bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diffusion tensor imaging: Concepts and applications
Authors: Le Bihan Denis , Mangin Jean‐François , Poupon Cyril , Clark Chris A. , Pappata Sabina , Molko Nicolas , Chabriat Hughes 
Published: August 2002

AbstractThe success of diffusion magnetic resonance imaging (MRI) is deeply rooted in the powerful concept that during their random, diffusion‐driven displacements molecules probe tissue structure at a microscopic scale well beyond the usual image resolution. As diffusion is truly a three‐dimensional process, molecular mobility in tissues may be anisotropic, as in brain white matter. With diffusion tensor imaging (DTI), diffusion anisotropy effects can be fully extracted, characterized, and exploited, providing even more exquisite details on tissue microstructure. The most advanced application is certainly that of fiber tracking in the brain, which, in combination with functional MRI, might open a window on the important issue of connectivity. DTI has also been used to demonstrate subtle abnormalities in a variety of diseases (including stroke, multiple sclerosis, dyslexia, and schizophrenia) and is currently becoming part of many routine clinical protocols. The aim of this article is to review the concepts behind DTI and to present potential applications. J. Magn. Reson. Imaging 2001;13:534–546. © 2001 Wiley‐Liss, Inc.
Safety assessment of gadobenate dimeglumine (MultiHance®): Extended clinical experience from phase I studies to post‐marketing surveillance
Authors: Kirchin Miles A. , Pirovano Gianpaolo , Venetianer Carol , Spinazzi Alberto 
Published: August 2002

AbstractClinical trials completed by September 2000 on gadobenate dimeglumine (Gd‐BOPTA; MultiHance®) included 2540 adult and pediatric subjects that were administered this agent. For adult patient volunteers, the overall incidence of adverse events (AEs) was 19.8%, although marked study‐ and indication‐related differences were apparent. Events potentially related to Gd‐BOPTA administration were reported for 15.1% of adult patients. The vast majority of AEs were non‐serious, mild, transient, and self‐resolving. Headache, injection site reaction, nausea, taste perversion, and vasodilation were the most common AEs, reported with a frequency of between 1.0% and 2.6%. Serious AEs potentially related to Gd‐BOPTA were reported for five (0.2%) patients overall. Controlled studies revealed no differences between Gd‐BOPTA and other gadolinium chelates or placebo in the incidence and type of AEs. Similarly, no differences with respect to adult patients and/or comparator were noted in studies on pediatric subjects and subjects with renal or liver insufficiency. Post‐marketing surveillance of approximately 100000 doses revealed an overall AE incidence of < 0.03% with serious AEs reported for < 0.005% of patients. J. Magn. Reson. Imaging 2001;14:281–294. © 2001 Wiley‐Liss, Inc.
Anorectal melanomas do not harbour the kaposi sarcoma‐associated human herpesvirus type 8 DNA
Authors: Helmke Burkhard M. , Deichmann Martin , Otto Herwart F. 
Published: August 2002

AbstractAnorectal melanomas are similar to cutaneous melanomas with regard to the mode of spread and to the immunophenotype. When compared with patients with cutaneous melanoma, those suffering from anorectal melanoma have a much worse outcome. The etiology of anorectal melanomas is as yet completely unknown. For anatomical reasons, ultra‐violet (UV‐B) radiation can not cause anorectal melanomas as in cutaneous tumours, that are associated with exposure of the skin to UV‐B radiation. As the cytokine interleukin‐6 (IL‐6) is known to stimulate melanoma tumour cell proliferation and a functional homologue of human IL‐6 has been identified recently in the HHV‐8 genome, this tumorigenic virus might be involved in the pathogenesis of anorectal melanomas. Twelve formalin fixed and paraffin embedded primary anorectal melanomas from seven female and five male patients with a mean age at diagnosis of 71 years (range 38–88 years) were investigated for the presence of HHV‐8 DNA. Using a specific and highly sensitive polymerase chain reaction protocol, this tumorigenic gamma‐herpesvirus was not detectable in any tumour. This data indicates that HHV‐8 is not involved in the development of anorectal melanomas. J. Med. Virol. 64:47–50, 2001. © 2001 Wiley‐Liss, Inc.
Molecular detection and sequencing of “Norwalk‐like viruses” in outbreaks and sporadic cases of gastroenteritis in Ireland
Authors: Foley Barbara , O'Mahony Jim , Hill Colin , Morgan John G. 
Published: August 2002

AbstractNorwalk‐like viruses (NLVs) are now established as the most important causative agents of epidemic gastroenteritis worldwide. The overall objective of this study was to determine the molecular epidemiology of Irish NLV isolates for the first time by obtaining sequence data from specimens originating from outbreaks and sporadic cases of gastroenteritis. Eight samples from sporadic cases of gastroenteritis and nine isolates from separate NLV outbreaks were examined. Of the sporadic isolates, six were shown to be genogroup 2 (G2) by RT‐PCR, while two were G1. All of the outbreak isolates were G2. All isolates were partially sequenced within a highly conserved region of ORF1 (RNA‐dependent RNA polymerase gene). Sequence data were aligned and a dendogram was constructed. The results indicated that the majority of G2 isolates were seen to cluster with Bristol and Lordsdale virus, while the two G1 specimens were related most closely to Southampton virus. Further downstream sequence analysis of a number of the isolates confirmed this result. It is concluded that the majority of NLV isolates circulating in Ireland belong to the Bristol/Lordsdale clade. J. Med. Virol. 65:388–394, 2001. © 2001 Wiley‐Liss, Inc.
Suppressive effects of ansamycins on inducible nitric oxide synthase expression and the development of experimental autoimmune encephalomyelitis
Authors: Murphy Patricia , Sharp Anthony , Shin Joseph , Gavrilyuk Vitaliy , Dello Russo Cinzia , Weinberg Guy , Sharp Frank R. , Lu Aigang , Heneka Michael T. , Feinstein Douglas L. 
Published: August 2002

AbstractThe production of nitric oxide by the inflammatory isoform of nitric oxide synthase (NOS2) in brain glial cells is thought to contribute to the causes and development of neurological diseases and trauma. We previously demonstrated that activation of a heat shock response (HSR) by hyperthermia reduced NOS2 expression in vitro, and in vivo attenuated the clinical and histological symptoms of the demyelinating disease experimental autoimmune encephalomyelitis (EAE; Heneka et al. [2001] J. Neurochem. 77:568–579). Benzoquinoid ansamycins are fungal‐derived antibiotics with tyrosine kinase inhibitory properties, and which also induce a HSR by allowing activation of HS transcription factor HSF1. We now show that two members of this class of drugs (geldanamycin and 17‐allylamino‐17‐demethoxygeldanamycin) also induce a HSR in primary rat astrocytes and rat C6 glioma cells. Both drugs dose‐dependently reduced nitrite accumulation, NOS2 steady‐state mRNA levels, and the cytokine‐dependent activation of a rat 2.2‐kB NOS2 promoter construct stably expressed in C6 cells. These inhibitory effects were partially reversed by quercetin, a bioflavonoid which prevents HSF1 binding to DNA and thus attenuates the HSR. Ansamycins increased mRNA levels of the inhibitory IκBα protein, suggesting that inhibition of NFκB activation could contribute to their suppressive effects. Finally, in C57BL/6 mice actively immunized to develop EAE, a single injection of geldanamycin at 3 days after immunization reduced disease onset by over 50%. These results indicate that ansamycins can exert potent anti‐inflammatory effects on brain glial cells which may provide therapeutic benefit in neuroinflammatory diseases. © 2002 Wiley‐Liss, Inc.
Brain‐derived neurotrophic factor applied to the motor cortex promotes sprouting of corticospinal fibers but not regeneration into a peripheral nerve transplant
Authors: Hiebert G.W. , Khodarahmi K. , McGraw J. , Steeves J.D. , Tetzlaff W. 
Published: August 2002

AbstractPrevious experiments from our laboratory have shown that application of brain‐derived neurotrophic factor (BDNF) to the red nucleus or the motor cortex stimulates an increase in the expression of regeneration‐associated genes in rubrospinal and corticospinal neurons. Furthermore, we have previously shown that BDNF application stimulates regeneration of rubrospinal axons into a peripheral graft after a thoracic injury. The current study investigates whether application of BDNF to the motor cortex will facilitate regeneration of corticospinal neurons into a peripheral nerve graft placed into the thoracic spinal cord. In adult Sprague Dawley rats, the dorsal columns and the corticospinal tract between T9 and T10 were ablated by suction, and a 5‐mm‐long segment of predegenerated tibial nerve was autograft implanted into the lesion. With an osmotic pump, BDNF was infused directly into the parenchyma of the motor cortex for 14 days. Growth of the corticospinal tract into the nerve graft was then evaluated by transport of an anterograde tracer. Anterogradely labeled corticospinal fibers were not observed in the peripheral nerve graft in animals treated with saline or BDNF. Serotinergic and noradrenergic fibers, as well as peripheral sensory afferents, were observed to penetrate the graft, indicating the viability of the peripheral nerve graft as a permissive growth substrate for these specific fiber types. Although treatment of the corticospinal fibers with BDNF failed to produce regeneration into the graft, there was a distinct increase in the number of axonal sprouts rostral to the injury site. This indicates that treatment of corticospinal neurons with neurotrophins, e.g., BDNF, can be used to enhance sprouting of corticospinal axons within the spinal cord. Whether such sprouting leads to functional recovery after spinal cord injury is currently under investigation. © 2002 Wiley‐Liss, Inc.
Use of cDNA microarray in the search for molecular markers involved in the onset of Alzheimer's disease dementia
Authors: Pasinetti Giulio Maria 
Published: August 2002

AbstractAlzheimer's disease (AD) is the most common form of dementia, affecting as many as 4 million older persons and results from abnormal changes in the brain that most likely begin long before cognitive impairment and other clinical symptoms become apparent. Thus, efforts aimed at identifying methods of early detection and diagnosis for improving AD care might be the most appropriate strategy to initiate promising new treatments and/or prevention. We used cDNA microarray technology to investigate the sequence of changes in gene expression in brain that may take place during the transition from normal cognitive functioning through the early stages of impairment to frank AD. We examined the expression of approximately 7,000 genes in the brains of cases at the early stage of AD dementia using reference sample cases characterized by normal cognitive status. Genes that are differentially regulated in early AD cases were identified and were categorized into gene clusters based on similarities in biological functions. This analysis revealed that selected biological processes, including protein and amino acid metabolism, cytoskeleton integrity, and fatty acid metabolism, are involved in early phases of AD dementia. Most notable is the observation that selected genes involved in neurotransmitter release are differentially regulated in the brains of cases at high risk for dimentia. This evidence supports the feasibility and usefulness of cDNA microarray techniques to study sequential changes of distinctive gene‐expression patterns in the brain as a function of the progression of AD dementia. The study suggests new means to dissect and classify stages of AD dementia, or neuropathology, at the molecular level. J. Neurosci. Res. 65:471–476, 2001. © 2001 Wiley‐Liss, Inc.
Altered gene expression in Schwann cells of connexin32 knockout animals
Authors: Nicholson Simone M. , Gomès Danielle , de Néchaud Béatrice , Bruzzone Roberto 
Published: August 2002

AbstractThe discovery that the dominant X‐linked form of Charcot‐Marie‐Tooth disease (CMTX), a genetic disease of the peripheral nervous system (PNS), is associated with mutations in connexin32 (Cx32) has brought attention to the importance of connexins in glial cell biology. To gain further insight into the consequences of Cx32 deficiency, we have undertaken a detailed characterization of the gene expression profile of Schwann cells isolated from the sciatic nerve of wild‐type and Cx32‐null mice. Schwann cells exhibit two distinct phenotypes, myelinating and nonmyelinating, which are defined by their different morphology with respect to axons and by their unique profile of gene expression. Our findings show that, regardless of the mouse genotype, cultured Schwann cells express similar levels of messages for a number of connexins and for genes characteristic of both the myelinating and the nonmyelinating phenotypes. Furthermore, we have identified Cx36, a member of the γ subclass of connexins, which are preferentially expressed in neuronal cells of mouse brain and retina, as an additional connexin present in Schwann cells. Mice lacking Cx32, however, exhibited a marked up‐regulation of glial fibrillary acidic protein (GFAP), a cytoskeletal protein usually synthesized only by nonmyelinating Schwann cells. This observation was extended to the PNS in vivo and did not reflect a general perturbation of the expression of other nonmyelinating Schwann cell genes. These findings demonstrate that the absence of Cx32 results in a distinct pattern of gene dysregulation in Schwann cells and that Schwann cell homeostasis is critically dependent on the correct expression of Cx32 and not just any connexin. Identifying the relationship between increased GFAP expression and the absence of Cx32 could lead to the definition of specific roles for Cx32 in the control of myelin homeostasis and in the development of CMTX. J. Neurosci. Res. 66:23–36, 2001. © 2001 Wiley‐Liss, Inc.
Estrogen stimulates brain‐derived neurotrophic factor expression in embryonic mouse midbrain neurons through a membrane‐mediated and calcium‐dependent mechanism
Authors: Ivanova Tatiana , Küppers Eva , Engele Jürgen , Beyer Cordian 
Published: August 2002

AbstractWe have provided evidence that 17β‐estradiol (E) synthesized in the midbrain promotes the differentiation of midbrain dopamine neurons through nonclassical steroid action. Because these developmental effects resemble those reported for brain‐derived neurotrophic factor (BDNF), we hypothesized that E influences dopaminergic cell differentiation through a BDNF‐dependent mechanism. Competitive RT‐PCR and ELISA techniques were employed to study first the developmental pattern of BDNF and trkB expression in the mouse midbrain. BDNF protein/mRNA levels peaked postnatally, whereas trkB did not fluctuate perinatally. To prove the hypothesis that E regulates BDNF expression in vivo, fetuses and newborns were treated with the aromatase antagonist CGS 16949A. CGS 16949A exposure reduced midbrain BDNF mRNA/protein levels. The coapplication of CGS 16949A and E abolished this effect. Midbrain cultures from mouse fetuses were used to investigate intracellular signaling mechanisms involved in transmitting E effects. Estrogen increased expression of BDNF but not of other neurotrophins. As concerns the related signaling mechanism, these effects were antagonized by interrupting intracellular Ca2+ signaling with BAPTA and thapsigargin but not by the estrogen receptor antagonist ICI 182,780. Insofar as E effects on BDNF mRNA expression were inhibited by cycloheximide, it appears likely that other, not yet characterized intermediate proteins take part in the estrogenic regulation of BDNF expression. We conclude that E exerts its stimulatory effect on the differentiation of dopaminergic neurons by coordinating BDNF expression. This particular E effect appears to be transmitted through Ca2+‐dependent signaling cascades upon activation of putative membrane estrogen receptors. J. Neurosci. Res. 66:221–230, 2001. © 2001 Wiley‐Liss, Inc.
Nongenomic mechanism mediates estradiol stimulation of axon growth in male rat hypothalamic neurons in vitro
Authors: Cambiasso M.J. , Carrer H.F. 
Published: August 2002

AbstractThe purpose of the present work was to investigate the participation of estradiol receptors (ER) in estrogen‐induced axon growth in vitro. Hypothalamic neurons from 16 day (E16) male rat fetuses were cultured with or without 17‐β‐estradiol at 1 × 10–7 M in basal medium or medium conditioned by astroglia derived from ventral mesencephalon (CM). After 48 hr in vitro, neurite outgrowth was quantified by morphometric analysis. An axogenic effect could be demonstrated for estradiol added to CM. With RT‐PCR, the mRNA transcript for ERα was found in the donor tissues as well as in the neuron cultures. In this model two specific nuclear ER blockers (tamoxifen and ICI 182,780) were ineffective in blocking the neuritogenic effect, and a membrane‐impermeable estrogen–albumin construct (E2‐BSA) was as effective as estradiol. These results indicate that the axogenic effect of estradiol at E16 is not exerted through the classical intracellular receptor signal transduction system and suggest the possibility of a membrane‐mediated mechanism. The data are discussed in light of our previous findings pointing to the interdependent activation of the estrogenic and the trophic factor signaling pathways that mediate stimulated axon growth. J. Neurosci. Res. 66:475–481, 2001. © 2001 Wiley‐Liss, Inc.
United Kingdom and Ireland precipitation variability and the North Atlantic sea‐level pressure field
Authors: Murphy Sarah J. , Washington Richard 
Published: August 2002

AbstractThe relationship between UK and Ireland (UK&I) precipitation variability and the North Atlantic sea‐level pressure (SLP) field is examined. Strong positive correlations between the North Atlantic Oscillation (NAO) and precipitation in the northwest of the UK&I, particularly in winter, are confirmed but correlations are insignificant at the 0.05 level in the southeast during all months. This paper identifies new patterns of SLP associated with precipitation variability both for regions and months where precipitation variability is not strongly linked with the NAO and for patterns that appear to be more closely related to UK&I precipitation than the NAO.Two indices of monthly UK&I precipitation variability are calculated using empirical orthogonal functions (EOFs) of monthly UK&I precipitation anomalies. EOF1 represents precipitation variability for the UK&I as a whole and EOF2 the variability in the north–south precipitation gradient across the UK&I. Correlations between both these monthly EOF derived precipitation indices and SLP show a north–south (sub‐tropical/mid‐latitude) dipole, which is particularly strong in winter. These correlation patterns are then used to construct new SLP indices, which necessarily relate more closely to UK&I precipitation. The first index resembles the East Atlantic pattern from September to April. The second may be thought of as an alternative index of the NAO, such that it is optimized with respect to precipitation variability and is located northeast of those centres of action most commonly used to calculate the NAO index.Stepwise linear regression models, incorporating the two new indices and the original NAOI, suggest that over 25% of UK&I precipitation variability this century (1900–1994) in each month can be explained by a simple index representation of the North Atlantic SLP field. This rises to over 40% of variance explained in nearly all regions of the UK&I. Copyright © 2001 Royal Meteorological Society
A comparison of methods to determine the onset of the growing season in northern Nigeria
Authors: Ati O. F. , Stigter C. J. , Oladipo E. O. 
Published: August 2002

AbstractIn the sudan savanna of northern Nigeria, with its semi‐arid climate, the ability to determine effectively or predict the start of actual productive rains cannot be overemphasized. Several methods exist for calculating the date of onset of the rains that may be taken as the start of the growing season. Five methods currently in use, which are relatively easy to apply on a large scale, were selected for comparison. One is a traditional technique (Ramadan method), two use accumulated rainfall totals (Walter's and Sivakumar's methods), and two use rainfall–evapotranspiration relationships (Kowal's and Benoit's methods). For the period 1961–91, the traditional technique performed most poorly. Walter's method gave quite early onsets and Sivakumar's method gave very late onsets, thereby seriously shortening the growing season. Kowal's and Benoit's determinations fell most often in between the results of Walter's and Sivakumar's methods in their performance. However, although generally to a lesser extent than the other methods, they are still significantly affected by false starts. To avoid incorrectly predicting the growing season's onset as far as possible, but to prevent an unacceptable shortening of the growing season, a combination of Kowal's and Sivakumar's criteria was used to develop an improved technique. This proved to work well for determining the onset date in the study area. However, because some false starts remain when using average onset dates, it is suggested that an operational advisory team should be constituted by the government. This team would be responsible for calculating onset dates in any year, on‐line for the ongoing season, in a participatory approach with farmers, and for disseminating such dates to the farmers. This could be done for any place for which the appropriate data can be made available. In the future, improved climate prediction skill may replace the classical probabilistic approaches presently suffering from increasing rainfall variabilities. Copyright © 2002 Royal Meteorological Society.
Changes in extreme high waters at Liverpool since 1768
Authors: Woodworth Philip L. , Blackman David L. 
Published: August 2002

AbstractChanges in values of annual maximum high water (AMxHW), annual maximum surge‐at‐high‐water (AMxSHW) and surge at annual maximum high water (SAMxHW) have been investigated using tide gauge data from Liverpool for the period 1768–1999. AMxHW and SAMxHW (measured with respect to mean high water) were found to vary considerably from year to year, but to exhibit no long‐term change over the 232 years. On the other hand, values of AMxSHW were found to be larger in the late‐18th, late‐19th and late‐20th centuries than for most of the 20th century, qualitatively consistent with knowledge of temporal variations in storminess in the region based on meteorological data and anecdotal information. The generalized extreme value method was used to present the available data on AMxHW and other annual extreme parameters in the ‘return period’ form most often employed by coastal engineers, with conclusions on the differences between each set of parameters in each epoch consistent with those obtained from the original time series. Finally, changes in the statistical distribution of surge‐at‐high‐water (SHW), demonstrated by investigation of variations of percentile levels of SHW values, provided additional information on the temporal variations in extreme surges to that provided by AMxSHW values, pointing in particular to increased storminess during the late‐18th and late‐20th centuries, with a suggested secular trend in distribution shape from the late‐18th century until recent decades. Copyright © 2002 Royal Meteorological Society.