Social status and nerve growth factor serum levels after agonistic encounters in mice

Ten repeated daily interactions (20 min each) of the same pairs of isolated male mice produced a clear distinction between attacking (dominant) and defeated (subordinate) animals. The fighting level remained fairly constant over the 10 days. One hr after the end of the 10th session, the increase in serum NGF levels described previously (2) was significantly more marked in subordinate than in dominant mice. The mean level of serum NGF was correlated with the number of fighting episodes, particularly in the case of dominant individuals. Moreover, within-pair differences in NGF values were correlated with differences in locomotor activity between dominants and subordinates; this makes it possible that stimuli other than those produced by fighting per se may be responsible for the increase in circulating NGF. As is well known, the adrenal hypertrophy produced by fighting stress is more marked in subordinate than in dominant mice, while previous work has shown that stress of a nonpsychosocial kind does not elevate serum NGF levels. Therefore, the present data support the hypothesis that NGF release contributes to the modulation of adrenal function in a situation-specific fashion.     

Peripheral blood mononuclear cell populations in men with "idiopathic" infertility with antisperm autoantibodies

Peripheral blood mononuclear cell populations in ten men, with idiopathic infertility with serum sperm agglutinating antibodies at a titre of 1/32, were evaluated. Mononuclear cells were enumerated using the monoclonal antibodies OKT3 (pan T cells), OKT4 (helper/inducer T cells), OKT8 (suppressor/cytotoxic T cells), Leu 7 (monocytes, null cells, and natural killer (NK) cells), OKIa (B cells, monocytes, null cells and activated T cells). Blood mononuclear cells with surface receptors for complement (B lymphocytes and a proportion of monocytes and null cells) were enumerated using a rosette test (EAC). The following abnormalities, compared to normal subjects, of blood mononuclear cell population were found: a decreased percentage of OKT3 (+) cells (p less than 0.01), a decreased percentage of OKT8 + cells (p less than 0.001) and increased OKT4/OKT8 ratio (p less than 0.001), an increased percentage of OKIAI cells (p less than 0.001). Levels of OKT4+ and Leu 7 cells and the percentage of EAC rosette forming cells were not significantly different from those in normal subjects. Regression analysis showed a significant correlation between the percentage of OKIAI cells and sperm agglutinating antibodies. After all that, significant correlation between humoral and cell-mediated immunity in patients with idiopathic infertility with antisperm autoantibodies, were observed.     

Immunochemical analysis of a cell transfected with an HLA-DR gene reveals a new alloantigenic specificity within HLA-DRw52

The HLA-DR antigen has been prepared from the surface of a mouse fibroblast cell line transfected with a single HLA-DR beta-chain gene as well as single HLA-DR alpha and invariant chain gene. Since the HLA-DR beta chain gene studied corresponds to the DR beta III locus, the DR serological specificities detected on the transformed cells can be assigned to this locus. The use of the HLA-DR-producing mouse cell line has led to the identification of a new serological specificity included within DRw52 and associated with some DR3, some DRw6 and all DR5 haplotypes studied. Most likely this new specificity corresponds to an allelic polymorphism at the DR beta III locus of DRw52 individuals and can serve as a new serological marker for this subset of DR3, DR5 and DRw6 haplotypes.     

Long-lasting protective effect of slow-release theophylline on asthma induced by ultrasonically nebulized distilled water

We investigated the intensity and duration of the effect of a single dose of slow-release theophylline on bronchial hyperresponsiveness to ultrasonically nebulized distilled water in asthma. In six subjects with a history of mild asthma, we measured airway responsiveness to ultrasonically nebulized distilled water and serum theophylline at 4, 8, and 12 hours after treatment with placebo or slow-release theophylline (10 +/- 1 mg/kg, orally). To assess bronchial responsiveness, dose-response curves were established by plotting the baseline value of FEV1 and the largest FEV1 after each doubling dose of nebulized distilled water against the dose of nebulized water. The degree of bronchoconstriction induced by ultrasonically nebulized distilled water was significantly inhibited at 4, 8, and 12 hours after treatment with theophylline, at serum levels of 14.8 +/- 4.6, 14.4 +/- 2.8, and 12.0 +/- 2.5 micrograms/mL theophylline (mean +/- SD). Tremor occurred in three patients and was associated with nausea, epigastric pain, and tachycardia in one of them. We conclude that a single dose of slow-release theophylline has a prolonged protective effect on bronchoconstriction induced by ultrasonically nebulized distilled water, but in some subjects is associated with side effects that limit its clinical usefulness.     

Equal suppression of cerebellar Purkinje cell activity by amphetamine stereoisomers

The two amphetamine isomers were compared for their ability to reduce spontaneous activity of noradrenoceptive Purkinje cells in the rat cerebellum. The drugs were applied iontophoretically to eliminate peripheral and remote central effects. Responses of Purkinje neurons were summed over several cycles of alternating (+)- and (?)-amphetamine, and poststimulus time histograms were compared. Inhibitions of Purkinje cell discharge by the two isomers were not statistically different over a wide range of pipette resistances. These data, taken together with studies showing equal effects of the two isomers on noradrenergic release and reuptake blockade and on locus coeruleus neuronal firing, indicate equipotency of the two isomers in their actions on noradrenergic mechanisms.     

Determination of body heat storage in clothing: calorimetry versus thermometry

Two methods of estimating body heat storage were compared under differing conditions of clothing, training, and acclimation to heat. Six male subjects underwent 8 weeks of physical training [60–80% of maximal aerobic power ( ) for 30–45 min · day–, 3–4 days · week^–1 at < 25 °C dry bulb (db)] followed by 6 consecutive days of heat acclimation (45–55% for 60 min · day^–1 at 40°C db, 30% relative humidity)]. Nine other male subjects underwent corresponding periods of control observation followed by heat acclimation. Before and after each treatment, subjects walked continuously on a treadmill (1.34 m · s^–1, 2% grade) in a climatic chamber (40°C db, 30% relative humidity) for an average of 118 min (range 92–120 min) when wearing normal light combat clothing and for an average of 50 min (range 32–68 min) when wearing protective clothing resistant to nuclear, biological, and chemical agents. The heat storage was determined calorimetrically (by the balance of heat gains and losses) and thermometrically [by the conventional equations, using one or two set(s) of relative weightings for the rectal temperature (T _re) to mean skin temperature _sk of 4:1 and 4:1, 2:1 and 4:1, or 2:1 and 9:1 in thermoneutral and hot environments, respectively]. _sk was calculated from 12-site measurements, weighted according to the regional distribution of body surface area and the first eigenvectors of principal component analysis. There were only minor differences (< 5%) between the heat storage values calculated by given weighting factors forT _re and _sk, whether the individual coefficients were derived from estimates of regional surface area or principal component methodologies. When wearing normal clothing, no significant differences were found between the two estimates of heat storage (calorimetry vs thermometry with an invariant relative weighting of 4:1) in any experimental condition, with one specific exception: when wearing protective clothing, thermometry underestimated the heat storage by 24–31%. This underestimation was attenuated by using two sets of relative weightings of 2: 1 and 4: 1 or 2: 1 and 9: 1. The results suggest that when subjects wearing protective clothing are transferred from thermoneutral to hot environments, the accuracy of thermometric estimates of heat storage can be improved by using two sets of weighting factors forT _re and _sk     

A quantitative study of the brainstem cholinergic projections to the ventral part of the oral pontine reticular nucleus (REM sleep induction site) in the cat

The ventral part of the cat oral pontine reticular nucleus (vRPO) is the site in which microinjections of small dose and volume of cholinergic agonists produce long-lasting rapid eye movement sleep with short latency. The present study determined the precise location and proportions of the cholinergic brainstem neuronal population that projects to the vRPO using a double-labeling method that combines the neuronal tracer horseradish peroxidase–wheat germ agglutinin with choline acetyltransferase immunocytochemistry in cats. Our results show that 88.9% of the double-labeled neurons in the brainstem were located, noticeably bilaterally, in the cholinergic structures of the pontine tegmentum. These neurons occupied not only the pedunculopontine and laterodorsal tegmental nuclei, which have been described to project to other pontine tegmentum structures, but also the locus ceruleus complex principally the locus ceruleus and peri-, and the parabrachial nuclei. Most double-labeled neurons were found in the pedunculopontine tegmental nucleus and locus ceruleus complex and, much less abundantly, in the laterodorsal tegmental nucleus and the parabrachial nuclei. The proportions of these neurons among all choline acetyltransferase positive neurons within each structure were highest in the locus ceruleus complex, followed in descending order by the pedunculopontine and laterodorsal tegmental nuclei and then, the parabrachial nuclei. The remaining 11.1% of double-labeled neurons were found bilaterally in other cholinergic brainstem structures: around the oculomotor, facial and masticatory nuclei, the caudal pontine tegmentum and the praepositus hypoglossi nucleus. The disperse origins of the cholinergic neurons projecting to the vRPO, in addition to the abundant noncholinergic afferents to this nucleus may indicate that cholinergic stimulation is not the only or even the most decisive event in the generation of REM sleep.     

High circulating levels of biologically inactive IL-6/SIL-6 receptor complexes in systemic juvenile idiopathic arthritis: evidence for serum factors interfering with the binding to gp130

We previously demonstrated that high levels of IL-6/sIL-6R complexes are present in sera of patients with systemic juvenile idiopathic arthritis (s-JIA) and that the amount of IL-6 estimated in the IL-6/sIL-6R complexes is markedly higher than that measured by the B9 assay. Here, we show that two additional bioassays, employing human myeloma XG-1 cells and human hepatoma Hep3B cells, detected serum IL-6 levels similar to those measured by the B9 assay and approximately 10-fold lower than the IL-6 levels estimated to be present in the IL-6/sIL-6R complex. Using an assay for the measurement of the amount of circulating IL-6 complexed with the sIL-6R and available for binding to gp130 (gp130 binding activity), we show that the IL-6/gp130 binding activity is similar to that detected by the bioassays and again significantly lower than that estimated to be present in the IL-6/sIL-6R complex. Addition of recombinant human IL-6 (rhIL-6) to sera of patients or controls results in a markedly lower increase in the gp130 binding activity in patients than in controls. Moreover, sera from s-JIA patients inhibited in a dose dependent manner the gp130 binding activity assay. These results show that sera from patients with s-JIA contain a factor, or factors, that inhibit(s) the binding of the IL-6/sIL-6R complex to gp130. This inhibitory activity does not appear to be due to soluble gp130, C-reactive protein or autoantibodies to IL-6.