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Biomedical subjects

A Karni

Publications and source records attributed to A Karni.

At least 19 recordsLinked to original sources
PubMed2001

A transition between eye and object rivalry determined by stimulus coherence.

Two orthogonal patterns presented to the two eyes, respectively, are perceived as alternating in time, a phenomenon often assumed to reflect competition between neuronal activities corresponding to the two eyes, presumably in the primary visual cortex. Recent evidence supports a competition between neuronal activities corresponding to the two patterns (objects) at some higher cortical processing stage after inputs from the two eyes have converged. Here, using textures made of Gabor signals, we present psychophysical data showing that the level of visual processing at which competition takes place and is resolved, is determined by the degree of stimulus coherence. Moreover, depending on stimulus parameters, competition may occur at several levels of processing at the same time.

Humans↗
PubMed2001

Traumatic head injury in the anticoagulated elderly patient: a lethal combination.

Warfarin is the most common oral anticoagulant used for chronic anticoagulation therapy. Even without any antecedent trauma overanticoagulation can result in intracranial hemorrhage. The triad of anticoagulation with warfarin, age greater than 65 years, and traumatic head injury frequently produces a lethal brain hemorrhage. A retrospective review of more than 2000 patients admitted to the Trauma Service between September 1998 and May 2000 produced 278 patients with head injury and CT-documented intracranial hemorrhage. Of these patients 21 were admitted with an elevated prothrombin time (PT) due to anticoagulation with warfarin. Eighteen patients (86%) were above the age of 70. The most common indications for anticoagulation were atrial fibrillation (71%), deep venous thrombosis (19%), aortic valve replacement (9%), and ischemic cerebral infarcts (9%). Fourteen injuries were the result of a fall, one resulted from a gunshot wound, and one resulted from an assault. The remaining five patients were excluded as their history, workup, and evaluation by neurosurgery suggested a spontaneous bleed leading to fall rather than a fall causing a traumatic bleed. The average Glasgow Coma Score on admission was 11. The average PT and International Normalized Ratio (INR) on admission were 19.2 and 2.99 respectively. Eight of the 16 patients analyzed died. The risk of intracranial hemorrhage with relatively minor head injury is increased dramatically in the anticoagulated patient. A mortality rate of 50 per cent far exceeds the mortality rate in patients with similar head injuries who are not anticoagulated. In addition the risk/benefit equation of anticoagulation for the elderly is more complex and differs from that for younger patients. Perhaps more frequent and judicious monitoring of prothrombin time levels with lower therapeutic ranges (INR 1.5-2) is necessary.

Adult↗
PubMed2000

Effects of sex hormones on experimental autoimmune myasthenia gravis.

To examine whether exacerbation of myasthenia gravis (MG) can be induced by changes in sex hormone levels we immunized 20 female Lewis rats with torpedo antigen to induce experimental autoimmune MG (EAMG). Ten of the animals underwent surgical ovariectomy prior to the induction of EAMG and 10 served as controls. Anti-acetylcholine receptor antibody (AChR-ab) titres and the degree of decrement on repetitive stimulation electromyography (REMG) at 3 Hz were obtained at base line and compared between rats with and without ovariectomy and a second control group of naïve rats. Three rats in each group were then injected with excess oestrogen and progesterone for one week, and three of the remaining rats in each group were given sham injections, and the degree of decrement on REMG and AchR-ab titres were re-evaluated. Immune reactivity of peripheral lymphocytes and splenic lymphocytes from all groups and controls was also determined. A comparable number of animals with and without ovariectomy developed clinical and electromyographic EAMG. The extent of decrement on REMG and AChR-ab titres did not change following hormonal replacement. Lymphocyte reactivity was similar for rats with and without ovariectomy. In conclusion, sex hormones do not appear to have an influence on the susceptibility to and the severity of MG.

Animals↗
PubMed1999

Association of MS with thyroid disorders.

A controlled prospective study was conducted to determine whether thyroid disorders are present with increased frequency in patients with MS. We found that thyroid disorders were at least three times more common in women with MS than in female controls. This was accounted for mainly by the prevalence of hypothyroidism among the female MS patients. Because hypothyroidism is usually due to Hashimoto's thyroiditis, its association with MS may support the hypothesis of autoimmune pathogenesis for MS. Our findings might have therapeutic implications because interferon treatment can induce antithyroid antibodies and thyroiditis.

Adult↗
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↗
PubMed1999

HLA class II susceptibility to multiple sclerosis among Ashkenazi and non-Ashkenazi Jews.

OBJECTIVE: To look for HLA class II alleles and haplotypes conferring susceptibility to multiple sclerosis (MS) in the Jewish population of Israel. DESIGN: Population-based cohort of clinically definite patients with MS tested prospectively over 7 years. SETTING: Referral center in a neurology clinic at a university hospital in the greater Jerusalem area in Israel. PATIENTS: A total of 162 consecutive patients with clinically definite MS from the 2 main ethnic Jewish groups in Israel: 104 Ashkenazi (80 with a relapsing remitting or secondary progressive and 24 with a primary chronic progressive course of the disease) and 58 non-Ashkenazi (36 with a relapsing remitting or secondary progressive course and 22 with a primary chronic progressive course of the disease), matched with 132 Ashkenazi and 120 non-Ashkenazi healthy controls. MAIN OUTCOME MEASURES: The relationship between the various HLA class II alleles and haplotypes and MS, as defined by the polymerase chain reaction and sequence-specific oligonucleotide probe hybridization, among the Ashkenazi and the non-Ashkenazi Jewish sections and with respect to the different clinical courses of the disease. RESULTS: The haplotype DRB1*1501, DQA1*0102, DQB1*0602 was found to be associated with MS among both Ashkenazi and non-Ashkenazi patients (P<.001 and P =.04, respectively). Among the non-Ashkenazi patients, a new association of haplotypes DRB1*1303, DQA1*05, and DQB1*030 with MS was detected (P = .03). The MS susceptibility alleles, DRB 1* 1501, DQA1*0102, and DQB1*0602 , were found in association with the Ashkenazi patients (P<.001, P=.02, and P=.01, respectively); DRB1*1501 and DRB1*1303 were more frequently observed among the non-Ashkenazi patients (P = .03, P = .04, respectively). On subdivision of the patients into clinical subgroups, associations of DRB1*0801, DQA1*0102, DQA1*0401, and DQB1*0602 with primary chronic progressive MS among the Ashkenazi patients were evident (P = .03, P = .04, P = .04 and P = .05, respectively), whereas DRB1* 1501, DRB1*03011, and DQB1*0602 were associated with relapsing remitting or secondary progressive among the non-Ashkenazi patients (P = .05, P = .05, and P = .03, respectively). CONCLUSIONS: This study, unlike previous ones, is the first to show a significant association between HLA class II alleles and MS in the Jewish population. The association with the HLA-DR2-related haplotype is similar to that among non-Jewish white patients with MS. Moreover, our data support the possibility that DRB1*1501 is the susceptibility allele responsible for the association between this haplotype and MS in the Jewish population. Our study also underscores differences in HLA profiles between Ashkenazi and non-Ashkenazi patients, and between the different clinical courses of the disease. The latter may indicate that the clinical courses of MS are influenced by the genetic background.

Alleles↗
PubMed1999

Evidence for the genetic role of human leukocyte antigens in low frequency DRB1*1501 multiple sclerosis patients in Israel.

A strong association exists between multiple sclerosis (MS) and the DRB1*1501 haplotype, in most populations. Linkage of Multiple Sclerosis (MS) with the MHC or HLA region on chromosome 6p21 has previously been observed in DRB1*1501 positive MS families. A group of 13 Israeli multiplex MS families with a very low frequency of DRB1*1501 haplotype were examined in this study. Association and a linkage test were performed in order to identify a non-DRB1*1501 effect of HLA on susceptibility for MS. MS multiplex families and healthy controls were molecularly typed for six highly polymorphic markers located within the MHC region: DRB1, DQA1 and DQB1, BAT-2, MIB and D6S248. Data analyses included: (a) an association study comparing the patient group with both healthy relative, and healthy control groups (b) a transmission test for linkage disequilibrium (TDT) of the MS-associated alleles in the multiplex families, and (c) multipoint non-parametric linkage (NPL) and parametric LOD score analyses using the GENEHUNTER program. The DRB1*1303 allele was significantly more frequent among the MS patients. There was a trend towards transmission disequilibrium of DRB1*1303, but was not statistically significant. Allele sharing and LOD score analyses revealed no evidence for linkage. The high frequency of DRB1*1303 observed in our family patients provides evidence to support the association with this allele that previously described in sporadic non-Ashkenazi MS patients. Thus, DRB1*1303 may serve as genetic risk factor for MS. Our study exemplifies the genetic heterogeneity in MS as there is a genetic effect of HLA on MS susceptibility in our low frequency DRB1*1501 patients.

Alleles↗
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↗