bluuebunny/crossref_metadata_2025 huggingface dataset:
Possible parent‐of‐origin effect of Dopa decarboxylase in susceptibility to bipolar affective disorder
Authors: Børglum A.D. , Kirov G. , Craddock N. , Mors O. , Muir W. , Murray V. , McKee I. , Collier D.A. , Ewald H. , Owen M.J. , Blackwood D. , Kruse T.A.
Published: January 2003

Dopa decarboxylase (DDC) catalyses the synthesis of both dopamine and serotonin as well as trace amines suggested to possess neuromodulating capabilities. We have previously reported evidence suggesting an association between DDC and bipolar affective disorder (BPAD) [Børglum et al., 1999]. To further investigate the possible role of DDC in BPAD, we analyzed a 1‐ and a 4‐bp deletion variant—both of putative functional significance—in two new samples: a case‐control sample with 140 cases and 204 controls, and 100 case‐parents trios. We also tested for association in subjects with familial disease in both the new and the previously investigated samples. The previously reported association was not replicated in either of the new samples. However, a preponderance of the 1‐bp deletion was increased by analysis of the familial cases separately for all case‐control samples investigated, indicating a possible association with familial disease (combined analysis, P = 0.02). In the trio sample, a preferential paternal transmission of the 4‐bp deletion was observed (P = 0.006). DDC is located next to the imprinted gene GRB10, which is expressed specifically from the paternal allele in fetal brains. Increased transmission of paternal DDC alleles has also been suggested in attention deficit hyperactivity disorder. We suggest that DDC might confer susceptibility to BPAD predominantly when paternally transmitted. © 2003 Wiley‐Liss, Inc.
Association of EEG coherence and an exonic GABABR1 gene polymorphism
Authors: Winterer Georg , Smolka Michael , Samochowiec Jerzy , Ziller Mario , Mahlberg Richard , Gallinat Jürgen , Rommelspacher Hans‐Peter , Herrmann Werner M. , Sander Thomas
Published: January 2003

The GABAB receptor 1 gene is mapped to chromosome 6p21.3 within the HLA class I region close to the HLA‐F gene. Susceptibility loci for epilepsy and schizophrenia have been mapped in this region. Based on pharmacological evidence, it has been suggested that GABAB receptors may play a crucial role in the synchronization of EEG oscillations, which in turn can be abnormal in neuropsychiatric disorders. In the present study, the hypothesis was tested, whether three exonic variants of the gene encoding the human GABAB receptor (GABABR1) modify cortical synchronization measured as scalp‐recorded EEG‐coherence. Two principal components of EEG coherence (frontal coherence, parietotemporal coherence) were investigated in 104 healthy subjects during three conditions: resting EEG, activated EEG, and event‐related EEG. No significant associations were found between the frontal coherence component and any polymorphism or between the parietotemporal coherence component and the exon 1a1 polymorphism. However, parietotemporal coherence showed statistically highly significant associations across all three experimental conditions with exon 7 and trend associations with exon 11. The results provide evidence that the translated polymorphism of exon 7 may be functionally meaningful and impact cortical EEG oscillations. Since variations of EEG coherence have been described for several neuropsychiatric disorders, the present association should be tested in clinical samples using EEG coherence as an intermediate phenotype. © 2003 Wiley‐Liss, Inc.
Defining the autism minimum candidate gene region on chromosome 7
Authors: Hutcheson Holli B. , Bradford Y. , Folstein S.E. , Gardiner M.B. , Santangelo S.L. , Sutcliffe J.S. , Haines J.L.
Published: January 2003

Previous genetic and cytogenetic studies provide evidence that points to one or more autism susceptibility genes residing on chromosome 7q (AUTS1, 115–149 cM on the Marshfield map). However, further localization using linkage analysis has proven difficult. To overcome this problem, we examined the Collaborative Linkage Study of Autism (CLSA) data‐set to identify only the families potentially linked to chromosome 7. Out of 94, 47 families were identified and 17 markers were used to generate chromosomal haplotypes. We performed recombination breakpoint analysis to determine if any portion of the chromosome was predominately shared across families. The most commonly shared region spanned a 6 cM interval between D7S501 and D7S2847. Additional markers at 1 cM intervals within this region were genotyped and association and recombination breakpoint analysis was again performed. Although no significant allelic association was found, the recombination breakpoint data points to a shared region between D7S496–D7S2418 (120–123 cM) encompassing about 4.5 Mb of genomic DNA containing over 50 genes. © 2003 Wiley‐Liss, Inc.
Atypical focal MRI lesions in a case of juvenile Alexander's disease
Authors: Probst Eva Neumaier , Hagel Christian , Weisz Vanja , Nagel Sandra , Wittkugel Oliver , Zeumer Hermann , Kohlschütter Alfried
Published: January 2003

We present a juvenile case of Alexander's disease with atypical focal magnetic resonance imaging–detected lesions and elevated levels of lactate in cerebrospinal fluid. The diagnosis was based on the neuropathological finding of a diffuse accumulation of Rosenthal fibers within the brain and the spinal cord. The diagnosis was confirmed by detection of a mutation in exon 1 at nucleotide position 249 of glial fibrillary acidic protein cDNA, a finding previously reported in cases of infantile Alexander's disease.
Primary progressive aphasia: PPA and the language network
Authors: Sonty Sreepadma P. , Mesulam M.‐Marsel , Thompson Cynthia K. , Johnson Nancy A. , Weintraub Sandra , Parrish Todd B. , Gitelman Darren R.
Published: January 2003

Primary Progressive Aphasia (PPA) is a behaviorally focal dementia syndrome with deterioration of language functions but relative preservation of other cognitive domains for at least the first two years of disease. In this study, PPA patients with impaired word finding but intact comprehension of conversational speech and their matched control subjects were examined using voxel‐based morphometry (VBM) and functional magnetic resonance imaging (fMRI). fMRI compared signal changes during phonological and semantic language tasks with those during a control task (matching letters). PPA patients showed longer reaction times and reduced accuracy versus controls on the language tasks, but no performance differences on the control task. VBM demonstrated reduced gray matter in left superior temporal and inferior parietal regions in the PPA group. However, these patients showed a normal pattern of activation within the classical language regions. In addition, PPA patients showed activations, not seen in normals, in fusiform gyrus, precentral gyrus, and intra‐parietal sulcus. These activations were found to correlate negatively with measures of naming and task performance. The additional activations in PPA may therefore represent a compensatory spread of language‐related neural activity or a failure to suppress activity in areas normally inhibited during language tasks. Ann Neurol 2003;53:000–000
Reduction of P/Q‐type calcium channels in the postmortem cerebellum of paraneoplastic cerebellar degeneration with Lambert‐Eaton myasthenic syndrome
Authors: Fukuda Taku , Motomura Masakatsu , Nakao Yoko , Shiraishi Hirokazu , Yoshimura Toshiro , Iwanaga Keisuke , Tsujihata Mitsuhiro , Dosaka‐Akita Hirotoshi , Eguchi Katsumi
Published: January 2003

The aim of this study was to clarify whether autoimmunity against P/Q‐type voltage‐gated calcium channels (VGCCs) in the cerebellum was associated with the pathogenesis of paraneoplastic cerebellar degeneration (PCD) with Lambert‐Eaton myasthenic syndrome (LEMS). We used human autopsy cerebellar tissues from three PCD‐LEMS patients and six other disease patients including one with LEMS as the controls. We compared cerebellar P/Q‐type VGCC in these patients and controls for the amount and ratio of autoantibody‐channel complex using an 125I‐ω‐conotoxin MVIIC‐binding assay with Scatchard analysis, and their distribution using autoradiography. The quantity of cerebellar P/Q‐type VGCC measured by Scatchard analysis were reduced in PCD‐LEMS patients (63.0 ± 7.0fmol/mg, n = 3), compared with the controls (297.8 ± 38.9fmol/mg, n = 6). The ratio of autoantibody‐VGCC complexes to total P/Q‐type VGCCs measured by immunoprecipitation assay were increased in PCD‐LEMS patients. We analysed cerebellar specimens by autoradiography using 125I‐ω‐conotoxin MVIIC, which specifically binds to P/Q‐type VGCCs. In PCD‐LEMS cerebellum, the toxin binding sites of P/Q‐type VGCCs were markedly reduced compared with controls, especially in the molecular layer, which is the richest area of P/Q‐type VGCCs in the normal cerebellum. This suggests that P/Q‐type VGCCs of the cerebellar molecular layer is the immunological target in developing PCD‐LEMS.
Mechanisms underlying PTEN regulation of vascular endothelial growth factor and angiogenesis
Authors: Gomez‐Manzano Candelaria , Fueyo Juan , Jiang Hong , Glass Tricia L. , Lee Ho‐Young , Hu Min , Liu Juinn‐Lin , Jasti Sushma L. , Liu Ta‐Jen , Conrad Charles A. , Yung W. K. Alfred
Published: January 2003

Inactivation of the tumor suppressor gene PTEN and overexpression of VEGF are two of the most common events observed in high‐grade malignant gliomas. The purpose of this study was to determine whether PTEN controls VEGF expression in gliomas under normoxic conditions. Transfer of PTEN to human glioma cells resulted in the transduction of a functional PTEN protein as evidenced by the upregulation of p27 and modification of the phosphorylation status of Akt. Under normoxic conditions, enzyme‐linked immunosorbent assay and Northern blot analyses showed downregulation of VEGF in PTEN‐treated cells. Moreover, conditioned media from PTEN‐treated glioma cells significantly diminished the ability of endothelial cells to grow and migrate. Western blot assays demonstrated that, in a normoxic environment, PTEN downregulates HIF‐1α. Finally, promoter activity assays showed that the VEGF promoter region containing the HIF‐1α binding site is necessary and sufficient for PTEN‐mediated downregulation of VEGF. Experiments with PI3‐K inhibitors and kinase assays suggested that PI3‐K is mediating the effect of PTEN on VEGF, and not the p42/p48 or p38 MAP kinases. These results indicate that restoration of PTEN function in gliomas may induce therapeutic effect by downregulating VEGF. Furthermore, this close functional relationship between PTEN and VEGF suggests that a better understanding of the transduction signal regulated by PTEN might enhance the knowledge of the cause and physiology of vascular and inflammatory diseases. Ann Neurol 2003
Environmental enrichment reverses cognitive and molecular deficits induced by developmental lead exposure
Authors: Guilarte Tomás R. , Toscano Christopher D. , McGlothan Jennifer L. , Weaver Shelley A.
Published: January 2003

Long‐term deficits in cognitive function are the principal effects of lead (Pb2+) exposure in children and can be modeled in experimental animals. Current therapeutic approaches in the treatment of childhood Pb2+ intoxication are not effective in reversing learning deficits once they have occurred. We report that environmental enrichment reverses long‐term deficits in spatial learning produced by developmental Pb2+ exposure in rats. Enhanced learning performance of Pb2+‐exposed animals reared in an enriched environment was associated with recovery of deficits in N‐methyl‐D‐aspartate receptor subunit 1 (NR1) mRNA and induction of brain‐derived neurotrophic factor (BDNF) mRNA in the hippocampus. The effect of environmental enrichment on NR1 and BDNF gene expression was specific to Pb2+‐exposed animals and was present in the absence of changes in the NR2B subunit of the N‐methyl‐D‐aspartate receptor, GluR1, αCamKII, or PSD‐95 gene expression measured in the same animals. Our findings demonstrate that the learning impairments and NR1 subunit mRNA deficits resulting from developmental Pb2+ exposure are reversible if the animals are provided with an enriched environment even after the exposure has occurred. We propose environmental enrichment as a basis for the treatment of childhood Pb2+ intoxication.
Treatment of refractory myasthenia: “Rebooting” with high‐dose cyclophosphamide
Authors: Drachman Daniel B. , Jones Richard J. , Brodsky Robert A.
Published: January 2003

Patients with myasthenia gravis (MG) who do not respond to conventional immunotherapeutic agents, or cannot tolerate their side effects, are considered “refractory.” Ablation of the immune system followed by bone marrow transplant has been shown to cure experimental MG in rats. It is now known that immunoablative treatment with high‐dose cyclophosphamide does not damage hematopoietic “stem cells,” permitting repopulation of the immune system without bone marrow transplant. Recent evidence indicates that this treatment can induce durable remissions in autoimmune diseases. We treated three myasthenic patients, for whom treatment with thymectomy, plasmapheresis, and conventional immunotherapeutic agents failed, by using high‐dose cyclophosphamide (50mg/kg/day intravenously for 4 days) followed by granulocyte colony stimulating factor. All three patients tolerated the treatment well and have had marked improvement in myasthenic weakness, permitting reduction of immunosuppressive medication to minimal levels. Acetylcholine receptor (AChR) antibody levels decreased in two AChR antibody–positive patients, and anti–MuSK antibody levels decreased in one “AChR antibody–negative” patient. The patients have been followed for up to 3.5 years, with no recurrence of symptoms. High‐dose cyclophosphamide treatment appears to be an effective and safe treatment for selected patients with refractory MG. Further follow‐up of these and additional patients will be needed to determine whether the benefit is durable.
FK506 is neuroprotective in a model of antiretroviral toxic neuropathy
Authors: Keswani Sanjay C. , Chander Bani , Hasan Chiler , Griffin John W. , McArthur Justin C. , Hoke Ahmet
Published: January 2003

Antiretroviral toxic neuropathy is the most common neurological complication of human immunodeficiency virus infection. This painful neuropathy not only affects the quality of life of human immunodeficiency virus–infected patients but also severely limits viral suppression strategies. We have developed an in vitro model of this toxic neuropathy to better understand the mechanism of neurotoxicity and to test potential neuroprotective compounds. We show that among the dideoxynucleosides, ddC appears to be the most neurotoxic, followed by ddI and then d4T. This reflects their potency in causing neuropathy. AZT, which does not cause a peripheral neuropathy in patients, does not cause significant neurotoxicity in our model. Furthermore, in this model, we show that the immunophilin ligand FK506 but not cyclosporin A prevents the development of neurotoxicity by ddC, as judged by amelioration of ddC‐induced “neuritic pruning,” neuronal mitochondrial depolarization, and neuronal necrotic death. This finding suggests a calcineurin‐independent mechanism of neuroprotection. As calcineurin inhibition underlies the immunosuppressive properties of these clinically used immunophilin ligands, this holds promise for the neuroprotective efficacy of nonimmunosuppressive analogs of FK506 in the prevention or treatment of antiretroviral toxic neuropathy. Ann Neurol 2003;53:000–000
Head cooling with mild systemic hypothermia in anesthetized piglets is neuroprotective
Authors: Tooley James R. , Satas Saulius , Porter Helen , Silver Ian A. , Thoresen Marianne
Published: January 2003

Hypothermia is potentially therapeutic in the management of neonatal hypoxic‐ischemic brain injury. However, not all studies have shown a neuroprotective effect. It is suggested that the stress of unsedated hypothermia may interfere with neuroprotection. We propose that selective head cooling (SHC) combined with mild total‐body hypothermia during anesthesia enhances local neuroprotection while minimizing the occurrence of systemic side effects and stress associated with unsedated whole‐body cooling. Our objective was to determine whether SHC combined with mild total‐body hypothermia while anesthetized for a period of 24 hours reduces cerebral damage in our piglet survival model of global hypoxia‐ischemia. Eighteen anesthetized piglets received a 45‐minute global hypoxic‐ischemic insult. The pigs were randomized either to remain normothermic or to receive SHC. We found that the severity of the hypoxic‐ischemic insult was similar in the SHC versus the normothermic group, and that the mean neurology scores at 30 and 48 hours and neuropathology scores were significantly better in the SHC group versus the normothermic group. We conclude that selective head cooling combined with mild systemic hypothermia and anesthesia is neuroprotective when started immediately after the insult in our piglet model of hypoxic‐ischemic encephalopathy. Ann Neurol 2003;53:000–000
Human lateral geniculate nucleus and visual cortex respond to screen flicker
Authors: Krolak‐Salmon Pierre , Hénaff Marie‐Anne , Tallon‐Baudry Catherine , Yvert Blaise , Guénot Marc , Vighetto Alain , Mauguière François , Bertrand Olivier
Published: January 2003

The first electrophysiological study of the human lateral geniculate nucleus (LGN), optic radiation, striate, and extrastriate visual areas is presented in the context of presurgical evaluation of three epileptic patients (Patients 1, 2, and 3). Visual‐evoked potentials to pattern reversal and face presentation were recorded with depth intracranial electrodes implanted stereotactically. For Patient 1, electrode anatomical registration, structural magnetic resonance imaging, and electrophysiological responses confirmed the location of two contacts in the geniculate body and one in the optic radiation. The first responses peaked approximately 40 milliseconds in the LGN in Patient 1 and 60 milliseconds in the V1/V2 complex in Patients 2 and 3. Moreover, steady state visual‐evoked potentials evoked by the unperceived but commonly experienced video‐screen flicker were recorded in the LGN, optic radiation, and V1/V2 visual areas. This study provides topographic and temporal propagation characteristics of steady state visual‐evoked potentials along human visual pathways. We discuss the possible relationship between the oscillating signal recorded in subcortical and cortical areas and the electroencephalogram abnormalities observed in patients suffering from photosensitive epilepsy, particularly video‐game epilepsy. The consequences of high temporal frequency visual stimuli delivered by ubiquitous video screens on epilepsy, headaches, and eyestrain must be considered.
New perspectives on developing acute stroke therapy
Authors: Fisher Marc , Ratan Rajiv
Published: January 2003

The development of additional acute stroke therapies to complement and supplement intravenous recombinant tissue‐type plasminogen activator within the first 3 hours after stroke onset remains an important and pressing need. Much has been learned about the presumed target of acute stroke therapy, the ischemic penumbra, and clinically available imaging modalities such as magnetic resonance imaging and computed tomography hold great promise for at least partially identifying this region of potentially salvageable ischemic tissue. Understanding the biology of ischemia‐related cell injury has also evolved rapidly. New treatment approaches to improve outcome after focal brain ischemia will likely be derived by looking at naturally occurring adaptive mechanisms such as those related to ischemic preconditioning and hibernation. Many clinical trials previously performed with a variety of neuroprotective and thrombolytic drugs provide many lessons that will help to guide future acute stroke therapy trials and enhance the likelihood of success in future trials. Combining knowledge from these three areas provides optimism that additional acute stroke therapies can be developed to maximize beneficial functional outcome in the greatest proportion of acute stroke patients possible.
Plasma and cerebrospinal fluid α1‐antichymotrypsin levels in Alzheimer's disease: Correlation with cognitive impairment
Authors: DeKosky Steven T. , Ikonomovic Milos D. , Wang Xiaoyan , Farlow Martin , Wisniewski Stephen , Lopez Oscar L. , Becker James T. , Saxton Judith , Klunk William E. , Sweet Robert , Kaufer Daniel I. , Kamboh M. Ilyas
Published: January 2003

α‐1‐Antichymotrypsin (ACT) is present in neuritic plaques in which it participates in the inflammatory cascade of Alzheimer's disease (AD). Reports of blood ACT levels in AD, and its usefulness as a disease biomarker, have been conflicting. In an effort to clarify this, we measured plasma ACT levels in 516 white subjects including 359 subjects with probable or possible AD, 44 subjects with other late‐life dementias, and 113 nondemented people. Subjects with systemic inflammatory diseases or who were taking antiinflammatory medications were excluded. All patients underwent extensive medical and detailed neuropsychological examinations at the time their blood was drawn. We found that plasma ACT levels were elevated in AD patients compared with the control group (p = 0.01) and were associated with severity of AD dementia; there was a negative association with the Mattis Dementia Rating Scale (a global measure of cognition) and a positive association with the Clinical Dementia Rating Scale (a global functional assessment). These relationships remained significant after controlling for demographic and genetic variables. When AD subjects were stratified into subgroups by dementia severity, matched by age, education, and gender, increased serum ACT correlated with Clinical Dementia Rating Scale (p = 0.0041) or Mattis Dementia Rating Scale (p = 0.0031) scores. ACT measurements in cerebrospinal fluid from an additional 34 AD cases and 16 controls showed elevated levels (p = 0.02) in AD. There was a negative correlation (p = 0.037) between cerebrospinal fluid ACT levels and clinical severity as measured by the Mini‐Mental State Examination. Our results demonstrate that peripheral ACT levels are elevated in AD, but not in dementias other than AD, and they increase with progression of AD dementia. Although not useful as a diagnostic biomarker, ACT may reflect disease severity and may be helpful as a within subject biomarker in interventions (particularly with antiinflammatory agents) directed at slowing or halting progression of disease.
Correlation between extracellular glucose and seizure susceptibility in adult rats
Authors: Schwechter Evan M. , Velís̆ková Jana , Velís̆ek Libor
Published: January 2003

In adult diabetic patients, periods of hyperglycemia may be associated with exacerbation of focal seizures. Our objective was to determine in the adult rats the correlation between seizure susceptibility and extracellular glucose concentration in two models of seizures. Male rats were injected with two doses of streptozocin (40mg/kg IP) on 2 consecutive days to induce diabetic hyperglycemia. Controls either received vehicle or were not injected. After 2 weeks, blood glucose concentration was measured, and the rats were subjected to flurothyl seizure test. Another group of rats received glucose solution (20%, 5ml IP) 30 minutes before testing to induce nondiabetic hyperglycemia. Thresholds for flurothyl‐induced clonic and tonic‐clonic seizures were determined. Finally, in vitro epileptiform activity was induced in the entorhinal cortex‐hippocampal slices from naive rats by perfusing with magnesium‐free medium with various glucose concentrations. In additional slices, paired‐pulse paradigm was determined in the perforant path. Susceptibility to clonic and tonic‐clonic flurothyl‐induced seizures positively correlated with blood glucose concentrations as the increased glucose concentration was associated with proconvulsant effects. Similarly, in the in vitro experiments, epileptiform activity was promoted by increased and suppressed by decreased glucose concentrations. Data indicate that, in the adult rats, high glucose concentrations are associated with proconvulsant effects.
Motor cortex excitability in Alzheimer's disease: A transcranial magnetic stimulation study
Authors: Ferreri Florinda , Pauri Flavia , Pasqualetti Patrizio , Fini Rita , Dal Forno Gloria , Rossini Paolo Maria
Published: January 2003

Motor deficits affect patients with Alzheimer's disease only at later stages. Recent studies demonstrate that the primary motor cortex is affected by neuronal degeneration accompanied by the formation of amyloid plaques and neurofibrillary tangles. It is conceivable that neuronal loss is compensated by reorganization of the neural circuitries occurring along the natural course of the disease, thereby maintaining motor performances in daily living. Cortical motor output to upper limbs was tested via motor‐evoked potentials from forearm and hand muscles elicited by transcranial magnetic stimulation of motor cortex in 16 patients with mild Alzheimer's disease without motor deficits. Motor cortex excitability was increased, and the center of gravity of motor cortical output, as represented by excitable scalp sites, showed a frontal and medial shift, without correlated changes in the site of maximal excitability (hot‐spot). This may indicate functional reorganization, possibly after the neuronal loss in motor areas. Hyperexcitability might be caused by a dysregulation of the intracortical GABAergic inhibitory circuitries and selective alteration of glutamatergic neurotransmission. Such findings suggest that motor cortex hyperexcitability and reorganization allows prolonged preservation of motor function during the clinical course of Alzheimer's disease.
Cardiac energetics correlates to myocardial hypertrophy in Friedreich's ataxia
Authors: Bunse Michael , Bit‐Avragim Nana , Riefflin Axel , Perrot Andreas , Schmidt Oliver , Kreuz Friedmar R. , Dietz Rainer , Jung Wulf‐Ingo , Osterziel Karl Josef
Published: January 2003

Friedreich's ataxia is a neurodegenerative disease frequently associated with hypertrophic cardiomyopathy. We have determined mitochondrial ATP, phosphocreatine, and intracellular inorganic phosphate levels by 31P nuclear magnetic resonance spectroscopy in the heart of 11 Friedreich's ataxia patients and 11 healthy controls. For the first time, to our knowledge, we showed a significant correlation between the extent of myocardial energy deficiency and the degree of myocardial hypertrophy. When combining our results with previous works on Friedreich's ataxia, these novel findings suggest that energy metabolism is most likely the cause and hypertrophy the effect in Friedreich's ataxia. Ann Neurol 2003;53:000–000
The MAZ protein is an autoantigen of Hodgkin's disease and paraneoplastic cerebellar dysfunction
Authors: Bataller Luis , Wade Deborly F. , Graus Francesc , Rosenfeld Myrna R. , Dalmau Josep
Published: January 2003

Probing a cerebellar expression library with TrAb sera from patients with Hodgkin's disease and paraneoplastic cerebellar degeneration resulted in the isolation of MAZ (myc‐associated zinc‐finger protein). Eleven of 19 TrAb sera and 16 of 131 controls reacted with MAZ, indicating a significant, although not specific, association between Tr and MAZ immunities (p < 0.001). Interestingly, 9 of 16 positive control patients also had cerebellar dysfunction. Purified MAZ antibodies reacted with Purkinje cells. In neuronal cells, MAZ interacts with DCC (Deleted in Colorectal Cancer product), the receptor for netrin‐1, a neuronal survival factor. These findings suggest epitope spreading between the Tr antigen and the MAZ–DCC complex and offer a possible model of immune‐mediated cerebellar disease. Ann Neurol 2003;53:000–000
Is the mitochondrial complex I ND5 gene a hot‐spot for MELAS causing mutations?
Authors: Liolitsa Danae , Rahman Shamina , Benton Sarah , Carr Lucinda J. , Hanna Michael G.
Published: January 2003

We identified two novel heteroplasmic mitochondrial DNA point mutations in the gene encoding the ND5 subunit of complex I: a 12770A→G transition identified in a patient with MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke‐like episodes) and a 13045A→C transversion in a patient with a MELAS/Leber's hereditary optic neuropathy/Leigh's overlap syndrome. Biochemical analysis of muscle homogenates showed normal or very mildly reduced complex I activity. Histochemistry was normal. Our observations add to the evidence that mitochondrial ND5 protein coding gene mutations frequently associate with the MELAS phenotype, and it highlights the role of complex I dysfunction in MELAS. Ann Neurol 2003
A novel L266V mutation of the tau gene causes frontotemporal dementia with a unique tau pathology
Authors: Kobayashi Tomonori , Ota Satoru , Tanaka Kuniaki , Ito Yuji , Hasegawa Masato , Umeda Yuri , Motoi Yumiko , Takanashi Masashi , Yasuhara Masahiro , Anno Midori , Mizuno Yoshikuni , Mori Hideo
Published: January 2003

We report a novel mutation of tau (L266V missense mutation in exon 9) which may cause a type of familial frontotemporal dementia. The brain of a patient showed Pick body–like inclusions and unique tau‐positive, argyrophilic astrocytes with stout filaments and naked, round, or irregular argyrophilic inclusions with deposits of both three‐repeat and four‐repeat tau. Recombinant tau with a L266V mutation showed a reduced ability to promote microtubule assembly, which may be the primary effect of the mutation. Ann Neurol 2003;53:000–000
Meningioma presenting with Cushing's syndrome: An unusual clinical presentation
Authors: Pecori Giraldi Francesca , Terreni Maria Rosa , Andreotti Claudia , Losa Marco , Lanzi Roberto , Pontiroli Antonio E. , Cavagnini Francesco
Published: January 2003

We report a patient with a meningioma presenting with Cushing's syndrome, an unprecedented paraneoplastic presentation. Molecular studies, bioassay, and high‐performance liquid chromatography of tumor specimens demonstrated the synthesis and secretion of bioactive corticotropin‐releasing hormone. To our knowledge, this appears to be the first report of a hormone‐secreting meningioma and, further, the first clearly proven case of Cushing's syndrome due to ectopic corticotropin‐releasing hormone secretion without concomitant corticotropin production. Ann Neurol 2003
Specialty polymeric membranes. XIV. Pervaporation of benzene/cyclohexane mixtures through modified polyamide membranes
Authors: Yoshikawa Masakazu , Matsumoto Masafumi , Igarashi Yutaka
Published: January 2003

Methyl methacrylate, ethyl methacrylate, propyl methacrylate, and styrene were graft‐polymerized onto the amorphous polyamide poly(hexamethylene terephthalamide/isophthalamide) (SELAR). Membranes were prepared from the modified SELAR and unmodified SELAR. The membranes were permeated benzene in preference to cyclohexane from benzene/cyclohexane mixtures by pervaporation. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 183–188, 2003
Characterization to the weathering extent of LLDPE/LDPE thin film
Authors: Zhao B. Y. , Yi X. W. , Li R. Y. , Zhu P. F. , Hu K. A.
Published: January 2003

A kind of LLDPE (linear low density polyethylene)/LDPE (low density polyethylene) thin film for farm applications was subjected to accelerated and natural weathering. Carbonyl group, melting point, tensile elastic modulus, and high‐temperature shearing modulus of weathered films were investigated as function of weathering time. Two kinds of carbonyl index, I1 and I2, which result from infrared spectroscopy (IR) spectra of the weathered films, were defined to characterize the weathering extent of the LLDPE/LDPE thin film. Based on I1 and I2, a correlation is made between the artificial and natural weathering of the film: 1 h of the artificial weathering is equivalent to about 10.73 h of the natural weathering. The difference between the accelerated weathering and the natural weathering was also discussed. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 12–16, 2003
Friedrich Sigmund Merkel and his “Merkel cell”, morphology, development, and physiology: Review and new results
Authors: Halata Zdenek , Grim Milos , Bauman Klaus I.
Published: January 2003

Merkel nerve endings are mechanoreceptors in the mammalian skin. They consist of large, pale cells with lobulated nuclei forming synapse‐like contacts with enlarged terminal endings of myelinated nerve fibers. They were first described by F.S. Merkel in 1875. They are found in the skin and in those parts of the mucosa derived from the ectoderm. In mammals (apart from man), the largest accumulation of Merkel nerve endings is found in whiskers. In all vertebrates, Merkel nerve endings are located in the basal layer of the epidermis, apart from birds, where they are located in the dermis. Cytoskeletal filaments consisting of cytokeratins and osmiophilic granules containing a variety of neuropeptides are found in Merkel cells. In anseriform birds, groups of cells resembling Merkel cells, with discoid nerve terminals between cells, form Grandry corpuscles. There has been controversy over the origin of Merkel cells. Results from chick/quail chimeras show that, in birds, Merkel cells are a subpopulation of cells derived from the neural crest, which thus excludes their development from the epidermis. Most recently, also in mammals, conclusive evidence for a neural crest origin of Merkel cells has been obtained. Merkel cells and nerve terminals form mechanoreceptors. Calcium ions enter Merkel cells in response to mechanical stimuli, a process which triggers the release of calcium from intracellular stores resulting in exocytosis of neurotransmitter or neuromodulator. Recent results suggest that there may be glutamatergic transmission between Merkel cell and nerve terminal, which appears to be essential for the characteristic slowly adapting response of these receptors during maintained mechanical stimuli. Thus, we are convinced that Merkel cells with associated nerve terminals function as mechanoreceptor cells. Cells in the skin with a similar appearance as Merkel cells, but without contact to nerve terminals, are probably part of a diffuse neuroendocrine system and do not function as mechanoreceptors. Probably these cells, rather than those acting as mechanoreceptors, are the origin of a highly malignant skin cancer called Merkel cell carcinoma. Anat Rec Part A 271A:225–239, 2003. © 2003 Wiley‐Liss, Inc.
A measure for the cohesion of weighted networks
Authors: Egghe Leo , Rousseau Ronald
Published: January 2003

A generalization of both the Botafogo‐Rivlin‐Shneiderman compactness measure and the Wiener index is presented. These new measures for the cohesion of networks can be used in case a dissimilarity value is given between nodes in a network or a graph. It is illustrated how a set of weights between connected nodes can be transformed into a set of dissimilarity measures for all nodes. The new compactness measure for the cohesion of weighted graphs has several desirable properties related to the disjoint union of two networks. Finally, an example is presented of the calculation of the new compactness measures for a co‐citation and a bibliographic coupling network.
Methods for identifying versioned and plagiarized documents
Authors: Hoad Timothy C. , Zobel Justin
Published: January 2003

The widespread use of on‐line publishing of text promotes storage of multiple versions of documents and mirroring of documents in multiple locations, and greatly simplifies the task of plagiarizing the work of others. We evaluate two families of methods for searching a collection to find documents that are coderivative, that is, are versions or plagiarisms of each other. The first, the ranking family, uses information retrieval techniques; extending this family, we propose the identity measure, which is specifically designed for identification of coderivative documents. The second, the fingerprinting family, uses hashing to generate a compact document description, which can then be compared to the fingerprints of the documents in the collection. We introduce a new method for evaluating the effectiveness of these techniques, and demonstrate it in practice. Using experiments on two collections, we demonstrate that the identity measure and the best fingerprinting technique are both able to accurately identify coderivative documents. However, for fingerprinting parameters must be carefully chosen, and even so the identity measure is clearly superior.
Individual differences in exploration using desktop VR
Authors: Modjeska David , Chignell Mark
Published: January 2003

With advances in computer graphics, a number of innovative approaches to information visualization have been developed (e.g., Card et al, 1991). Some of these approaches create a mapping between information and corresponding structure in a virtual world. The resulting virtual worlds can be fully three dimensional (3D) or they can be implemented as a series of 2D birds‐eye “snapshots” that are traversed as if they were in 3D, using operations such as panning and zooming interactively (2.5D). This paper reports a study that contrasted 3D and 2.5D performance for people with differing levels of spatial and structure learning ability. Four data collection methods were employed: search task scoring; subjective questionnaires; navigational activity logging and analysis; and administration of tests for spatial and structure‐learning abilities. Analysis of the results revealed statistically significant effects of user abilities, and information environment designs. Overall, this research did not find a performance advantage for using a 3D rather than a 2.5D virtual world. In addition, users in the lowest quartile of spatial ability had significantly lower search performance in the 3D environment. The findings suggest that individual differences in traits such as spatial ability may be important in determining the usability and acceptability of 3D environments.
Multimodal geographic information systems: Adding haptic and auditory display
Authors: Jeong Wooseob , Gluck Myke
Published: January 2003

The goal of this study was to discover the feasibility of adding haptic and auditory displays to traditional visual geographic information systems (GIS). The experiment was conducted with 51 participants to explore the difference in user performance (task completion time and accuracy) and user satisfaction with a multimodal GIS system, which was implemented with a haptic display, auditory display, and combined display. The experiment consisted of a series of 36 tasks in which the participants were asked to identify the highest or the middle valued state among nine U.S. states on maps. The results showed that haptic displays produce faster and more accurate performance than auditory displays and combined displays for more complex tasks. In terms of user satisfaction, the participants preferred the combined display even though they performed best with the haptic display.
Self‐citation and self‐reference: Credibility and promotion in academic publication
Authors: Hyland Ken
Published: January 2003

Author self‐citation has long been of interest to those working in informetrics for what it reveals about the publishing behavior of individuals and their relationships within academic networks. While this research has produced interesting insights, it typically assumes either that self‐citation is a neutral form of reporting not unlike references to others' work or an unsavory kind of academic egotism. By examining self‐citation in a wider context of self‐mention, however, the phenomenon can be seen as part of a more comprehensive rhetorical strategy for emphasizing a writer's personal contribution to a piece of research and strengthening his or her knowledge claims, research credibility, and wider standing in the discipline. These meanings are not easily revealed through quantitative bibliometric methods and require careful text analyses and discourse‐based interviews with academics. In this paper I explore the use of self‐citation and authorial mention in a corpus of 240 research articles and 800 abstracts in eight disciplines. Through an analysis of these texts and interviews with expert informants I show how self‐mention is used and the ways these uses reflect both the promotional strategies of individuals and the epistemological practices of their disciplines.
From here to obscurity?: Media substitution theory and traditional media in an on‐line world
Authors: Kaye Barbara K. , Johnson Thomas J.
Published: January 2003

An online survey targeted to politically interested Internet users assesses whether traditional media use is decreasing, increasing or remaining the same since users first started using the Web, bulletin boards/electronic mailing lists and chat rooms. Associations are made between media use gratifications, political attitudes and demographics and traditional media use, and further analysis determines whether these factors predict changes in the amount of time online users spend with traditional media. This study's findings are compared with a similar study conducted in 1996. News magazines and radio news took the hardest hit from the Internet in 2000 but in 1996 television news suffered the most. Generally, in both years the Internet had not altered media use patterns. In 1996 and 2000 more users claimed that the time they spent seeking political information from traditional media sources had stayed the same than had changed. However, the trend indicates that those Internet users whose media patterns have changed are abandoning traditional media at a much greater rate than they are increasing their use.
Stereotype‐based versus personal‐based filtering rules in information filtering systems
Authors: Kuflik Tsvi , Shapira Bracha , Shoval Peretz
Published: January 2003

Rule‐based information filtering systems maintain user profiles where the profile consists of a set of filtering rules expressing the user's information filtering policy. Filtering rules may refer to various attributes of the data items subject to the filtering process. In personal rule‐based filtering systems, each user has his/her own personal filtering rules. In stereotype rule‐based filtering systems, a user is assigned to a group of similar users (his/her stereotype) from which he/she inherits the stereotype's filtering profile. This study compares the effectiveness of the two alternative rule‐based filtering methods: stereotype‐based rules versus personal rules. We conducted a comparison between filtering effectiveness when using the personal rules or when using the stereotype‐based rules. Although, intuitively, personal filtering rules seem to be more effective because each user has his own tailored rules, our comparative study reveals that stereotype filtering rules yield more effective results. We believe that this is because users find it difficult to evaluate their filtering preferences accurately. The results imply that by using a stereotype it is possible not only to overcome the problem of user effort required to generate a manual rule‐based profile, but at the same time even provide a better initial user profile.
Significance of apoptosis in surgical oncology
Authors: Sarela A I , Guillou P J
Published: January 2003

Improved prognostic information and anticancer agents
Septic complications after treatment of haemorrhoids
Authors: Guy R J , Seow-Choen F
Published: January 2003

Background

Recent reports of serious sepsis following stapled haemorrhoidectomy have raised concerns about the appropriate treatment of haemorrhoidal disease.

Methods

A Medline search was undertaken for reports of sepsis following the commonly practised conservative and surgical treatments of haemorrhoids.

Results

Published accounts of significant septic complications after injection sclerotherapy, rubber-band ligation, cryotherapy, open and closed haemorrhoidectomy, and stapled haemorrhoidectomy are discussed. This is supplemented by the authors' own experiences of stapled haemorrhoidectomy.

Conclusion

Septic complications following both conservative and surgical treatment of haemorrhoids are rare but may be catastrophic. Immunological compromise poses an additional risk for many treatment modalities. The technique of stapled haemorrhoidectomy should be learned diligently to avoid septic complications.
Clinicopathological and molecular biological features of colorectal cancer in patients less than 40 years of age
Authors: Liang J T , Huang K C , Cheng A L , Jeng Y M , Wu M S , Wang S M
Published: January 2003

Background

The aim of the present study was to identify the clinicopathological and molecular biological characteristics of early-onset colorectal cancers.

Methods

The clinicopathological and molecular biological parameters of 138 consecutive patients with colorectal cancer aged less than 40 years were compared with those of 339 patients aged 60 years or more.

Results

The younger patients with colorectal cancer had more mucin-producing (14·5 versus 4·7 per cent; P < 0·001) and poorly differentiated (7·2 versus 3·3 per cent; P = 0·015) tumours, a higher incidence of synchronous (5·8 versus 1·2 per cent; P = 0·007) and metachronous (4·0 versus 0·6 per cent; P = 0·023) colorectal cancers, and more advanced tumour stage (P < 0·001) than older patients. The operative mortality rate was lower (0·7 versus 5·0 per cent; P = 0·026), and cancer-specific survival was similar (in stage I, II and III disease; P > 0·05) or better (in stage IV disease; 95 per cent confidence interval 22·50 to 28·41 versus 12·61 to 17·05 months; P < 0·001). There was a higher percentage of normal p53 expression (61·1 versus 46·8 per cent; P = 0·023) and high-frequency microsatellite instability (MSI-H) (29·4 versus 6·3 per cent; P < 0·001), and a similar family history of cancer (17·5 versus 14·2 per cent; P > 0·05), compared with older patients.

Conclusion

Young patients with colorectal cancer have several distinct clinicopathological and molecular biological features. The mechanisms underlying the inconsistency between the presence of MSI-H and a family history of cancer in these early-onset colorectal cancers deserve further investigation.
Treatment of perianal abscess and fistula-in-ano in children
Authors: Macdonald A , Wilson-Storey D , Munro F
Published: January 2003

Drain, don't probe
Growth factors in the treatment of diabetic foot ulcers
Authors: Bennett S P , Griffiths G D , Schor A M , Leese G P , Schor S L
Published: January 2003

Background

Chronic foot ulceration is a major source of morbidity in diabetic patients. Despite traditional comprehensive wound management, including vascular reconstruction, there remains a cohort of patients with non-responding wounds, often resulting in amputation. These wounds may benefit from molecular manipulation of growth factors to enhance the microcirculation.

Methods

A review of the current literature was performed using Pubmed, with secondary references obtained from key articles.

Results and conclusion

There has been a generally disappointing clinical outcome from growth factor trials, although topical platelet-derived growth factor has shown significant benefit and should be considered in non-healing, well perfused ulcers after failure of conventional wound care. The modulatory role of the extracellular matrix in the cellular response to growth factors and data from regenerative-type fetal wound healing are further areas of interest. The chemical induction of microvessel formation may become a future therapeutic option.