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Biomedical subjects

A Karni

Publications and source records attributed to A Karni.

At least 19 recordsLinked to original sources
PubMed1999

Elevated levels of antibody to myelin oligodendrocyte glycoprotein is not specific for patients with multiple sclerosis.

OBJECTIVE: To evaluate the presence and specificity of anti-myelin oligodendrocyte glycoprotein (MOG) antibody in the cerebrospinal fluid and plasma of patients with multiple sclerosis (MS). DESIGN: Case-control study of patients with clinically definite MS compared with patients with other neurologic diseases (ONDs) of the central nervous system and control subjects. SETTING: Referral center in the Department of Neurology of Hadassah University Hospital, greater Jerusalem area, Israel. PARTICIPANTS: Consecutive cerebrospinal fluid samples from 31 patients with MS, 31 patients with ONDs, and 28 healthy controls; and plasma samples from 33 patients with MS, 28 patients with ONDs, and 31 healthy controls were taken from the cerebrospinal fluid and plasma bank of the Department of Neurology, Hadassah University Hospital. MAIN OUTCOME MEASURES: Levels and frequencies of anti-MOG antibody in patients with MS, as defined by enzyme-linked immunosorbent assay. RESULTS: Cerebrospinal fluid levels of antibodies to MOG and to myelin basic protein were significantly higher in patients with MS (P<.001 and P = .001, respectively) and patients with ONDs (P = .005 and P = .03, respectively) compared with controls; frequency of antibodies to MOG, but not to myelin basic protein, was higher in patients with MS and patients with ONDs (P = .01 and P = .003, respectively, for the frequency of anti-MOG antibody, and P = .65 and P = .41, respectively, for the frequency of anti-myelin basic protein antibody). Plasma levels of antibodies to MOG and to myelin basic protein were higher in patients with MS compared with patients with ONDs (P = .003 for both comparisons) and with controls (P = .03 and P = .04, respectively); however, the frequency of antibodies to MOG and myelin basic protein was similar in patients with MS, patients with ONDs (P=.54 and P = .82, respectively), and controls (P = .50 and P = .14, respectively). CONCLUSIONS: The elevated presence of anti-MOG antibody is not specific for MS because a similar appearance was also demonstrated in patients with ONDs. Therefore, it is not clear whether this antibody is pathogenic in MS or, on the contrary, has a defensive role against further immune-mediated damage after myelin breakdown.

Adolescent↗
PubMed1998

Hemispheric specialization for English and ASL: left invariance-right variability.

Functional magnetic resonance imaging (fMRI) was used to compare the cerebral organization during sentence processing in English and in American sign language (ASL). Classical language areas within the left hemisphere were recruited by both English in native speakers and ASL in native signers. This suggests a bias of the left hemisphere to process natural languages independently of the modality through which language is perceived. Furthermore, in contrast to English, ASL strongly recruited right hemisphere structures. This was true irrespective of whether the native signers were deaf or hearing. Thus, the specific processing requirements of the language also in part determine the organization of the language systems of the brain.

Adult↗
PubMed1998

The acquisition of skilled motor performance: fast and slow experience-driven changes in primary motor cortex.

Behavioral and neurophysiological studies suggest that skill learning can be mediated by discrete, experience-driven changes within specific neural representations subserving the performance of the trained task. We have shown that a few minutes of daily practice on a sequential finger opposition task induced large, incremental performance gains over a few weeks of training. These gains did not generalize to the contralateral hand nor to a matched sequence of identical component movements, suggesting that a lateralized representation of the learned sequence of movements evolved through practice. This interpretation was supported by functional MRI data showing that a more extensive representation of the trained sequence emerged in primary motor cortex after 3 weeks of training. The imaging data, however, also indicated important changes occurring in primary motor cortex during the initial scanning sessions, which we proposed may reflect the setting up of a task-specific motor processing routine. Here we provide behavioral and functional MRI data on experience-dependent changes induced by a limited amount of repetitions within the first imaging session. We show that this limited training experience can be sufficient to trigger performance gains that require time to become evident. We propose that skilled motor performance is acquired in several stages: "fast" learning, an initial, within-session improvement phase, followed by a period of consolidation of several hours duration, and then "slow" learning, consisting of delayed, incremental gains in performance emerging after continued practice. This time course may reflect basic mechanisms of neuronal plasticity in the adult brain that subserve the acquisition and retention of many different skills.

Adult↗
PubMed1998

Cerebral organization for language in deaf and hearing subjects: biological constraints and effects of experience.

Cerebral organization during sentence processing in English and in American Sign Language (ASL) was characterized by employing functional magnetic resonance imaging (fMRI) at 4 T. Effects of deafness, age of language acquisition, and bilingualism were assessed by comparing results from (i) normally hearing, monolingual, native speakers of English, (ii) congenitally, genetically deaf, native signers of ASL who learned English late and through the visual modality, and (iii) normally hearing bilinguals who were native signers of ASL and speakers of English. All groups, hearing and deaf, processing their native language, English or ASL, displayed strong and repeated activation within classical language areas of the left hemisphere. Deaf subjects reading English did not display activation in these regions. These results suggest that the early acquisition of a natural language is important in the expression of the strong bias for these areas to mediate language, independently of the form of the language. In addition, native signers, hearing and deaf, displayed extensive activation of homologous areas within the right hemisphere, indicating that the specific processing requirements of the language also in part determine the organization of the language systems of the brain.

Adult↗
PubMed1998

Exacerbation of myasthenia gravis during the menstrual period.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disorder mediated by antiacetylcholine receptor antibodies. It has long been suspected to exacerbate during the menstrual period but this has never been adequately documented. SUBJECTS AND METHODS: We questioned 120 female myasthenic patients of different ages, about their myasthenic symptoms before and during the menstrual period. We also evaluated the effect of medications, pain and stress during or before the menstrual period on the exacerbation rate. Exclusion criteria were postmenopausal age and incomplete information available in the questionnaire. RESULTS: Forty two premenopausal women with generalized disease were included in the study. Twenty eight (67%) of the patients reported exacerbation of their myasthenic symptoms 2 to 3 days prior to the menstrual period. This exacerbation persisted in 22 of them to the third day of the menstrual period. In nine of the women this clinical worsening necessitated an increased intake of medications during the days prior to menstruation. No correlation could be found between the presence of antiacetylcholine receptor antibodies, pain, stress, use of oral contraceptives or the type of antimyasthenic therapy and the rate of exacerbation before and during the menstrual period. CONCLUSIONS: (1) MG frequently exacerbates before and during the menstrual period in 67% of MG patients. (2) The rate of exacerbation is unrelated to the presence of stress or pain prior to or during the menstrual period. (3) Different therapies directed against MG, as well as oral contraceptives do not influence the clinical course. (4) Menstrual exacerbations occur in both seronegative and seropositive patients. (5) These exacerbations may frequently necessitate therapeutic changes.

Adult↗
PubMed1997

Predominance of the autoimmune response to myelin oligodendrocyte glycoprotein (MOG) in multiple sclerosis: reactivity to the extracellular domain of MOG is directed against three main regions.

Our previous analysis of the T cell reactivity to myelin antigens in a group of 24 patients with multiple sclerosis (MS) and 16 control individuals revealed that the autoimmune response to myelin oligodendrocyte glycoprotein (MOG) predominates in MS over that to myelin basic protein (MBP), proteolipid protein or myelin-associated glycoprotein, suggesting a prevalent role for the autoimmune response to MOG in the pathogenesis of MS. Using a recombinant human MOG (rhMOG) preparation corresponding to the extracellular immunoglobulin-like domain of the MOG molecule, we have now analyzed another group of 52 MS patients and 49 control individuals for reactivity of their peripheral blood lymphocytes (PBL) to rhMOG and to MBP concomitantly. Of the 52 MS patients tested 24 responded to MOG and 10 out of 49 responded to MBP, whereas only 5 MOG-reactive and 4 MBP-reactive control individuals were detected out of the 49 tested. These results are therefore highly confirmatory of the predominant reactivity to MOG in MS. The analysis of the primary proliferative response to 11 synthetic overlapping peptides (phMOG) spanning the extracellular domain of human MOG by PBL from 9 MS patients and 15 control individuals (9 healthy controls and 6 patients with neurological diseases other than MS) further supports a prevalent role for the autoimmune response to MOG in MS, as only 1 of the 15 controls tested showed reactivity to any of the phMOG, whilst 5 out of the 9 patients studied reacted to at least 1 of the phMOG. PBL from 10 MS patients, and from 4 controls, were selected in vitro with each of the phMOG. Of the 10 patients studied 7 reacted to at least 1 phMOG upon secondary stimulation and the reactivity was mostly directed to epitopes localized within three main regions (amino acids 1-22, 34-56 and 64-96), as was observed for the primary response of PBL. The predominant response to MOG of PBL from MS patients as demonstrated in two separate studies using native MOG and rhMOG as antigens, and the high incidence of reactivity of these PBL compared to the lack of response to phMOG by control PBL, emphasize the relevance of MOG in MS pathogenesis and support a primary role for the autoimmune T cell response to MOG in disease development.

Adult↗
PubMed1997

Learning perceptual skills: behavioral probes into adult cortical plasticity.

Recent studies of the improvement of perceptual performance as a function of training - perceptual learning - have provided new insights into the neuronal substrates of this type of skill learning in the adult brain. Issues such as where in the brain, when and under what conditions practice-related changes occur are under investigation. The results of these studies suggest that a behaviorally relevant degree of plasticity is retained in the adult cortex, even within early, low-level representations in sensory and motor processing streams. The acquisition and retention of skills may share many characteristics with the functional plasticity subserving early-life learning and development. While the specificity of learning provides localization constraints, an important clue to the nature of the underlying neuronal changes is the time course of learning.

Adult↗
PubMed1997

Reactivity of T cells from seronegative patients with myasthenia gravis to T cell epitopes of the human acetylcholine receptor.

Seronegative (SN) patients with myasthenia gravis (MG) have clinical and electrophysiologic features similar to those of seropositive (SP) patients, and they respond to the same therapeutic measures. However, because SN patients lack detectable (by standard radioimmunoassays) serum antibodies to acetylcholine receptor (AChR), which are considered to have a crucial role in MG, the pathophysiologic basis for the disease is not clear. We therefore compared the ability of peripheral blood lymphocytes (PBL) of SN patients (11) and SP patients (39) to respond to myasthenogenic T cell epitopes of human AChR. We tested two aspects that relate to T-cell immunity: 1) T cell responses to myasthenogenic peptides by proliferation and IL-2 production, and 2) the ability of antigen-presenting cells to bind these T-cell epitopes. T cells of SN patients did not differ from those of SP patients in their ability to respond and to bind the two human AChR-derived myasthenogenic peptides. This supports the belief that most SN patients indeed suffer from an autoimmune disease directed against the AChR. The presence of T-cell immunity in the absence of antibodies may emphasize the importance of AChR-specific T cells in MG.

Adult↗
PubMed1996

Peptide analogs to pathogenic epitopes of the human acetylcholine receptor alpha subunit as potential modulators of myasthenia gravis.

Myasthenia gravis is an autoimmune disease in which T cells specific to epitopes of the autoantigen, the human acetylcholine receptor, play a role. We identified two peptides, p195-212 and p259-271, from the alpha subunit of the receptor, which bound to major histocompatibility complex (MHC) class II molecules on antigen-presenting cells (APCs) from peripheral blood lymphocytes of myasthenia gravis patients and stimulated lymphocytes of >80% of the patients. We have prepared analogs of these myasthenogenic peptides and tested their ability to bind to MHC class II determinants and to interfere specifically with T-cell stimulation. We first determined relative binding efficiency of the myasthenogenic peptides and their analogs to APCs of patients. We found that single substituted analogs of p195-212 (Ala-207) and p259-271 (Lys-262) could bind to human MHC molecules on APCs as efficiently as the original peptides. Moreover, dual analogs containing the two single substituted analogs in one stretch (either sequentially, Ala-207/Lys-262, or reciprocally, Lys-262/Ala-207) could also bind to APCs of patients, including those that failed to bind one of the single substituted analogs. The single substituted analogs significantly inhibited T-cell stimulation induced by their respective myasthenogenic peptides in >95% of the patients. The dual analogs were capable of inhibiting stimulation induced by either of the peptides: They inhibited the response to p195-212 and p259-271 in >95% and >90% of the patients, respectively. Thus, the dual analogs are good candidates for inhibition of T-cell responses of myasthenia gravis patients and might have therapeutic potential.

Adult↗
PubMed1995

Functional MRI evidence for adult motor cortex plasticity during motor skill learning.

Performance of complex motor tasks, such as rapid sequences of finger movements, can be improved in terms of speed and accuracy over several weeks by daily practice sessions. This improvement does not generalize to a matched sequence of identical component movements, nor to the contralateral hand. Here we report a study of the neural changes underlying this learning using functional magnetic resonance imaging (MRI) of local blood oxygenation level-dependent (BOLD) signals evoked in primary motor cortex (M1). Before training, a comparable extent of M1 was activated by both sequences. However, two ordering effects were observed: repeating a sequence within a brief time window initially resulted in a smaller area of activation (habituation), but later in larger area of activation (enhancement), suggesting a switch in M1 processing mode within the first session (fast learning). By week 4 of training, concurrent with asymptotic performance, the extent of cortex activated by the practised sequence enlarged compared with the unpractised sequence, irrespective of order (slow learning). These changes persisted for several months. The results suggest a slowly evolving, long-term, experience-dependent reorganization of the adult M1, which may underlie the acquisition and retention of the motor skill.

Adult↗
PubMed1995

Applications of magnetic resonance imaging to the study of human brain function.

Important questions relating to the coupling of local neuronal activity to the hemodynamic response measured using functional magnetic resonance imaging (fMRI), as well as issues concerning imaging sequence, paradigm design and data analysis processing, have been addressed during the past year. Initial fMRI studies identified visual, somatosensory, auditory and motor activation areas in the primary cortices. Current 'second generation' studies aim to identify changes in the fMRI signal associated with specific tasks and stimulus parameters. Dynamic aspects of brain processing for performing higher order cognitive functions, such as language, attention, mental imagery, and learning and memory, have also been explored.

Animals↗
PubMed1994

Dependence on REM sleep of overnight improvement of a perceptual skill.

Several paradigms of perceptual learning suggest that practice can trigger long-term, experience-dependent changes in the adult visual system of humans. As shown here, performance of a basic visual discrimination task improved after a normal night's sleep. Selective disruption of rapid eye movement (REM) sleep resulted in no performance gain during a comparable sleep interval, although non-REM slow-wave sleep disruption did not affect improvement. On the other hand, deprivation of REM sleep had no detrimental effects on the performance of a similar, but previously learned, task. These results indicate that a process of human memory consolidation, active during sleep, is strongly dependent on REM sleep.

Adolescent↗
PubMed1993

The time course of learning a visual skill.

Several examples of experience-dependent perceptual improvement (perceptual learning) suggest that plasticity in specific neuronal loci could underlie the learning process. For a basic visual discrimination task (using an optimal stimulus for 'automatic' pre-attentive texture segregation), discrete retinal input-dependent changes within a very early stage in the stream of visual processing were indicated as the locus of a large and consistent learning effect. When do these changes occur? Here we report that except for a fast, rapidly saturating improvement early in the first practice session, performance was very stable within sessions. Indeed, observers showed little or no improvement until up to 8 hours after their last training session (latent phase). But large improvements occurred thereafter. Finally, there was almost no forgetting; what was gained was retained for at least 2-3 years. We conjecture that some types of perceptual experience trigger permanent neural changes in early processing stages of the adult visual system. These may take many hours to become functional.

Discrimination, Psychological↗
PubMed1991

Where practice makes perfect in texture discrimination: evidence for primary visual cortex plasticity.

In terms of functional anatomy, where does learning occur when, for a basic visual discrimination task, performance improves with practice (perceptual learning)? We report remarkable long-term learning in a simple texture discrimination task where learning is specific for retinal input. This learning is (i) local (in a retinotopic sense), (ii) orientation specific but asymmetric (it is specific for background but not for target-element orientation), and (iii) strongly monocular (there is little interocular transfer of learning). Our results suggest that learning involves experience-dependent changes at a level of the visual system where monocularity and the retinotopic organization of the visual input are still retained and where different orientations are processed separately. These results can be interpreted in terms of local plasticity induced by retinal input in early visual processing in human adults, presumably at the level of orientation-gradient sensitive cells in primary visual cortex.

Discrimination, Psychological↗
PubMed1991

The influence of pyridostigmine administration on human neuromuscular functions--studies in healthy human subjects.

Pyridostigmine has a protective effect against organophosphate poisoning when given in a dosage of 30 mg three times daily causing 20-40% cholinesterase inhibition. To test its safety in the human neuromuscular system, a double-blind study on 35 subjects divided into two matched groups was performed. One group was treated with pyridostigmine in a dose of 30 mg three times daily and the other group was treated similarly with placebo, both for a 10-day period. The resultant average cholinesterase inhibition in the treatment group was 23%. Muscle strength and endurance were tested before, during (on the 8th day), and after treatment. Electrodiagnostic studies, including nerve conduction, electromyography, and response to repetitive stimulation, were carried out on four subjects of the treatment group and on two subjects of the placebo group, both before and during treatment (eighth day). Isometric handgrip strength, isokinetic elbow flexor, and extensor strength did not differ between groups as a result of the treatment. Knee flexor and extensor isokinetic strength showed a small (but statistically significant) trend to improve more during placebo treatment, whereas knee extensor endurance decreased slightly in the placebo group. Both these effects are probably due to large fluctuations in performance of the placebo group, whereas the treatment group performance was quite constant. They probably do not represent any adverse effect of pyridostigmine. No electrophysiological changes were found in any of the subjects during treatment. We conclude that pyridostigmine does not cause any significant neuromuscular effect in healthy subjects when taken in a dosage of 90 mg daily for 8 days, causing 20-30% inhibition of cholinesterase.

Adolescent↗