bluuebunny/crossref_metadata_2025 huggingface dataset:
Zic4, a zinc‐finger transcription factor, is expressed in the developing mouse nervous system
Authors: Gaston‐Massuet Carles , Henderson Deborah J. , Greene Nicholas D.E. , Copp Andrew J.
Published: May 2005

Zic genes comprise a family of transcription factors, characterized by the presence of a zinc‐finger domain containing two cysteines and two histidines (C2‐H2). Whereas the embryonic expression patterns of Zic1, 2, 3, and 5 have been described in detail, Zic4 has not yet received close attention. We studied the expression of Zic4 by in situ hybridization during mouse embryogenesis. Zic4 mRNA was first detected at low intensity at embryonic day (E) 9 and, by E10.5, expression was up‐regulated in the dorsal midline of the forebrain with a strong, expanded expression domain at the boundary between the diencephalon and telencephalon, the septum, and the lamina terminalis. The choroid plexus of the third ventricle expresses Zic4, as does the dorsal part of the spinal neural tube, excluding the roof plate. The dorsal sclerotome and the dorsomedial lip of the dermomyotome also express Zic4 whereas dorsal root ganglia are negative. At E12.5, Zic4 continues to be expressed in the midline of the forebrain and in the dorsal spinal neural tube. Postnatally, Zic4 is expressed in the granule cells of the postnatal day 2 cerebellum, and in the periventricular thalamus and anterior end of the superior colliculus. We conclude that Zic4 has an expression pattern distinct from, but partly overlapping with, other members of the Zic gene family. Developmental Dynamics 233:1110–1115, 2005. © 2005 Wiley‐Liss, Inc.
Cloning and functional characterization of a novel connexin expressed in somites of Xenopus laevis
Authors: De Boer Teun P. , Kok Bart , Neuteboom Kirsten I.E. , Spieker Nicole , De Graaf Jochum , Destrée Olivier H.J. , Rook Martin B. , Van Veen Toon A.B. , Jongsma Habo J. , Vos Marc A. , De Bakker Jacques M.T. , Van Der Heyden Marcel A.G.
Published: May 2005

Connexin‐containing gap junctions play an essential role in vertebrate development. More than 20 connexin isoforms have been identified in mammals. However, the number identified in Xenopus trails with only six isoforms described. Here, identification of a new connexin isoform from Xenopus laevis is described. Connexin40.4 was found by screening expressed sequence tag databases and carrying out polymerase chain reaction on genomic DNA. This new connexin has limited amino acid identity with mammalian (<50%) connexins, but conservation is higher (∼62%) with fish. During Xenopus laevis development, connexin40.4 was first expressed after the mid‐blastula transition. There was prominent expression in the presomitic paraxial mesoderm and later in the developing somites. In adult frogs, expression was detected in kidney and stomach as well as in brain, heart, and skeletal muscle. Ectopic expression of connexin40.4 in HEK293 cells, resulted in formation of gap junction like structures at the cell interfaces. Similar ectopic expression in neural N2A cells resulted in functional electrical coupling, displaying mild, asymmetric voltage dependence. We thus cloned a novel connexin from Xenopus laevis, strongly expressed in developing somites, with no apparent orthologue in mammals. Developmental Dynamics 233:864–871, 2005. © 2005 Wiley‐Liss, Inc.
Comparative analysis of the natriuretic peptide precursor gene cluster in vertebrates reveals loss of ANF and retention of CNP‐3 in chicken
Authors: Houweling Arjan C. , Somi Semir , Massink Maarten P.G. , Groenen Martien A. , Moorman Antoon F.M. , Christoffels Vincent M.
Published: May 2005

We identified and characterized the chicken natriuretic peptide precursor gene cluster and found its organization to be highly conserved compared with the mammalian Nppb‐Nppa cluster. However, phylogenetic analysis indicated that the putative chicken natriuretic peptide precursor genes are the homologues of CNP‐3 and Nppb, respectively. Comparative expression analysis revealed that, in human, mouse, and rat hearts, Nppb is a novel marker for the differentiating working myocardium. Its expression pattern is strikingly similar to that of Nppa before birth, and diverges only after birth. In contrast, whereas the chicken Nppb gene expression profile resembled that of mammalian Nppb, the CNP‐3 gene showed very limited expression in the heart, not resembling the pattern of either Nppa or Nppb. These results show that, in chicken, the Nppa gene has been lost from the natriuretic peptide precursor gene cluster, whereas the CNP‐3 gene has been retained. Developmental Dynamics 233:1076–1082, 2005. © 2005 Wiley‐Liss, Inc.
Cx31 and Cx43 double‐deficient mice reveal independent functions in murine placental and skin development
Authors: Kibschull Mark , Magin Thomas M. , Traub Otto , Winterhager Elke
Published: May 2005

The overlapping expression of gap junctional connexins in tissues has indicated that the channels may compensate for each other. During development, Cx31 and Cx43 are coexpressed in preimplantation embryos, in the spongiotrophoblast of the placenta and in the epidermis. This study shows that Cx31/Cx43 double‐deficient mice exhibit the known phenotypes of the single‐knockout strains but no combined effects. Thus, Cx43, coexpressed with Cx31 at midgestation in the spongiotrophoblast of the placenta, cannot be responsible for a partial rescue of the lethal Cx31 knockout phenotype, as assumed before (Plum et al. [ 2001] Dev Biol 231:334–337). It follows that both connexins have unique functions in placental development. Despite an altered expression of other epidermal connexin mRNAs, epidermal differentiation and physiology was unaltered by the absence of Cx31 and Cx43. Therefore, in epidermal and preimplantation development, gap junctional communication can probably be compensated by other isoforms coexpressed with Cx31 and Cx43. Developmental Dynamics 233:853–863, 2005. © 2005 Wiley‐Liss, Inc.
Histone deacetylase 1 is required for cell cycle exit and differentiation in the zebrafish retina
Authors: Stadler Jochen A. , Shkumatava Alena , Norton William H.J. , Rau Marlene J. , Geisler Robert , Fischer Sabine , Neumann Carl J.
Published: May 2005

Histone acetylation is an important epigenetic mechanism for the control of eukaryotic transcription. The histone deacetylase 1 (HDAC1) gene has been implicated in controlling the transcription of core cell cycle regulators, but the in vivo role of HDACs in cell cycle regulation is still poorly understood. Loss of HDAC1 activity causes underproliferation in several contexts during vertebrate development. In contrast, we show here that HDAC1 has the opposite effect in the zebrafish visual system, where loss of HDAC1 activity leads to failure of cells to exit the cell cycle in the retina and in the optic stalk. The effect of HDAC1 on cell cycle exit is cell‐autonomous, and loss of HDAC1 in the retina leads to up‐regulation of cyclin D and E transcripts. These results demonstrate that the in vivo role of HDAC1 in regulating cell cycle progression is region‐specific, as HDAC1 promotes cell cycle exit in the retina but stimulates proliferation in other cellular contexts. Developmental Dynamics 233:883–889, 2005. © 2005 Wiley‐Liss, Inc.
Discovery of plate‐type scyphocrinoid loboliths in the uppermost Pr̆ídolían–lowermost Lochkovian Upper Setul limestone of Peninsular Malaysia
Authors: Lee Chai Peng
Published: May 2005

Scyphocrinoid loboliths, the bulbous floats attached to the roots of a group of large Late Silurian to Early Devonian crinoids, were found within the top part of the Upper Setul limestone at two localities, in a band of limestone at Memplam Bay and in limestone blocks from a soil quarry at Guar Jentik, in northwest Peninsular Malaysia. The loboliths belong to the plate type, characterized by having plated chamber walls, few internal chambers and the presence of chamber openings near the axil of each primary root. Plate loboliths belong to species of Marhoumacrinus and Camarocrinus of the uppermost Pr̆ídolían to lowermost Lochkovian, and occur generally above cirrus loboliths, which are Pr̆ídolían only. Armoured floats are believed to have provided better protection against predators and the physical elements. These loboliths are important for correlation with other occurrences worldwide and especially within the Shan‐Thai or SIBUMASU (SinoBurMalayaSumatra) terrane of southeast Asia. Copyright © 2005 John Wiley & Sons, Ltd.
The late Pleistocene hutias (Geocapromys brownii) of Red Hills Fissure, Jamaica
Authors: McFarlane Donald A. , Blake Jerome
Published: May 2005

Red Hills Fissure (RHF) is an in‐filled, karstic solutional feature exposed by a roadcut in southern Jamaica. The site was discovered in 1988 and immediately recognized as an unusually rich source of late Quaternary gastropods and vertebrate bone dating from the late Pleistocene. Recent work on RHF has focused on the abundant remains of the endemic, mid‐sized rodent Geocapromys brownii. Morphological data on a collection of hemi‐mandibles has facilitated the construction of a life table for the species in the late Pleistocene: the first for any West Indian Pleistocene vertebrate. Studies of fluorine uptake in the fossil bone have also defined the time‐span of the RHF deposit, approximately 25–40 kyr BP. Copyright © 2005 John Wiley & Sons, Ltd.
Upper Llandovery (Telychian) crinoids (Echinodermata) of Devil's Dingle, Buildwas, Shropshire
Authors: Donovan Stephen K. , Lewis David N.
Published: May 2005

Two crinoids with strong North American affinities are described from the Telychian (Upper Llandovery, Lower Silurian) of Devil's Dingle, near Buildwas, Shropshire. The disparid Myelodactylus convolutus Hall is easily differentiated from other members of this genus from the Silurian of the British Isles by its distinctive stem geometry. This species was hitherto only known with certainty from North America, although an unsubstantiated report had identified it previously from the Much Wenlock Limestone Formation. The sagenocrinid flexible Clidochirus? sp. is tentatively assigned to a genus originally identified from Gotland, but best known from North America. The specimen from Devil's Dingle is probably a new species, with arms branching only twice and a distinctive sculpture to the tertibrachials, but only one side of the crown is exposed. Copyright © 2005 John Wiley & Sons, Ltd.
Response of anterior temporal cortex to syntactic and prosodic manipulations during sentence processing
Authors: Humphries Colin , Love Tracy , Swinney David , Hickok Gregory
Published: May 2005

Previous research has implicated a portion of the anterior temporal cortex in sentence‐level processing. This region activates more to sentences than to word‐lists, sentences in an unfamiliar language, and environmental sound sequences. The current study sought to identify the relative contributions of syntactic and prosodic processing to anterior temporal activation. We presented auditory stimuli where the presence of prosodic and syntactic structure was independently manipulated during functional magnetic resonance imaging (fMRI). Three “structural” conditions included normal sentences, sentences with scrambled word order, and lists of content words. These three classes of stimuli were presented either with sentence prosody or with flat supra‐lexical (list‐like) prosody. Sentence stimuli activated a portion of the left anterior temporal cortex in the superior temporal sulcus (STS) and extending into the middle temporal gyrus, independent of prosody, and to a greater extent than any of the other conditions. An interaction between the structural conditions and prosodic conditions was seen in a more dorsal region of the anterior temporal lobe bilaterally along the superior temporal gyrus (STG). A post‐hoc analysis revealed that this region responded either to syntactically structured stimuli or to nonstructured stimuli with sentence‐like prosody. The results suggest a parcellation of anterior temporal cortex into 1) an STG region that is sensitive both to the presence of syntactic information and is modulated by prosodic manipulations (in nonsyntactic stimuli); and 2) a more inferior left STS/MTG region that is more selective for syntactic structure. Hum Brain Mapp, 2005. © 2005 Wiley‐Liss, Inc.
Prevalence of and Risk Factors for Nonalcoholic Fatty Liver Disease: The Dionysos Nutrition and Liver Study * #
Authors: Bedogni Giorgio , Miglioli Lucia , Masutti Flora , Tiribelli Claudio , Marchesini Giulio , Bellentani Stefano
Published: May 2005

The prevalence of and the risk factors for fatty liver have not undergone a formal evaluation in a representative sample of the general population. We therefore performed a cross-sectional study in the town of Campogalliano (Modena, Italy), within the context of the Dionysos Project. Of 5,780 eligible persons aged 18 to 75 years, 3,345 (58%) agreed to participate in the study. Subjects with suspected liver disease (SLD), defined on the basis of elevated serum alanine aminotransferase (ALT) and γ-glutamyl-transferase (GGT) activity, hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV)-RNA positivity, were matched with randomly selected subjects of the same age and sex without SLD. A total of 311 subjects with and 287 without SLD underwent a detailed clinical, laboratory, and anthropometrical evaluation. Fatty liver was diagnosed by ultrasonography, and alcohol intake was assessed by using a 7-day diary. Multinomial logistic regression was used to detect risk factors for normal liver versus nonalcoholic fatty liver disease (NAFLD) and for alcoholic fatty liver (AFLD) versus NAFLD. The prevalence of NAFLD was similar in subjects with and without SLD (25

vs.

20%,

P

= .203). At multivariable analysis, normal liver was more likely than NAFLD in older subjects and less likely in the presence of obesity, hyperglycemia, hyperinsulinemia, hypertriglyceridemia, and systolic hypertension; AFLD was more likely than NAFLD in older subjects, males, and in the presence of elevated GGT and hypertriglyceridemia, and less likely in the presence of obesity and hyperglycemia.
In conclusion,
NAFLD is highly prevalent in the general population, is not associated with SLD, but is associated with many features of the metabolic syndrome. (Hepatology 2005.)
Purification and Characterization of Mouse Fetal Liver Epithelial Cells With High In Vivo Repopulation Capacity *
Authors: Nierhoff Dirk , Ogawa Atsushi , Oertel Michael , Chen Yuan-Qing , Shafritz David A.
Published: May 2005

Epithelial cells in embryonic day (ED) 12.5 murine fetal liver were separated from hematopoietic cell populations using fluorescence-activated cell sorting (FACS) and were characterized by immunocytochemistry using a broad set of antibodies specific for epithelial cells (α-fetoprotein [AFP], albumin [ALB], pancytokeratin [PanCK], Liv2, E-cadherin, Dlk), hematopoietic/endothelial cells (Ter119, CD45, CD31), and stem/progenitor cells (c-Kit, CD34, Sca-1). AFP+/ALB+ cells represented approximately 2.5% of total cells and were positive for the epithelial-specific surface markers Liv2, E-cadherin, and Dlk, but were clearly separated and distinct from hematopoietic cells (Ter119+/CD45+). Fetal liver epithelial cells (AFP+/E-cadherin+) were Sca-1+ but showed no expression of hematopoietic stem cell markers c-Kit and CD34. These cells were enriched by FACS sorting for E-cadherin to a purity of 95% as defined by co-expression of AFP and PanCK. Purified fetal liver epithelial cells formed clusters in cell culture and differentiated along the hepatocytic lineage in the presence of dexamethasone, expressing glucose-6-phosphatase (G6P) and tyrosine amino transferase. Wild-type ED12.5 murine fetal liver cells were transplanted into adult dipeptidyl peptidase IV knockout mice and differentiated into mature hepatocytes expressing ALB, G6P, and glycogen, indicating normal biochemical function. Transplanted cells became fully incorporated into the hepatic parenchymal cords and showed up to 80% liver repopulation at 2 to 6 months after cell transplantation.
In conclusion
, we isolated and highly purified a population of epithelial cells from the ED12.5 mouse fetal liver that are clearly separate from hematopoietic cells and differentiate into mature, functional hepatocytes

in vivo

with the capacity for efficient liver repopulation.

Supplementary material for this article can be found on the Hepatology website

(
http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index.html
). (Hepatology 2005;.)
Expression pattern of four membrane‐type matrix metalloproteinases in the normal and diseased mouse mammary gland
Authors: Szabova Ludmila , Yamada Susan S. , Birkedal‐Hansen Henning , Holmbeck Kenn
Published: May 2005

Both mammary gland development and mammary carcinogenesis involve extensive remodeling of the mammary gland extracellular matrix. The expression of four membrane‐type matrix metalloproteinases (MT‐MMPs) with matrix remodeling potential in development and tumorigenesis was evaluated by in‐situ hybridization on mouse mammary gland sections. MT1‐MMP and MT3‐MMP were found in the mammary stroma mainly around epithelial structures in both developing and mature mammary gland. In contrast, MT2‐MMP was found exclusively in the mammary epithelium. Lactating gland expressed none of the examined MT‐MMPs. Mammary gland tumors expressed MT1‐MMP, MT2‐MMP, and MT3‐MMP while MT4‐MMP was not expressed in any developmental or cancerous stage analyzed here. Our results suggest that MT1‐MMP, MT2‐MMP, and MT3‐MMP may be involved in remodeling of both the normal and diseased mammary gland either directly or indirectly by activation of other MMPs. Published 2005 Wiley‐Liss, Inc.
Trying to compose the puzzle with all the pieces: Epidermal growth factor receptor tyrosine kinase inhibitors in non‐small cell lung cancer
Authors: Di Maio Massimo , Gridelli Cesare , Normanno Nicola , Perrone Francesco , Ciardiello Fortunato
Published: May 2005

Small molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have shown promising activity in patients with non‐small cell lung cancer (NSCLC). Gefitinib has been the first of these drugs to be licensed for third‐line treatment of advanced NSCLC patients. More recently, erlotinib has been shown to be more effective than placebo in increasing overall survival (OAS) and has been approved for NSCLC patients after failure of chemotherapy. However, a large body of clinical and experimental evidence suggests that the benefit from these drugs is limited to a subgroup of patients. The availability of clinical or molecular criteria for predicting sensitivity to EGFR‐TKIs is the most relevant issue for their correct use and for planning future research. Determination of EGFR expression is not sufficient to predict sensitivity to EGFR‐TKIs. However, several clinical features (female gender, adenocarcinoma/bronchioloalveolar histotype, never‐smoking status, Oriental Asian origin) are associated with major clinical responses. The identification of somatic mutations in the tyrosine kinase domain of the EGFR gene represents the most important molecular marker of sensitivity to EGFR‐TKIs. These “activating” mutations can be found in a high proportion of gefitinib‐ or erlotinib‐responding patients. However, clinical effectiveness might not be limited to patients carrying EGFR mutations, in which the objective response is probably the detectable effect of apoptosis induction in cancer cells. In fact, clinical efficacy with gefitinib or erlotinib is also observed in another subgroup of patients, in which a tumor growth delay, determined by a block in cancer cell proliferation, could induce a prolonged and clinically relevant disease stabilization. © 2005 Wiley‐Liss, Inc.
Induction of TGF‐β1 in the trabecular meshwork under cyclic mechanical stress
Authors: Liton P.B. , Liu X. , Challa P. , Epstein D.L. , Gonzalez P.
Published: May 2005

The pathophysiological mechanisms involved in the failure of the trabecular meshwork (TM) to maintain normal levels of aqueous outflow in glaucoma are not yet understood. Aberrant activation of the transforming growth factor beta‐1 (TGF‐β1) pathway has been implicated in several degenerative diseases. We investigated the possibility that chronic cyclic mechanical stress that affects the TM might result in increased production of TGF‐β1. Primary cultures of TM cells subjected to cyclic mechanical stress (5% stretching, 1 cycle/sec) demonstrate a significant increase in total and biologically active secreted TGF‐β1 that was associated with activation of the TGF‐β1 promoter, measured using a recombinant adenovirus expressing the secreted reporter gene secreted alkaline phosphatase protein (SEAP) under the TGF‐β1 gene promoter (AdTGFβ1‐SEAP). Associated changes in the transcription of MMP‐2, TIMP‐2, and CTGF were assessed by semiquantitative PCR. Immunohistochemical analysis of TGF‐β1 in organ culture of human eyes revealed a generalized accumulation of this protein in the extracellular matrix (ECM) of the TM, while expression of the TGF‐β1 promoter, analyzed using the LacZ reporter gene, was localized in some specific cells within the outflow pathway. Induction of the TGF‐β1 promoter in organ culture was demonstrated using a novel model for cyclic mechanical stress in human perfused anterior segments infected with AdTGFβ1‐SEAP. Given the relevant physiological and pathophysiological roles of TGF‐β1, its induction after cyclic mechanical stress in the TM supports the hypothesis that this cytokine might play a significant role in the physiology of the TM, and contribute to the pathological changes of this tissue in certain forms of glaucoma. © 2005 Wiley‐Liss, Inc.
Properties of Mg2+‐dependent cation channels in human leukemia K562 cells
Authors: Semenova Svetlana B. , Fomina Alla F. , Vassilieva Irina O. , Negulyaev Yuri A.
Published: May 2005

The endogenous Mg2+‐inhibited cation (MIC) current was recently described in different cells of hematopoietic lineage and was implicated in the regulation of Mg2+ homeostasis. Here we present a single channel study of endogenously expressed Mg2+‐dependent cation channels in the human myeloid leukemia K562 cells. Inwardly directed unitary currents were activated in cell‐attached experiments in the absence of Ca2+ and Mg2+ in the pipette solution. The current–voltage (I–V) relationships displayed strong inward rectification and yielded a single channel slope conductance of ∼30 pS at negative potentials. The I–V relationships were not altered by patch excision into divalent‐free solution. Channel open probability (Po) and mean closed time constant (τC) were strongly voltage‐dependent, indicating that gating mechanisms may underlie current inward rectification. Millimolar concentrations of Ca2+ or Mg2+ applied to the cytoplasmic side of the membrane produced slow irreversible inhibition of channel activity. The Mg2+‐dependent cation channels described in this study differ from the MIC channels described in human T‐cells, Jurkat, and rat basophilic leukemia (RBL) cells in their I–V relationships, kinetic parameters and dependence on intracellular divalent cations. Our results suggested that endogenously expressed Mg2+‐dependent cation channels in K562 cells and the MIC channels in other hematopoietic cells might be formed by different channel proteins. © 2005 Wiley‐Liss, Inc.
Meeting report on the 12th International Congress of Histochemistry and Cytochemistry (ICHC)
Authors: De Falco Maria , De Luca Antonio
Published: May 2005

The International Congress of Histochemistry and Cytochemistry (ICHC) promoted in San Diego La Jolla (CA, USA), the 12th meeting where researchers of all over the world presented their work and the most innovative methods in histochemical disciplines. A summary of the last meeting is reported. © 2005 Wiley‐Liss, Inc.
LIGHT regulates CD86 expression on dendritic cells through NF‐κB, but not JNK/AP‐1 signal transduction pathway
Authors: Zou Gang‐Ming , Hu Wen‐Yang
Published: May 2005

The members of the tumor necrosis factor (TNF) family play pivotal roles in the regulation of the immune system. LIGHT is a type II transmembrane protein belonging to the TNF family that was originally identified as a weak inducer of apoptosis. This cytokine has been extensively studied for its role in T cell regulation. Recently, we identified its role in inducing maturation of dendritic cells, such as LIGHT upregulated CD86 expression on dendritic cells in our previous report. However, the signal transduction pathway on this regulation remains unknown. In this study, we found that LIGHT activated NF‐κB, p44/42 MAPK, but not JNK. LIGHT upregulates CD86 expression on DCs through activation of NF‐κB, but not p44/42 signal pathway, because inhibition of NF‐κB activity by its inhibitor could blunt the effect of LIGHT in up‐regulation of CD86 expression, but neither inhibitor of p44/42 MAPK nor JNK inhibitor has this effect. Thus we demonstrate that LIGHT regulates CD86 expression through NF‐κB signal transduction pathway but neither p44/42 MAPK nor JNK/AP‐1 signaling pathway. We conclude that NF‐κB signal plays a key role in LIGHT‐mediated upregulation of CD86 expression. © 2005 Wiley‐Liss, Inc.
Negative regulation of melanogenesis by phospholipase D1 through mTOR/p70 S6 kinase 1 signaling in mouse B16 melanoma cells
Authors: Ohguchi Kenji , Banno Yoshiko , Nakagawa Yoshihito , Akao Yukihiro , Nozawa Yoshinori
Published: May 2005

Melanogenesis is a principal parameter of differentiation in melanocytes and melanoma cells. Our recent study has demonstrated that phospholipase D1 (PLD1) regulates the melanogenic signaling through modulating the expression of tyrosinase, the rate‐limiting step enzyme in the melanin biosynthesis. The current study was designed to gain more insight into the involvement of PLD1 in the regulation of melanogenesis. To investigate the role of PLD1, we examined the effect of knockdown of endogenous PLD1 by small interference RNA (siRNA) on melanogenesis in B16 melanoma cells. It was shown that the melanin synthesis was induced in PLD1‐knockdowned cells, and also that the level of melanin synthesis was well correlated with increases in expression level of tyrosinase and its related proteins (Tyrp1 and Dct). Furthermore, the reduction of expression levels of PLD1 by siRNA transfection was accompanied by diminution of ribosomal S6 kinase 1 (S6K1) phosphorylation. The activity of mammalian target of rapamycin (mTOR) is essential for phosphorylation of S6K1 and the treatment malanoma cells with rapamycin, a potent inhibitor of mTOR effectively induced melanogenesis. The results obtained here provide possible evidence that PLD1 exerts a negative regulatory role in the melanogenic process through mTOR/S6K1 signaling. © 2005 Wiley‐Liss, Inc.
Gastric cancer: New genetic developments
Authors: Lynch Henry T. , Grady William , Suriano Gianpaolo , Huntsman David
Published: May 2005

Gastric cancer's (GC) incidence shows large geographic differences worldwide with the lowest rates occurring in most Western industrialized countries including the United States and the United Kingdom; in contrast, relatively high rates of GC occur in Japan, Korea, China, and South America, particularly Chile. The Laurén classification system classifies GC under two major histopathological variants: 1) an intestinal type and 2) a diffuse type. The intestinal type is more common in the general population, more likely to be sporadic and related to environmental factors such as diet, particularly salted fish and meat as well as smoked foods, cigarette smoking, and alcohol use. It exhibits components of glandular, solid, or intestinal architecture, as well as tubular structures. On the other hand, the diffuse type is more likely to have a primary genetic etiology, a subset of which, known as hereditary diffuse gastric cancer (HDGC), is due to the E‐cadherin (CDH1) germline mutation. The diffuse type pathology is characterized by poorly cohesive clusters of cells which infiltrate the gastric wall, leading to its widespread thickening and rigidity of the gastric wall, known as linitis plastica. Helicobacter pylori infection is associated with risk for both the intestinal and diffuse varieties of gastric cancer. Germline truncating mutations of the CDH1 gene, which codes for the E‐cadherin protein, were initially identified in three Maori families from New Zealand that were predisposed to diffuse GC. Since then, similar mutations have been described in more than 40 additional HDGC families of diverse ethnic backgrounds. It is noteworthy that two‐thirds of HDGC families reported to date have proved negative for the CDH1 germline mutation. A number of candidate genes have been identified through analysis of the molecular biology of E‐cadherin. Patients with evidence of the CDH1 germline mutation in the context of a family history of HDGC must be considered as candidates for prophylactic gastrectomy, given the extreme difficulty in its early diagnosis and its exceedingly poor prognosis when there is regional or distant spread. Specifically, the E‐cadherin cytoplasmic tail interacts with catenins, assembling the cell‐adhesion complex involved with E‐cadherin mediated cell:cell adhesion. β‐catenin and γ‐catenin compete for the same binding site on the E‐cadherin cytoplasmic tail, directly linking the adhesion complex to the cytoskeleton through α‐catenin. β‐catenin gene (CTNNB1) mutations have been described predominantly in intestinal‐type gastric cancers and CTNNB1 gene amplification and overexpression have recently been described in a mixed‐type gastric cancer. This paper reviews the genetics of both intestinal and diffuse types of gastric carcinoma, their differential diagnosis, molecular genetics, pathology, and, when known, their mode of genetic transmission within families. J. Surg. Oncol. 2005;90:114–133. © 2005 Wiley‐Liss, Inc.
New strategies for the prevention of gastric cancer: Helicobacter pylori and genetic susceptibility
Authors: Correa Pelayo
Published: May 2005

Recently acquired knowledge points to the potential of markedly improved strategies for the prevention of gastric cancer. The International Agency for Cancer Research has reached the conclusion that infection with Helicobacter pylori (H. pylori) is carcinogenic to humans (Group I) 1. The bacterium displays marked genetic heterogeneity. Virulence related genes, especially cag A and vac A s1 m1 are associated with an increased cancer risk. Genetic susceptibility, especially polymorphisms of the cytokine genes may increase cancer risk. Highly susceptible individuals infected with high virulence bacterial genotypes have a markedly increased gastric cancer risk. They should be targeted for endoscopic monitoring to detect advanced precancerous lesions. The state of the art is briefly reviewed and the needed research identified. J. Surg. Oncol. 2005;90:134–138. © 2005 Wiley‐Liss, Inc.
Recent advances in sentinel node navigation for gastric cancer: A paradigm shift of surgical management
Authors: Kitagawa Yuko , Fujii Hirofumi , Kumai Koichiro , Kubota Tetsuro , Otani Yoshihide , Saikawa Yoshiro , Yoshida Masashi , Kubo Atsushi , Kitajima Masaki
Published: May 2005

The sentinel node (SN) is defined as the first draining node from the primary lesion and it has proven to be a good indicator of the metastatic status of regional lymph nodes in solid tumors. In the past 5 years, the validity of SN concept for gastric cancer has been demonstrated by a number of single institutional studies. Using a dual tracer method as the optimal procedure, the radio‐guided method allows us to confirm the complete harvest of SNs by gamma probing, while the dye procedure enables us to perform real time observation of the lymphatic vessels. From previous reports, clinically staged T1N0 gastric cancer seems to be a good entity on which to try to change the therapeutic approach based on SN biopsy. At present, two large scale prospective multicenter trials are on‐going in Japan. To overcome some remaining issues, such as limited sensitivity of intra‐operative diagnosis of metastasis, and technical difficulty in laparoscopic SN detection, further technical and instrumental developments will be required. During this transitional phase, focused lymph node dissection targeted to sentinel lymphatic basins and modified resection of the stomach is an acceptable approach. Although there are several remaining issues, SN navigation should provide a paradigm shift for the surgical management of early gastric cancer in near future. J. Surg. Oncol. 2005;90:147–151. © 2005 Wiley‐Liss, Inc.
Status of extended lymph node dissection: Locoregional control is the only way to survive gastric cancer
Authors: Hartgrink Henk H. , van de Velde Cornelis J.H.
Published: May 2005

There are many factors that are of influence on gastric cancer treatment. The only way to survive is complete locoregional control. More extended dissections should lead to better outcome, but increased morbidity and mortality probably offset its long‐term effect in survival in randomised studies. In this article the factors of influence on outcome of gastric cancer treatment such as the extent of lymph node dissection, splenectomy, pancreatectomy, age, volume and additional treatments are discussed. A literature review of these factors in relation to the latest results of the Dutch Gastric Cancer Trials are presented. If morbidity and mortality can be reduced there might be an advantage of extended lymph node dissection. Splenectomy and pancreatectomy should be performed only in case of direct in growth from the tumour into these organs. Centralisation of gastric cancer treatment should be achieved in order to improve results and to facilitate research. By refining selection criteria in the treatment of gastric cancer further improvements are to be expected. J. Surg. Oncol. 2005;90:153–165. © 2005 Wiley‐Liss, Inc.
Role of post‐operative chemoradiation in resected gastric cancer
Authors: Macdonald John S.
Published: May 2005

The curative management of gastric adenocarcinoma depends upon complete resection of the primary tumor. In patients with lymph node metastases in the resected specimen, the relapse and death rates from recurrent cancer are at least 70%–80%. There is continued debate over whether more extensive lymph node dissection (D2) improves survival when compared to less extensive operations. Until recently, attempts at preventing recurrence have employed adjuvant chemotherapy and have been ineffective. A large U.S. Intergroup study (INT‐0116) demonstrated that combined chemoradiation following complete gastric resection improves median time to relapse (30 vs. 19 months, P < 0.0001) and overall survival (35 vs. 28 months, P = 0.01). The improvements in disease‐free and overall survival resulting from post‐operative chemoradiation have defined a new standard of care. An update of the results of INT‐0116 analysis performed in 2004 with 7 years median follow‐up, not only confirms the benefits from post‐operative chemoradiation but also shows that chemoradiation does not produce significant long‐term toxicity. The recent publication of the first large adequately powered III neoadjuvant chemotherapy trial suggested this technique might downstage tumors and increase resectability. Future advances in the therapy of resectable gastric cancer may come from studies of pre‐operative neoadjuvant chemoradiation and the application of targeted therapies such as growth receptor antagonists and antiangiogenesis agents. J. Surg. Oncol. 2005;90:166–170. © 2005 Wiley‐Liss, Inc.
Minimally invasive treatment for gastric cancer: Approaches and selection process
Authors: Noh Sung Hoon , Hyung Woo Jin , Cheong Jae‐Ho
Published: May 2005

Minimally invasive treatment of gastric cancer has emerged as a result of the technical advances, better understanding of gastric physiology, and more knowledge of the biologic behavior of gastric cancer. This treatment results in improved quality of life embodied by smaller incisions, reduced length of hospital stay, and a faster return to productive life. However, minimally invasive treatment for gastric cancer must take into consideration the potential effects of these techniques on tumor dissemination at the time of the treatment procedure, as well as the rates of recurrence and overall survival. Several technical treatment approaches to gastric cancer have now become possible, utilizing endoscopy, laparoscopy, or an open method. Endoscopic mucosal resection (EMR), limited resection, and laparoscopic surgical resection are the currently practiced modalities as the minimally invasive treatment. Lymph node dissection with the minimally invasive techniques is a barrier to its wide application. Although it is not commonly performed in Western countries, the use of minimally invasive treatment for gastric cancer is growing, especially in Korea and Japan. Minimally invasive treatment for early gastric cancer (EGC) has already been shown to be safe and effective in many retrospective series though no prospective randomized studies comparing it to open resection have been performed. Therefore, routine implementation of these procedures must await confirmatory outcomes generated by well‐done randomized prospective clinical trials. J. Surg. Oncol. 2005;90:188–193. © 2005 Wiley‐Liss, Inc.
Gastric GI stromal tumors (GISTs): The role of surgery in the era of targeted therapy
Authors: Heinrich Michael C. , Corless Christopher L.
Published: May 2005

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm arising in the stomach. These tumors were previously classified as smooth muscle tumors, but in recent years it has become clear that they are clinically, pathologically, and molecularly distinct from other tumors and are much more common than previously appreciated. Historically, patients with primary localized or advanced GIST have been managed surgically, as there was no proven role of other treatment modalities such as radiation or chemotherapy. However, the field of GIST was revolutionized with the 1998 discovery that the vast majority of these tumors have oncogenic gain‐of‐function mutations of the KIT receptor tyrosine kinase. Follow‐up studies have confirmed that KIT is both a useful diagnostic marker and an excellent therapeutic target. Imatinib, an inhibitor of KIT kinase activity, is now the standard front‐line therapy for patients with advanced GIST. In this review, we discuss pathological and molecular features of gastric GISTs and review the historic and current roles of surgery in the treatment of patients with primary or metastatic GIST. The importance of a multi‐disciplinary approach using both surgery and imatinib therapy is emphasized. J. Surg. Oncol. 2005;90:195–207. © 2005 Wiley‐Liss, Inc.
Alkaline Phosphatase Encapsulated in Gellan‐Chitosan Hybrid Capsules
Authors: Fujii Toshihiro , Ogiwara Daisuke , Ohkawa Kousaku , Yamamoto Hiroyuki
Published: May 2005

Summary: Alkaline phosphatase (ALP) was encapsulated in gellan‐chitosan polyion complex (PIC) capsules using a convenient procedure. The recovery of ALP was about 50% when the capsules were prepared by dropping a solution of ALP and gellan mixture (ALP/gellan) into a chitosan solution. When p‐nitrophenyl phosphate (p‐NPP) and 5‐bromo‐4‐chloro‐3‐indolyl phosphate (BCIP) were incubated with ALP/gellan‐chitosan capsules as substrates for ALP, the transparent colorless capsules changed to yellow and blue, respectively. The encapsulation of ALP into the PIC capsules was also confirmed by SDS‐PAGE and immunoblot analyses. The ALP and polypeptides of more than 30 kDa remained without release even after incubation at 4 °C for 14 d. The biochemical properties of the encapsulated ALP activity were similar to those of the intact enzyme. When the solution containing p‐NPP was loaded on a column packed with ALP/gellan‐chitosan capsules at 27 °C, approximately 75% of p‐NPP was hydrolyzed by passing through the column. No significant leakage of ALP was observed during the procedure, indicating that the capsules were resistant to pressure in the chromatographic operation. Furthermore, 70% of the hydrolytic activity of the packed capsules remained after storage at 4 °C for one month. These results suggest that the polyion complex capsules could be useful materials for protein fixation without chemical modification.

Encapsulation of ALP into PIC capsules and the morphological changes seen in the absence of the ALP substrate and in the presence of p‐NPP and BICP.

magnified image

Encapsulation of ALP into PIC capsules and the morphological changes seen in the absence of the ALP substrate and in the presence of p‐NPP and BICP.
Vascular Endothelial and Smooth Muscle Cell Culture on NaOH‐Treated Poly(ε‐caprolactone) Films: A Preliminary Study for Vascular Graft Development
Authors: Serrano María Concepción , Portolés María Teresa , Vallet‐Regí María , Izquierdo Isabel , Galletti Lorenzo , Comas Juan Valentín , Pagani Raffaella
Published: May 2005

Summary: Tissue engineering offers the potential of providing vessels that can be used to replace diseased and damaged native blood vessels. The endothelization of a synthetic vascular graft minimizes the failures associated with blood clotting and platelet activation. The aim of this study was to culture vascular‐derived endothelial and smooth muscle cells on both untreated and NaOH‐treated poly(ε‐caprolactone) (PCL) films, a biocompatible and bio‐resorbable polymer, and to evaluate the behavior of both cell types as a preliminary study for vascular graft development. PCL films were prepared by hot pressing; characterized by DSC, IR, SEM, and scanning force microscopy; and treated with NaOH to increase the surface hydrophilicity before cell culture. Endothelial and smooth muscle cells, isolated from pig cava vein, were characterized by immunofluorescence and confocal microscopy studies of endothelial nitric oxide synthase and α‐smooth muscle actin. Good adhesion, growth, viability and morphology of both the endothelial and smooth muscle cells on PCL films were obtained, but a light stimulation of mitochondrial activity was observed during short culture times. NaOH treatment improved the adhesion and enhanced the proliferation in both cell types. This verified the possible use of this modified polymer as a support in the preparation of a synthetic vascular graft.

SEM micrograph of smooth muscle cells cultured on NaOH‐treated PCL film. (Original magnification: 1 000×).

magnified image

SEM micrograph of smooth muscle cells cultured on NaOH‐treated PCL film. (Original magnification: 1 000×).
Preparation of α‐Cyclodextrin‐Terminated Polyrotaxane Consisting of β‐Cyclodextrins and Pluronic as a Building Block of a Biodegradable Network
Authors: Ooya Tooru , Ito Akihiro , Yui Nobuhiko
Published: May 2005

Summary: A β‐CD‐based biodegradable polyrotaxane was prepared by capping both terminals of polypseudorotaxane consisting of hydrazide‐terminated PEG‐block‐PPG‐block‐PEG (Pluronic P‐105®) and β‐CD‐succinates with mono‐aldehyde α‐CDs. By decreasing pH, the fluorescent intensity of TNS was increased with time, indicating cleavage of the terminal hydrazone bonds followed by β‐CD‐succinate release. The terminal α‐CD moieties of the polyrotaxane are useful for self‐assembled formation with some guest molecules.

magnified image
Highly Branched Stimuli Responsive Poly[(N‐isopropyl acrylamide)‐co‐(1,2‐propandiol‐3‐methacrylate)]s with Protein Binding Functionality
Authors: Carter Steven , Rimmer Stephen , Sturdy Alice , Webb Michelle
Published: May 2005

Summary: Highly branched poly(NIPAM) have been prepared using the technique of reversible addition‐fragmentation chain transfer (RAFT) polymerisation using a chain transfer agent that allows the incorporation of imidazole functionality in the polymer chain‐ends. The lower critical solution temperature (LCST) of the polymers can be controlled by the amount of hydrophobe and GMA incorporated during copolymerisation procedures. These thermally responsive “smart” polymers were used to purify a His‐tagged BRCA‐1 protein fragment by affinity precipitation.

magnified image
Back Cover: Macromol. Biosci. 5/2005
Authors: Wang Shi‐Bin , Xu Fei‐Hai , He Hong‐Shan , Weng Lian‐Jin
Published: May 2005

Back Cover: This picture shows microscopy photos of blank and Hb‐loaded alginate‐PLHis microcapsules. Poly(L‐histidine) (PLHis) was used as a new membrane material for microcapsules, and it can be expected to be used as a therapeutic and biodegradable drug carrier. Further details can be found in the Full Paper by S. B. Wang,* F. H. Xu, H. S. He, and L. J. Weng on page 408.
Investigation into the correlation between sensation and leg movement in restless legs syndrome
Authors: Birinyi Paul V. , Allen Richard P. , Lesage Susan , Dean Terry , Earley Christopher J.
Published: May 2005

We evaluated rest effects on restless legs syndrome (RLS) sensory and motor symptoms. During two 60‐minute Suggested Immobilization Tests (SIT) subject's signals of RLS leg sensations and periodic leg movements while awake (PLMW) were recorded. Sensations, PLMW, sensations preceding or after PLMW, sensations occurring without following PLMW, and PLMW occurring without preceding sensation were determined. The RLS patients were divided into equal‐sized high and low PLMW groups for further analysis. Data from 46 subjects (28 RLS and 18 controls) revealed sensations increased linearly with rest in RLS patients and controls. Movement rate increased linearly with rest for controls but increased rapidly for the first 45 minutes for all RLS patients. PLMW/hour increased with further rest for low but not high PLMW patients. Sensations followed by PLMW and PLMW without preceding sensations followed similar patterns. Sensations without subsequent PLMW increased dramatically in the last 15 minutes of the SITs. Whereas both sensory and motor signs of RLS increase with rest, there is minimal increase for controls. Patients with higher but not lower PLMW rates reached a ceiling for PLMW after 35 to 40 minutes. The temporal dissociation between sensory and motor events supports viewing these motor and sensory events as separate but loosely linked manifestations of RLS. © 2005 Movement Disorder Society
Coexistence of movement disorders and epilepsia partialis continua as the initial signs in probable Creutzfeldt–Jakob disease
Authors: Donmez Berril , Çakmur Raif , Men Süleyman , Oztura Ibrahim , Kitis Arzu
Published: May 2005

Movement disorders and epilepsy rarely occur in the early stage of Creutzfeldt–Jakob disease (CJD) but have not been reported concurrently. We report on a 47‐year‐old patient with probable CJD who presented with generalized chorea and focal dystonia with myoclonic jerks on the right hand. Myoclonic jerks progressed to epilepsia partialis continua within 5 days of admission to the hospital. The diagnosis of our patient was compatible with probable CJD on the basis of clinical course, electroencephalogram, and diffusion‐weighted magnetic resonance imaging findings, and presence of 14‐3‐3 protein in cerebrospinal fluid. To our knowledge, this is the first report of a case developing both movement disorders and epilepsia partialis continua in the early stage of the disease. © 2005 Movement Disorder Society
Speech‐activated myoclonus: An uncommon form of action myoclonus
Authors: Slee Mark , Parasivam Sharavanan , Blessing Bill , Truck Kate , Day Bruce , Thyagarajan Dominic
Published: May 2005

We describe an unusual form of facial myoclonus activated by speech in 3 patients with different underlying neurological diseases and present the electrophysiological investigations and results of structural and functional imaging. In 1 of 2 patients in whom jerk‐locked electroencephalogram (EEG) back‐averaging was done, a cortical potential clearly preceded the facial jerks. In the second patient, a cortical potential preceding the jerk was not certain. In the third patient, the resting EEG contained outbursts of symmetric, slower frequencies of indeterminate significance. An epileptiform disorder was suspected in this patient. © 2005 Movement Disorder Society