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Biomedical subjects

A Vincent

Publications and source records attributed to A Vincent.

At least 199 records · Page 11Linked to original sources
PubMed1997

Effects of tobacco smoking and gender on interhemispheric cognitive function: performance and confidence measures.

Cognitive function in tasks involving interhemispheric processing of verbal and spatial information was studied in 31 college students in a 2 x 2 factorial design with chronic smoking status [smoker (10+ cigarettes per day) versus non-smoker (no history of smoking)] and gender as the main between-subject factors. The subjects participated in two sessions on two consecutive days. The same task was repeated within the same session with a 15 min interval: smokers were tested before and after smoking whereas non-smokers rested during the interval. Dependent behavioral variables included those of performance (speed and accuracy) and confidence (low rate of non-responding). The verbal task yielded an expected female advantage, and smoking had the gender-specific effect of increasing both speed and accuracy more clearly in males. In addition, smoking decreased the rate of non-responding (increase confidence) in women, thereby affecting preferred strategies for problem solving by shifting the female pattern towards the male pattern. The spatial task, which probably involved a more perceptual, rather than cognitive, level of functioning, produced no clear effects of smoking and gender, and yielded some laterality effects. The acute within-subject smoking manipulation wherein, among smokers, the first test was preceded by 10+ h of deprivation, whereas the second repeated task was preceded by the smoking of a cigarette (i.e. deprivation followed by partial release) did not affect the behavioral measures. In conclusion, smoking had a gender-specific effect on cognitive function: it improved the performance of males in a verbal task and increased the subjective confidence of females thereby affecting the preferred cognitive strategies for problem solving.

Adult↗
PubMed1996

Association of arthrogryposis multiplex congenita with maternal antibodies inhibiting fetal acetylcholine receptor function.

Arthrogryposis multiplex congenita (AMC), characterized by multiple joint contractures developing in utero, results from lack of fetal movement. Some cases are genetically determined, but AMC occasionally complicates pregnancy in patients with myasthenia gravis (MG) suggesting involvement of circulating maternal antibodies. We previously demonstrated antibodies that inhibited the function of fetal acetylcholine receptor (AChR) in one healthy woman with an obstetric history of recurrent AMC. Here we study sera from this woman, from one other with a similar history, and from three (one asymptomatic) whose babies had neonatal MG and AMC. All five maternal sera had high titers of antibodies that inhibited alpha-Bungarotoxin (alpha-BuTx) binding to fetal AChR, and their sera markedly inhibited fetal AChR function with little effect on adult AChR function. Moreover, in a further survey, 3 of 20 sera from anti-AChR negative AMC mothers inhibited fetal AChR function significantly at 1:100 dilution. These results demonstrate the role of antibodies to fetal AChR and perhaps other muscle antigens in some cases of AMC. More generally, they suggest that placental transfer of antibodies directed at fetal antigens should be considered as a cause of other recurrent fetal or perinatal disorders.

Adult↗
PubMed1996

Cloning of cDNA encoding human rapsyn and mapping of the RAPSN gene locus to chromosome 11p11.2-p11.1.

We have isolated and sequenced cDNA clones for the human 43-kDa acetylcholine receptor-associated protein rapsyn. The cDNA encodes a 412-amino-acid protein that has a predicted molecular mass of 46,330 Da and shows 96% sequence identity with mouse rapsyn. Analysis of PCR amplifications, first from somatic cell hybrids and subsequently from radiation hybrids, localizes the human RAPSN gene locus to chromosome 11p11.2-p11.1 in close proximity to ACP2.

Amino Acid Sequence↗
PubMed1996

Collier, a novel regulator of Drosophila head development, is expressed in a single mitotic domain.

BACKGROUND: Segmentation of the Drosophila embryo is based on a cascade of hierarchical gene interactions that is initiated by maternal morphogens; these interactions define spatially restricted domains of zygotic gene expression within the blastoderm. Although the hierarchy of the segmentation genes that subdivide the trunk is well established, the patterning of the head is less well understood. Seven head segments can be assigned on the basis of metameric patterns of segment-polarity gene expression and internal sensory organs. The domains of expression of head gap-like genes broadly overlap, with their posterior margins out of phase by one segment. Taken together with the lack of pair-rule gene expression in the head, these observations led to the suggestion that head gap genes act in a combinatorial manner, determining head segmental borders and segmental identity at the same time. RESULTS: We have identified a new Drosophila gene, collier (col), whose expression at the blastoderm stage is restricted to a single stripe of cells corresponding to part of the intercalary and mandibular segment primordia, possibly parasegment O. Reduction of col activity in early gastrula embryos by antisense RNA expression results in a specific lack of head structures derived from these segments. The expression of col coincides with a mitotic domain, which supports the proposal that cells in this domain undergo a concerted mitotic and differentiation program that is orchestrated at the transcriptional level. Col is an ortholog of mammalian early B-cell factor/Olfactory-1. These proteins define a new family of transcription factors that contain a helix-loop-helix dimerization motif and a new type of DNA-binding domain that is highly conserved during evolution. CONCLUSIONS: Here we describe Col, the first Drosophila member of a new family of transcription factors. Col may act as a "second-level regulator' of head patterning. The structural conservation of Col during evolution raises the questions of its conservation of function in head specification and its interactions with other factors conserved between insects and vertebrates.

Amino Acid Sequence↗
PubMed1996

Stable functional expression of the adult subtype of human muscle acetylcholine receptor following transfection of the human rhabdomyosarcoma cell line TE671 with cDNA encoding the epsilon subunit.

The human rhabdomyosarcoma cell line TE671 expresses the foetal subtype of muscle acetylcholine receptor (AChR). By transfecting TE671 cells with cDNA encoding the human muscle AChR epsilon subunit under the control of the cytomegalovirus promoter we have established a stable cell clone that, in addition, constitutively expresses the adult AChR subtype. Both subtypes are inserted into the plasma membrane and demonstrate their respective characteristic single channel properties. The level of expression of the adult AChR subtype is two- to three-fold higher than that of the foetal subtype. The new cell clone provides a relatively abundant source of human adult AChR for immunological and pharmacological investigations.

DNA, Complementary↗
PubMed1996

A somatically mutated human antiganglioside IgM antibody that induces experimental neuropathy in mice is encoded by the variable region heavy chain gene, V1-18.

IgM paraproteins associated with autoimmune peripheral neuropathy and anti-Pr cold agglutinins react with sialic acid epitopes present on disialylated gangliosides including GD1b, GT1b, GQ1b, and GD3. A causal relationship between the paraprotein and the neuropathy has never been proven experimentally. From peripheral blood B cells of an affected patient, we have cloned a human hybridoma secreting an antidisialosyl IgM mAb, termed Ha1, that shows identical structural and functional characteristics to its serum counterpart. Variable region analysis shows Ha1 is encoded by the same VH1 family heavy chain gene, V1-18, as the only other known anti-Pr antibody sequence and is somatically mutated, suggesting that it [correction of is] arose in vivo in response to antigenic stimulation. In the rodent peripheral nervous system, Ha1 immunolocalizes to dorsal root ganglia, motor nerve terminals, muscle spindles, myelinated axons, and nodes of Ranvier. After intraperitoneal injection of affinity-purified antibody into mice for 10 d, electrophysiological recordings from the phrenic nerve-hemidiaphragm preparation demonstrated impairment of nerve excitability and a reduction in quantal release of neurotransmitter. These data unequivocally establish that an antidisialosyl antibody can exert pathophysiological effects on the peripheral nervous system and strongly support the view that the antibody contributes to the associated human disease.

Amino Acid Sequence↗
PubMed1996

The estrogen receptor locus is associated with a major gene influencing litter size in pigs.

Identification of individual major genes affecting quantitative traits in livestock species has been limited to date. By using a candidate gene approach and a divergent breed cross involving the Chinese Meishan pig, we have shown that a specific allele of the estrogen receptor (ER) locus is associated with increased litter size. Female pigs from synthetic lines with a 50% Meishan background that were homozygous for this beneficial allele produced 2.3 more pigs in first parities and 1.5 more pigs averaged over all parities than females from the same synthetic lines and homozygous for the undesirable allele. This beneficial ER allele was also found in pigs with Large White breed ancestory. Analysis of females with Large White breed background showed an advantage for females homozygous for the beneficial allele as compared to females homozygous for the other allele of more than 1 total pig born. Analyses of growth performance test records detected no significant unfavorable associations of the beneficial allele with growth and developmental traits. Mapping of the ER gene demonstrated that the closest known genes or markers were 3 centimorgans from ER. To our knowledge, one of these, superoxide dismutase gene (SOD2), was mapped for the first time in the pig. Analysis of ER and these linked markers indicated that ER is the best predictor of litter size differences. Introgression of the beneficial allele into commercial pig breeding lines, in which the allele was not present, and marker-assisted selection for the beneficial allele in lines with Meishan and Large White background have begun.

Animals↗
PubMed1996

Modulation of acetylcholine receptor function in TE671 (rhabdomyosarcoma) cells by non-AChR ligands: possible relevance to seronegative myasthenia gravis.

The acetylcholine receptor (AChR) is the main target antigen in myasthenia gravis (MG), but about 15% of patients with typical immunologically mediated MG do not have detectable anti-AChR antibodies. Previous studies showed that plasma from these 'seronegative' patients (SNMG) reduced AChR function in the human AChR-expressing TE671 cell line, and it was proposed that SNMG plasmas may act indirectly via phosphorylation of AChR. We show here that substances such as the beta 2-adrenergic agonist, salbutamol, calcitonin-gene-related-peptide (CGRP), and cholera toxin, that increase intracellular cAMP via binding to specific cell-surface receptors, reduced AChR function in TE671 cells. Moreover, non-specific activation of cell surface proteins by lectins achieved similar results. These observations lead us to hypothesise that SNMG immunoglobulins act in TE671 cells by cross-linking of specific cell surface antigen(s) resulting in generation of intracellular cAMP and/or other second messengers. The role of such antibodies at the neuromuscular junction in vivo could be reduction in AChR function by desensitization and/or damage to the postsynaptic membrane following complement activation.

Adrenergic beta-Agonists↗
PubMed1996

Soluble complement receptor 1 (sCR1) protects against experimental autoimmune myasthenia gravis.

The loss of muscle function seen in myasthenia gravis and in the animal model of the disease, experimental autoimmune myasthenia gravis (EAMG) is in part due to the activation of complement by anti-acetylcholine receptor (AChR) antibodies at the motor end-plate. In this study we describe the effects of a soluble recombinant form of human complement receptor 1 (sCR1) on the development of clinical disease and receptor loss in EAMG induced passively by administration of anti-AChR antibodies. Daily intraperitoneal injection of sCR1 significantly reduced the weight loss and severity of clinical symptoms seen and allowed treated animals to recover normal muscle function. These data suggest that sCR1 could provide a useful additional therapeutic agent in myasthenia.

Animals↗
PubMed1996

Relations among memory performance, mental workload and cardiovascular responses.

The levels of processing paradigm has been a powerful research framework in the study of memory for close to a quarter century. However, an objective index of depth of processing is still lacking. Two experiments using lists of words, presented to male subjects, wee performed to compare the effects of depth of processing, rate of presentation, and task incentive on recognition memory performance, self-reported workload, and cardiovascular responding. Memory performance results from the two experiments demonstrated higher recognition levels associated with deeper processing and slower presentation rates. Deeply encoded items were associated with faster recognition latencies. Self-reported workload levels were higher for deeper processing and faster presentation rates. Cardiovascular responses were generally amplified with the addition of a task incentive. Increased blood pressure was associated with faster presentation rates. Increased heart rate and decreased T-wave amplitude (i.e., increased sympathetic activity) were uniquely associated with the deep encoding of information presented at the fastest rate. This particular encoding condition was associated with increased recognition levels. Deeply encoded items were associated with increased suppression of heart rate variability during recognition. This combination of behavioral and cardiovascular measures may provide the basis for an objective index of depth of processing.

Adult↗
PubMed1996

Autoimmunity to ion-channels and other proteins in paraneoplastic disorders.

Paraneoplastic neurological disorders are rare conditions caused by immune responses against tumour antigens that cross-react with neuronal antigens. In the past year, there have been advances in the definition of some of the antigens that are recognized by patients' antibodies, and new observations on the results of passive and active immunization against the antigens.

Animals↗
PubMed1996

A simple method for delivering morpholino antisense oligos into the cytoplasm of cells.

We report a simple and effective means for delivering Morpholino antisense oligos into the cytosol of cultured anchorage-dependent animal cells. This method, referred to as scrape-loading, is carried out in a matter of seconds, uses a common inexpensive laboratory implement, and has minimal detrimental impact on the cells. Using this delivery method, a Morpholino oligo present at 0.1 microM and 1 microM in the extracellular medium inhibited its targeted genetic sequence within cultured Hela cells at levels of 56% and 85%, respectively. Lack of inhibition by two control Morpholino oligos at concentrations up to 3 microM indicates good sequence specificity by this structural type. Also described is a test system for simple, rapid, and sensitive quantitation of antisense activity in cultured cells.

Animals↗
PubMed1996

Attention disturbance in clinical depression. Deficient distractor inhibition or processing resource deficit?

Cognitive impairments in depression have recently been proposed as secondary to more basic attentional disturbances. Studies have shown that performance on the Stroop Color-Word Test is impaired in depressives, but it is not clear whether this impairment reflects a primary distractor inhibition disturbance or a more global cognitive dysfunction, such as a reduction of processing resources. In the present study, unmedicated clinical depressives were evaluated using a computerized Stroop Color-Word Test and the Visuo-Spatial Interference Test, a selective attention task that makes fewer demands on resources. Compared with normal subjects, depressives presented increased choice reaction times (CRT) and interference in both tests. Correlations were found between CRT and interferences only in depressives, favoring the processing resource hypothesis. Further exploratory analysis comparing the more rapid depressives and the slower normal subjects on CRT revealed that although these subgroups had comparable CRT, rapid depressives still exhibited increased interference on the Visuo-Spatial Interference Test. Thus, in non- or mildly retarded patients, a specific distractor inhibition deficit was observed in absence of resource deficit.

Adult↗
PubMed1996

Developmental study of N-methyl-D-aspartate-induced firing activity and whole-cell currents in nucleus tractus solitarii neurons.

Whole-cell recordings of rat nucleus tractus solitarii (NTS) neurons were performed on a slice preparation. We investigated possible postnatal changes in firing activities and currents induced by N-methyl-D-aspartate (NMDA) application. A total of 42 neurons were selected and fell into the following age groups: 0-5 days (n = 15), 10-15 days (n = 9) and 30-60 days (adult, n = 18). During this period, input resistance and spike duration decreased by approximately 40%. At all ages, bath application of NMDA elicited a bursting firing activity when the membrane potential was held between -60 and -75 mV. However, in the youngest cells the rhythmic bursting activity was irregular and was characterized by a progressive firing inactivation during a burst. In a tetrodotoxin-containing saline, NMDA-induced oscillations of membrane potential were retained in all age groups. The membrane current-voltage relationship of the NMDA-induced inward current (INMDA) was characterized by a region of negative slope conductance which was similar in all age groups. Thus the voltage-dependent block of INMDA is present in NTS neurons from birth, allowing NTS neurons to display membrane potential oscillations. However, postnatal maturation of repolarizing conductances, as suggested by changes in spike characteristics, could render the oscillatory activity more stable than at birth.

Aging↗
PubMed1996

Effects of intravenous immunoglobulin on muscle weakness and calcium-channel autoantibodies in the Lambert-Eaton myasthenic syndrome.

Intravenous immunoglobulin improves many antibody-mediated autoimmune disorders, but its mode of action is unknown. We investigated its effects on muscle strength and on the serum titer of the calcium-channel autoantibodies that are likely to be pathogenic in the Lambert-Eaton myasthenic syndrome (LEMS). In a randomized, double-blind, placebo-controlled crossover trial, serial indices of limb, respiratory, and bulbar muscle strength and the serum titer of calcium-channel antibodies in nine patients were compared over an 8-week period, using the area-under-the-curve approach, following infusion on two consecutive days of immunoglobulin at 1 g/kg body weight/day (total dose 2.0 g/kg body weight) or placebo (equivalent volume of 0.3% albumin). Calcium-channel antibodies were measured by radioimmunoassay using 125I-omega-conotoxin MVIIC. Direct anti-idiotypic actions of immunoglobulin were tested in this assay. Immunoglobulin infusion was followed by significant improvements in the three strength measures (p = 0.017 to 0.038) associated with a significant decline in serum calcium-channel antibody titers (p = 0.028). Improvement peaked at 2 to 4 weeks and was declining by 8 weeks. Mean serum titers were unchanged at 1 week, however, and direct anti-idiotypic neutralization by immunoglobulin was not demonstrable in vitro. We conclude that immunoglobulin causes a short-term improvement in muscle strength in LEMS that probably results from the induced reduction in calcium-channel autoantibodies. The reduction is not due to a direct neutralizing action of the immunoglobulin, but a delayed anti-idiotypic action cannot be excluded. Improvement following intravenous immunoglobulin in other autoantibody-mediated disorders may similarly be associated with decline in levels of pathogenic autoantibodies.

Adolescent↗
PubMed1996

A transfected human muscle cell line expressing the adult subtype of the human muscle acetylcholine receptor for diagnostic assays in myasthenia gravis.

Immunoprecipitation of human acetylcholine receptor (AChR) is used in the diagnostic assay for myasthenia gravis (MG). We compared human AChR derived from TE671 cells, which express fetal-type AChR, with AChR from TE671-epsilon cells, which we have engineered to express adult-type AChR. Some low-titer MG sera distinguished strikingly between the two subtypes. Four out of seven MG sera that had equivocal titers in standard assays gave positive titers with TE671-epsilon AChR, whereas only one out of seven gave a positive titer with TE671 cells. The new cell line provides a greater concentration of adult AChR than can be obtained from normal human muscle and increases the sensitivity of the diagnostic assay.

Binding Sites↗