bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppression of complex I gene expression induces optic neuropathy
Authors: Qi Xiaoping , Lewin Alfred S. , Hauswirth William W. , Guy John 
Published: January 2003

AbstractOptic nerve degeneration is a feature common to diseases with mutations in genes that encode complex I of the respiratory chain. Vulnerability of this central nervous system tract is a mystery, because of the paucity of animal models used to investigate effects of the mutated DNA in tissues rather than isolated in cultured cells. Using a ribozyme designed to degrade the mRNA encoding a critical nuclear‐encoded subunit gene of complex I (NDUFA1), we tested whether oxidative phosphorylation deficiency can recapitulate the optic neuropathy of mitochondrial disease. Injection of adenoassociated virus expressing this ribozyme led to axonal destruction and demyelination, the hallmarks of Leber hereditary optic neuropathy. Ann Neurol 2003
Plasticity of the nigropallidal pathway in Parkinson's disease
Authors: Whone Alan L. , Moore Robert Y. , Piccini Paola P. , Brooks David J. 
Published: January 2003

AbstractThe degeneration of nigrostriatal dopamine neurons in early Parkinson's disease (PD) is compensated in part by increased transmitter turnover in surviving neurons of the pathway. In this 18F‐dopa positron emission tomography study, we demonstrate compensatory changes in PD in another midbrain dopamine projection to the basal ganglia, the nigropallidal projection to the internal segment of the globus pallidus (GPi). Increased 18F‐dopa uptake in the GPi is seen in early PD which then is lost in advanced PD. Our early PD cases show an absence of significant clinical progression in the face of a continuing loss of nigrostriatal projections. This indicates a compensatory neuronal plasticity that we now show to involve the nigropallidal dopamine pathway to the GPi but not to the external segment of the globus pallidus (GPe). Enhanced function of the dopamine projection to the GPi serves, we propose, to maintain a more normal pattern of pallidal output to ventral thalamus and motor cortex in early PD, whereas loss of this adaptive pathway in advanced disease may be a pivotal step in the progression of the disease.
Homocysteine, white matter hyperintensities, and cognition in healthy elderly people
Authors: Dufouil Carole , Alpérovitch Annick , Ducros Véronique , Tzourio Christophe 
Published: January 2003

AbstractHyperhomocysteinemia is associated with an increased risk of vascular disease, and recent results suggest that it also could increase the risk of dementia. We examined the relationship between homocysteine and cognitive decline in 1,241 subjects aged 61 to 73 years, followed up over 4 years. Plasma homocysteine levels were determined in all participants as well as cardiovascular risk factors, apolipoprotein E genotype, plasma levels of folate, and vitamin B12. Cognitive performances were assessed repeatedly by using Mini‐Mental State Examination, Trail Making Test, Digit Symbol Substitution Test, and Finger Tapping Test. At 2‐year follow‐up, 841 subjects underwent cerebral magnetic resonance imaging, and white matter hyperintensities were rated visually. Analyses were adjusted for all cardiovascular risk factors. Cross‐sectional analyses showed that higher concentrations of homocysteine were significantly related to poorer performances at all neuropsychological tests. Longitudinal analyses confirmed this finding. The odds of cognitive decline was 2.8‐fold (p < 0.05) higher in subjects with homocysteine levels above 15μmol/L compared with those with homocysteine levels below 10μmol/L. In participants who underwent magnetic resonance imaging, the relationship between homocysteine and cognition was unchanged after taking into account white matter hyperintensities suggesting that white matter hyperintensities do not mediate the association between homocysteine and cognition. Ann Neurol 2003;53:000–000
Lack of creatine in muscle and brain in an adult with GAMT deficiency
Authors: Schulze Andreas , Bachert Peter , Schlemmer Heinz , Harting Inga , Polster Tilman , Salomons Gajja S. , Verhoeven Nanda M. , Jakobs Cornelis , Fowler Brian , Hoffmann Georg F. , Mayatepek Ertan 
Published: January 2003

AbstractGuanidinoacetate methyltransferase deficiency, which so far has been exclusively detected in children, was diagnosed in a 26‐year‐old man. The full‐blown spectrum of clinical symptoms already had been present since infancy without progression of symptoms during adolescence. Cranial magnetic resonance imaging showed normal findings. Ophthalmological examination showed no retinal changes. Besides creatine deficiency in the brain, a distinct lack of phosphocreatine in skeletal muscle was proved by 31P magnetic resonance spectroscopy. Creatine substitution combined with a guanidinoacetate‐lowering diet introduced first at the age of 26 years was shown to be effective by an impressive improvement of epileptic seizures, mental capabilities, and general behavior and by normalization of the 31P spectrum in the skeletal muscle.
Oculobulbar involvement is typical with Lambert–Eaton Myasthenic Syndrome
Authors: Burns Ted M. , Russell James A. , LaChance Daniel H. , Jones H. Royden 
Published: January 2003

AbstractOculobulbar symptoms and/or signs were present in 18 of 23 (78%) of Lambert–Eaton myasthenic syndrome (LEMS) patients evaluated at the Lahey Clinic (Table). Sixty‐five percent (15 of 23) of our patients had ptosis and/or diplopia, each present in 11 individuals. Bulbar signs and symptoms, including dysarthria in 10 and dysphagia in 8 patients, also were observed among our LEMS population. More than one prereferral oculobulbar feature occurred in 13 of our LEMS patients. Prereferral diagnostic considerations included myasthenia gravis, myopathies, and psychiatric disorders. These findings suggest that these atypical characteristics served to dissuade some colleagues from a diagnosis of LEMS. Thus, the presence of oculobulbar symptoms and signs cannot be used to exclude LEMS from the differential diagnosis.
High exogenous homocysteine modifies eye development in early chick embryos
Authors: Maestro De Las Casas Carmen , Epeldegui Marta , Tudela Consuelo , Varela‐Moreiras Gregorio , Pérez‐Miguelsanz Julia 
Published: January 2003

AbstractBACKGROUNDHomocysteine is a nonessential aminoacid whose increase is related to the appearance of neural tube defects in humans. In chick embryos, high levels of homocysteine produce neural tube defects and alteration of neural crest cell migration.METHODSIn our study, 8 μl of L‐homocysteine thiolactone (20 μmol) was added to chick embryos of Stages 3–8/10 (Hamburger and Hamilton, 1951), (12–38 hr of incubation). Three days later, 50 embryos, externally normal or carrying isolated spinal neural tube defects, were sectioned and stained by hematoxilin‐eosin or anti‐fibrillin‐1 antibody.RESULTSThe eye showed alterations of the optic cup as microphthalmia, or lens dislocation. In both cases, the incidence of alterations diminished with the age of the homocysteine‐increased embryos. Optic cup modifications are probably associated with central nervous system alterations, because most of the affected embryos exhibited isolated spinal neural tube defects and had altered neural crest cells. We have shown for the first time that high exogenous homocysteine during early development could produce a caudally‐displaced lens axis before the zonule is formed. Fibrillin‐1 is the main component of elastic microfibrils, and in the adult human it is seen as a protein particularly susceptible to homocysteine attack.CONCLUSIONSAntibody staining against fibrillin‐1 showed no evident morphological differences in distribution between experimental and control embryos in the lens, suggesting that fibrillin‐1 was not the cause, and malformations may be attributed to other mechanisms. Birth Defects Research (Part A) 67:35–40, 2003. © 2003 Wiley‐Liss, Inc.
Defects in cervical vertebrae in boric acid‐exposed rat embryos are associated with anterior shifts of hox gene expression domains
Authors: Wéry Nathalie , Narotsky Michael G. , Pacico Nathalie , Kavlock Robert J. , Picard Jacques J. , Gofflot Françoise 
Published: January 2003

AbstractBACKGROUNDPreviously, we showed that prenatal exposure to boric acid (BA), an industrial agent with large production, causes alterations of the axial skeleton in rat embryos, reminiscent of homeotic transformations. Indeed, Sprague‐Dawley rats exposed in utero to BA on gestation day 9 (GD 9) had only six, rather than the normal seven, cervical vertebrae. This finding, observed in 91% of GD 21 fetuses, suggests posterior transformations of vertebrae. The present study attempts to determine if these skeletal alterations could be explained by modifications of the hox code, involved in the establishment of positional information along the craniocaudal axis of the embryo.METHODSPregnant rats were treated by gavage with BA (500 mg/kg, twice) on GD 9. Embryos were collected on GD 11 or GD 13.5 and processed for in situ hybridization. Several hox genes were selected according to the position of their cranial limit of expression in the cervical and thoracic region.RESULTSAt GD 13.5, we detected a cranial shift of the anterior limit of expression of hoxc6 and hoxa6. We observed no difference between control and treated embryos in the location of the cranial limit of expression of the other genes: hoxd4, hoxa4, hoxc5, and hoxa5.CONCLUSIONSOur results demonstrate that following in utero exposure to BA on GD 9, a disturbance of the expression of hox genes involved in the specification of most anterior vertebrae is observed at GD 13.5. Based on their expression domain and on their implication in the definition of the cervicothoracic vertebral boundary, it is likely that the anteriorization of hoxc6 and hoxa6 reported here is correlated to the morphological phenotype observed in BA‐exposed fetuses at GD 21. Birth Defects Research (Part A) 67:59–67, 2003. © 2003 Wiley‐Liss, Inc.
Human c‐fos promoter mediates high‐level, inducible expression in various mammalian cell lines
Authors: Bi Jing‐Xiu , Buhr Petra , Zeng An‐Ping , Wirth Manfred 
Published: January 2003

AbstractThe promoter activity of the human c‐fos and human cytomegalovirus (CMV) immediate early promoter was compared in transient and stable transfection experiments with six cell lines of mouse, human, and hamster origin which are all of commercial importance. The c‐fos promoter was 1.8–5.6‐fold stronger than the CMV promoter in BHK‐A, BHK‐B, CHO‐DHFR−, and mouse NIH‐3T3 in stable transfectants and less effective in mouse myeloma or human 293 cells, suggesting a new transcriptional control element for high‐level expression and protein production in mammalian cells. The induction profiles determined in the presence and absence of serum are dependent on the cell line used. Induction levels of up to 8‐fold could be achieved in preselected cell pools. © 2003 Wiley Periodicals. Biotechnol Bioeng 81: 848–854, 2003.
Capture of a recombinant protein from unclarified canola extract using streamline expanded bed anion exchange
Authors: Bai Yun , Glatz Charles E. 
Published: January 2003

AbstractThe feasibility of applying expanded bed adsorption technology to recombinant protein recovery from extracts of transgenic canola (rapeseed) was assessed. The extraction step results in a suspension of high solids content that is difficult to clarify. The coarse portion of the solids can be removed easily, and our aim was to operate the expanded bed in the presence of the recalcitrant particulates. Recombinant β‐glucuronidase (rGUS) produced in transgenic canola seed was the model system. Diethylaminoethyl (DEAE) and Streamline DEAE resin exhibited similar binding and elution properties for both rGUS and native canola proteins. More than 95% of native canola proteins did not bind to DEAE resins at pH 7.5, whereas the bound proteins were fractionated by two‐step salt elution into two groups with the first peak, containing 70% of total bound proteins, at 20 mS/cm, followed by elution of rGUS at 50 mS/cm. The adsorption isotherm was only slightly influenced by the presence of up to 14 mg solids/mL extract; Cm and Kd changed by −1% and +39%, respectively. Bed expansion was semiquantitatively predictable from physical properties of the fluid together with Stokes's law and the Richardson–Zaki correlation for both clarified and partially clarified extracts. The presence of 1.4% solids did not change rGUS breakthrough behavior of the expanded bed; however, a small difference between expanded bed and packed bed was observed early in the sample loading stage, during which bed expansion adjusts. Canola solids moved through the column in approximately plug flow with no detriment to bed stability. Seventy‐two percent recovery of 34‐fold purified rGUS was obtained after initial loading of 1.4% (w/w) solids extract to 25% breakthrough. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 81: 855–864, 2003.
Integrated optical sensing of dissolved oxygen in microtiter plates: A novel tool for microbial cultivation
Authors: John Gernot T. , Klimant Ingo , Wittmann Christoph , Heinzle Elmar 
Published: January 2003

AbstractMicrotiter plates with integrated optical sensing of dissolved oxygen were developed by immobilization of two fluorophores at the bottom of 96‐well polystyrene microtiter plates. The oxygen‐sensitive fluorophore responded to dissolved oxygen concentration, whereas the oxygen‐insensitive one served as an internal reference. The sensor measured dissolved oxygen accurately in optically well‐defined media. Oxygen transfer coefficients, kLa, were determined by a dynamic method in a commercial microtiter plate reader with an integrated shaker. For this purpose, the dissolved oxygen was initially depleted by the addition of sodium dithionite and, by oxygen transfer from air, it increased again after complete oxidation of dithionite. kLa values in one commercial reader were about 10 to 40 h−1. kLa values were inversely proportional to the filling volume and increased with increasing shaking intensity. Dissolved oxygen was monitored during cultivation of Corynebacterium glutamicum in another reader that allowed much higher shaking intensity. Growth rates determined from optical density measurement were identical to those observed in shaking flasks and in a stirred fermentor. Oxygen uptake rates measured in the stirred fermentor and dissolved oxygen concentrations measured during cultivation in the microtiter plate were used to estimate kLa values in a 96‐well microtiter plate. The resulting values were about 130 h−1, which is in the lower range of typical stirred fermentors. The resulting maximum oxygen transfer rate was 26 mM h−1. Simulations showed that the errors caused by the intermittent measurement method were insignificant under the prevailing conditions. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 81: 829–836, 2003.
On the organic solvent and thermostability of the biocatalytic redox system of Rhodococcus ruber DSM 44541
Authors: Stampfer Wolfgang , Kosjek Birgit , Kroutil Wolfgang , Faber Kurt 
Published: January 2003

AbstractThe sec‐alcohol dehydrogenase activity of whole cells of Rhodococcus ruber DSM 44541 has been employed as an efficient biocatalytic redox system due to the use of acetone and 2‐propanol at elevated concentrations for cofactor regeneration in the oxidation and reduction mode, respectively, and external addition of NADH/NAD+ can be omitted. The operational half‐life time of the redox system is 29 hours in 20% v/v acetone and 37 hours in 30% v/v 2‐propanol. The Redox system allows the enantioselective oxidation of sec‐alcohols and the asymmetric reduction of ketones to furnish (S)‐configurated alcohols in high optical purity. The stability of the cells towards further organic solvents was investigated. In addition, the system displays thermostability of up to 60°C and pH stability of up to pH 11. The system represents a simple to handle tool for environmentally benign redox reactions. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 81: 865–869, 2003.
Objective countertransference: do patients' interpersonal impacts generalize across therapists?
Authors: Hafkenscheid Anton 
Published: January 2003

AbstractObjective countertransference refers to the constricted feelings, attitudes and reactions of a therapist, that are induced primarily by the patient's maladaptive behaviour and that are generalizable to other therapists (and to other significant others in the patient's life). In interpersonal theory and therapy, the equivalent of objective countertransference is the impact message concept. Impact messages refer to the cognitions, emotions and action tendencies evoked in the therapist by a particular patient's interpersonal pressures. This paper tests the interpersonal hypothesis that interpersonal impact generalizes across therapists (and by extension across interpersonal relationships). Generalizability of impact messages across therapists was determined for different combinations of therapist pairs, independently rating a total of 131 psychiatric outpatients with the IMI‐C (Impact Message Inventory, revised circumplex version). It was found that impact messages were most clearly generalizable across therapists for the Dominance (D) category, followed by the Hostile–Dominant (HD) and Hostile–Submissive (HS) categories. In contrast, the other five categories of impact messages turned out to be poorly generalizable across therapists. Impact messages within the Dominance (D) category were also strikingly stable over a period of time of 12 months or longer. Some possible causes of the limited generalizability of most impact message categories are discussed. Copyright © 2002 John Wiley & Sons, Ltd.
A metamodel of theories of psychotherapy: a guide to their analysis, comparison, integration and use
Authors: Morris Steven J. 
Published: January 2003

AbstractEvery theory of psychotherapy is composed of a myth and an associated ritual. A myth is a conceptual scheme for explaining clinical problems. A ritual is based upon a myth and is a model of the clinical change process. This article goes far beyond the observation that theories of psychotherapy consist of a myth and a ritual to propose that they share a common underlying structure. The central purpose of this article is to delineate this structure. This structure constitutes a metamodel of theories of psychotherapy. The article shows how the metamodel is a fresh conceptual tool (a) for understanding, analysing, comparing and contrasting, and integrating the basic concepts and principles of theories of psychotherapy and (b) for building case formulations and treatment plans from a theory of psychotherapy. Copyright © 2003 John Wiley & Sons, Ltd.
Tales of regeneration in zebrafish
Authors: Poss Kenneth D. , Keating Mark T. , Nechiporuk Alex 
Published: January 2003

AbstractComplex tissue regeneration involves exquisitely coordinated proliferation and patterning of adult cells after severe injury or amputation. Certain lower vertebrates such as urodele amphibians and teleost fish have a greater capacity for regeneration than mammals. However, little is known about molecular mechanisms of regeneration, and cellular mechanisms are incompletely defined. To address this deficiency, we and others have focused on the zebrafish model system. Several helpful tools and reagents are available for use with zebrafish, including the potential for genetic approaches to regeneration. Recent studies have shed light on the remarkable ability of zebrafish to regenerate fins. Developmental Dynamics 226:202–210, 2003. © 2003 Wiley‐Liss, Inc.
Hydra regeneration and epitheliopeptides
Authors: Fujisawa Toshitaka 
Published: January 2003

AbstractHydra has been well known for over 200 years for its remarkable regenerative capacity. In addition to small pieces excised from the body, reaggregates of dissociated single cells can also regenerate. Although the cellular events involved in the regeneration process have been well characterized, the underlying molecular mechanisms are yet to be uncovered. Recently, however, transcription factors and signaling molecules, both proteins and short peptides, have been identified and their role suggested in patterning and morphogenesis. In this article, a regeneration study at the tissue level is first described and then the importance of epithelial cells in regeneration is stressed. Finally, the recent study on morphogenetic peptides derived from epithelial cells is reviewed. Developmental Dynamics 226:182–189, 2003. © 2003 Wiley‐Liss, Inc.
Retinoic acid, a regeneration‐inducing molecule
Authors: Maden Malcolm , Hind Matthew 
Published: January 2003

AbstractRetinoic acid (RA) is the biologically active metabolite of vitamin A. It is a low molecular weight, lipophilic molecule that acts on the nucleus to induce gene transcription. In amphibians and mammals, it induces the regeneration of several tissues and organs and these examples are reviewed here. RA induces the “super‐regeneration” of organs that can already regenerate such as the urodele amphibian limb by respecifying positional information in the limb. In organs that cannot normally regenerate such as the adult mammalian lung, RA induces the complete regeneration of alveoli that have been destroyed by various noxious treatments. In the mammalian central nervous system (CNS), which is another tissue that cannot regenerate, RA does not induce neurite outgrowth as it does in the embryonic CNS, because one of the retinoic acid receptors, RARβ2, is not up‐regulated. When RARβ2 is transfected into the adult spinal cord in vitro, then neurite outgrowth is stimulated. In all these cases, RA is required for the development of the organ, in the first place suggesting that the same gene pathways are likely to be used for both development and regeneration. This suggestion, therefore, might serve as a strategy for identifying potential tissue or organ targets that have the capacity to be stimulated to regenerate. Developmental Dynamics 226:237–244, 2003.© 2003 Wiley‐Liss, Inc.
Muscle regeneration in amphibians and mammals: Passing the torch
Authors: Carlson Bruce M. 
Published: January 2003

AbstractSkeletal muscle in both amphibians and mammals possesses a high regenerative capacity. In amphibians, a muscle can regenerate in two distinct ways: as a tissue component of an entire regenerating limb (epimorphic regeneration) or as an isolated entity (tissue regeneration). In the absence of epimorphic regenerative ability, mammals can regenerate muscles only by the tissue mode. This review focuses principally on the regeneration of entire muscles and covers what is known and what remains to be elucidated about fundamental mechanisms underlying muscle regeneration at this level. Developmental Dynamics 226:167–181, 2003. © 2003 Wiley‐Liss, Inc.
Eye regeneration at the molecular age
Authors: Rio‐Tsonis Katia Del , Tsonis Panagiotis A. 
Published: January 2003

AbstractEye tissues such as the lens and the retina possess remarkable regenerative abilities. In amphibians, a complete lens can be regenerated after lentectomy. The process is a classic example of transdifferentiation of one cell type to another. Likewise, retina can be regenerated, but the strategy used to replace the damaged retina differs, depending on the animal system and the age of the animal. Retina can be regenerated by transdifferentiation or by the use of stem cells. In this review, we present a synthesis on the regenerative capacity of eye tissues in different animals with emphasis on the strategy and the molecules involved. In addition, we stress the place of this field at the molecular age and the importance of the recent technologic advances. Developmental Dynamics 226:211–224, 2003. © 2003 Wiley‐Liss, Inc.