Biomarkers of cardiometabolic health are associated with body composition characteristics but not physical activity in persons with spinal cord injury

Objective: To examine (i) the associations between physical activity dimensions, cardiorespiratory fitness and body composition and, (ii) the associations between physical activity dimensions, cardiorespiratory fitness, body composition and biomarkers of cardiometabolic health in persons with spinal cord injury (SCI).

Methods: A cross-sectional prospective cohort study with 7-day follow-up was conducted. Body composition, cardiorespiratory fitness and biomarkers of cardiometabolic health were measured in thirty-three participants with SCI (> 1 year post injury). Physical activity dimensions were objectively assessed over 7-days.

Results: Activity energy expenditure (r =.43), physical activity level (r =.39), and moderate-to-vigorous physical activity (MVPA) (r =.48) were significantly (P < 0.001) associated with absolute (L/min) peak oxygen uptake (?O₂ peak). ?O₂ peak was significantly higher in persons performing ≥150 MVPA minutes/week compared to <40 minutes/week (P?=?0.003). Individual physical activity dimensions were not significantly associated with biomarkers of cardiometabolic health. However, body composition characteristics (BMI, waist and hip circumference) showed significant (P < 0.04), moderate (r >.30) associations with parameters of metabolic regulation, lipid profiles and inflammatory biomarkers. Relative ?O₂ peak (ml/kg/min) was moderately associated with only insulin sensitivity (r?=?0.37, P?=?0.03).

Conclusions: Physical activity dimensions are associated with cardiorespiratory fitness; however, stronger and more consistent associations suggest that poor cardiometabolic health is associated with higher body fat content. Given these findings, the regulation of energy balance should be an important consideration for researchers and clinicians looking to improve cardiometabolic health in persons with SCI.     

La relation mère-fille. Une histoire sans nom de Barbey d’Aurevilly

In 1967, some hematologists who were inspired by Barbey d’Aurevilly’s novel, “A story without a name”, described the syndrome of Lasthénie de Ferjol: recurrent anemia resulting from voluntarily provoked hemorrhages. We used the same novel as a basis for studying the mother-daughter relationship. Madame de Ferjol is widowed, and lives a reclusive life with her only daughter, Lasthénie, until such time as a capuchin priest enters their life during Lent. This unexpected encounter with sexuality (Lasthénie becomes pregnant) has a marked effect upon the young woman; she withdraws into total silence, and displays self-mutilating behavior (provoked bouts of anemia) which leads to her death and to that of her unborn child. In this tale, we see a paradigm of the mother-child relationship that has already been observed in anorexia nervosa. Mother and daughter are caught up in a narcissistic dyad fom which neither is able to extricate herself. The mother remains in a pathological state of mourning, and we put forward the hypothesis that this dead mother is affected by a melancholic process in which her hatred is projected onto her daughter. Finally, we have attempted to examine the connections between hysteria and anorexia nervosa, as in this story rivalry between mother and daughter also plays a role, and in which sexuality—therefore involving a third party—is unmentionable.     

Cancer of the cardia. Prognostic factors and treatment]

Pronostic of carcinoma of the esogastric junction is worsened by the potential two-way route of spread in case of lymph node metastasis: mediastinum and abdomen. During the last 10 years the authors observed 71 cases of adenocarcinoma of the gastric cardia, including 7 cases of linitis plastica. Histopathologic and clinical follow-up data are presented. The aims of the study were to evaluate prognostic factors and to define the best surgical treatment. There were mainly elderly patients with a poor physical status. Ten patients did not undergo surgery (14%). Among 57 patients undergoing radial resection (80.3%), total gastrectomy and upper polar esogastrectomy were performed in respectively 29 and 28 cases. The carcinomas were truly located to the gastric cardia in only 37 cases (65%). Operative mortality was 12.3%, not depending of the surgical technique. All patients five-year survival rate was 10.2%, improving to 15% in case of curative resection. The value of lymph node metastasis (80.7% of the patients) as a prognostic factor depended of the proximal or distal localization of the nodes. A positive surgical margin (15.7% of the patients) was a poor prognostic factor with a 6.9 months mean survival. The authors conclude that an aggressive surgical approach is worthwhile, because of the carcinoma invasion (nodes, margin), but not always possible (poor physical status).     

Characterization of persistent poliovirus mutants selected in human neuroblastoma cells

Six Sabin-derived persistent poliovirus mutants were selected in human neuroblastoma IMR-32 cells. The mutants had a titer 30 to 10⁵ times lower in nonneural HEp-2c cells than in IMR-32 cells. When the growth cycles of persistent viruses in the two cell lines were compared, the most striking feature was a delay of 2 to 4 hr in virus release from HEp-2c cells. In HEp-2c cells, type 1 mutants could spontaneously establish a persistent infection in the absence of any exogenous viral inhibitor. Mutations at a rate of 1 every 210 nucleotides had accumulated in the genome of the type 1 mutants selected in neuroblastoma cells, modifying cell specificity and conferring the ability to persist in some non-neural cells. These results indicate that mutants of poliovirus with highly modified biological properties can be selected in vitro in cells of neural origin.     

Childhood fractures are associated with decreased bone mass gain during puberty: an early marker of persistent bone fragility?

Whether peak bone mass is low among children with fractures remains uncertain. In a cohort of 125 girls followed over 8.5 years, 42 subjects reported 58 fractures. Among those, BMC gain at multiple sites and vertebral bone size at pubertal maturity were significantly decreased. Hence, childhood fractures may be markers of low peak bone mass acquisition and persistent skeletal fragility. INTRODUCTION: Fractures in childhood may result from a deficit in bone mass accrual during rapid longitudinal growth. Whether low bone mass persists beyond this period however remains unknown. MATERIALS AND METHODS: BMC at the spine, radius, hip, and femur diaphysis was prospectively measured over 8.5 years in 125 girls using DXA. Differences in bone mass and size between girls with and without fractures were analyzed using nonparametric tests. The contribution of genetic factors was evaluated by mother-daughter correlations and that of calcium intake by Cox proportional hazard models. RESULTS: Fifty-eight fractures occurred in 42 among 125 girls (cumulative incidence, 46.4%), one-half of all fractures affecting the forearm and wrist. Girls with and without fractures had similar age, height, weight. and calcium intake at all time-points. Before and during early puberty, BMC and width of the radius diaphysis was lower in the fracture compared with no-fracture group (p < 0.05), whereas aBMD and BMAD were similar in the two groups. At pubertal maturity (Tanner's stage 5, mean age +/- SD, 16.4 +/- 0.5 years), BMC at the ultradistal radius (UD Rad.), femur trochanter, and lumbar spine (LS), and LS projected bone area were all significantly lower in girls with fractures. Throughout puberty, BMC gain at these sites was also decreased in the fracture group (LS, -8.0%, p = 0.015; UD Rad., -12.0%, p = 0.004; trochanter, -8.4%, p = 0.05 versus no fractures). BMC was highly correlated between prepuberty and pubertal maturity (R = 0.54-0.81) and between mature daughters and their mothers (R = 0.32-0.46). Calcium intake was not related to fracture risk. CONCLUSIONS: Girls with fractures have decreased bone mass gain in the axial and appendicular skeleton and reduced vertebral bone size when reaching pubertal maturity. Taken together with the evidence of tracking and heritability for BMC, these observations indicate that childhood fractures may be markers for low peak bone mass and persistent bone fragility.     

Transfection of pancreatic acinar cells (AR4-2J) by bFGF modifies cell morphology and biosynthesis of pancreatic secretory enzymes]

Basic fibroblast growth factor (bFGF or FGF-2) is present in the basal membrane of pancreatic cells during the pancreatic embryonic development. The expression of bFGF receptors has been described in normal pancreatic cells. By contrast, pancreatic cancer cells express not only the bFGF receptors but also the bFGF itself. With the aim of understanding the effects induced by the production of bFGF by pancreatic cancer cells, the pancreatic acinar cell line (AR4-2J) was used. AR4-2J cells do not produce bFGF but express bFGF receptors. These cells were transfected with a vector containing the bFGF cDNA encoding the three different forms of bFGF characterized in tumor cells. Results showed that the bFGF expression induced important phenotypic and enzymatic modifications. The transfected cells lost some morphological features of the acinar cells and expressed amylase and lipase at low levels (a 90% decrease for amylase activity, whereas lipase activity was barely detectable). These results suggest that bFGF could be involved in maintaining pancreatic cells in a slightly differentiated state.     

Cyclic AMP increases the release of parathyroid hormone-related protein from a lung-cancer cell line

Parathyroid hormone-related protein (PTHrP) plays an important role in the pathogenesis of malignant hypercalcemia by stimulating bone resorption and/or renal tubular reabsorption of calcium. In cultured cancer cells, its production can be influenced by various factors or ions, but the regulation of its production is still poorly understood. We investigated the effects of stimulators of cAMP synthesis on PTHrP release by a human lung squamous-carcinoma cell line (BEN). In supervised cells grown on microcarrier beads, PTHrP production was significantly increased after incubation with calcitonin for only 20 min. The release of immunoreactive and bioactive PTHrP was increased by incubating the cells with forskolin, 3-isobutyl-I-methylxanthine or dibutyryl cAMP even in the presence of the protein-synthesis inhibitor cycloheximide for 6 hr. The calcitonin-mediated stimulation was not accompanied by. concomitant changes in PTHrP mRNA. The microfilament-disrupter cytocha-lasin D was shown to enhance the basal and calcitonin-induced production of PTHrP. These results indicate that stimulators of cAMP synthesis enhanced PTHrP release by BEN cells.     

Bone density ligand, Sclerostin, directly interacts with LRP5 but not LRP5G171V to modulate Wnt activity.

We compared and contrasted the mechanism of action for the cysteine knot protein subfamily, Wise and Sost (Sclerostin). Our data suggest that functional interactions between Sost or Wise and LRP5/LRP6 have the potential to regulate bone deposition by modulating the Wnt pathway. INTRODUCTION: The human disease sclerosteosis exhibits an increase in bone mass thought to be caused by hyperactive osteoblasts. Sclerostin, SOST, the gene affected in this disease, has been postulated to exert its activity by functioning as a BMP antagonist. However, recent evidence indicates that SOST is highly related to Wise, which can also modulate the Wnt pathway by binding to LRP5 and LRP6. MATERIALS AND METHODS: For this study, we used cell culture to test the BMP and Wnt activity function of both Wise and Sost. In addition, we used Xenopus in vivo Wnt assays along with Xenopus in vitro Wnt assays to support our cell culture results. Epitope tagged cell supernatants containing either Sost or soluble mutant or wildtype LRP5/LRP6 were used for immunoprecipitation. Sost immunoprecipitation results were confirmed in vivo using cell culture. Finally, to support our in vitro data, we co-localized Sost, Wise, LRP5, and LRP6 in mouse long bone sections. Results: In this study, we report in vitro and in vivo evidence to show that Sost physically interacts with Lrp5 and Lrp6 and inhibits the canonical Wnt signaling pathway. Furthermore, using in vitro and in vivo assays, we showed that a variant of LRP5 (LRP5(G171V)) known to cause the human high bone mass (HBM) trait and a homologous change in LRP6 (LRP6(G158V)) abolished protein interactions with Sost. We used variants of Sost amino acids to further identify the contact points between Sost and LRP6. In Xenopus and mammalian cell culture assays, we showed that SOST is able to attenuate Wnt signaling and that this attenuation can be rescued by the addition of alpha-Sost antibodies or by the introduction of single amino acid substitution that alter its binding to LRP6. Sost differs from Wise in that it is unable to stimulate Wnt signaling. Using immunohistochemistry, we found that Sost and Wise are co-localized to osteoblasts, along with LRP5 and LRP6. CONCLUSIONS: Our data suggest that functional interactions between Sost or Wise and LRPs have the potential to regulate bone deposition by modulating Wnt signaling.     

High-resolution x-ray computed tomography in lymphoid interstitial pneumonia

Three patients with lymphoid interstitial pneumonia (two HIV 1+ patients with chronic lymphadenopathic syndromes and one with a not-characterized autoimmune disease) have been studied with high-resolution computed tomography (HR-CT). This technique reveals septal lines, small reticulonodular opacities, polyhedral micronodular opacities, "ground-glass" opacities and a dense, subpleural, curved broken line in one patient. The lesions dominate in the bases of the lungs. They are not characteristic for lymphoid interstitial pneumonia. If a patient present with a chronic lymphadenopathic syndrome, the diagnosis of an opportunistic infection should not be automatically made, since the syndrome can be caused by lymphoid interstitial pneumonia.     

France: a focus on the new reproduction

This bibliographic essay's initial focus is on publications reflecting European concern with the ethical implications of reproductive technologies. Titles by P. Verspieren, the Institut Catholique de Lyon, C. Lefèvre, E. Loumaye and J-F. Malherbe, and J-L. Baudouin and C. Labrusse-Riou are briefly discussed. Also mentioned are recently published works on biomedical technologies by B. Edelman, M-A. Hermite, Labrusse-Riou, and M. Remond-Gouilloud; on the social impact of science by G. Hottois, J. DeVooght, R. Rasmont, and P. Van Gansen; on medical ethics by C. Ambroselli, and by Malherbe; on AIDS by E. Hirsch, by E. Conan, and by Malherbe and S. Zorrilla. All cited titles are in French.