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.     

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.     

Expression of dentin sialoprotein (DSP) and other molecular determinants by a new cell line from dental papillae, MDPC-23

The purpose of this study was to characterize the molecular expression of a spontaneously immortalized and cloned cell line (MDPC-23) derived from 18-19 day CD-I fetal mouse molar dental papillae to determine if these cells were odontoblast-like. Western blots showed that a protein band, at approximately 105 kDa, reacting positively with anti-DSP antibodies and co-migrating with mouse DSP, was present in lysates of cells from passages 7, 37 and 77, in serum-free conditioned medium from passage 37 cells, and in mouse dentin extract. A minor band at 55 kDa was also apparent in cell lysates. Using a cDNA probe for a 486bp mouse DSP coding sequence, DSP or DSP-PP mRNA expression was detected by Northern analysis as well as Southern analysis after RT-PCR in all three passages. It was also shown that in these cells 1,25 (OH)2 vitamin D3 upregulated both osteopontin and osteocalcin mRNA, and dexamethasone downregulated alkaline phosphatase and alpha2(I) collagen mRNA. Thus, MDPC-23 cells express proteins which are common to mineralizing tissue. The expression of DSP and DSP-PP strongly suggests that this cell line is from the odontoblast lineage.     

Exhaled breath condensate isoprostanes are elevated in patients with acute lung injury or ARDS

BACKGROUND: Oxidant stress is a purported mechanism of tissue damage in patients with ARDS and acute lung injury (ALI). Isoprostanes, prostanoid compounds primarily formed nonenzymatically via lipid peroxidation, are precise markers of in vivo oxidant stress. Plasma levels of metabolites of 8-iso-prostaglandin-F2alpha (8-iso-PGF2alpha) correlate with outcome in patients with ARDS. OBJECTIVE: To examine exhaled breath condensate levels of 8-iso-PGF2alpha as a noninvasive quantification of pulmonary oxidant stress in patients with, or at risk for, ARDS/ALI. METHODS: Breath condensate was collected from 22 patients with, or at risk for, ARDS/ALI by placing Tygon tubing submerged in an ice bath in line with the expiratory limb of the ventilator circuit. Ten patients without lung disease, who were intubated while undergoing minor surgical procedures, served as control subjects. Between 1 and 3 mL of condensate was collected over a 30- to 60-min period, then immediately frozen and stored at -70 degrees C until analysis. The 8-iso-PGF2alpha was purified and derivatized, then quantified by stable isotope dilution in conjunction with gas chromatography/mass spectrometry. RESULTS: The mean level of exhaled 8-iso-PGF2alpha in the patients with ALI/ARDS, 87+/-28 pg/mL, was significantly higher than the mean in the normal group, 7+/-4 pg/mL (p = 0.007). The 8-iso-PGF2alpha levels were greater than two standard deviations above the mean of the normal group in 12 of 22 patients with or at risk for ARDS/ALI. CONCLUSIONS: These results provide further evidence that lipid peroxidation does occur in patients with ARDS/ALI. The measurement of exhaled isoprostanes provides a novel, noninvasive method to quantify oxidant stress in such patients.     

Dysrhythmia update. Case study: analysis of dual chamber rate responsive pacing in atrial fibrillation

This article presents a case study of a patient who required a dual chamber rate responsive pacemaker to assist in managing atrial fibrillation. The patient developed significant bradycardia when treated with the dose of propafenone required to convert atrial fibrillation, so the pacemaker was inserted. An example of a paced rhythm is presented and a differential diagnosis approach is used to discuss the possible interpretations of the rhythm. A brief explanation of the actual cause of the observed paced rhythm is presented.