Fertility in myotonic dystrophy in Saguenay-Lac-St-Jean: a historical perspective

Myotonic dystrophy (MD) is an autosomal dominant disorder that has a high prevalence in Saguenay-Lac-St-Jean. A case-control study, based on a population register, of 373 MD patients who married in this region between 1855 and 1971 was conducted to determine whether their fertility was affected by the disorder. Six demographic parameters, that is the number of children, the age at marriage, the ages at the time of birth of the first and the last child, the interval between the marriage and the birth of the first child, and the interval between consecutive births, were analyzed. The mean number of children born to MD and control individuals was not different (P > 0.05). However, MD males had more children than MD females although they have started delaying their marriage since 1921. Fertility fell significantly in both the MD and control groups during the period of observation. This change reflects the decline in fertility of French Canadians in general during this period, but mainly after 1940.     

Long-term follow-up of patients with tuberculosis as a complication of tumour necrosis factor (TNF)-alpha antagonist therapy: safe re-initiation of TNF-alpha blockers after appropriate anti-tuberculous treatment.

This study investigated the long-term outcome of patients with tuberculosis (TB) as a complication of tumour necrosis factor (TNF)-alpha blocker therapy. All TB cases (n = 21) complicating TNF-alpha blocker therapy from French university hospitals were collated between January 2000 and September 2002. Outcome was assessed via a postal questionnaire during September 2005. The mortality rate after 4 years was 4.8%, and one patient had relapsed and six (29%) patients had recommenced TNF-alpha antagonist treatment, after appropriate anti-TB therapy, without reactivation. These data support the concept that TNF-alpha antagonists can be restarted in TB patients provided that adequate anti-TB treatment has been completed.     

Specific pattern of ionic channel gene expression associated with pacemaker activity in the mouse heart

Even though sequencing of the mammalian genome has led to the discovery of a large number of ionic channel genes, identification of the molecular determinants of cellular electrical properties in different regions of the heart has been rarely obtained. We developed a high-throughput approach capable of simultaneously assessing the expression pattern of ionic channel repertoires from different regions of the mouse heart. By using large-scale real-time RT-PCR, we have profiled 71 channels and related genes in the sinoatrial node (SAN), atrioventricular node (AVN), the atria (A) and ventricles (V). Hearts from 30 adult male C57BL/6 mice were microdissected and RNA was isolated from six pools of five mice each. TaqMan data were analysed using the threshold cycle ( C _t) relative quantification method. Cross-contamination of each region was checked with expression of the atrial and ventricular myosin light chains. Two-way hierarchical clustering analysis of the 71 genes successfully classified the six pools from the four distinct regions. In comparison with the A, the SAN and AVN were characterized by higher expression of Navβ1, Navβ3, Cav1.3, Cav3.1 and Cavα2δ2, and lower expression of Kv4.2, Cx40, Cx43 and Kir3.1. In addition, the SAN was characterized by higher expression of HCN1 and HCN4, and lower expression of RYR2, Kir6.2, Cavβ2 and Cavγ4. The AVN was characterized by higher expression of Nav1.1, Nav1.7, Kv1.6, Kvβ1, MinK and Cavγ7. Other gene expression profiles discriminate between the ventricular and the atrial myocardium. The present study provides the first genome-scale regional ionic channel expression profile in the mouse heart.     

Macrophage killing of human papillomavirus type 16-transformed cells

Papillomaviruses (HPV) are involved in proliferation of epithelial cells and are implicated in several human malignancies. We determined the capability of activated macrophages to exert cytostatic and/or cytolytic activities against HPV type 16 DNA-transformed cells. Both NIH-3T3 and A31-3T3 cells transformed with HPV DNA were susceptible to killing by activated macrophages; however, transformed and nontransformed cells were not susceptible to killing by soluble mediators. The HPV-transformed cells were as resistant as their nontransformed counterparts to recombinant TNF-alpha. These data suggest that the killing of the HPV-16-transformed 3T3 cells by macrophages occurred by a mechanism independent of TNF-alpha.     

Low-probability transmission of neocortical and entorhinal impulses through the perirhinal cortex

One model of episodic memory posits that during slow-wave sleep (SWS), the synchronized discharges of hippocampal neurons in relation to sharp waves "replay" activity patterns that occurred during the waking state, facilitating synaptic plasticity in the neocortex. Although evidence of replay was found in the hippocampus in relation to sharp waves, it was never shown that this activity reached the neocortex. Instead, it was assumed that the rhinal cortices faithfully transmit information from the hippocampus to the neocortex and reciprocally. Here, we tested this idea using 3 different approaches. 1) Stimulating electrodes were inserted in the entorhinal cortex and temporal neocortex and evoked unit responses were recorded in between them, in the intervening rhinal cortices. In these conditions, impulse transfer occurred with an extremely low probability, in both directions. 2) To rule out the possibility that this unreliable transmission resulted from the artificial nature of electrical stimuli, crosscorrelation analyses of spontaneous neocortical, perirhinal, and entorhinal firing were performed in unanesthetized animals during the states of waking and SWS. Again, little evidence of propagation could be obtained in either state. 3) To test the idea that propagation occurs only when large groups of neurons are activated within a narrow time window, we computed perievent histograms of neocortical, perirhinal, and entorhinal neuronal discharges around large-amplitude sharp waves. However, these synchronized entorhinal discharges also failed to propagate across the perirhinal cortex. These findings suggest that the rhinal cortices are more than a relay between the neocortex and hippocampus, but rather a gate whose properties remain to be identified.     

Infectious viral diarrheas. Comparison of research methods for rotaviruses

Radioimmunoassay and enzyme immunoassay (EIA) are generally recommended for routine diagnosis of rotavirus infection in childhood gastroenteritis. Expensive and delicate, these techniques are ill-suited for processing a small number of samples. Recently, Latex agglutination tests have been introduced than can be performed by non specialized hospital laboratories. However, some questions have been raised as to the sensitivity and specificity of these tests. We have sought a direct appraisal of latex agglutination testing by comparing two enzyme immunoassays and two latex tests (Rotazyme, Enzygnost-Rotavirus, Rotalex, Slidex Rota-kit). Three comparative studies that involved 1217 stool samples from children with gastroenteritis were carried out. Specificity, sensitivity, of latex tests compared favorably with the more sophisticated EIA, they represent a very convenient alternative for routine laboratory use provided latex tests with low rate of non-specific agglutinations are chosen.     

Major histocompatibility complex class II-restricted presentation of secreted and endoplasmic reticulum resident antigens requires the invariant chains and is sensitive to lysosomotropic agents

We have tested the involvement of the invariant chains (Ii) p31 and p41 in the presentation of peptides derived from hen egg lysozyme (HEL) constructs targeted to different intracellular compartments within transfected fibroblasts. The endogenous HEL constructs were either present in the cytosol (HELc), secreted (HELs), or linked to the mammalian (KDEL C-terminal sequence that causes retention of HEL in the endoplasmic reticulum (ER)/pre-Golgi recycling compartment (HELr). Using Ii-negative antigen-presenting cells, the presentation of HELr to a HEL 46-61 specific T cell hybridoma was far less efficient than the presentation of the HELs. High levels of Ii expression enhanced drastically the presentation of the HEL 46-61 determinant derived from both HELr and HELs. HELr and HELs presentation was fully sensitive to lysosomotropic agents such as chloroquine, indicating that the formation of complexes between major histocompatibility complex (MHC) class II molecules and determinants derived from endogenous antigens entering the secretory pathway is taking place in an acidic compartment. The degradation and dissociation of Ii might be a prerequisite for the efficient presentation of endogenously derived determinants by MHC class II molecules, as for the presentation of most exogenous antigens. All our results are compatible with the notion that endogenous molecules being translocated into the lumen of the ER could be presented by class II molecules through a processing pathway involving an acidic compartment in which Ii chains dissociate from class II molecules.     

Production of a monoclonal antibody with specificity for deoxynivalenol, 3‐acetyldeoxynivalenol and 15‐acetyldeoxynivalenol

Monoclonal antibodies reactive with deoxynivalenol were generated following the immunization of mice with a deoxynivalenol‐mouse serum albumin conjugate. One of the anti‐deoxynivalenol monoclonal antibodies, designated C6–1, exhibited cross‐reactivity with 3‐acetyldeoxynivalenol and 15‐acetyldeoxynivalenol but not with nivalenol, T‐2 tetraol or scirpentriol. An indirect competitive ELISA based on this monoclonal antibody gave 50% inhibition values of 0–6 μg ml^‐1 for deoxynivalenol, 0–2 μg ml^‐1 for 15‐acetyldeoxynivalenol and 10 μg ml^‐1 for 3‐acetyldeoxynivalenol.     

BMI in the Trois‐Rivières study: Child–adult and child–parent relationships

This study evaluated intraindividual child–adult and interindividual child–parent relationships of body mass index (BMI) using data from the Trois‐Rivières semilongitudinal study of growth and development. Intraindividual correlations between age 12 and 35 years were substantial (r² = 36% of variance in women, 30% of variance in men). Interindividual child–parent correlations for mothers and fathers age 36.6 ± 0.4 and 39.5 ± 0.4 years, respectively, were very low to low for daughters age 12 years (r = 0.09, NS and 0.34, P < 0.001 vs. father and mother, respectively) but all very low for sons age 12 years (r = 0.07, NS and 0.16, NS vs. father and mother, respectively). A multiple regression analysis predicted adult BMI from the individual's BMI at 10, 11, 12 years plus the maternal and paternal BMIs as calculated from self‐reported heights and weights. The BMI at age 12 years was a better predictor of adult BMI than the parental BMI in both men and women (P < 0.001) and multivariate analysis revealed that this index at age 12 years was the sole significant predictor of adult BMI for both men and women. The results from our study do not support the hypothesis that parental BMI is a stronger predictor of adult BMI than childhood BMI. However, useful information for the prediction and prevention of adult overweight can be obtained from the BMI at age 12 years. Our results suggest that environmental influences may be the major factor in the present obesity epidemic. Am. J. Hum. Biol. 15:187–191, 2003. © 2003 Wiley‐Liss, Inc.