Gait parameters in a reference sample of healthy Spanish schoolchildren: multivariate descriptive statistics and asymmetries observed in left and right cycles.

INTRODUCTION: Instrumental gait analysis is an emerging technology used increasingly to evaluate motor disorders in children. Normal reference data is necessary in order to evaluate patients, but there are few reference resources for the Spanish paediatric population. OBJECTIVE: We aim to describe the values of 16 clinically relevant gait variables in healthy Spanish schoolchildren, and identify any linear associations or left-right asymmetries. SUBJECTS AND METHODS: The values of 16 gait variables were determined in schoolchildren (n=27, aged 5-13 years) using instrumental gait analysis. We analysed asymmetries for each variable (Student's t-test for dependent samples) and calculated their confidence intervals (95% of the standardised difference in right and left means [SMD]). Values and associations between variables were represented using a heat map. RESULTS: Our project presents normal values tables for 16 variables in the gait cycle. Significant asymmetries were detected in the mean values for minimum hip flexion (SMD: 0.25 95% CI, 0.11-0.39) and peak hip abduction in swing (SMD: -1.05 95% CI: -1.71--0.27). Functional associations among gait variables are present. CONCLUSIONS: We present a reference dataset for Spanish school-aged children in which left-right asymmetries and functional associations may be observed for different variables.

[Pain and Achilles tendon shortening in patients with idiopathic toe walking]. / Dolor y acortamiento aquíleo en pacientes con marcha de puntillas idiopática.

INTRODUCTION: Idiopathic toe walking (ITW) is a heterogeneous disorder, which is associated with muscle shortening in lower limbs, pain and neurodevelopmental disorders. We try to study the frequency of clinical features in patients with ITW. PATIENTS AND METHODS: Out of 100 patients evaluated with toe walking in a pediatric rehabilitation clinic, 77 (24,7% women) patients were diagnosed with ITW by means of TWT questionnaire. Achilles' tendon shortening with Silfverskiold manoeuvre, pain and attention deficit hyperactivity disorder (ADHD) were studied. In the group of patients with pain (n = 30), we studied pain evolution by means of a telephonic interview which assessed intensity, location, school absenteeism and used therapies. RESULTS: Out of 77 patients, 44.2% had family history of toe walking. 37.7% and 9.1% showed Achilles' tendon shortening and Knee flexor shortening, respectively. Confirmed diagnosed of ADHD was present in 9.1% and was suspected in 20.8%. The older the patient was, the higher frequency of pain and the lower passive ankle dorsiflexion. Pain has a moderate-severe intensity, was related with school absenteeism in 42.3% of the patients with pain. Pain was located mainly on the calf, the ankle and the foot. It was treated with physiotherapy, oral pain relievers, orthosis and botulinum toxin type A (BTxA). CONCLUSIONS: Pain in ITW is frequent, have a moderate-severe intensity, interferes in normal life and is referred in older children with lower ankle dorsiflexion. We found a common association between ITW and ADHD which points out ITW as alarm sign of learning problems.

TITLE: Dolor y acortamiento aquíleo en pacientes con marcha de puntillas idiopática.Introducción. La marcha de puntillas idiopática (MPI) es una entidad heterogénea que asocia acortamientos musculares en las extremidades inferiores, dolor y trastornos del neurodesarrollo. Pretendemos estudiar la frecuencia de ciertas características clínicas en pacientes diagnosticados de MPI. Pacientes y métodos. De un total de 100 pacientes evaluados por marcha de puntillas en una consulta de rehabilitación infantil, se diagnosticó a 77 pacientes (24,7% mujeres) como con MPI con ayuda del cuestionario Toe Walking Tool. Mediante la maniobra de Silfverskiöld pudo determinarse el acortamiento aquíleo y mediante test adaptados también el dolor y la asociación con el trastorno por déficit de atención/hiperactividad (TDAH). En el grupo con dolor (n = 30), estudiamos su evolución mediante encuesta telefónica evaluando la intensidad, la localización, el absentismo escolar asociado y el tratamiento utilizado. Resultados. De los 77 pacientes, el 44,2% presentó antecedentes familiares de marcha de puntillas, el 37,7% tuvo acortamiento aquíleo y el 9,1%, de los flexores de la rodilla. El 9,1% de ellos tuvo TDAH confirmado y el 20,8%, sólo sospecha. A mayor edad, encontramos mayor frecuencia de dolor y menor ángulo de dorsiflexión pasiva del tobillo. El dolor fue de moderada-alta intensidad, produjo un 42,3% de absentismo escolar y se localizó predominantemente en la pantorrilla, el tobillo y el pie, y se prescribió fisioterapia, analgesia oral, ortesis y/o toxina botulínica principalmente. Conclusiones. El dolor en la MPI es frecuente, de intensidad moderada-alta, interfiere en la vida diaria y es más referido en niños más mayores que asocian menor dorsiflexión del tobillo. Encontramos asociación de la MPI y el TDAH con frecuencia, lo que anima a profundizar más su estudio como signo de alerta.

Glucocorticoid-mediated control of the activation and clonal deletion of peripheral T cells in vivo.

Poly- and oligoclonal T cell stimuli like anti-CD3 epsilon monoclonal antibody or Staphylococcus aureus enterotoxin B (SEB), injected at doses that per se are not lethal, provoke acute death within less than 24 h, provided that endogenous glucocorticoids (GC) are depleted by adrenalectomy or by injection of saturating amounts of the GC receptor antagonist RU-38486 (mifepristone). Pharmacological doses of the GC agonist dexamethasone (DEX) alter the in vivo response of splenic V beta 8+ T cells to SEB, thus impeding the expansion of such cells and causing their rapid (3 d) clonal deletion. In contrast, coadministration of RU-38486 counteracts a SEB-induced early (12 h) reduction of V beta 8+CD4+ and V beta 8+CD8+ spleen cells. In vivo T cell stimulation by injection of bacterial superantigen induces a rapid (peak at 90-120 min) increase in corticosterone serum levels, suggesting that endogenous GC might control early T cell activation. Accordingly, kinetic studies revealed that RU-38486 has to be administered within 2 h after superantigen administration to exert its lethal effect. Similarly, exogenous GC must be injected during this critical phase (2 h) to rescue animals from acute death induced by coinjection of SEB and D-galactosamine (GalN). Adrenalectomy, injection of RU-38486 and priming with GalN per se provoke the programmed death of peripheral CD4+ and CD8+ T cells. Thus, three manipulations that sensitize mice for the lethal effect of T cell stimulation also exert a proapoptotic effect on peripheral T cells. In synthesis, endogenous and exogenous GC regulate T cell responses and determine the propensity of peripheral T cells to undergo apoptosis.

Distinct expression and function of the novel mouse chemokine monocyte chemotactic protein-5 in lung allergic inflammation.

We have cloned a novel mouse CC chemokine cDNA from the lung during an allergic inflammatory reaction. The protein encoded by this cDNA is chemotactic for eosinophils, monocytes, and lymphocytes in vitro and in vivo. Based on its similarities in sequence and function with other CC chemokines, we have named it mouse monocyte chemotactic protein-5 (mMCP-5). Under noninflammatory conditions, expression of mMCP-5 in the lymph nodes and thymus is constitutive and is generally restricted to stromal cells. Neutralization of mMCP-5 protein with specific antibodies during an allergic inflammatory reaction in vivo resulted in a reduction in the number of eosinophils that accumulated in the lung. Moreover, mMCP-5 mRNA expression in vivo is regulated differently from that of other major CC chemokines in the lung during the allergic reaction, including Eotaxin. The presence of lymphocytes is essential for expression of mMCP-5 by alveolar macrophages and smooth muscle cells in the lung, and the induction of mMCP-5 RNA occurs earlier than that of the eosinophil chemokine Eotaxin during allergic inflammation. In contrast to Eotaxin, mRNA for mMCP-5 can be produced by mast cells. From these results, we postulate that mMCP-5 plays a pivotal role during the early stages of allergic lung inflammation.

The coordinated action of CC chemokines in the lung orchestrates allergic inflammation and airway hyperresponsiveness.

The complex pathophysiology of lung allergic inflammation and bronchial hyperresponsiveness (BHR) that characterize asthma is achieved by the regulated accumulation and activation of different leukocyte subsets in the lung. The development and maintenance of these processes correlate with the coordinated production of chemokines. Here, we have assessed the role that different chemokines play in lung allergic inflammation and BHR by blocking their activities in vivo. Our results show that blockage of each one of these chemokines reduces both lung leukocyte infiltration and BHR in a substantially different way. Thus, eotaxin neutralization reduces specifically BHR and lung eosinophilia transiently after each antigen exposure. Monocyte chemoattractant protein (MCP)-5 neutralization abolishes BHR not by affecting the accumulation of inflammatory leukocytes in the airways, but rather by altering the trafficking of the eosinophils and other leukocytes through the lung interstitium. Neutralization of RANTES (regulated upon activation, normal T cell expressed and secreted) receptor(s) with a receptor antagonist decreases significantly lymphocyte and eosinophil infiltration as well as mRNA expression of eotaxin and RANTES. In contrast, neutralization of one of the ligands for RANTES receptors, macrophage-inflammatory protein 1alpha, reduces only slightly lung eosinophilia and BHR. Finally, MCP-1 neutralization diminishes drastically BHR and inflammation, and this correlates with a pronounced decrease in monocyte- and lymphocyte-derived inflammatory mediators. These results suggest that different chemokines activate different cellular and molecular pathways that in a coordinated fashion contribute to the complex pathophysiology of asthma, and that their individual blockage results in intervention at different levels of these processes.

Leukocytosis and resistance to septic shock in intercellular adhesion molecule 1-deficient mice.

Intercellular adhesion molecule 1 (ICAM-1) is one of three immunoglobulin superfamily members that bind to the integrins lymphocyte function associated 1 (LFA-1) and Mac-1 on leukocytes. We have generated mice that are genetically and functionally deficient in ICAM-1. These mice have elevated numbers of circulating neutrophils and lymphocytes, as well as diminished allogeneic T cell responses and delayed type hypersensitivity. Mutant mice are resistant to lethal effects of high doses of endotoxin (lipopolysaccharide [LPS]), and this correlates with a significant decrease in neutrophil infiltration in the liver. Production of inflammatory cytokines such as tumor necrosis factor alpha or interleukin 1 is normal in ICAM-1-deficient mice, and thus protection appears to be related to a diminution in critical leukocyte-endothelial interactions. After sensitization with D-galactosamine (D-Gal), ICAM-1-deficient mice are resistant to the lethal effect of low doses of exotoxin (Staphylococcus aureus enterotoxin B [SEB]), which has been shown to mediate its toxic effects via the activation of specific T cells. In this model, ICAM-1-mediated protection against SEB lethality correlates with a decrease in the systemic release of inflammatory cytokines, as well as with prevention of extensive hepatocyte necrosis and hemorrhage. ICAM-1-deficient mice sensitized with D-Gal, however, are not protected from lethality when challenged with low doses of endotoxin (LPS). These studies show that the different contribution of ICAM-1 in the activation of either T cells or macrophages is decisive for the fatal outcome of the shock in these two models. This work suggests that anti-ICAM-1 therapy may be beneficial in both gram-positive and -negative septic shock, either by reducing T cell activation or by diminishing neutrophil infiltration.

Intercellular adhesion molecule-1 deficiency prolongs survival and protects against the development of pulmonary inflammation during murine lupus.

One of the characteristic features of the lupus syndrome in humans and mice is the organ-specific accumulation of leukocytes within a variety of different tissues; however, the etiology of this phenomenon remains unclear. The work presented here determined the role of intercellular adhesion molecule (ICAM)-1 in the development of pulmonary leukocyte accumulation by generating MRL/MpJ-Faslpr mice that are genetically deficient in this critical adhesion molecule. Interestingly, these MRL/MpJ-Faslpr ICAM-1 knockout mice exhibit prolonged survival times compared to littermates expressing ICAM-1. We have determined that lack of ICAM-1 completely abrogates the development of pulmonary inflammation but does not prevent the development of autoantibodies, lymphadenopathy, and glomerulonephritis. Furthermore, the lack of pulmonary inflammation was found to be due to decreased migration of leukocytes to the lung rather than decreased in situ proliferation of cells.

Eosinophil recruitment to the lung in a murine model of allergic inflammation. The role of T cells, chemokines, and adhesion receptors.

Eosinophil accumulation is a distinctive feature of lung allergic inflammation. Here, we have used a mouse model of OVA (ovalbumin)-induced pulmonary eosinophilia to study the cellular and molecular mechanisms for this selective recruitment of eosinophils to the airways. In this model there was an early accumulation of infiltrating monocytes/macrophages in the lung during the OVA treatment, whereas the increase in infiltrating T-lymphocytes paralleled the accumulation of eosinophils. The kinetics of accumulation of these three leukocyte subtypes correlated with the levels of mRNA expression of the chemokines monocyte chemotactic peptide-1/JE, eotaxin, and RANTES (regulated upon activation in normal T cells expressed and secreted), suggesting their involvement in the recruitment of these leukocytes. Furthermore, blockade of eotaxin with specific antibodies in vivo reduced the accumulation of eosinophils in the lung in response to OVA by half. Mature CD4+ T-lymphocytes were absolutely required for OVA-induced eosinophil accumulation since lung eosinophilia was prevented in CD4+-deficient mice. However, these cells were neither the main producers of the major eosinophilic chemokines eotaxin, RANTES, or MIP-1alpha, nor did they regulate the expression of these chemokines. Rather, the presence of CD4+ T cells was necessary for enhancement of VCAM-1 (vascular cell adhesion molecule-1) expression in the lung during allergic inflammation induced by the OVA treatment. In support of this, mice genetically deficient for VCAM-1 and intercellular adhesion molecule-1 failed to develop pulmonary eosinophilia. Selective eosinophilic recruitment during lung allergic inflammation results from a sequential accumulation of certain leukocyte types, particularly T cells, and relies on the presence of both eosinophilic chemoattractants and adhesion receptors.

Cloning of the human eosinophil chemoattractant, eotaxin. Expression, receptor binding, and functional properties suggest a mechanism for the selective recruitment of eosinophils.

The CC chemokine eotaxin, identified in guinea pigs and also recently in mice, may be a key element for the selective recruitment of eosinophils to certain inflamed tissues. Using a partial mouse eotaxin CDNA probe, the human eotaxin gene was cloned and found to be 61.8 and 63.2% identical at the amino acid level to guinea pig and mouse eotaxin. Human eotaxin protein was a strong and specific eosinophil chemoattractant in vitro and was an effective eosinophil chemoattractant when injected into the skin of a rhesus monkey. Radiolabeled eotaxin was used to identify a high affinity receptor on eosinophils (0.52 nM Kd), expressed at 4.8 x 10(4) sites per cell. This receptor also bound RANTES and monocyte chemotactic protein-3 with lower affinity, but not macrophage inflammatory protein-1 alpha. Eotaxin could desensitize calcium responses of eosinophils to RANTES and monocyte chemotactic protein-3, although RANTES was able to only partially desensitize eosinophil calcium responses to eotaxin. Immunohistochemistry on human nasal polyp with antieotaxin mAbs showed that certain leukocytes as well as respiratory epithelium were intensely immunoreactive, and eosinophil infiltration occurred at sites of eotaxin upregulation. Thus eotaxin in humans is a potent and selective eosinophil chemoattractant that is expressed by a variety cell types in certain inflammatory conditions.

Dolor y acortamiento aquíleo en pacientes con marcha de puntillas idiopática / Pain and Achilles tendon shortening in patients with idiopathic toe walking

Introducción: La marcha de puntillas idiopática (MPI) es una entidad heterogénea que asocia acortamientos musculares en las extremidades inferiores, dolor y trastornos del neurodesarrollo. Pretendemos estudiar la frecuencia de ciertas características clínicas en pacientes diagnosticados de MPI. Pacientes y métodos: De un total de 100 pacientes evaluados por marcha de puntillas en una consulta de rehabilitación infantil, se diagnosticó a 77 pacientes (24,7% mujeres) como con MPI con ayuda del cuestionario Toe Walking Tool. Mediante la maniobra de Silfverskiöld pudo determinarse el acortamiento aquíleo y mediante test adaptados también el dolor y la asociación con el trastorno por déficit de atención/hiperactividad (TDAH). En el grupo con dolor (n = 30), estudiamos su evolución mediante encuesta telefónica evaluando la intensidad, la localización, el absentismo escolar asociado y el tratamiento utilizado. Resultados: De los 77 pacientes, el 44,2% presentó antecedentes familiares de marcha de puntillas, el 37,7% tuvo acortamiento aquíleo y el 9,1%, de los flexores de la rodilla. El 9,1% de ellos tuvo TDAH confirmado y el 20,8%, sólo sospecha. A mayor edad, encontramos mayor frecuencia de dolor y menor ángulo de dorsiflexión pasiva del tobillo. El dolor fue de moderada-alta intensidad, produjo un 42,3% de absentismo escolar y se localizó predominantemente en la pantorrilla, el tobillo y el pie, y se prescribió fisioterapia, analgesia oral, ortesis y/o toxina botulínica principalmente. Conclusiones: El dolor en la MPI es frecuente, de intensidad moderada-alta, interfiere en la vida diaria y es más referido en niños más mayores que asocian menor dorsiflexión del tobillo. Encontramos asociación de la MPI y el TDAH con frecuencia, lo que anima a profundizar más su estudio como signo de alerta.(AU)

Introduction: Idiopathic toe walking (ITW) is a heterogeneous disorder, which is associated with muscle shortening in lower limbs, pain and neurodevelopmental disorders. We try to study the frequency of clinical features in patients with ITW. Patients and methods: Out of 100 patients evaluated with toe walking in a pediatric rehabilitation clinic, 77 (24,7% women) patients were diagnosed with ITW by means of TWT questionnaire. Achilles’ tendon shortening with Silfverskiöld manoeuvre, pain and attention deficit hyperactivity disorder (ADHD) were studied. In the group of patients with pain (n = 30), we studied pain evolution by means of a telephonic interview which assessed intensity, location, school absenteeism and used therapies. Results: Out of 77 patients, 44.2% had family history of toe walking. 37.7% and 9.1% showed Achilles’ tendon shortening and Knee flexor shortening, respectively. Confirmed diagnosed of ADHD was present in 9.1% and was suspected in 20.8%. The older the patient was, the higher frequency of pain and the lower passive ankle dorsiflexion. Pain has a moderate-severe intensity, was related with school absenteeism in 42.3% of the patients with pain. Pain was located mainly on the calf, the ankle and the foot. It was treated with physiotherapy, oral pain relievers, orthosis and botulinum toxin type A (BTxA). Conclusions: Pain in ITW is frequent, have a moderate-severe intensity, interferes in normal life and is referred in older children with lower ankle dorsiflexion. We found a common association between ITW and ADHD which points out ITW as alarm sign of learning problems.(AU)

Immunoregulation by cytokines.

The study of cytokine biology relevant to the in vivo (patho)physiology of the immune response is complicated by a series of features inherent to the cytokine system. The present survey focuses on the mechanisms governing the function of cytokines that may give rise to methodological and conceptual problems concerning in vivo manipulations of immunologically relevant cytokines. Special emphasis is laid on the complex interrelation between individual cytokines (cascades, synergy, anergy, pleiotropism, and redundancy), as well as on the mechanisms that guarantee a compartmentalization of cytokines, i.e., a chronological, spatial, cell-type differentiation stage, and activation-dependent restriction of their function. The in vivo effects of cytokines can be studied either by augmenting their concentration or reducing their bioavailability. The advantages of local and systemic cytokine injections, usage of transgenes, or expression as gene products encoded by recombinant viruses are discussed and contrasted with different manipulations provoking cytokine deficiencies, namely the application of cytokine antagonists, neutralizing antibodies and receptor derivates, receptor-targeted cytotoxic drugs, and germ line disruption of cytokine genes. Both types of intervention are afflicted with major problems. Whereas providing an excess of cytokines in vivo, especially at the systemic level, constitutes an essentially non-physiological intervention, the induction of cytokine deficiencies will only unravel essential effects, but is incapable of elucidating the many pleiotropic cytokine effects that, by virtue of the redundancy of the system, compensate for each other.

The Bispectral Index Scale: its use in the detection of brain death.

OBJECTIVE: To evaluate the Bispectral Index Scale (BIS) monitor as a method of brain death (BD) detection. PATIENTS AND METHODS: We performed an observational prospective study in an intensive care unit (ICU) of a university hospital of 19 patients hospitalized nonconsecutively in the ICU with serious neurologic pathology and evolution toward BD. A BIS monitor, XP model, and the sensor "BIS Quatro" were used to continuously record values: suppression ratio (SR), quality of the signal index, and electromyographic (EMG) activity. RESULTS: The BD diagnosis was made through neurological clinical exploration and electroencephalogram (EEG) in all the cases. Additionally, transcranial Doppler was used in 13 patients. Coincident with clinical worsening, it was observed that there was a gradual decrease of the BIS value, together with a rise in the SR. In all the patients in which the BD diagnosis was confirmed, the BIS showed values of 0 and suppression rates of 100. Only one patient showed interferences, due to EMG activity, the same problem was detected when a conventional EEG was performing. After using a neuromuscular blocker, the values of BIS and SR were 0 and 100, respectively. CONCLUSIONS: The BIS is a noninvasive, simple, and easy to interpret method. All the patients with BD diagnosis except for one had a BIS value of 0 and TS of 100, showing a perfect correlation with the other diagnostic methods. The BIS cannot be used on its own for the confirmation of the BD, but it is a useful tool to detect the beginning of brain herniation.

Dynamic scaling in diluted systems: deactivation through thermal dilution.

Activated scaling is confirmed to hold in transverse field-induced phase transitions of randomly diluted Ising systems. Quantum Monte Carlo calculations have been made not just at the percolation threshold (pc) but also well below and above it. We follow the evolution of the activated scaling at zero temperature in the phase transition from ferromagnetic to quantum Griffiths phase (p>pc) at the phase boundary (p=pc) and for transitions inside the nonferromagnetic quantum Griffiths phase (p

[Diagnosis of brain death by multislice CT scan: angioCT scan and brain perfusion]. / Diagnóstico de muerte encefálica mediante tomografía computarizada multicorte: angio-TC y perfusión cerebral.

BD was diagnosed by clinical examination, electroencephalogram (EEG), Transcranial Doppler (TCD) and multislice CT of 64 detectors. Initially, a brain perfusion study was performed. This was followed by supra-aortic trunk and brain artery angiography with acquisition of images using 0.5 mm slices, from the origin of the aortic root to the vertex. In all the patients, BD diagnosis was verified by clinical examination, EEG and TCD. Brain perfusion never detected brain blood flow. The angioCT through internal carotid arteries and vertebral arteries demonstrated complete absence of intracranial circulation, observing circulation of the external carotid artery branches. Sensitivity and specificity of the method compared with clinical examination was 100%. These findings demonstrate that the study of brain perfusion and brain angiography by multislice CT scan is a rapid and minimally invasive technique, that is easily available and that shows the absence of brain blood flow through the four vascular trunks. This technique makes it possible to made the diagnosis of BD with high diagnostic safety. Its use has special interest in patients with clinical diagnostic difficulty due to treatment with sedative drugs and serious metabolic alterations.

Self-averaging of random and thermally disordered diluted Ising systems.

Self-averaging of singular thermodynamic quantities at criticality for randomly and thermally diluted three-dimensional Ising systems has been studied by the Monte Carlo approach. Substantially improved self-averaging is obtained for critically clustered (critically thermally diluted) vacancy distributions in comparison with the observed self-averaging for purely random diluted distributions. Critically thermal dilution, leading to maximum relative self-averaging, corresponds to the case when the characteristic vacancy ordering temperature (theta) is made equal to the magnetic critical temperature for the pure three-dimensional (3D) Ising systems (T(3D)(c)). For the case of a high ordering temperature (theta>>T(3D)(c)), the self-averaging obtained is comparable to that in a randomly diluted system.

Staphylococcal enterotoxin B promotes deletion and functional inactivation of CD4V beta 8-positive cells in the absence of CD8 T cells.

The staphylococcal enterotoxins stimulate discrete subsets of T cells depending on their expression of particular V genes. Among these, staphylococcal enterotoxin B (SEB) vigorously stimulates V beta 8+ cells. This stimulation results in proliferation of both CD4+V beta 8+ and CD8+ T cells and eventually to anergy and clonal deletion in the former subset. We have examined the possible role of CD8+ T cells in the response of CD4+ cells to SEB, by in vivo CD8+ T-cell-depletion. We found no qualitative difference in the responses of untreated and CD8+ T-cell depleted mice to SEB; however, a small quantitative difference in deletion was observed. Thus it appears that on the whole the response of CD4+V beta 8+ T cells to SEB is independent of CD8+ T-cell effector function, although the latter may play a partial role.

Dissociation of autoaggression and self-superantigen reactivity.

Self-superantigens have been described as products of endogenous retroviruses of the mouse ('minor lymphocyte stimulating loci') that are capable of interacting without prior processing with conserved domains of TCR V beta chains, causing the activation and deletion of most T cells expressing products of determined V beta gene families [1-4]. The fact that superantigens activate a far higher percentage of T cells (1-20%) than conventional, peptidic antigens (< 0.1%) provides the methodological advantage that the degree of clonal deletion may be measured by the analysis of the TCR repertoire using appropriate anti-V beta antibodies. Although much information on the spatio-temporal organization of repertoire-purging has been gathered by virtue of self-superantigens, serious doubts exist as to the possibility that such structures serve as pathogenetically relevant autoantigens. Thus, certain inbred mice spontaneously develop autoimmune diseases, although they bear T-cell repertoires that appear to be purged from self-superantigen-reactive V beta products. In addition, therapeutic interventions targeted to V beta gene products that are not specific for self-superantigens are successful in preventing disease development. The lack of correlation between superantigen-related V beta deletions and autoimmune disease development is substantiated in further models of murine autoimmunity. Based on these observations, we formulate the hypothesis that self-superantigen-reactive T cells are not involved in the development of autoimmune diseases.