bluuebunny/crossref_metadata_2025_split huggingface dataset:
RACK1 regulates Ki‐Ras‐mediated signaling and morphological transformation of NIH 3T3 cells
Authors: Bjørndal Bodil , Myklebust Line M. , Rosendal Ken Roger , Myromslien Frøydis D. , Lorens James B. , Nolan Garry , Bruland Ove , Lillehaug Johan R. 
Published: December 2006

AbstractActivating Ras mutations are involved in a significant fraction of human tumors. A suppressor screen using a retroviral mouse fibroblast cDNA library was performed to identify novel factors in Ras‐mediated transformation. We identified a novel potent inhibitor of Ras‐mediated morphological transformation encoded by a truncated version of the receptor for activated C‐kinase (RACK1). The truncated protein, designated RACK1ΔWD1, lacked the N‐terminal 49 amino acids encoding the first of the 7 WD40 repeats in RACK1. RACK1ΔWD1 expression restored contact inhibition, stress fiber formation and reduced ERK phosphorylation in Ki‐Ras transformed NIH 3T3 cells. We demonstrate that truncated RACK1 is involved in complexes consisting of wild‐type RACK1 and protein kinase C isoforms α, βI and δ, compromising the transduction of an activated Ras signal to the Raf‐MEK‐ERK pathway. The cellular localization of RACK1ΔWD1 differed from wtRACK1, indicating that signaling complexes containing the truncated version of RACK1 are incorrectly localized. Notably, 12‐O‐tetradecanoyl‐13‐phorbol acetate (TPA) mediated intracellular translocation of RACK1‐interacting PKC α and δ was abrogated in RACK1ΔWD1‐expressing cells. Our data support a model where RACK1 acts as a key factor in Ki‐Ras‐mediated morphological transformation. © 2006 Wiley‐Liss, Inc.
An ecologic study of cancer mortality rates in Spain with respect to indices of solar UVB irradiance and smoking
Authors: Grant William B. 
Published: December 2006

AbstractThere is increasing evidence that vitamin D reduces the risk of many types of cancer. Geographic variations in cancer mortality rates in Spain are apparently linked to variations in solar ultraviolet (UV) irradiances and other factors. Cancer mortality rates for 48 continental Spanish provinces for 1978–1992 were used in linear regression analyses with respect to mortality rates for latitude (an index of solar UVB levels), skin cancer (an index of high cumulative UVB irradiance), melanoma (an index related to solar UV irradiance and several other factors) and lung cancer (an index of cumulative effects of smoking). The 9 cancers with mortality rates significantly correlated with latitude for 1 or both sexes were brain, gastric, melanoma, nonmelanoma skin cancer (NMSC), non‐Hodgkin's lymphoma (NHL), pancreatic, pleural, rectal and thyroid cancer. Inverse correlations with latitude were found for laryngeal, lung and uterine corpus cancer. The 17 cancers inversely correlated with NMSC are bladder, brain, breast, colon, esophageal, gallbladder, Hodgkin's lymphoma, lung, melanoma, multiple myeloma, NHL, ovarian, pancreatic, pleural, rectal, thyroid and uterine corpus cancer. The 16 correlated with melanoma are bladder, brain, breast, colon, gallbladder, leukemia, lung, multiple myeloma, NHL, ovarian, pancreatic, pleural, prostate, rectal, renal and uterine corpus cancer. The results for lung cancer were in accordance with the literature. These results provide more support for the UVB/vitamin D/cancer hypothesis and indicate a new way to investigate the role of solar UV irradiance on cancer risk. They also provide more evidence that melanoma and NMSC have different etiologies. © 2006 Wiley‐Liss, Inc.
Nerve growth factor enhances voltage‐gated Na+ channel activity and Transwell migration in Mat‐LyLu rat prostate cancer cell line
Authors: Brackenbury William J. , Djamgoz Mustafa B.A. 
Published: December 2006

AbstractThe highly dynamic nature of voltage‐gated Na+ channel (VGSC) expression and its controlling mechanism(s) are not well understood. In this study, we investigated the possible involvement of nerve growth factor (NGF) in regulating VGSC activity in the strongly metastatic Mat‐LyLu cell model of rat prostate cancer (PCa). NGF increased peak VGSC current density in a time‐ and dose‐dependent manner. NGF also shifted voltage to peak and the half‐activation voltage to more positive potentials, and produced currents with faster kinetics of activation; sensitivity to the VGSC blocker tetrodotoxin (TTX) was not affected. The NGF‐induced increase in peak VGSC current density was suppressed by both the pan‐trk antagonist K252a, and the protein kinase A (PKA) inhibitor KT5720. NGF did not affect the Nav1.7 mRNA level, but the total VGSC α‐subunit protein level was upregulated. NGF potentiated the cells' migration in Transwell assays, and this was not affected by TTX. We concluded that NGF upregulated functional VGSC expression in Mat‐LyLu cells, with PKA as a signaling intermediate, but enhancement of migration by NGF was independent of VGSC activity. J. Cell. Physiol. 210: 602–608, 2007. © 2006 Wiley‐Liss, Inc.
CMTM8 induces caspase‐dependent and ‐independent apoptosis through a mitochondria‐mediated pathway
Authors: Jin Caining , Wang Ying , Han Wenling , Zhang Yingmei , He Qihua , Li Dan , Yin Caihua , Tian Linjie , Liu Dazhen , Song Quanshen , Ma Dalong 
Published: December 2006

AbstractThe mitochondria‐mediated apoptotic pathway is regulated by members of the Bcl‐2 family. Epidermal growth factor (EGF) induces Bad phosphorylation at Ser112via mitogen‐activated protein kinase (MAPK), impairing its binding to Bcl‐2 and Bcl‐xL and interfering with their anti‐apoptotic functions. In the current study, we utilized Western blot, immunofluorescence, flow cytometry, and confocal microscopy to examine the effects of CMTM8 overexpression on apoptosis. Our data indicated levels of Bad‐S112phosphorylation were lower in CMTM8‐transfected cells compared to pCDB‐transfected cells. Caspase‐dependent and independent mediated apoptosis, induced by CMTM8 overexpression, was facilitated by the mitochondria and inhibited by knockdown of Bad or overexpression of Bcl‐xL. Previous research in our laboratory also demonstrated CMTM8 attenuated EGFR‐mediated signaling pathways by decreasing ERK1/2phosphorylation levels. These data implicate CMTM8 as a negative regulator of EGF‐induced signaling, with potential use as a novel therapeutic gene for EGFR‐targeted anticancer gene therapy. J. Cell. Physiol. 211: 112–120, 2007. © 2006 Wiley‐Liss, Inc.
Lipopolysaccharide reduces electrical coupling in microvascular endothelial cells by targeting connexin40 in a tyrosine‐, ERK1/2‐, PKA‐, and PKC‐dependent manner
Authors: Bolon Michael L. , Kidder Gerald M. , Simon Alexander M. , Tyml Karel 
Published: December 2006

AbstractElectrical coupling along the endothelium is central in the arteriolar conducted response and in control of vascular resistance. It has been shown that exposure of endothelium to lipopolysaccharide (LPS, an initiating factor in sepsis) reduces intercellular communication in vitro and in vivo. The molecular basis for this reduction is not known. We examined the effect of LPS on electrical coupling in monolayers of cultured mouse microvascular endothelial cells (MMEC) derived from the mouse hindlimb skeletal muscle. To assess coupling, we measured the spread of electrical current injected into the monolayer and computed the monolayer intercellular resistance (inverse measure of coupling). LPS (10 µg/ml, 1 h) reduced coupling (i.e., increased resistance) in MMEC isolated from wild‐type, connexin37 (Cx37) null and Cx43G60S (nonfunctional mutant) mice, but not in MMEC derived from Cx40 null mice. LPS also activated JNK1/2, p38 and ERK1/2 MAP kinases. Pretreatment of WT monolayers with ERK1/2 inhibitor U0126 (20 µM, 1 h) prevented the LPS‐induced decrease in coupling, while inhibition of JNK1/2 with SP600125 (20 µM, 1 h) and p38 with a p38 inhibitor (10 nM, 1 h) had no effect. Furthermore, inhibition of tyrosine kinases with PP‐2 (10 nM, 1 h), activation of PKA by 8‐bromo‐cAMP (1 mM, 5 min), and activation of PKC by bryostatin‐2 (10 nM, 1 h) also prevented the reduction in coupling. We propose that LPS reduces inter‐endothelial electrical coupling via tyrosine‐, ERK1/2‐, PKA‐, and PKC‐dependent signaling that targets Cx40. We suggest that this mechanism contributes to compromised arteriolar function following LPS exposure. J. Cell. Physiol. 211: 159–166, 2007. © 2006 Wiley‐Liss, Inc.
Visualization of Rab3A dissociation during exocytosis: A study by total internal reflection microscopy
Authors: Lin C.‐C. , Huang C.‐C. , Lin K.‐H. , Cheng K.‐H. , Yang D.‐M. , Tsai Y.‐S. , Ong R.‐Y. , Huang Y.‐N. , Kao L.‐S. 
Published: December 2006

AbstractRab3A is a small G protein in the Rab3 subfamily, and is thought to act at late stage of exocytosis. However, the detailed mechanism of its action is not completely understood. To study the role of Rab3A in exocytosis, we used a total internal reflection fluorescence microscope to examine the fluorescence changes of EGFP‐Rab3A‐labeled and NPY‐EGFP‐labeled vesicles in PC12 cells upon stimulation. The fluorescence of EGFP‐Rab3A‐labeled and NPY‐EGFP‐labeled vesicles decreased while showing different patterns. The NPY‐EGFP‐labeled vesicles that exocytosed showed a transient fluorescence increase before NPY‐EGFP fluorescence disappearance, which represents fusion and NPY release. This transient increase was diminished in cells that co‐expressed the GDP‐bound Rab3A mutant. The fluorescence of EGFP‐Rab3A‐labeled vesicles dispersed before disappearance, which represents the dissociation of Rab3A from the vesicles. The dispersion was not found in GTP‐bound Rab3A mutant‐labeled vesicles. Interestingly, EGFP‐Rab3A F59S, a mutant unable to bind rabphilin, dissociates slower from the vesicles than wild type Rab3A and caused a slower release of NPY‐EGFP. The results provide direct evidence to support the hypothesis that GTP hydrolysis and rabphilin are involved in Rab3A dissociation from the vesicles and the occurrence of exocytosis. J. Cell. Physiol. 211: 316–326, 2007. © 2006 Wiley‐Liss, Inc.
Gray‐scale sonography of solid breast masses: Diagnosis of probably benign masses and reduction of the number of biopsies
Authors: Chala Luciano , Endo Erica , Kim Su , de Castro Flávio , Moraes Paula , Cerri Giovanni , de Barros Nestor 
Published: December 2006

AbstractPurpose.To identify probably benign breast masses using gray‐scale sonography and to see if this strategy could reduce the number of biopsies of breast masses.Methods.This retrospective study included 229 masses in 203 women who underwent sonographically guided percutaneous biopsy. Masses with a negative predictive value for malignancy >98% were retrospectively considered probably benign, and the potential impact of gray‐scale sonography in reducing the number of biopsies if these masses were not biopsied was assessed. Assessments were performed considering all masses as a group as well as various subgroups.Results.Round, ellipsoid, or lobulated masses with 3 or fewer lobulations, circumscribed margins, a longitudinal–anteroposterior diameter ratio ≥1.0 and no marked hypoechogenicity, posterior acoustic shad owing, internal microcalcifications, or altered surrounding breast tissue were considered probably benign. The sensitivity of gray‐scale sonography to identify this subgroup was 98%, with a negative predictive value of 99%. If these masses were not biopsied, there would be a 42% reduction in the number of biopsies considering all masses, a 36% reduction for masses classified as Breast Imaging Reporting and Data System category 4, and a 59% reduction for masses exclusively analyzed with sonography.Conclusions.It is possible to identify probably benign breast masses using gray‐scale sonography, and thereby to reduce the number of biopsies performed. © 2006 Wiley Periodicals, Inc. J Clin Ultrasound 2007
Contrast‐enhanced three‐dimensional fusion sonography of small liver metastases with pathologic correlation
Authors: Yukisawa Seigo , Ohto Masao , Masuya Yoshio , Okabe Shinichirou , Fukuda Hiroyuki , Yoshikawa Masaharu , Ebara Masaaki , Saisho Hiromitsu , Ohtsuka Masayuki , Miyazaki Masaru , Kondo Fukuo 
Published: December 2006

AbstractPurpose.To demonstrate that liver metastases with a diameter of ≤40 mm show characteristic features on three‐dimensional (3D) fusion sonographic images and that these sonographic findings can be correlated with histopathologic features of surgical specimens.Methods.Liver metastases measuring ≤40 mm were examined via contrast‐enhanced 3D fusion sonography. The characteristic sonographic findings of 17 tumor nodules in 11 patients with a histopathologically confirmed diagnosis of liver metastases were investigated, and their correspondence to the pathologic features were examined in 12 resected nodules.Results.On sonograms, central vessels were visualized in all 17 tumor nodules and peripheral vessels were visualized in 12 nodules. On histopathologic examination, the portal triad vessels corresponded to the central vessels and were located at the center of the tumors. A thin layer of peritumoral hepatocytes showing various changes was also observed, and a group of tiny vessels were seen running along this layer of cells.Conclusions.Liver metastases measuring 40 mm or less in diameter were characterized by the presence of both central and peripheral vessels on contrast‐enhanced 3D fusion sonography. There was good correlation between sonographic and histopathologic findings. © 2006 Wiley Periodicals, Inc. J Clin Ultrasound 2007
Doppler sonography evaluation of flow velocity and volume of the extracranial internal carotid and vertebral arteries in healthy adults
Authors: Albayrak Ramazan , Degırmencı Bumin , Acar Murat , Haktanır Alpay , Colbay Mehmet , Yaman Mehmet 
Published: December 2006

AbstractPurpose.To measure with Doppler sonography the velocity and volume of blood flow in the extracranial internal carotid artery (ICA) and vertebral artery (VA) of healthy adults and to calculate total cerebral blood flow volume (tCBFV).Methods.Bilateral ICA and VA were examined sonographically in 180 healthy adults. Angle‐corrected peak systolic (Vps), end‐diastolic (Ved), and time‐averaged maximum blood flow velocity (TAV) were measured in pulsed Doppler mode, and the resistance index (RI) and pulsatility index (PI) were calculated. The cross‐sectional area (A) was measured on gray‐scale images. Volume flow was calculated as FV = TAV × A, and tCBFV was calculated as the sum of the right and left ICA and VA volume flow.Results.tCBFV was 651 ± 96 ml/min for the entire population. There was a significant decrease in Vps, Ved, TAV, and tCBFV with age in all arteries. RI and PI values initially declined and then increased with age. Cross‐sectional area increased with age in ICA but not in VA. PI and RI were higher in men than in women. Blood flow velocity and volume were higher, and RI was lower in the left than in the right VA.Conclusion.The Doppler sonographic assessment of extracranial ICA and VA blood flow volume may be useful for the study of cerebral hemodynamic changes in patients with cerebrovascular disorders. Age‐dependent changes should be considered, for instance, in the management of intensive care patients with impaired cerebral perfusion. © 2006 Wiley Periodicals, Inc. J Clin Ultrasound 2007
Melanophores: A model system for neuronal transport and exocytosis?
Authors: Aspengren Sara , Hedberg Daniel , Wallin Margareta 
Published: December 2006

AbstractBlack pigment cells, melanophores, from lower vertebrates are specialized in bidirectional and coordinated translocation of pigment granules, melanosomes, in the cytoplasm. Melanophores develop from the neuronal crest and are most abundant in the dermal and epidermal layers of the skin, where the intracellular distribution of the pigment significantly influences the color of the animal. The transport of pigment is dependent on an intact cytoskeleton and motor proteins associated with cytoskeletal components. The easily cultured melanophores have proved to be excellent models for organelle transport because the intracellular movements of pigment can be visualized via light microscopy, and the granules move in response to defined chemical signals. The ease of achieving a combination of morphological and functional transport studies is the advantage of the melanophore system, and studies on pigment cells have revealed new components of the transport machinery, including molecular motors, their adapters, and transfer of vesicles to other cells. Many cellular components are transported with a combination of the actin‐ and microtubule‐based transport systems, and, since all eukaryotic organisms rely on functional intracellular transport and an intact cytoskeleton, studies on melanophores are important for many aspects of cell biology, including axonal transport. In this review, we present an overview of the research on the pigment transport system and the potential use of pigment cells as a model system. © 2006 Wiley‐Liss, Inc.
Mouse and rat BDNF gene structure and expression revisited
Authors: Aid Tamara , Kazantseva Anna , Piirsoo Marko , Palm Kaia , Timmusk Tõnis 
Published: December 2006

AbstractBrain‐derived neurotrophic factor (BDNF) has important functions in the development of the nervous system and in brain plasticity‐related processes such as memory, learning, and drug addiction. Despite the fact that the function and regulation of rodent BDNF gene expression have received close attention during the last decade, knowledge of the structural organization of mouse and rat BDNF gene has remained incomplete. We have identified and characterized several mouse and rat BDNF transcripts containing novel 5′ untranslated exons and introduced a new numbering system for mouse and rat BDNF exons. According to our results both mouse and rat BDNF gene consist of eight 5′ untranslated exons and one protein coding 3′ exon. Transcription of the gene results in BDNF transcripts containing one of the eight 5′ exons spliced to the protein coding exon and in a transcript containing only 5′ extended protein coding exon. We also report the distinct tissue‐specific expression profiles of each of the mouse and rat 5′ exon‐specific transcripts in different brain regions and nonneural tissues. In addition, we show that kainic acid‐induced seizures that lead to changes in cellular Ca2+ levels as well as inhibition of DNA methylation and histone deacetylation contribute to the differential regulation of the expression of BDNF transcripts. Finally, we confirm that mouse and rat BDNF gene loci do not encode antisense mRNA transcripts, suggesting that mechanisms of regulation for rodent and human BDNF genes differ substantially. © 2006 Wiley‐Liss, Inc.
Cellular prion protein is increased in the plasma and peri‐infarcted brain tissue after acute stroke
Authors: Mitsios Nicholas , Saka Mohamad , Krupinski Jerzy , Pennucci Roberta , Sanfeliu Coral , Miguel Turu Marta , Gaffney John , Kumar Pat , Kumar Shant , Sullivan Matthew , Slevin Mark 
Published: December 2006

AbstractThe physiologic properties of the normal cellular prion protein (PrPC) have not been established fully, although recent evidence showed its upregulation in cerebral ischaemia. Using patients, animal models, and in vitro studies we aimed to identify in detail the expression and localization of PrPC in ischemic stroke. Patients in acute phase of ischaemic stroke had increased plasma levels of circulating PrPC as compared to healthy age‐ and gender‐matched controls (3.1 ± 1.4 vs. 1.9 ± 0.7 ng/ml, P = 0.002). Immunohistochemistry showed increased expression of PrPC in the soma of peri‐infarcted neurones as well as in the endothelial cells (EC) of micro‐vessels and inflammatory cells in peri‐infarcted brain tissue from patients who survived for 2–34 days after an initial stroke. The same pattern was repeated 1–48 hr after MCAO. RT‐PCR showed increased gene expression of PrPC by human foetal neurons (HFN) after 12 hr of oxygen glucose deprivation (OGD), which remained increased after 24 hr reperfusion. Western blotting confirmed that protein expression was similarly upregulated, and fluorescent labeling showed a notable increase in peri‐nuclear and axonal PrPC staining intensity. Increased plasma PrPC seems to reflect endogenous expression in acute stroke‐affected brain tissue. Increased cellular expression in peri‐infarcted regions may influence hypoxia‐induced cell damage, although the effects on EC survival and angiogenesis remain to be elucidated. © 2006 Wiley‐Liss, Inc.
Augmentation of osseous phenotypes in vivo with a synthetic peptide
Authors: Lin Xinhua , Elliot J.J. , Carnes D.L. , Fox W.C. , Peña L.A. , Campion S.L. , Takahashi K. , Atkinson B.L. , Zamora P.O. 
Published: December 2006

AbstractThe synthetic peptide B2A2‐K‐NS augmented the in vitro expression of osseous phenotypes when cells were stimulated with BMP‐2, an osteoinductive growth factor. B2A2‐K‐NS significantly enhanced the effects of BMP‐2‐induced alkaline phosphatase activity and mineralization. In the absence of BMP‐2, B2A2‐K‐NS did not have an effect on these endpoints. Based on these observations, in vivo studies were conducted to evaluate if B2A2‐K‐NS could augment osseous phenotypes in an osteoinductive environment in which BMP‐2 should be present. In one study, human demineralized bone matrix (DBM) was used to generate an osteoinductive environment and the effects of B2A2‐K‐NS on ectopic mineralization of subcutaneous implants evaluated. In the second study, a noncritical sized defect in rabbit ulnas with inherent reparative capacity was used as the osteoinductive environment and was treated with or without B2A2‐K‐NS. In the DBM studies, B2A2‐K‐NS augmented mineralization as determined using a combination of radiographic analysis and von Kossa staining at 4 weeks postimplant. In the rabbit ulna model, B2A2‐K‐NS significantly increased the radiographic bone density in the defects compared to carrier‐only or no‐treatment controls after 6 weeks. Histological staining confirmed that B2A2‐K‐NS generated a pronounced bone repair response. The results are consistent with the hypothesis that B2A2‐K‐NS augments osseous phenotypes in an osteoinductive environment, and suggests that B2A2‐K‐NS may have clinical utility. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:531–539, 2007