbed reached a plateau after 30 min. The plateau level was higher on the CH3 compared to the COOH surface. The adhesion force (Fadh), measured using Si3N4 AFM tips in water, decreased with time of contact with the HSA solution on the CH3 surface. This time‐dependent change in the adhesiveness of the adsorbed protein is best explained by a change in the conformation or orientation. In contrast, Fadh was independent of the time of contact with the HSA solution on the COOH surface, indicating that once adsorbed, the HSA molecules do not undergo further conformation or orientation changes. The perturbation induced by scanning with the AFM in water on the adsorbed HSA layers was greater on CH3 surfaces than on COOH surfaces, suggesting a weaker protein–substratum interaction on the CH3‐terminated SAMs. This was further confirmed by a stronger desorption of HSA following sodium dodecyl sulfate (SDS) treatment on the CH3 surface compared to the COOH surface. Taken together, these data suggest that for COOH SAMs, (1) there is a strong interaction between HSA and the substratum; (2) there is an absence of reorientation with time; and (3) there is a smaller amount of adsorbed protein at 24 h, possibly due to increased but rapid spreading/denaturation of the protein. On the CH3 surface, less deformation of HSA occurs and the molecules maintain a higher mobility at short adsorption times. AFM measurements performed after aging of an adsorbed HSA layer in buffer suggests the role played by HSA in solution in determining the time‐dependent conformation and/or orientation changes. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 548–558, 2003
Interactions of antithrombin and proteins in the plasma contact activation system with immobilized functional heparin
Authors: Cornelius Rena M. , Sanchez Javier , Olsson Per , Brash John L. 
Published: October 2003

AbstractThe interactions of antithrombin (AT) and the contact phase clotting factors with two commercially available heparinized surfaces are reported. The Carmeda (CBAS) and Corline surfaces along with controls (a sulfonated polyethylene surface and a CBAS analog in which the heparin used was devoid of specific AT‐binding sequences) were exposed to human plasma. Adsorbed proteins were eluted and examined by sodium dodecyl sulfate‐polyacrylamide gel electrophoresis and immunoblotting. The CBAS and Corline surfaces adsorbed large amounts of AT, whereas adsorption on the controls was negligible. Immunoblots for the four contact phase clotting factors indicated less contact activation on the CBAS and Corline surfaces than on the controls. Determination of adsorbed functional AT using a FXa inhibition assay showed that the CBAS surface adsorbed about 4 times as much AT as the Corline surface. Adsorption of AT to the control surfaces was minimal. Assays for adsorbed FXII and FXIIa based on kallikrein generation showed that all four surfaces adsorbed similar amounts of FXII. However, on the controls, most of the FXII was in activated form, whereas on the CBAS and Corline surfaces very little activation occurred. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 475–483, 2003
A study on the effect of dual blasting with TiO2 on titanium implant surfaces on functional attachment in bone
Authors: Rønold Hans Jacob , Lyngstadaas Ståle Petter , Ellingsen Jan Eirik 
Published: October 2003

AbstractIn the present study, the effect of a dual treatment of titanium implants and the subsequent bone response after implantation were investigated. Coin‐shaped c.p. titanium implants were placed into the tibias of 12 rabbits. The implant, which was dually blasted with TiO2 particles of two different sizes, was compared with implants that were blasted with only one of these particle sizes. Implants in group 1 were grit blasted with small particles, 22–28 μm in size, and group 2 with coarser particles, 180–220 μm size. These two treatments gave different surface micro textures. To test the effect of a combination of two different treatments, group 3 implants were blasted first with the 180‐ to 220‐μm and subsequently with the 22‐ to 28‐μm particles. The surface topography of the implant specimens was examined by scanning electron microscopy and by a confocal laser scanner and a numeric evaluation of Sa, St, and Sdr was recorded. Group 2 implants, which were blasted with only the coarse particles, showed a significantly better functional attachment (p < 0.001) than the other two groups. Group 1, which was blasted with only small particles, showed the lowest retention in bone. There was a positive correlation between the topographical and mechanical evaluation of the surfaces. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 524–530, 2003
Sphingosine 1‐phosphate induces cell contraction via calcium‐independent/Rho‐dependent pathways in undifferentiated skeletal muscle cells
Authors: Formigli L. , Meacci E. , Vassalli M. , Nosi D. , Quercioli F. , Tiribilli B. , Tani A. , Squecco R. , Francini F. , Bruni P. , Orlandini S. Zecchi 
Published: October 2003

AbstractWe have previously shown that sphingosine 1‐phosphate (S1P) can induce intracellular Ca2+ mobilization and cell contraction in C2C12 myoblasts and that the two phenomena are temporally unrelated. Although Ca2+‐independent mechanisms of cell contraction have been the focus of numerous studies on Ca2+ sensitization of smooth muscle, comparatively less studies have focused on the role that these mechanisms play in the regulation of skeletal muscle contractility. Phosphorylation and activation of myosin by Rho‐dependent kinase mediate most of Ca2+‐independent contractile responses. In the present study, we examined the potential role of Rho/Rho‐kinase cascade activation in S1P‐induced C2C12 cell contraction. First, we showed that depletion of Ca2+, by pre‐treatment with BAPTA, did not affect S1P‐induced myoblastic contractility, whereas it abolished S1P‐induced Ca2+ transients. These results correlated with the absence of troponin C and with the immature cytoskeletal organization of these cells. Experimental evidence demonstrating the involvement of Rho pathway in S1P‐stimulated myoblast contraction included: the activation/translocation of RhoA to the membrane in response to agonist‐stimulation in cells depleted of Ca2+ and the inhibition of dynamic changes of the actin cytoskeleton in cells where Rho functions had been inhibited either by overexpression of RhoGDI, a physiological inhibitor of GDP dissociation from Rho proteins, or by pretreatment with Y‐27632, a specific Rho kinase inhibitor. Contribution of protein kinase C in this cytoskeletal rearrangement was also evaluated. However, the pretreatment with Gö6976 or rottlerin, specific inhibitors of PKCα and PKCδ, respectively, failed to inhibit the agonist‐induced myoblastic contraction. Single particle tracking of G‐actin fluorescent probe was performed to statistically evaluate actin cytoskeletal dynamics in response to S1P. Stimulation with S1P was also able to increase the phosphorylation level of myosin light chain II. In conclusion, our results strongly suggest that Ca2+‐independent/Rho‐Rho kinase‐dependent pathways may exert an important role in S1P‐induced myoblastic cell contraction. J. Cell. Physiol. 198: 1–11, 2004© 2003 Wiley‐Liss, Inc.
Sialoadenectomy alters liver cell turn‐over and function in mice
Authors: Buira Irma , Poch Enric , Sánchez Olga , Fernández‐Varo Guillermo , Grau Montserrat , Tebar Francesc , Ramírez Ignasi , Soley Maria 
Published: October 2003

AbstractIn rodents, submandibular salivary glands accumulate a number of biologically active peptides, and release some of them to both saliva and the bloodstream. Surgical removal of these glands (sialoadenectomy) alters the ability of the liver to regenerate after partial hepatectomy. We show here that 5 weeks after surgery, the liver of sialoadenectomized mice contained 40% fewer hepatocytes than the liver of sham‐operated mice. We did not obtain evidence of necrotic cell death after surgery. In contrast, sialoadenectomy transiently increased apoptotic hepatocyte death, as revealed by terminal deoxynucleotidyl transferase(TdT)‐mediated dUTP nick‐end labeling (TUNEL) assay. DNA synthesis was determined in vivo by the incorporation of bromo‐deoxyuridine (BrdU) into hepatocyte nuclei. BrdU‐labeling progressively increased after sialoadenectomy. We conclude that sialoadenectomy induced a transient wave of apoptotic cell death followed by a rise in DNA synthesis but not by cell division. This reduced cell number but increased mean cell volume. In spite of these alterations in cellularity, the liver responded adequately to several stressful conditions, as judged by the lack of any differential effect of sialoadenectomy on liver glycogen and plasma glucose concentration after immobilization, aggressive encounter, or fasting. However, the liver of sialoadenectomized mice was more sensitive to the effect of a non‐lethal dose of bacterial lipopolysaccharide (LPS) combined with d‐galactosamine, as shown by the enhanced rise in plasma alanine aminotransferase and aspartate aminotransferase, and liver myeloperoxidase (MPO) activities. All these results indicate that a submandibular salivary glands–liver axis is involved in the maintenance of liver structure in mice. A disturbance of this axis induces an adaptive response that preserves the metabolic function of the liver but renders it more sensitive to bacterial endotoxins. J. Cell. Physiol. 198: 12–21, 2004© 2003 Wiley‐Liss, Inc.
Prey transport in “palatine‐erecting” elapid snakes
Authors: Deufel Alexandra , Cundall David 
Published: October 2003

AbstractCobras and mambas are members of a group of elapid snakes supposedly united by the morphology and inferred behavior of their palatine bone during prey transport (palatine erectors). The palatine erectors investigated (Dendroaspis polylepis, Naja pallida, Ophiophagus hannah, Aspidelaps scutatus, A. lubricus) show differences in the morphology of their feeding apparatus that do not affect the overall behavior of the system. We delineated the structures directly involved in producing palatine erection during prey transport. Palatine erection can be achieved by a colubroid muscle contraction pattern acting on a palato‐pterygoid bar with a movable palato‐pterygoid joint and a palatine that is stabilized against the snout. The palatine characters originally proposed to cause palatine erection are not required to produce the behavior and actually impede it in Naja pallida. Palatine‐erecting elapids share a fundamental design of the palato‐maxillary apparatus with all higher snakes. A set of plesiomorphic core characters is functionally integrated to function in prey transport using the pterygoid walk. Variant characters are either part of a structural periphery unrelated to the core structures that define function or patterns of variation are subordinate character sets operating within functional thresholds of a single system. J. Morphol. 258:358–375, 2003. © 2003 Wiley‐Liss, Inc.
Host‐pathogens cross‐talk. Indigenous bacteria and probiotics also play the game
Authors: Freitas Miguel , Tavan Emmanuelle , Cayuela Chantal , Diop Laurent , Sapin Catherine , Trugnan Germain 
Published: October 2003

AbstractMicroflora‐born bacteria or probiotic strains are able to modulate host‐pathogens interactions in the gut. In vivo and in vitro studies indicate that species‐specific modulations of intestinal cell glycosylation may represent a simple, general and efficient mechanism to adapt the host defense toward pathogens.