bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of the Dietary Supplement S-Adenosyl-L-Methionine
Authors: Fetrow CW , Avila Juan R 
Published: June 2003

OBJECTIVE: To review existing published clinical evidence surrounding the dietary supplement SAMe ( S-adenosyl-L-methionine). DATA SOURCES: The majority of information was obtained from primary published literature identified through MEDLINE search (1966–February 2001). Information was also obtained through secondary and tertiary sources when available. STUDY SELECTION AND DATA EXTRACTION: All articles identified from data sources were evaluated and all relevant information included in this review. DATA SYNTHESIS: The majority of clinical trial evidence surrounds the application of SAMe for various depressive disorders, osteoarthritis, and fibromyalgia. Sample sizes of these trials and the dose employed have varied considerably. Several reviews and at least two meta-analyses have examined the available evidence surrounding SAMe in the therapy of depression for trials completed prior to 1994 and concluded that SAMe was superior to placebo in treating depressive disorders and approximately as effective as standard tricyclic antidepressants. Much of this information exists in the form of isolated case reports or solitary clinical trials. SAMe appears to be well tolerated, with the majority of adverse effects presenting as mild to moderate gastrointestinal complaints. However, it is apparent that this agent is not without risk of more significant psychiatric and cardiovascular adverse events. Information documenting drug or food interactions with SAMe is very limited. CONCLUSIONS: Consumers should be instructed to avoid unmonitored consumption of this dietary supplement until sufficient discussion has taken place with their primary healthcare provider. Although there exists significant potential for therapeutic application of SAMe, its uncertain risk profile precludes definitive recommendation at this time. Healthcare providers and consumers should likely temper their enthusiasm for this dietary supplement until sufficient information becomes available.
Severe musculoskeletal phenotype associated with an unbalanced t(6;10) translocation: Clarification of the locus for this phenotype on distal 6p
Authors: James Paul A. , Aftimos Salim , Oei Paul 
Published: May 2003

AbstractLarsen syndrome is a congenital condition consisting of multiple large joint dislocations associated with a distinctive facial appearance and frequently other abnormalities. The syndrome is probably genetically heterogeneous, with both dominant and recessive inheritance reported. Previously two cases have been reported where a Larsen‐like syndrome was associated with unbalanced chromosomal translocations resulting in partial trisomy 1q and monosomy distal 6p. We now report a child with an unbalanced translocation resulting in a distal 6p deletion and partial trisomy 10q, who has Larsen‐like features and has also severe developmental delay. A G‐banded preparation revealed a karyotype 46,XX,der(6),t(6:10)(p25;q25.2) and the breakpoint at 6p25 was confirmed by FISH using YAC probes (between 6p25 at D6s477/F13A1 and 6p24 at 6WI13606). Our case provides further evidence for a Larsen‐like locus at distal 6p and reduces the potential critical region. © 2003 Wiley‐Liss, Inc.
A new autosomal recessive syndrome with Zellweger‐like manifestations
Authors: Ahn Joe K. , Lev Dorit , Leshinsky‐Silver Esther , Ginzberg Mira , Lerman‐Sagie Tally 
Published: May 2003

AbstractA son and daughter of consanguineous Ashkenazi Jewish parents presented with phenotypic features that are typically seen in Zellweger syndrome: high forehead, broad nasal bridge, epicanthal fold, upslanting palpebral fissures, and micrognathia. In addition to the physical anomalies, they also have severe psychomotor retardation and hypotonia. However, results of peroxisomal studies including very long chain fatty acids and plasmalogen functions, were normal. There was partial deficiency of respiratory chain complexes. We suggest that this is a new autosomal recessive syndrome that could be due to a nuclear‐encoded mitochondrial defect. © 2003 Wiley‐Liss, Inc.
Epidemiology of triploidy in a population‐based birth defects registry, Hawaii, 1986–1999
Authors: Forrester Mathias B. , Merz Ruth D. 
Published: May 2003

AbstractTriploidy is a highly lethal chromosomal abnormality with few fetuses surviving to term. Triploidy has not been extensively studied using data from a population‐based birth defect registry. This investigation examined the epidemiology of triploidy using data from the Hawaii Birth Defects Program (HBDP) and compared its findings with the literature. Of the 38 identified cases of triploidy delivered in Hawaii during 1986–1999, 31 (82%) were early fetal deaths, 3 (8%) late fetal deaths, and 4 (11%) elective terminations. The distribution of cases by sex chromosome combination was 15 (39%) XXX, 22 (58%) XXY, and 1 (3%) XYY. Triploidy was prenatally diagnosed in eight (21%) of the cases, of which four were electively terminated, two resulted in early fetal death, and two resulted in late fetal death. The detected triploidy prevalence in 1993–1999 was higher than the prevalence in 1986–1992, although the difference was not statistically significant (rate ratio (RR) 1.20, 95% confidence interval (CI) 0.73–1.86). The detected triploidy prevalence for maternal age of 35 years or greater was significantly higher than the prevalence for maternal age less than 35 years (RR 4.07, 95% CI 2.22–6.83). In spite of under detection of cases, many aspects of the epidemiology of triploidy identified in a population‐based birth defects registry were consistent with that reported in the literature. © 2003 Wiley‐Liss, Inc.
Prevalence of myotonic dystrophy in Israeli Jewish communities: Inter‐community variation and founder premutations
Authors: Segel Reeval , Silverstein Shira , Lerer Israela , Kahana Esther , Meir Rachel , Sagi Michal , Zilber Nelly , Korczyn Amos D. , Shapira Yehuda , Argov Zohar , Abeliovich Dvorah 
Published: May 2003

AbstractIn a comprehensive epidemiological survey among Jews living in Israel, the average prevalence of myotonic dystrophy (DM) was 15.7/105 (1 case in 6,369) with intercommunity variations; the Ashkenazi Jews had the lowest rate, 5.7/105 (1 case in 17,544) as compared to the rate in the Sephardim/Oriental Jews 20/105 (1 case in 5,000) and the in the Yemenite Jews 47.3/105 (1 case in 2,114). The rate of unrelated DM‐sibships per 106 people of each community was used as an estimate of the transition rate from stable to unstable DMPK‐(CTG)n alleles assuming that each transition is a beginning of a new DM sibship. This study indicated that the difference in the incidence of DM is a result of higher mutation rate in the non‐Ashkenazi Jews (>50/106) as compared to the rate in the Ashkenazi Jews (16.3/106). The intragenic haplotype of the DM alleles was the same as that of the DM in many populations all over the world. However, two DM closely linked markers D19S207 and D19S112 were in linkage disequilibrium with the DM mutation in patients of Yemenite and Moroccan (the largest subgroup in the Sephardim Jews) extractions and not in the Ashkenazi patients. This observation indicated a common ancestral origin for the DM premutation in patients of the same ethnic origin. We concluded that the difference in the prevalence of DM among the Jewish communities is a consequence of founder premutations in the non‐Ashkenazi Jewish communities. © 2003 Wiley‐Liss, Inc.
Inv(X)(p21.1;q22.1) in a man with mental retardation, short stature, general muscle wasting, and facial dysmorphism: Clinical study and mutation analysis of the NXF5 Gene
Authors: Frints Suzanna G.M. , Jun Lin , Fryns Jean‐Pierre , Devriendt Koen , Teulingkx Rudi , Berghe Lut Van den , Vos Bernice De , Borghgraef Martine , Chelly Jamel , Portes Vincent Des , Bokhoven Hans Van , Hamel Ben , Ropers Hans‐Hilger , Kalscheuer Vera , Raynaud Martine , Moraine Claude , Marynen Peter , Froyen Guy 
Published: May 2003

AbstractWe describe a 59‐year‐old male (patient A059) with moderate to severe mental retardation (MR) and a pericentric inversion of the X‐chromosome: inv(X)(p21.1;q22.1). He had short stature, pectus excavatum, general muscle wasting, and facial dysmorphism. Until now, no other patients with similar clinical features have been described in the literature. Molecular analysis of both breakpoints led to the identification of a novel “Nuclear RNA export factor” (NXF) gene cluster on Xq22.1. Within this cluster, the NXF5 gene was interrupted with subsequent loss of gene expression. Hence, mutation analysis of the NXF5 and its neighboring homologue, the NXF2 gene was performed in 45 men with various forms of syndromic X‐linked MR (XLMR) and in 70 patients with nonspecific XLMR. In the NXF5 gene four nucleotide changes: one intronic, two silent, and one missense (K23E), were identified. In the NXF2 gene two changes (one intronic and one silent) were found. Although none of these changes were causative mutations, we propose that NXF5 is a good candidate gene for this syndromic form of XLMR, given the suspected role of NXF proteins is within mRNA export/transport in neurons. Therefore, mutation screening of the NXF gene family in phenotypically identical patients is recommended. © 2003 Wiley‐Liss, Inc.
Noninvasive technique for the repeated sampling of salivary free cortisol in awake, unrestrained squirrel monkeys
Authors: TIEFENBACHER S. , LEE B. , MEYER J.S. , SPEALMAN R.D. 
Published: May 2003

AbstractThe use of noninvasive measures of hypothalamic‐pituitary‐adrenal (HPA) axis function is of growing interest among preclinical and clinical investigators. This report describes a method for the repeated assessment of salivary free cortisol in awake, unrestrained squirrel monkeys (Saimiri sciureus) based on a saliva sampling technique previously developed for rhesus monkeys. Individually housed adult male squirrel monkeys were trained to chew on dental rope attached to a pole, from which saliva was extracted by centrifugation and analyzed for cortisol by radioimmunoassay (RIA). Eight of nine monkeys readily acquired the task, reliably providing adequate saliva samples for the assay. Salivary free cortisol levels were examined in these subjects under basal conditions and in response to two types of neuroendocrine challenge. Levels of salivary free cortisol showed relatively low intra‐ and interindividual variability, with mean individual morning levels ranging between 17.1 and 37.9 µg/dl. Squirrel monkeys demonstrated a consistent daily rhythm in salivary free cortisol ranging from a high of 27.4 ± 5.2 µg/dl (mean ± SEM) at 12 P.M. to a low of 7.5 ± 1.6 µg/dl at 6 P.M.. Intravenous (IV) challenges with 1 µg/kg ACTH, or 10 and 50 µg/kg CRF resulted in significant increases in salivary free cortisol. The described sampling technique provides a reliable and sensitive means for repeated measurement of HPA activity in unrestrained, awake squirrel monkeys. In addition, our findings illustrate several features of HPA system rhythmicity and reactivity using salivary cortisol instead of blood plasma or serum. Am. J. Primatol. 60:69–75, 2003. © 2003 Wiley‐Liss, Inc.
Mitochondrial uncoupling protein‐2 protects the immature brain from excitotoxic neuronal death
Authors: Sullivan Patrick G. , Dubé Celine , Dorenbos Kristina , Steward Oswald , Baram Tallie Z. 
Published: May 2003

AbstractExcitotoxic cell death is the fundamental process responsible for many human neurodegenerative disorders, yet the basic mechanisms involved are not fully understood. Here, we exploited the fact that the immature brain is remarkably resistant to seizure‐induced excitotoxic cell death and examined the underlying protective mechanisms. We found that, unlike in the adult, seizures do not increase the formation of reactive oxygen species or result in mitochondrial dysfunction in neonatal brain, because of high levels of the mitochondrial uncoupling protein (UCP2). UCP2 expression and function were basally increased in neonatal brain by the fat‐rich diet of maternal milk, and substituting a low‐fat diet reduced UCP2, restored mitochondrial coupling, and permitted seizure‐induced neuronal injury. Thus, modulation of UCP2 expression and function by dietary fat protects neonatal neurons from excitotoxicity by preventing mitochondrial dysfunction. This mechanism offers novel neuroprotective strategies for individuals, greater than 1% of the world's population, who are affected by seizures. Ann Neurol 2003
Functional organization of the brain with malformations of cortical development
Authors: Janszky Jozsef , Ebner Alois , Kruse Bernd , Mertens Markus , Jokeit Hennric , Seitz Ruediger J. , Witte Otto W. , Tuxhorn Ingrid , Woermann Friedrich G. 
Published: May 2003

AbstractWe examined the localization of cerebral functions in 28 patients with focal epilepsy and malformations of cortical development (MCDs). Polymicrogyria occurred in nine, hemimegalencephaly in four, heterotopia in eight, and focal cortical dysplasia (FCD) in nine cases. We used simple (sensomotor, visual) or complex (language, memory) functional magnetic resonance imaging (fMRI) paradigms. Two thirds of MCDs were activated by simple fMRI paradigms, whereas they less frequently showed activity during complex cognitive fMRI paradigms. During simple paradigms, all disturbances of cortical organization (polymicrogyria, schizencephaly, and mild‐type FCD) showed activity, whereas other MCDs (disturbances of earlier steps of cortical development: hemimegalencephaly, Taylor‐type FCD, and heterotopia) showed activity in only 44% (p < 0.01). The association between the pathophysiology and morphology of MCDs confirms the recently proposed classification system. Both focal neurological signs (p < 0.05) and focal electroencephalogram slowing (p < 0.05) independently correlated with MCD inactivity, confirming that fMRI showed neuronal functions of MCDs. Conclusively, fMRI visualizes the MCD functions and their relationship to the eloquent cortex, providing useful information before epilepsy surgery. Surgery of cortical organization disturbances should be cautiously performed because these malformations may participate to some degree in brain functions. Ann Neurol 2003;53:759–767
Cortical anomalies associated with visuospatial processing deficits
Authors: Isaacs Elizabeth B. , Edmonds Caroline J. , Chong Wui K. , Lucas Alan , Gadian David G. 
Published: May 2003

AbstractChildren born preterm provide a fruitful population for studying structure–function relationships because they often have specific functional deficits in the context of normal neurological status. We selected a group of preterm adolescents with deficits in judgment of line orientation. Despite their very low birth weight, all were neurologically normal with no consistent abnormalities on conventional magnetic resonance imaging. However, voxel‐based morphometric analysis of their magnetic resonance imaging scans showed areas of decreased gray matter and increased white matter most prominently in right ventral extrastriate cortex, close to an area previously implicated in the line orientation task. We suggest that these anomalies of cortical architecture relate to impaired performance on the line orientation task. Ann Neurol 2003;53:768–773
Slowing of electroencephalogram in rapid eye movement sleep behavior disorder
Authors: Livia Fantini Maria , Gagnon Jean‐François , Petit Dominique , Rompré Sylvie , Décary Anne , Carrier Julie , Montplaisir Jacques 
Published: May 2003

AbstractRapid eye movement (REM) sleep behavior disorder (RBD) is characterized by a loss of atonia and an increase in phasic muscle activity during REM sleep, leading to complex nocturnal motor behaviors. Brainstem structures responsible for the pathogenesis of RBD are also implicated in cortical activation. To verify the hypothesis that electroencephalogram (EEG) activation will be impaired in RBD, we performed quantitative analyses of waking and REM sleep EEG in 15 idiopathic RBD patients and 15 age‐ and gender‐matched healthy subjects. During wakefulness, RBD patients showed a considerably higher θ power in frontal, temporal, and occipital regions with a lower β power in the occipital region. The dominant occipital frequency was significantly lower in RBD. During REM sleep, β power in the occipital region was lower in RBD. This study shows for the first time an impaired cortical activation during both wakefulness and REM sleep in idiopathic RBD, despite an absence of changes on sleep architecture compared with controls. EEG slowing in these patients may represent an early sign of central nervous system dysfunction, perhaps paralleled by subclinical cognitive deficits. The topographical distribution of EEG slowing and possible pathophysiological mechanisms are discussed in light of the known association between RBD and neurodegenerative disorders. Ann Neurol 2003;53:774–780
Toward therapy for DYT1 dystonia: Allele‐specific silencing of mutant TorsinA
Authors: Gonzalez‐Alegre Pedro , Miller Victor M. , Davidson Beverly L. , Paulson Henry L. 
Published: May 2003

AbstractA three‐nucleotide (GAG) deletion in the TOR1A gene is the most common cause of inherited dystonia, DYT1. Because the mutant protein, TorsinA (TA), is thought to act in a dominant manner to cause disease, inhibiting expression from the mutant gene represents a potentially powerful therapeutic strategy. In an effort to develop therapy for this disease, we tested whether small interfering RNA (siRNA) could selectively silence expression of mutant TA. Exploiting the three–base pair difference between wild‐type and mutant alleles, we designed siRNAs to silence expression of mutant, wild‐type, or both forms of TA. In transfected cells, siRNA successfully suppressed wild‐type or mutant TA in an allele‐specific manner: for example, mutant‐specific siRNA reduced the levels of mutant TA to less than 1% of controls with minimal effect on wild‐type TA expression. In cells expressing both alleles, thus simulating the heterozygous state, siRNA‐mediated suppression remained robust and allele specific. Our siRNA studies demonstrate allele‐specific targeting of a dominant neurogenetic disease gene and suggest the broad therapeutic potential of siRNA for DYT1 dystonia and other dominantly inherited neurological diseases. Ann Neurol 2003;53:781–787
Validation of diagnostic magnetic resonance imaging criteria for multiple sclerosis and response to interferon β1a
Authors: Barkhof Frederik , Rocca Mara , Francis Gordon , van Waesberghe Jan‐Hein T. M. , Uitdehaag Bernard M. J. , Hommes Otto R. , Hartung Hans‐Peter , Durelli Luca , Edan Gilles , Fernández Oscar , Seeldrayers Pierette , Sørensen Per , Margrie Simon , Rovaris Marco , Comi Giancarlo , Filippi Massimo ,   for the Early Treatment of Multiple Sclerosis Study Group
Published: May 2003

AbstractIn the recently proposed diagnostic criteria for multiple sclerosis (MS) by McDonald, the modified magnetic resonance imaging (MRI) Barkhof criteria have been incorporated. We examined the validity of this implementation in the Early Treatment of MS study, a randomized, double‐blind, placebo‐controlled study of 22μg interferon β1a given subcutaneously once weekly in 309 patients with a first episode consistent with demyelinating disease (and abnormal MRI). Conversion to clinically definite MS (CDMS) within 2 years of follow‐up, as evidenced by a new clinical episode, occurred in 41% of patients (independent of treatment) with gadolinium enhancement or nine or more T2 lesions versus 11% of those without either finding (p = 0.017); similarly, proportions converting were 44% versus 31% for infratentorial lesions (p = 0.026), 40% versus 35% for juxtacortical lesions (p = 0.413), and 41% versus 17% for three or more periventricular lesions (p = 0.034). The rate of conversion to CDMS based on the number of modified Barkhof criteria was 22% for two or fewer positive criteria, increasing to 47% with four positive criteria. For a cutoff of three positive criteria, the hazard ratio for time to CDMS was 2.3 (95% confidence interval, 1.17–4.55; p = 0.016). Treatment effect seemed more evident as the number of positive criteria increased, and the number of patients needed to avoid one patient converting to CDMS decreased from 50 in patients with one or two positive criteria to 5.6 in patients with four positive criteria. However, the study was not powered to detect statistically significant treatment by variable interaction, and this remains an important issue for further study.Ann Neurol 2003;53:718–724
Endothelial dysfunction precedes C‐fiber abnormalities in primary (AL) amyloidosis
Authors: Berghoff Martin , Kathpal Madeera , Khan Faisal , Skinner Martha , Falk Rodney , Freeman Roy 
Published: May 2003

AbstractPrimary (AL; immunoglobulin light‐chain associated) amyloidosis is characterized by the deposition of pathological proteins in the extracellular matrix of tissues and organs. Autonomic and sensory peripheral neuropathy is a common feature of this disorder. The pathogenesis of the neuropathy is poorly defined. The aims of this study were to investigate vascular and neural function in the cutaneous microcirculation of AL amyloidosis patients. Seven patients with AL amyloidosis and controls were studied. Acetylcholine and sodium nitroprusside were iontophoresed into the forearm skin. Endothelial, smooth muscle, and C‐fiber–mediated cutaneous blood flow (CuBF) were recorded by laser Doppler flowmetry. Endothelial vasodilation in the forearm skin was attenuated in AL amyloidosis patients (p = 0.007). Maximum endothelium‐mediated CuBF in the patient group was reduced (p = 0.047). No group differences could be detected in the C‐fiber response or smooth muscle vasodilation (p value not significant). Maximum C‐fiber and endothelium‐independent CuBF did not differ between the two groups (p value not significant). Early in the disease, AL amyloidosis patients present with impaired endothelial function. At this stage, C‐fiber and smooth muscle function are still preserved. These data suggest that endothelial abnormalities precede and may contribute to the pathogenesis of the neuropathy associated with AL amyloidosis. Ann Neurol 2003;53:725–730
Intracerebral hemorrhage induces macrophage activation and matrix metalloproteinases
Authors: Power Christopher , Henry Scot , Del Bigio Marc R. , Larsen Peter H. , Corbett Dale , Imai Yumi , Yong Voon Wee , Peeling James 
Published: May 2003

AbstractIntracerebral hemorrhage (ICH) is characterized by parenchymal hematoma formation with surrounding inflammation. Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of neurological diseases defined by inflammation and cell death. To investigate the expression profile and pathogenic aspects of MMPs in ICH, we examined MMP expression in vivo using a collagenase‐induced rat model of ICH. ICH increased brain MMP‐2, ‐3, ‐7, and ‐9 mRNA levels relative to sham‐injected (control) animals in the vicinity of the hematoma, but MMP‐12 (macrophage metalloelastase) was the most highly induced MMP (>80‐fold). Immunohistochemistry showed MMP‐12 to be localized in activated monocytoid cells surrounding the hematoma. In vitro studies showed that thrombin, released during ICH, induced MMP‐12 expression in monocytoid cells, which was reduced by minocycline application. Similarly, in vivo minocycline treatment significantly reduced MMP‐12 levels in brain. Neuropathological studies disclosed marked glial activation and apoptosis after ICH that was reduced by minocycline treatment. Neurobehavioral outcomes also were improved with minocycline treatment compared with untreated ICH controls. Thus, select MMPs exhibit increased expression after ICH, whereas minocycline is neuroprotective after ICH by suppressing monocytoid cell activation and downregulating MMP‐12 expression.Ann Neurol 2003;53:731–742