Antagonistic effects of dexamethasone and 1,25-dihydroxyvitamin D3 on the synthesis of nerve growth factor.

Dexamethasone is known to decrease the pool of nerve growth factor (NGF) mRNA in various experimental systems. The negative regulatory effect of the glucocorticoid was first observed in mouse fibroblast-like L929 cells, and was subsequently reported to take place in many experimental systems, including in vivo following sciatic nerve injury. Conversely, another steroid hormone, 1,25-dihydroxy-vitamin D3 (1,25-(OH)2D3) was recently reported to promote NGF synthesis in mouse L929 cells. The present work was undertaken to investigate the effect of the concomitant addition of both steroids to L929 cells. Measurements of NGF mRNA and assays of the mature protein secreted by the cells provide evidence that the negative regulation exerted by dexamethasone may be counteracted in a dose-dependent manner by the positive action of 1,25-(OH)2D3, and vice versa. Therefore, the expression of the NGF gene can be regulated in a subtle way by the balance between the two steroids. It may be expected on the basis of these observations that in tissues that are responsive to both hormones, administration of 1,25-(OH)2D3 should be able to reverse the down-regulation of NGF synthesis elicited by glucocorticoids.     

Lymphocyte homing after left or right brain neocortex ablation

The cerebral neocortex is known to modulate the immune system in an asymmetrical way. Ablations of the left cortex decrease, whereas symmetrical right lesions have no effect, or enhance, T cell functions measured 6-8 weeks after lesioning. However, modifications of immune responses induced by lesions of the brain neocortex could result from a lymphocyte redistribution mediated by glucocorticoids, like that observed during stress. We tested this possibility in the present experiments. Cortical lesions modulated concanavalin A-induced proliferation of both lymph node and spleen lymphocytes in a similar way. Cortical lesions of either side modified neither the lymphocyte distribution of 51Cr-labelled injected lymph node cells, nor the percentage of blood cell subsets. These results show that cortical lesions do not affect lymphocyte homing, and suggest that the brain neocortex immunomodulatory effects are not mediated by glucocorticoids.     

Sex-dependent association between immune function and paw preference in two substrains of C3H mice

Asymmetry in brain modulation of the immune system has been previously described in mice. Paw preference is known to be associated with immune reactivity but the respective roles of sex and genetic background in this association remain to be elucidaded. In this work, made and female mice of the C3H/He and C3H/OuJIco substrains were selected as right- and left-handers. Mitogen-induced lymphoproliferation and natural killer cell activity were then tested. Left-handed female mice of both C3H substrains exhibited higher mitogenesis than right-handers but no association between paw preference and NK cell activity was found in females. Conversely, in males of both substrains, right-handers showed enhanced NK cell activity compared to left-handers but no association between paw preference and mitogenesis was observed in males. Only small differences in the strength, but not in the direction, of the association between paw preference and immune functions were observed between the two C3H substrains. These results show that the association between paw preference and immune reactivity in mice varies according to the immune parameters tested and is a sex-dependent phenomenon in which the genetic background may be involved.     

Association between left-handedness and allergy: a reappraisal

There are conflicting reports in the literature about the possible association between left-handedness and immune disorders, including autoimmune diseases as well as allergies. In this study we compared the distribution of right- and left-handers, assessed with the Edinburgh Handedness Inventory, in a group of patients consulting an allergy clinic and a control population with a similar sex and age distribution. There was no overall association between left-handedness and allergies, although we found a tendency towards left-handedness in patients whose allergic symptoms started before puberty, suggesting that left-handers may have an increased predisposition to allergic disease that manifests itself during early life.     

Time-course analysis of hepcidin, serum iron, and plasma cytokine levels in humans injected with LPS

Hepatic peptide hormone hepcidin is the key regulator of iron metabolism and the mediator of anemia of inflammation. Previous studies indicated that interleukin-6 (IL-6) mediates hepcidin increase and consequent hypoferremia during inflammation. Here we used an in vivo human endotoxemia model to analyze the effects of lipopolysaccharide (LPS) as a more upstream inflammation activator. The temporal associations between plasma cytokines, hepcidin levels, and serum iron parameters were studied in 10 healthy individuals after LPS injection. IL-6 was dramatically induced within 3 hours after injection, and urinary hepcidin peaked within 6 hours, followed by a significant decrease in serum iron. Serum prohepcidin showed no significant change within a 22-hour time frame. These in vivo human results confirm the importance of the IL-6-hepcidin axis in the development of hypoferremia in inflammation and highlight the rapid responsiveness of this iron regulatory system.     

Immune alterations induced by social defeat do not alter the course of an on-going BCG infection in mice

The timing for applying stressor and primary immunization is known to influence the nature of the immune alterations induced by stress. The aim of the present study was to investigate the consequences of a stress occurring several days after the beginning of a primary infection on the host resistance. For this purpose, we investigated the effects of repeated social defeat on the immune response of mice infected with BCG 11 days before. In vitro production of cytokines in response to LPS or tuberculin, and the sensitivity of spleen cells to corticosterone were assessed 8 days after the end of the stress. Bacterial growth was assessed in the spleen. We demonstrated that social defeat in BCG-infected mice induced a long-term increase in IL-6 and IL-10 production in response to LPS but did not modify the sensitivity of spleen cells to corticosterone. Stress did not affect the specific response to BCG, as shown by the production of cytokines in tuberculin-stimulated cultures. Accordingly, social defeat was unable to influence the mycobacterial growth in vivo. These results support the hypothesis postulating that stress does not affect antigen-specific response when it is applied after priming.     

Preterm neonates with nephrocalcinosis: natural course and renal function

The aim of the study was to evaluate the natural course of nephrocalcinosis (NC) in preterm neonates and the effect of NC on blood pressure and renal glomerular and tubular function. In a prospective observational study of 201 preterm neonates (gestational age <32 weeks) NC was present at term in 83 patients (41%), who were subsequently examined at 6, 12, and 24 months, and until August 2000 annually (with a maximum of 4 years) if NC persisted. Examination consisted of blood pressure measurement, renal ultrasonography, and glomerular and tubular function tests. The probability that NC, when present at term, would persist for 15 and 30 months was 34% [21–45, 95% confidence interval (CI)] and 15% (5–25, 95% CI) (Kaplan-Meier), respectively. Urinary tract infection did not occur more frequently in patients with NC (2.5%) than patients without NC at term (4.4%). Systolic and diastolic blood pressures above the 95th percentile were found in 39% and 48% of patients at 1 year and 30% and 34% at 2 years (P<0.001). Mean glomerular filtration rate (GFR) (inulin clearance) at 1 and 2 years was 92 and 102 ml/min per 1.73 m², respectively. TP/GFR and excretion of ₁-microglobulin were normal. The desmopressin test was impaired in 4 of 30 patients at 1 year and 2 of 25 at 2 years. It was concluded that while proximal tubular function is unaffected in children with neonatal NC, high blood pressure and impaired glomerular and distal tubular function might occur more frequently than in healthy children. Although no relationship can be proven between NC and hypertension or diminished renal function in this study, these results justify a large follow-up study with matched controlled study groups.     

Serial analysis of gene expression predicts structural differences in hippocampus of long attack latency and short attack latency mice

The genetically selected long attack latency (LAL) and short attack latency (SAL) mice differ in a wide variety of behavioural traits and display differences in the serotonergic system and the hypothalamus-pituitary-adrenocortical (HPA)-axis. Serial analysis of gene expression (SAGE) was used to generate a hippocampal expression profile of almost 30 000 genes in LAL and SAL mice. Using SAGE, we found differential expression of 191 genes. Among these were genes involved in growth, signal transduction, and cell metabolism. The SAGE study was supported by GeneChip analysis (Affymetrix). Strikingly, both SAGE and GeneChips showed a higher expression of numerous cytoskeleton genes, such as cofilin and several tubulin isotypes in LAL mice. LAL mice also showed a higher expression of several calmodulin-related genes and genes encoding components of a MAPK cascade, namely raf-related oncogene and ERK2. The findings were confirmed by in situ hybridization. Our results of differential expression of cytoskeleton and signal transduction genes therefore suggest differential regulation of the raf/ERK pathway that may be related to structural differences in the hippocampus of LAL and SAL mice. As stress-related disorders, such as depression, are also linked to differential regulation of the HPA-axis and the serotonergic system and are associated with altered hippocampal morphology, differential regulation of these genes may be involved in the pathogenesis of these diseases.     

Electrophysiological and psychophysical differences between early- and late-onset strabismic amblyopia

PURPOSE: To compare visual evoked potentials (VEPs) and contrast sensitivity in adults with early- or late-onset strabismic amblyopia. METHODS: Twelve adults with early- and 12 with late-onset strabismic amblyopia with similar ranges of visual acuity were studied. Pattern-onset VEPs to 30-minute checks were recorded at a range of contrast levels. Contrast sensitivity (CS) was measured at 3.2 cyc/deg using a two-alternative, forced-choice staircase method. RESULTS: There was no significant difference in VEP CII latency or amplitude between amblyopic and fellow eyes across all contrast levels for the early-onset group, but in the late-onset group, CII latencies were significantly longer and amplitudes smaller in the amblyopic eye. CII responses in both amblyopic and fellow eyes of the early-onset amblyopes were of significantly shorter latency and smaller amplitude than normal. In the late-onset group the CII responses from the amblyopic eye were of significantly increased latency and reduced amplitude compared with normal, whereas latency and amplitude of fellow eye responses did not differ significantly from normal. Late-onset amblyopes showed reduced CS across the central field for the amblyopic eye, but increased CS for the fellow eye compared with normal. In the early-onset group, central CS did not differ between amblyopic and fellow eyes or from normal. CONCLUSIONS: There are significant differences in the electrophysiological and psychophysical characteristics of adults with early- and late-onset strabismic amblyopia.