Mature T cell reactivity altered by peptide agonist that induces positive selection

Recent studies have investigated how defined peptides influence T cell development. Using a T cell receptor-transgenic beta2-microglobulin-deficient model, we have examined T cell maturation in fetal thymic organ cultures in the presence of various peptides containing single-alanine substitutions of the strong peptide agonist, p33. Cocultivation with the peptide A4Y, which contains an altered T cell contact residue, resulted in efficient positive selection. Several in vitro assays demonstrated that A4Y was a moderate agonist relative to p33. Although A4Y promoted positive selection over a wide concentration range, high doses of this peptide could not induce clonal deletion. Thymocytes maturing in the presence of A4Y were no longer able to respond to A4Y, but could proliferate against p33. These studies demonstrate that (a) peptides that induce efficient positive selection at high concentrations are not exclusively antagonists; (b) some agonists do not promote clonal deletion; (c) positive selection requires a unique T cell receptor-peptide-major histocompatibility complex interaction; and (d) interactions with selecting peptides during T cell ontogeny may define the functional reactivity of mature T cells.     

Lidocaine-induced CNS toxicity--a case report

One hundred and twenty-six cases of cerebellopontine angle tumors with various histologies are presented. Results of 75 operated vestibular neurinomas, 22 meningiomas, and 16 tumors with other histologies are discussed. The method of irradiation and non-radical surgery may be an alternative for treatment.     

Changes in neural modulation and motor control during voluntary movement of older individuals

BACKGROUND: Changes in the modulation of soleus alpha motoneuron excitability, as assessed by H reflexes, and temporal sequencing of the soleus and tibialis anterior muscles during voluntary ankle dorsiflexions and plantar flexions of young (24.7 +/- 11.5; n = 13) and older (68.7 +/- 5.4; n = 13) subjects were assessed to determine potential neural mechanisms that might contribute to motor control changes associated with aging. METHODS: A repetitive stimulation (5 Hz) soleus H-reflex testing protocol and surface electromyography (EMG) were used to assess the latencies of soleus H-reflex changes in relation to tibialis anterior and soleus EMG activations of standing subjects during voluntary ankle dorsiflexions and plantar flexions at self-selected speeds. The pattern and latency of H-reflex changes in relation to EMG activity were compared between young and old subjects. RESULTS: There were no differences in the relative amount of antagonist muscle (soleus) inhibition during voluntary ankle dorsiflexions between young and old subjects (26.4% and 27.2% decrease from resting H-reflex values, respectively). Older subjects, however, required additional time to achieve these levels of inhibition. Delays in the activation of soleus H reflexes during the plantar flexion task were also observed in older subjects. Older subjects also had considerable intra- and intersubject variability in muscle temporal sequencing patterns during ankle plantar flexions. CONCLUSIONS: Although older subjects exhibited similar relative levels of alpha motoneuron inhibition and excitation during voluntary movements, this modulation was delayed when compared to younger subjects. Temporal sequencing of distal muscle activations also appears to undergo change with aging.     

Late-onset rheumatoid arthritis: is pitting oedema of the hands at onset a good prognostic indicator?

Selectin and alpha 4 beta 7-integrins have been shown to mediate transient leucocyte interactions with endothelial cells which is a crucial step in the initial immune response to pathogens. We have previously shown that stimulation of T lymphocytes via L-selectin results in activation of a signalling cascade from the L-selectin molecule via the tyrosine kinase p56lck and tyrosine phosphorylation of L-selectin to the stimulation of p21Ras and Rac proteins. In the present study we demonstrate that stimulation of Jurkat T lymphocytes via L-selectin results in an activation of Jun N-terminal kinase (JNK) but not of p38-K. L-selectin-initiated activation of JNK is mediated by src-like tyrosine kinases and the small G-protein Rac 1/2, since genetic or pharmacological inhibition of p56lck or Rac proteins prevent the stimulation of JNK by L-selectin. Thus, the data point to a novel signalling cascade from L-selectin via src-like tyrosine kinases and Rac proteins to JNK.     

Comparison of commercial slide agglutination kits with a tube coagulase test for the rapid identification of Staphylococcus aureus from blood culture

Eighty clinical specimens of BACTEC 9240 blood culture vials, culture positive for staphylococci (38 Staphylococcus aureus and 42 coagulase negative staphylococci), were tested directly for the presence of clumping factor/protein A and free coagulase. Seven commercial slide agglutination kits were compared with a direct-tube coagulase (DTC) method. All tests were performed on blood culture pellets. Sensitivity, specificity, and negative and positive predictive values for the seven commercial kits were extremely variable, whereas a two-hour DTC test was highly predictive of S aureus. There was no significant difference between a two-, six- or 24-hour DTC test. Three (8%) S aureus isolates remained DTC negative even after 24 hours' incubation. Staphylococcal slide agglutination kits should not be used directly on blood culture broths. In contrast, a two-hour DTC test is a useful, rapid screening test for S aureus bacteraemia, provided isolates from DTC negative blood culture broths are re-tested using standard laboratory techniques.     

Defects at center P underlie diabetes-associated mitochondrial dysfunction

Detailed respiration studies on isolated liver mitochondria from streptozotocin-induced diabetic Sprague-Dawley rats revealed a disease-associated decrease in the ADP/O ratio, a marker for mitochondrial ability to couple the consumption of oxygen to the phosphorylation of ADP. This decrease was observed following induction of respiration with glutamate/malate, succinate, or duroquinol, which enter the electron transport chain selectively at complexes I (NADH dehydrogenase), II (succinate dehydrogenase), or III (cytochrome bc1 complex), respectively. These data, coupled with studies using respiratory inhibitors (most importantly antimycin A and myxothiazol), localize at least a portion of this defect to a single site within the electron transport chain (center P in the Q-cycle portion of complex III). These results suggest that liver mitochondria from diabetic animals may generate increased levels of reactive oxygen species at the portion of the electron transport chain already established as the major site of mitochondrial free radical generation. The reduction in the ADP/O ratio occurred in mitochondria that do not have overt defects in the respiratory control ratio or in State 3 and State 4 respiration. The data in this paper suggest that defects in center P of the electron transport chain likely increase mitochondrial exposure to oxidants in the diabetic. This data may partially explain the evidence of altered exposure and/or response to reactive species in mitochondria from diabetics. This work thus provides further clues to the interaction between oxidative stress and diabetes-associated mitochondrial dysfunction.     

Structural studies of EcoRII methylase: exploring similarities among methylases

EcoRII methyltransferase (M.EcoRII) is a cytosine-C5 DNA methylating enzyme. A model of its three-dimensional structure is proposed on the basis of homology modeling. Crystal structures of two members of the same family of enzymes, HaeIII and HhaI methyltransferases (M.HaeIII and M.HhaI respectively), were used as template molecules. Molecular dynamics was used to ensure sampling of conformationally stable structures. The final model has good geometry. The DNA and cofactor binding residues are in expected positions and form proper interactions. M.EcoRII is 147 amino acids longer than the template molecules, and hence the model contains several loops that are significantly longer than those in M.HaeIII and M.HhaI. The model provides a framework for interpretation and designing site-directed mutants that have a potential to improve crystallization experiments of this enzyme, and possibly other similar enzymes.     

A case report: cephalic replacement and emergency caesarean section for the resolution of shoulder dystocia

Shoulder dystocia is a serious complication of delivery. Various manoeuvres had been described, all aim at achieving shoulder descent and vaginal delivery. We report a case whereby shoulder dystocia was managed by a rather unique technique--the foetal head was replaced in the vagina and baby delivered by emergency Caesarean Section.