High-intensity intermittent running training improves pulmonary function and alters exercise breathing pattern in children

We investigated the effects of short duration running training on resting and exercise lung function in healthy prepubescent children. One trained group (TrG) (n = 9; three girls and six boys; age = 9.7 ± 0.9 year) participated in 8 weeks of high-intensity intermittent running training and was compared to a control group (ContG) (n = 9; four girls and five boys; age = 10.3 ± 0.7 year). Before and after the 8-week period, the children performed pulmonary function tests and an incremental exercise test on a cycle ergometer. After the 8-week period, no change was found in pulmonary function in ContG. Conversely, an increase in forced vital capacity (FVC) (+7 ± 4% ; P = 0.026), forced expiratory volume in one second (+11 ± 6% ; P = 0.025), peak expiratory flows (+17 ± 4% ; P = 0.005), maximal expiratory flows at 50% (+16 ± 10% ; P = 0.019) and 75% (+15 ± 8% ; P = 0.006) of FVC were reported in TrG. At peak exercise, TrG displayed higher values of peak oxygen consumption (+15 ± 4% ; P<0.001), minute ventilation (+16 ± 5% ; P = 0.033) and tidal volume (+15 ± 5% ; P = 0.019) after training. At sub-maximal exercise, ventilatory response to exercise was lower (P = 0.017) in TrG after training, associated with reduced end-tidal partial oxygen pressure (P<0.05) and higher end-tidal partial carbon dioxide pressure (P = 0.026). Lower deadspace volume relative to tidal volume was found at each stage of exercise in TrG after training (P<0.05). Eight weeks of high-intensity intermittent running training enhanced resting pulmonary function and led to deeper exercise ventilation reflecting a better effectiveness in prepubescent children.     

Sperm analysis by FISH in a case of t(17; 22) (q11; q12) balanced translocation: case report

Individual sperm from men with balanced translocations have different chromosomal contents. Thus, an estimation of the overall sperm chromosomal imbalance of such patients could help to give the couple an adapted genetic counselling. We report here the study of a balanced translocation carrier, t(17;22) (q11;q12) whose reproductive history reported four miscarriages. Moreover, he had an abnormal semen analysis with oligoteratozoospermia. The meiotic segregation pattern was examined in 700 sperm, using fluorescence in-situ hybridization (FISH). Nineteen percent of the sperm had balanced translocations or were normal. All other sperm were unbalanced (81%) and their distribution was observed as follows: the frequencies of adjacent 1, adjacent 2 and 3:1 segregations were 12.9, 5.8 and 46.8% respectively. Among the segregations scored, 13.7% were related to second meiotic division abnormalities. Less than 2% of the total sperm scored were not explained. The 3:1 segregation was present at a very high rate, which is very unusual. In cases of balanced translocations, we believe that no general features can be drawn. Thus, the FISH technique may be very helpful for genetic counselling, which remains an important step and must be done with care.     

Recombinant congenic strains of mice from B10.D2 and DBA/2: Their contribution to behavior genetic research and application to audiogenic seizures

Recombinant congenic strains (RCS) represent a series of related strains, each of which carries a small fraction of the genome of one strain (donor strain) on the genetic background of another strain (background strain). Recombinant inbred strains (RIS) are commonly used to identify major gene segregation and linkage and associations between behavior and quantitative trait loci, whereas recombinant congenic strains (RCS) open other complementary leads. The variability in the reactivity of RCS to a trait is thus the expression of few minor-effect genes originating from the donor strain, because the probability that major genes are present in any one RCS is low. Unlike RIS in which minor-effect genes are often masked by major genes, RCS enable the effects of minor genes to be studied. With our method, for a given trait, an estimate can be made of the gene strength distribution as well as an estimate of the minimal number of genes involved having a certain strength.This study was supported by the Centre National de la Recherche Scientifique (URA 1924 and CSEAL-UPS 44, CNRS), Université René-Descartes, Paris V UFR Biomédicale, and the Fondation pour la Recherche Médicale.     

An inhibitor of cytotoxic functions produced by CD8+CD57+ T lymphocytes from patients suffering from AIDS and immunosuppressed bone marrow recipients

An inhibitor of the cytotoxic functions (ICF) mediated by human immunodeficiency virus (HIV)- or HLA-specific cytotoxic T lymphocytes, natural killer and lymphokine-activated killer (LAK) cells is secreted by CD8⁺CD57^? T lymphocytes, a subset expanded during infection with HIV and after bone marrow transplantation. We previously showed an apparent molecular mass of 20–30 kDa for this soluble glycosylated concanavalin A-binding inhibitor which is distinct from known cytokines. Here, we report a characterization of the mechanism of action of this CD8⁺CD57⁺ ICF. We show that the ICF-induced inhibition of LAK cell cytolytic activity is transient, with a spontaneous recovery of cytolytic potential after 18 h. When testing interactions of ICF with a large set of cytokines we found that the ICF-mediated inhibition of cytotoxic functions is antagonized by two cytokines: recombinant interleukin (rIL)-4 and recombinant interferon (rIFN)-γ. Finally, we show that ICF acts at the level of cytolytic effector cells, where it induces a significant increase of cyclic AMP (cAMP) level. In contrast, no modification of either cell surface antigen expression or of target/effector cell conjugate formation could be evidenced. Addition of rIL-4 and rIFN-γ reverses such an increase of cAMP levels and in parallel restores the cytolytic activity. Altogether, these data demonstrate that the glycoprotein ICF produced by CD8⁺CD57⁺ cells (1) inhibits cell-mediated cytotoxicity by sensitizing cytolytic effector cells to the cAMP pathway, and (2) is part of a cytokine network controlling cell-mediated cytotoxic functions.     

A comparison of three methods of scoring penile circumference changes

There are presently three widely used methods of scoring penile circumference data. The present experiment attempted to determine the ability of each method to explain the variance within a data set. A total of 19 subjects were presented with 20 photographic slides assigned to five categories: neutral, female adult, female adolescent, male adult, and male adolescent. Erectile responses to each slide were recorded and the data analyzed in terms of the raw scores, percentage of full erection, and a z-score transformation. Results indicated that the z scores captured the highest proportion of the variance (52.7%), followed by the percentage scores (32.5%), and the raw scores (30.1%). Findings are discussed in terms of their research and clinical implications.     

Agonist-mediated conformational changes of β-adrenoceptors could occur independent of functional coupling to Ns

Summary Agonist and antagonist binding characteristics of -adrenoceptors in turkey erythrocyte ghosts were determined at different temperatures ranging between 7°C and 42°C. [³H]-DHA saturation binding experiments revealed that the antagonist-receptor interaction is entropy-driven with a small enthalpic contribution. Isoproterenol/[³H]-DHA competition binding followed the law of mass action at all the investigated temperatures. The agonist-receptor interaction is enthalpy driven with a small unfavorable decrease in entropy. This is consistent with the agonist's ability to favor an endoenergetic transconformation of the receptors.Only part of the agonist-bound receptors can undergo functional coupling to the stimulatory component of the adenylate cyclase system (Ns). This coupling process is associated with locking-in of the agonist and becomes persistent in the presence of the alkylating reagent N-ethylmaleimide. The number of agonist/N-ethylmaleimide-sensitive sites (i.e. coupling-prone receptors) increases with the temperature until it reaches a plateau value of 50% between 27–32°C. Qualitatively similar data were obtained for rat lung and turkey erythrocyte membranes. These observations suggest that the whole receptor population can undergo agonist-mediated conformational changes but that only part of them can couple to Ns.     

Gene Replacement Strategies for Lung Cancer

Advances in our understanding of the molecular genetics of cancer present an opportunity to develop prevention and treatment strategies based on the reversal of specific genetic lesions. This strategy is analogous to the classic concept of gene therapy for replacement of defective or nonfunctioning genes. The gene families implicated in carcinogenesis include dominant oncogenes and tumor suppressor genes. Regional administration of viral vectors expressing wildtype p53 and antisense K-ras prevents tumor growth for tumors with the specific genetic lesions in orthotopic tumor models and mediates regression of large established tumors. These studies provide a rationale for a new clinical protocol recently approved by the National Institutes of Health Recombinant DNA Advisory Committee and Food and Drug Administration to replace a defective p53 gene with intratumor injection of recombinant retrovirus expressing wild-type p53 or elimination of activated K-ras by expression of antisense K-ras messenger RNA. If these agents are efficacious, their lack of toxicity may provide a sufficiently high therapeutic index such that they could be used as an adjuvant to surgery to treat patients with earlier stages of cancer or as prevention for second primary cancers for individuals with genetic abnormalities in premalignant lesions. Although much research needs to be done, the possibility of specific gene targeting with a high therapeutic index makes this a promising area of investigation.     

Mapping of c-fos gene expression in the brain during morphine dependence and precipitated withdrawal, and phenotypic identification of the striatal neurons involved

The c-fos gene is expressed in the central nervous system in response to various neuronal stimuli. Using in situ hybridization, we examined the effects of chronic morphine treatment and withdrawal on c-fos mRNA in the rat brain, and particularly within identified striatal neurons. Morphine dependence was induced by subcutaneous implantation of two pellets of morphine for 6 days and withdrawal was precipitated by administration of naltrexone. Placebo animals and morphine-dependent rats showed a very weak c-fos mRNA expression in all the structures studied. Our study emphasized the spatial variations in c-fos mRNA expression, and also revealed a peak expression of c-fos mRNA at 1 h after naltrexone-precipitated withdrawal in the projection areas of dopaminergic neurons, noradrenergic neurons and in several regions expressing opiate receptors. Interestingly, morphine withdrawal induces c-fos mRNA expression in the two efferent populations of the striatum (i.e. striatonigral and striatopallidal neurons) both in the caudate putamen and nucleus accumbens. Moreover, the proportions of activated neurons during morphine withdrawal are different in the caudate putamen (mostly in striatopallidal neurons) and in the shell and core parts of the nucleus accumbens (mostly in striatonigral neurons). The activation of striatopallidal neurons suggests a predominant dopaminergic regulation on c-fos gene expression in the striatum during withdrawal. On the contrary, c-fos induction in striatonigral neurons during withdrawal seems to involve a more complex regulation like opioid-dopamine interactions via the mu opioid receptor and the D1 dopamine receptor coexpressed on this neuronal population or the implication of other neurotransmitter systems.