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Staphylococcal enterotoxins (SEs) are known superantigens for T cells expressing the alpha beta T-cell receptor (TCR). They bind to MHC class II molecules on antigen-presenting cells and can subsequently trigger T-cell responses by binding to V beta-gene products. The reactivity of gamma delta T cells with enterotoxins is less well defined although both proliferative and cytotoxic responses have been described. In the present study we have tested the cytotoxic reactivity of a panel of 41 gamma delta T-cell clones against target cells coated with the enterotoxins SEA, SEB, SEC1, SEC2, SEC3, SED, SEE or TSST. Three reaction patterns were observed with the gamma delta T-cell clones: (1) clones that specifically lysed SEA-coated target cells only; (2) clones that specifically lysed SEE-coated target cells only, and (3) clones that specifically lysed SEA-coated target cells only in the presence of certain human sera. The presence of SEA-specific antibodies in such human sera could be demonstrated. Moreover, gamma delta T-cell clones of this third category expressed the IgG FcRIII (CD16) which indicates that these clones are capable of mediating antibody-dependent cellular cytotoxicity towards SEA-coated target cells. Thus, the cytotoxic response of gamma delta T cells to SEs is mediated by two distinct pathways: an antibody-independent and an antibody-dependent pathway. The antibody-independent reactivity of gamma delta T cells was directed to either SEA or SEE, whereas antibody-dependent reactivity was found only towards SEA. The capacity of gamma delta T-cell clones to respond to stimulation with SEs, combined with their high cytolytic capacity in vitro, suggests that these cells can be involved in SE-directed immune responses and efficiently kill SE-coated target cells in vivo.

In a previous study we have shown that synovial fluid mononuclear cells from many rheumatoid arthritis (RA) patients exhibit an enhanced response to M. tuberculosis antigens as compared to peripheral blood mononuclear cells. The 65-kDa heat-shock protein of M. tuberculosis was shown not to play an important role in this response, therefore other mycobacterial proteins must be involved. In this study we have investigated the possibility that synovial fluid T cells from RA patients predominantly recognize a limited number of M. tuberculosis antigens, as a result of a lesion-specific activation of only those M. tuberculosis-reactive T cells that have cross-reacted with joint-related autoantigens. From the synovial fluid of four RA patients M. tuberculosis-reactive T cell clones were isolated and analyzed for their phenotype, HLA-DR restriction and proliferation to immunoblot fractions containing sodium dodecyl sulfate-polyacrylamide gel-separated M. tuberculosis proteins of known molecular weight range. The overall M. tuberculosis immunoblot recognition pattern of the clones was strikingly heterogeneous. Within a panel of 15 clones 12 different antigenic specificities could be distinguished. In other words, we did not observe a dominant recognition of a few M. tuberculosis antigens by synovial fluid T cells. This argues against the hypothesis that the elevated synovial T cell reactivity against M. tuberculosis is a reflection of an in vivo expansion of a limited number of different types of M. tuberculosis-reactive T cells as a result of a cross-reaction with putative joint autoantigens.

The aim of the study was to define a therapy to be combined with an immunosuppressive drug such as cyclosporin A, in order to partially reduce the nephrotoxic and hepatotoxic effects in the treated rats. Two drugs were considered: enalapril, which is an inhibitor of the angiotensin-converting enzyme, and spironolactone, which is an antagonist of aldosterone. These two drugs interrupt the renin-angiotensinogen-angiotensin chain after this has been activated by cyclosporin A, preventing peripheral vasoconstriction and more specifically the constriction of both glomerular arterioles and hepatic vessels from occurring, thus diminishing the cyclosporin A toxicity in both liver and kidney.

A pattern of correlative changes in lateralization in individuals with known or suspected brain injury recently has been advanced as the syndrome of pathological left-handedness (PLH). This syndrome, which is believed to be caused by an early left-sided cerebral lesion, may include asymmetric motor and/or trophic changes on the right side of a body part in addition to changes in higher-level cognitive processing abilities. Several clinical case studies have provided support for such a syndrome. Despite their clinical subject to inherent biases of selection. The present study was therefore designed to evaluate the PLH syndrome in a systematic fashion by using a large number of brain-injured and normal subjects. The incidence of each of the putative elements of the PLH syndrome was investigated. The results suggest that traits such as atypical cerebral speech representation, motor impairment of the nondominant hand, and hypoplasia of the right foot are salient features of the syndrome. The results are discussed with reference to clinical diagnostic implications.

Determinants of inter- and intrahemispheric organization following left focal injury were examined with data deriving from four different studies that used three different assessment methods (amobarbital, temporal lobectomy, dichotic listening). With regard to interhemispheric reorganization, the results revealed that the earlier the lesion onset, the higher the probability of a biomodal hemispheric reorganization (speech and hand). A unimodal reorganization (speech only) was tied to a later occurring lesion, but one before age six. Furthermore, interhemispheric speech reorganization was associated with an early lesion onset while intrahemispheric speech maintenance was linked to a later lesion onset. The results are discussed in terms of hemispheric plasticity and functional maturity.

Handedness within a sample of mentally retarded subjects was assessed using a procedure that includes a large number of items appropriate for lower functioning subjects, with multiple presentations within and between sessions one week apart. Results revealed a dramatic shift from the normal right-handed bias primarily due to the presence of a large mixed-handedness subtype, which proved to be ambiguously handed in that these subjects showed inconsistent hand preference within items. Reasons why this subtype has not been reported previously were discussed, and a model was postulated to explain the resultant handedness distribution in terms of probable central nervous system substrate.

To understand why there are so many inconsistencies and contradictory findings among hemispheric-asymmetry studies, data were analyzed from a large study of 300 left-handers. These data included information on familial sinistrality (FS), handwriting posture (HPO), a measure of cognitive performance, and five measures of hemispheric specialization. Using computer simulation methodology, 40 independent samples of 36 to 65 subjects each were drawn randomly with replacement. The sample data were analyzed and the results compared to those of the parent "population." Often, the samples poorly reflected the parent "population," and some procedures substantially inflated error rates. These procedures are discussed and specific guidelines suggested. These results are also discussed in the broader context of the necessity for investigators in neuropsychology to differentiate between the statistical and clinical significance of research findings; and to develop a more positive attitude toward the design, execution, and publication of replication studies.

The present study reports preliminary data from two unselected samples of carefully diagnosed autistic subjects (children and adults) and an assessment procedure that includes a large sample of items, appropriate for lower-functioning autistic subjects, with multiple presentations within and between sessions 1 week apart. The study seeks to determine (1) whether a raised incidence of non-right-handedness exists in these samples (2) if so, what constructs best represent this shift in the handedness distribution (i.e., phenotype and CNS substrate) and (3) whether these handedness phenotypes are associated with different levels of cognitive functioning. The results reveal a dramatic shift away from right-handedness in both autistic samples, due to a raised incidence of two phenotypes, manifest left-handedness and ambiguous handedness. The ambiguously handed, who were postulated to represent substantial bilateral CNS pathology due to early brain injury, were found to have much lower intellectual scores in one of the study samples.

The literature on the relationship between familial sinistrality (FS) and laterality is conflicting. A large scale investigation employing multiple measures of laterality assessment and rigorous methods of handedness and FS determination was conducted with a normal population of left- and right-handers. The results failed to find a relationship between FS and hemispheric representation of speech despite the fact that a robust relationship was found between handedness and hemispheric speech specialization. Possible reasons for these null findings are discussed.

The relationship between pedal asymmetries and handedness has been the subject of several investigations. Support for pedal asymmetries occurring in the normal population have been reported which are claimed to be a function of handedness and sex. If true, these asymmetries would confound the assessment of trophic changes due to localized brain injury. However, at least four attempts to replicate these results have failed. The present study was undertaken to reassess this hypothesis using more rigorous measurement of handedness and foot length with a more representative sample allowing for larger hand by sex groups than has been previously used. No differences in the direction of foot size were found regardless of hand or sex classification.

A clinical syndrome of pathological left-handedness (PLH) is proposed to identify the pattern of correlative changes in lateral development associated with early brain injury in some manifest left-handers. This syndrome is believed to be caused by a hemispheric lesion that is predominantly left-sided (or bilateral asymmetric), which onsets before Age 6, and which encroaches upon the critical speech zones of the frontotemporal/frontoparietal cortex. The pattern of changes may include any or all of the following features: shifts in manual dominance, trophic changes in the extremities, transfer of hemispheric speech, and/or intrahemispheric reorganization of visuospatial cognitive functions. Although some of these correlates of PLH have long been known, they have not been recognized as an interrelated pattern of traits that constitute a clinical syndrome. Identification of these individuals, all manifest left-handers, will be shown to have implications for diagnosis/remediation and for models of recovery of function.