bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differences of globin transgene expression in stably transfected cell lines and transgenic mice
Authors: Li Qiliang , Emery David W. , Han Hemei , Sun Jin , Yu Man , Stamatoyannopoulos George 
Published: December 2004

AbstractPrevious studies demonstrated that DNase I hypersensitive site -40 (HS-40) of the α-globin locus is capable of greatly enhancing expression of a hybrid β/γ-globin transcriptional unit in plasmid-transfected murine erythroleukemia (MEL) cells. However, as reported here, this same γ-globin gene expression cassette was only transcribed at trace amounts in erythroid cells of transgenic mice. This lack of expression was not directly attributable to the β/γ-globin transcriptional unit, since this same unit linked to a composite β-globin locus control region was expressed at high levels in transgenic mice. This lack of expression was also not directly attributable to chromosomal position effects, since addition of chromatin insulators failed to increase the frequency of expression. DNase I hypersensitivity and chromatin immunoprecipitation assays demonstrated that the lack of expression was correlated with a closed chromatin structure. We hypothesize that transgenes undergo dynamic changes in chromatin conformation following chromosomal integration and that the discrepant results reported here can be attributed to the relatively high level of chromatin remodeling that occurs in the transgenic mouse model, coupled with the relative inability of the HS-40 element to maintain an open chromatin state under such conditions. (Blood. 2005;105: 3346-3352)
HIF-2α regulates murine hematopoietic development in an erythropoietin-dependent manner
Authors: Scortegagna Marzia , Ding Kan , Zhang Quiyang , Oktay Yavuz , Bennett Michael J. , Bennett Michael , Shelton John M. , Richardson James A. , Moe Orson , Garcia Joseph A. 
Published: December 2004

AbstractErythropoiesis in the adult mammal depends critically on erythropoietin, an inducible cytokine with pluripotent effects. Erythropoietin gene expression increases under conditions associated with lowered oxygen content such as anemia and hypoxia. HIF-1α, the founding member of the hypoxia-inducible factor (HIF) alpha class, was identified by its ability to bind and activate the hypoxia-responsive enhancer in the erythropoietin regulatory region in vitro. The existence of multiple HIF alpha members raises the question of which HIF alpha member or members regulates erythropoietin expression in vivo. We previously reported that mice lacking wild-type HIF-2α, encoded by the EPAS1 gene, exhibit pancytopenia. In this study, we have characterized the etiology of this hematopoietic phenotype. Molecular studies of EPAS1-null kidneys reveal dramatically decreased erythropoietin gene expression. EPAS1-null as well as heterozygous mice have impaired renal erythropoietin induction in response to hypoxia. Treatment of EPAS1-null mice with exogenous erythropoietin reverses the hematopoietic and other defects. We propose that HIF-2α is an essential regulator of murine erythropoietin production. Impairments in HIF signaling, involving either HIF-1α or HIF-2α, may play a prominent role in conditions involving altered hematopoietic or erythropoietin homeostasis.
HIV-1 Nef interferes with M-CSF receptor signaling through Hck activation and inhibits M-CSF bioactivities
Authors: Suzu Shinya , Harada Hideki , Matsumoto Takahiro , Okada Seiji 
Published: December 2004

AbstractHIV-1 Nef protein is a major determinant of the pathogenicity of the virus. It has been shown that Nef activates Hck, a member of Src family kinase, in monocytes/macrophages and that the interaction is critical for AIDS-like disease progression in a mouse model. However, it was unclear how the molecular interaction in monocytes/macrophages leads to disease progression. Here, we show for the first time that Nef interferes with the macrophage colony-stimulating factor (M-CSF)/M-CSF receptor signal pathway. In this study, we introduced a conditionally active Nef into myeloid leukemia TF-1-fms cells and analyzed their responsiveness to M-CSF. We found that Nef-activated Hck constitutively associated with the M-CSF receptor complex. The formation of the molecular complex should occur under physiologic conditions, that is, on M-CSF stimulation. Because of aberrant molecular association, the tyrosine-phosphorylation/activation of the receptor in response to M-CSF was markedly diminished in Nef-active cells. Consequently, Nef activation caused the inhibition of M-CSF-mediated proliferation of TF-1-fms cells and macrophage differentiation of the cells induced by M-CSF and 12-O-tetradecanoylphorbol 13-acetate. These results indicate that HIV-1 Nef interferes with M-CSF receptor signaling through Hck activation and thereby inhibits M-CSF functions in monocytes/macrophages. (Blood. 2005;105:3230-3237)
FLT3-ITD-TKD dual mutants associated with AML confer resistance to FLT3 PTK inhibitors and cytotoxic agents by overexpression of Bcl-x(L)
Authors: Bagrintseva Ksenia , Geisenhof Stefanie , Kern Ruth , Eichenlaub Sabine , Reindl Carola , Ellwart Joachim W. , Hiddemann Wolfgang , Spiekermann Karsten 
Published: December 2004

AbstractFLT3 (fms-like tyrosine kinase 3) is constitutively activated in about 30% of patients with acute myeloid leukemia (AML) and represents a disease-specific molecular marker. Although FLT3-LM (length mutation) and TKD (tyrosine kinase domain) mutations have been considered to be mutually exclusive, 1% to 2% of patients carry both mutations. However, the functional and clinical significance of this observation is unclear. We demonstrate that FLT3-ITD-TKD dual mutants induce drug resistance toward PTK inhibitors and cytotoxic agents in in vitro model systems. As molecular mechanisms of resistance, we found that FLT3-ITD-TKD mutants cause hyperactivation of STAT5 (signal transducer and activator of transcription-5), leading to upregulation of Bcl-x(L) and RAD51 and arrest in the G2M phase of the cell cycle. Overexpression of Bcl-x(L) was identified as the critical mediator of drug resistance and recapitulates the PTK inhibitor and daunorubicin-resistant phenotype in FLT3-ITD cells. The combination of rapamycin, a selective mTOR inhibitor, and FLT3 PTK inhibitors restored the drug sensitivity in FLT3 dual mutant–expressing cells. Our data provide the molecular basis for understanding clinical FLT3 PTK inhibitor resistance and point to therapeutical strategies to overcome drug resistance in patients with AML.
The role of CXCL12 in the organ-specific process of artery formation
Authors: Ara Toshiaki , Tokoyoda Koji , Okamoto Rika , Koni Pandelakis A. , Nagasawa Takashi 
Published: December 2004

AbstractCXC chemokine ligand 12 (CXCL12; stromal cell-derived factor-1 [SDF-1]/pre-B-cell growth-stimulating factor [PBSF]) and its receptor CXCR4 are essential for vascularization in the gastrointestinal tract as well as B lymphopoiesis and colonization of bone marrow by hematopoietic cells. However, the mechanism by which CXCL12/CXCR4 functions in blood vessel formation remains elusive. Here, we have found a novel mode of organ vascularization and determined the roles of CXCL12 in these processes. In the developing small intestine, many short interconnecting vessels form between larger superior mesenteric artery (SMA) and the neighboring primary capillary plexus surrounding the primitive gut, and they elongate and become the arteries supplying the small intestine. Mice lacking CXCL12 or CXCR4 lack the interconnecting vessels but have normal venous networks. The mutants lack filopodial extension and intussusception from endothelial cells of SMAs seen in wild-type embryos. CXCR4 is specifically expressed in arteries in the developing mesenteries and its expression is severely reduced in CXCL12–/– embryos. Mice in which CXCR4 is specifically deleted in the endothelium reveal vascular defects identical to those observed in the conventional CXCR4–/– embryos. Together, CXCL12 acts on arterial endothelial cells of SMA to up-regulate CXCR4 and mediate the connection between the larger artery and neighboring capillary plexus in an organ-specific manner.
Steuerung der ebenen Fahrzeugbewegung mit optimaler Nutzung der Kraftschlusspotentiale aller vier Reifen (Vehicle Dynamics Feedforward Control with Optimal Utilisation of the Adhesion Potentials of all four Tyres)
Authors: Orend Ralf 
Published: December 2004

Abstract
Zur Steuerung der Längs- und Querbewegung eines Fahrzeugs mit Einzelradlenkung, Einzelradbremse, Einzelradantrieb und aktivem Fahrwerk wird eine Strategie entwickelt, mit der sich desssen fahrdynamisches Potential voll ausschöpfen lässt. Die Kräfte an den Rädern werden dabei durch Lösen einer konvexen Optimierungsaufgabe derart betimmt, dass sich alle vier Reifen möglichst weit unterhalb ihrer Krafschlussgrenzen befinden.
Entwicklungsumgebung mit echtzeitfähigen Gesamtfahrzeugmodellen für sicherheitskritische Fahrerassistenzsysteme (Development Environment with Real-time Models for Safety Assistance Systems)
Authors: Schmitt Jürgen , Schorn Matthias , Stählin Ulrich , Isermann Rolf 
Published: December 2004

Abstract
Simulationen gewinnen bei der Funktionsentwicklung für Fahrdynamikregelungen speziell im Stadium der Vorentwicklung immer mehr an Bedeutung. Die Bewertung von Fahrerassistenzsystemen oder Fahrdynamikregelungen ist jedoch aufgrund des subjektiven Fahrgefühls schwierig. Aus diesem Grund wurden ein Force-Feedback-Lenkrad und eine Pedaleinheit mit einem in Fahrversuchen verifizierten echtzeitfähigen Zweispurmodell gekoppelt, die es dem Fahrer ermöglichen, das Gesamtfahrzeugmodell realitätsnah zu steuern. Den aktuellen Fahrzustand erhält der Fahrer über eine 3D-Animation von Fahrzeug und Umgebung in verschiedenen Perspektiven. Mithilfe dieser Entwicklungsumgebung werden neue Ansätze zur Fahrdynamikregelung mit kombiniertem Lenk- und Bremseingriff untersucht.
Systemsicherheit des Active Front Steering (Active Front Steering – System Safety)
Authors: Reinelt Wolfgang , Klier Willy , Reimann Gerd 
Published: December 2004

Abstract
Active Front Steering ist ein elektronisch geregeltes Lenksystem für Kraftfahrzeuge, das situationsabhängig eine Überlagerung eines Winkels zum Lenkradwinkel erlaubt und somit eine Variation der Lenkübersetzung ermöglicht. Für ein solches System muss die funktionale Sicherheit gewährleistet sein. Ziele der funktionalen Sicherheit werden erläutert und messbare Kriterien und deren Nachweisbarkeit dafür diskutiert. Der Analyseprozess, der Sicherheitsintegritätslevel des Systems und der Komponenten bestimmt, wird erläutert, gefolgt von der Spezifikation der Sicherheitsanforderungen und Überwachungsfunktionen. Zum Schluss werden einige modellbasierte Überwachungsfunktionen beschrieben, wie sie im technischen Sicherheitskonzept, speziell in der Verifikation der Eingangssignale des Active Front Steering der Nachfolgegeneration Anwendung finden sollen.
Prüfstandtaugliche Lasermassenspektrometrie von Abgasinhaltsstoffen an Otto- und Dieselmotoren (Laser Mass Spectrometry of Compounds in Exhaust Emissions from Otto and Diesel Engines Adapted for Use at Motor Test Facilities)
Authors: Boesl Ulrich , Weishäupl Ronald , Püffel Peter , Thiel Wolfgang 
Published: December 2004

Abstract
Die Lasermassenspektrometrie zum simultanen Nachweis von Stickoxiden, Ammoniak und anderer Abgaskomponenten (N2O, CO, O2, H2O, Aromaten) wird vorgestellt. Am Motorprüfstand wurden ausführliche Messserien an Otto- und Dieselmotoren vor und nach Katalysatoren, im Zylinder und im Vergleich mit konventionellen Methoden durchgeführt.
Coupling of an induced fit enzyme to polydiacetylene thin films: Colorimetric detection of glucose
Authors: Cheng Quan , Stevens Raymond C. 
Published: December 2004

A new biosensor design is demonstrated, in which a protein conformational change is used as a trigger mechanism for a low‐cost, solid‐state sensor (see also the cover). The figure illustrates the principle: an enzyme (hexokinase, large white shape) immobilized on a lipid polydiacetylene (PDA) layer undergoes a conformational change when glucose (dark shape) binds to it. The resulting stress in the PDA layer produces a color change. magnified image
A prospective study of nontraumatic coma: Methods and results in 310 patients
Authors: Bates D. , Caronna J. J. , Cartlidge N. E. F. , Knill‐Jones R. P. , Levy D. E. , Shaw D. A. , Plum F. 
Published: December 2004

AbstractNeurological signs and outcome are compared in the first 310 patients from a continuing prospective study of coma not caused by trauma or drugs. Sixteen percent of the patients achieved an independent existence within a month; severe disability or the vegetative state developed in 25% of patients comatose for six hours and in 79% of those still in coma after a week. The chance of regaining an independent existence was greater in patients who, by one day, obeyed commands or moved the limbs appropriately in response to noxious stimuli or who had attained any of the following: orienting eye movements, normal responses to oclulocephalic or ocluovestibular stimulation, or normal muscle tone. Conversely, the chance of regaining an independent existence fell in patients who, after one day, had either extensor responses of the limbs or failed to move them in response to noxious stimuli or who lacked eye opening, pupillary reactions, corneal responses, or any eye movement in response to oculovestibular or oculocephalic stimulation. Beyond these general guidelines, numbers of patients with particular signs are presently too small for confident prediction of outcome.
Pharmacological prophylaxis against the development of kindled amygdaloid seizures
Authors: Turner Ira M. , Newman Stephen M. , Louis Sydney , Kutt Henn 
Published: December 2004

AbstractThe kindling of amygdaloid and cortical seizures in cats was used to study the prophylactic effects of phenobarbital, phenytoin, ethosuximide, acetazolamide, and dexamethasone. Phenobarbital prevented the evolution of such seizures beyond stage 4 in all amygdaloid‐kindling animals during 160 days of study. The prophylactic effect persisted on periodic challenge after the drug had been discontinued. Phenytoin, ethousuximide, acetazolamide, and dexamethasone appeared to have no prophylactic effect against the development of kindled amygdaloid seizures. With cortical kindling, both phenobarbital and phenytoin retarded the evolution of seizures without achieving true prophylaxis. The drugs appeared to act as suppressants. Prophylaxis was not an “all‐or‐none” phenomenon but rather a limitation of the stage of seizure evolution.
The relationship between parkinson syndrome and vascular siderosis: An electron microprobe study
Authors: Duckett Serge , Galle Pierre , Kradin Richard 
Published: December 2004

AbstractVascular siderosis (VS) refers to the presence of mineralized small and medium‐sized arteries in the globus pallidus, usually regarded as reflecting an aging process. The electron probe analysis of deposits in vascular siderosis in 10 patients dying of parkinsonism and in 8 other patients without parkinsonism is reported here. The microprobes identified a total of 11 elements in the VS in these 18 patients. Five elements—lead, aluminum, sulfur, manganese, and barium—were present only in VS associated with parkinsonism. Statistically, the association of lead was highly significant while that of aluminium and sulfur was only suggestive. Lead was present in 7 of the 10 patients with parkinsonism and aluminium and sufur in 4. The significance of the presence of sulfur is difficult to assess since its compounds are normally present in large quantities in the brain. These findings raise the question whether lead and aluminum may be associated in some way with the pathogenesis of certain forms of Parkinson disease.
Pedigree testing in duchenne muscular dystrophy
Authors: Roses A. D. , Roses M. J. , Metcalf B. S. , Hull K. L. , Nicholson G. A. , Hartwig G. B. , Roe C. R. 
Published: December 2004

AbstractFemale relatives of 41 Duchenne muscular dystrophy proband cases were studied with a panel of carrier‐detection tests. A total of 277 relatives were tested in order to determine which mothers had affected sons as a result of new mutation. In 39 of 41 pedigrees the data demonstrate that a mutation cannot be postulated; the 2 negative pedigrees were inadequately tested. Our data suggest that all mothers of affected sons should be considered genetic carriers (heterozygotes) until proved otherwise. Our findings also raise questions concerning what mechanisms skew the indirect statistical estimates of mutation that are in common use.
Familial paroxysmal dystonic choreoathetosis and its differentiation from related syndromes
Authors: Lance James W. 
Published: December 2004

AbstractFour generations of a family are described in which 7 of 8 affected members suffered from prolonged dystonic seizures; the eighth member's attacks were those of paroxysmal choreoathetosis. The attacks lasted up to 4 hours, were precipitated by alcohol, emotion, or fatigue, and responded poorly to phenytoin and barbiturates but were controlled by clonazepam. Autopsy on an affected child who died a “crib death” at the age of 2 years disclosed no major abnormality of the brain. This family appears to have the same condition as that described by Mount and Reback in 1940, Forssman in 1961, and Richards and Barnett in 1968, which the last authors termed paroxysmal dystonic choreoathetosis to distinguish it from the more common movement‐induced (kinesigenic) form of the disorder.Analysis of reports of 100 cases of paroxysmal kinesigenic choreoathetosis shows that the attacks last less than 5 minutes, are precipitated by sudden movement or startle, and usually respond well to phenytoin or barbiturates. A clinical classification is presented in which the kinesigenic form is divided into a familial group (72% of cases) and a sporadic group (28% of cases) and contrasted with paroxysmal dystonic choreoathetosis. One family with an intermediate form, in which dystonic choreoathetosis was provoked by continued exertion and lasted for up to 30 minutes, is also reported.
Programmed feeding as a model of chronic alcoholism in the rat
Authors: Craig J. R. , Munsat T. L. , Chuang M. 
Published: December 2004

AbstractProgrammed‐feeding polydipsia results in a reliable model of chronic alcoholism in the rat. High oral ethanol consumption and a predictable withdrawal reaction associated with audiogenic seizures are produced. The maintenance of high blood ethanol levels for three weeks in 18 male Charles River rats was associated with audiogenic seizures after 6 to 8 hours of withdrawal. These chronic alcoholic rats had enhanced blood clearance of ethanol. The cerebral cortical crude mitochondrial function showed a decrease in total and magnesium‐dependent adenosine triphosphatase activity in alcoholic and control (water‐fed) rats compared with normal rats.
Acute measles encephalitis of the delayed type
Authors: Lyon Gilles , Ponsot Gérard , Lebon Pierre 
Published: December 2004

AbstractAn acute measles encephalitis with epilepsia partialis continua occurred three months after measles in a previously healthy child with no detectable immunological defect. Levels of measles antibodies in serum and cerebrospinal fluid were high, and tubular inclusions of the type seen in subacute sclerosing panencephalitis were found in nerve cell nuclei. A communicating high‐pressure hydrocephalus developed in the later stage of the disease. This case demonstrates that measles encephalitis of the delayed type should systematically be considered in children with acute encephalitis.
Cysticercosis of the nervous system: Diagnosis by means of specific radioimmunoscan
Authors: Skromne‐Kadlubik Gregorio , Celis Cesar , Ferez Antonio 
Published: December 2004

AbstractA new method for diagnosing cerebral cysticercosis by means of specific radioimmunoscan is described. The method has been evaluated in 24 patients with encouraging results. The technique involves a single intravenous injection followed by brain scanning and thus far has been entirely nontoxic. The accuracy of the scan was confirmed in 6 patients by surgical removal of lesions that coincided in location and number with the diagnostic scan of the parasites.
Tissue culture studies of demyelinating disease: A critical review
Authors: Seil Fredrick J. 
Published: December 2004

AbstractTissue culture studies of human and experimental demyelinating diseases have demonstrated that sera from patients with multiple sclerosis reversibly demyelinate central nervous system cultures. Similar changes are evoked by sera from animals with experimental allergic encephalomyelitis induced by inoculation with whole central nervous system tissue but not by encephalitogenic myelin basic protein. Sera and buffy coat or lymph node cells from humans with idiopathic polyneuritis and animals with experimental allergic neuritis demyelinate cultures of peripheral nervous system tissue.While these studies have contributed to speculations about pathogenetic mechanisms of demyelinating diseases, including the role of both circulating antibodies and delayed hypersensitivity factors, a number of important questions remain unanswered. Among these are the identity of the antigens that evoke antimyelin antibodies and the precise relationship of serum or cellular antimyelin factors to the pathogenesis or clinical course of the demyelinating diseases. Further studies with this technique may provide more complete information about the role of immunological events in induction of disease.
Growth rates of epidermoid tumors
Authors: Alvord Ellsworth C. 
Published: December 2004

AbstractConsideration of the most likely method of growth of epidermoid tumors, either congenital or traumatic in origin, suggests that they grow linerarly, at rates approximating those reported for normal human skin, rather than exponentially, as most tumors do. Such a linear rate of growth would be expected of tumors derived from a single layer of basal germinal cells spread out over a surface area.
Tonic pupils with acute ophthalmoplegic polyneuritis
Authors: Keane James R. 
Published: December 2004

AbstractTwo patients with the symmetrical ophthalmoplegic varient of acute idopathic polyneuritis (Fisher's syndrome) developed bilateral dilated pupils with cholinergic supersensitivity and light‐near dissociation (tonic pupils), indicating involvement of the postganglionic parasympathetic neuron within the orbit. Supranuclear eye movement dysfunction also was present, indicated by relative levator sparing in both patients and by preservation of Bell's phenomenon in 1 patient despite paralysis of voluntary upward gaze.The lesions that produce the eye signs of ophthalmoplegic polyneuritis are not necessarily restricted to the cranial nerve trunks. The present cases support a relationship between the ophthalmoplegic variant of the Guillain‐Barré syndrome and acute postifectius encephalomyelitis (brainstem encephalitis) on the one hand, and idiopathic autonomic neuropathies such as the Holmes‐Adie syndrome and pandysautonomia on the other.