Leucine supplementation improves muscle protein synthesis in elderly men independently of hyperaminoacidaemia

The present study was designed to assess the effects of dietary leucine supplementation on muscle protein synthesis and whole body protein kinetics in elderly individuals. Twenty healthy male subjects (70 ± 1 years) were studied before and after continuous ingestion of a complete balanced diet supplemented or not with leucine. A primed (3.6 μmol kg⁻¹) constant infusion (0.06 μmol kg⁻¹ min⁻¹) of l -[1-¹³C]phenylalanine was used to determine whole body phenylalanine kinetics as well as fractional synthesis rate (FSR) in the myofibrillar fraction of muscle proteins from vastus lateralis biopsies. Whole body protein kinetics were not affected by leucine supplementation. In contrast, muscle FSR, measured over the 5-h period of feeding, was significantly greater in the volunteers given the leucine-supplemented meals compared with the control group (0.083 ± 0.008 versus 0.053 ± 0.009% h⁻¹, respectively, P < 0.05). This effect was due only to increased leucine availability because only plasma free leucine concentration significantly differed between the control and leucine-supplemented groups. We conclude that leucine supplementation during feeding improves muscle protein synthesis in the elderly independently of an overall increase of other amino acids. Whether increasing leucine intake in old people may limit muscle protein loss during ageing remains to be determined.     

Haemophilus ducreyi Outer membrane determinants, including DsrA, define two clonal populations

The Haemophilus ducreyi outer membrane component DsrA (for ducreyi serum resistance A) is necessary for complete resistance to normal human serum (NHS). When DsrA expression in 19 temporally and geographically diverse clinical isolates of H. ducreyi was examined by Western blotting, 5 of the strains expressed a different immunotype of the DsrA protein (DsrA(II)) than the well-characterized prototypical strain 35000HP (DsrA(I)). The predicted DsrA proteins expressed by the DsrA(II) strains were 100% identical to each other but only 48% identical to that of strain 35000HP. In addition to the DsrA(II) protein, class II strains also expressed variant forms of other outer membrane proteins (OMPs) including NcaA (necessary for collagen adhesion A), DltA (ducreyi lectin A), Hlp (H. ducreyi lipoprotein), major OMP, and/or OmpA2 (for OMP A2) and synthesized a distinct, faster-migrating lipooligosaccharide. Based on these data, strains expressing DsrA(I) were termed class I, and those expressing DsrA(II) were termed class II. Expression of dsrA(II) from strain CIP 542 ATCC in the class I dsrA(I) mutant FX517 (35000HP background), which does not express a DsrA protein, rendered this strain resistant to 50% NHS. This demonstrates that DsrA(II) protein is also critical to serum resistance. Taken together, these results indicate that there are two clonal populations of H. ducreyi. The implications of two classes of H. ducreyi strains differing in important antigenic outer membrane components are discussed.     

CHARGE syndrome: developmental and behavioral data

Kabuki syndrome (KS) is associated with multiple organ system involvement. Characteristic features include long palpebral fissures with everted lower lids, prominent ears, skeletal abnormalities, mental retardation, and short stature. An increased incidence of infection has been reported in KS, and a few patients have been noted to have immune defects. However, the frequency and severity of the immune deficiency has not been clearly defined. Immunologic evaluation of 19 consecutive individuals with KS was performed at The Children's Hospital of Philadelphia. Decreased IgA levels were noted in 15/19 individuals (79%), 2 of whom had undetectable levels. Eight patients (42%) also had low total IgG levels. Specific IgG subclass abnormalities were found in 6 of 13 patients evaluated. IgM levels were less frequently decreased. One patient failed to generate anti-tetanus antibodies despite immunization. This study suggests that hypogammaglobulinemia is a frequent finding in children with KS. The pattern of antibody abnormalities seen in children with KS resembles common variable immune deficiency (CVID). Due to this increased susceptibility to infection, children with KS should have immunologic evaluations at the time of diagnosis in order to reduce preventable morbidity and mortality.     

Whole blood real-time quantitative PCR for cytomegalovirus infection follow-up in transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) remains a major opportunistic agent among transplant recipients. While detection of CMV pp65-lower matrix protein (pp65Ag) is still widely used for monitoring CMV infection, real-time PCR assays have been recently developed for routine quantitation of CMV DNA. However, correlations are lacking between results of pp65Ag and quantitative PCR assays and there is no consensus yet as to the more appropriate blood compartment (whole blood (WB), leukocytes, plasma) to be tested with PCR assays. OBJECTIVES: The aims of the study were to determine, in a population of transplant recipients: (i) the correlation between pp65Ag and CMV quantitative real-time PCR in our setting and (ii) the utility of plasma CMV DNA quantitation in comparison to WB quantitation. METHODS: In 170 blood samples (from 61 solid organ or bone marrow transplant recipients) with pp65Ag results, CMV quantitation was performed in WB and plasma using an in-house real-time quantitative PCR. RESULTS: Real-time PCR and pp65Ag results in WB were correlated: thresholds of 10 and 50(+) cells/200,000 cells were equivalent to 3.3 log(10)copies/mL (2,000 copies/mL) and 3.8 log(10)copies/mL (6,300 copies/mL), respectively. When WB viral load was >or=3.6 log(10)copies/mL, the risk to have a negative plasma CMV DNA result was 相似文献   

A member of a conserved Plasmodium protein family with membrane-attack complex/perforin (MACPF)-like domains localizes to the micronemes of sporozoites

Pore-forming proteins are employed by many pathogens to achieve successful host colonization. Intracellular pathogens use pore-forming proteins to invade host cells, survive within and productively interact with host cells, and finally egress from host cells to infect new ones. The malaria-causing parasites of the genus Plasmodium evolved a number of life cycle stages that enter and replicate in distinct cell types within the mosquito vector and vertebrate host. Despite the fact that interaction with host-cell membranes is a central theme in the Plasmodium life cycle, little is known about parasite proteins that mediate such interactions. We identified a family of five related genes in the genome of the rodent malaria parasite Plasmodium yoelii encoding secreted proteins all bearing a single membrane-attack complex/perforin (MACPF)-like domain. Each protein is highly conserved among Plasmodium species. Gene expression analysis in P. yoelii and the human malaria parasite Plasmodium falciparum indicated that the family is not expressed in the parasites blood stages. However, one of the genes was significantly expressed in P. yoelii sporozoites, the stage transmitted by mosquito bite. The protein localized to the micronemes of sporozoites, organelles of the secretory invasion apparatus intimately involved in host-cell infection. MACPF-like proteins may play important roles in parasite interactions with the mosquito vector and transmission to the vertebrate host.     

Prognostic values of galectin-3 and the macrophage migration inhibitory factor (MIF) in human colorectal cancers.

This study aims to investigate whether the immunohistochemical levels of expression of galectin-3 and the macrophage migration inhibitory factor (MIF) are associated with prognostic values in human colorectal tumors. This was performed on 99 specimens including 69 colorectal tumors (17 Dukes A, 19 Dukes B, 15 Dukes C and 18 metastatic tumors that we labeled as D), 10 hepatic metastases from colorectal cancers and 20 normal specimens (biopsies). The immunohistochemical levels of expression of MIF and galectin-3 were quantified on routine histological slides by means of computer-assisted microscopy. Separate analyses were performed on epithelial and connective tissue. The levels of expression of both MIF and galectin-3 were very significantly higher in epithelial tumor tissue when compared with normal epithelial specimens. A positive and significant correlation between MIF and galectin-3 expression was evidenced in connective tumor tissue, and in particular in the cases associated with short survival periods (less than 5 years). In the case of the Dukes A or B tumors, we established two new prognostic groups (labeled I and II) on the basis of the levels of galectin-3 expression measured in the tumor epithelium. In the case of the Dukes C or D tumors, we established two other prognostic groups (labeled III and IV) on the basis of the levels of MIF expression measured in the connective tissue. Kaplan-Meyer analyses confirmed the additional prognostic values (as compared with conventional clinical staging) given by this new classification (groups I to IV). They show that the Dukes A or B tumors characterized by low levels of galectin-3 expression in the tumor epithelium are associated with significantly better prognoses than those characterized by high levels. In addition, the Dukes C or D tumors characterized by high levels of MIF expression in the connective tumor tissue are associated with significantly better prognoses than those characterized by low levels. In conclusions, MIF and galectin-3 expression levels in colorectal tumors are related to their levels of biological aggressiveness. These markers could be used to identify patients at risk, for whom more aggressive adjuvant therapy seems to be indicated.     

Jogging geht mit niedrigem Absentismus einher (Berner L?uferstudie'84)

Zusammenfassung 4358 männliche Läufer, Teilnehmer am 16-km-Lauf «GP von Bern» 1984, bilden die Studienpopulation einer Querschnittsuntersuchung, in welcher unter anderem die Beziehungen zwischen Jogging und Absentismus analysiert wurden. Die Laufzeit für die 16-km-Strecke und die Zahl der gefehlten Arbeitstage korrelieren positiv (p<0,001); die Laufaktivität (pro Woche im Mittel gelaufene Kilometer) und Absentismus korrelieren entsprechend invers, allerdings nur bis zu einem Trainingsumfang von nicht mehr als ca. 50 km/Woche. Zigarettenrauchende Läufer weisen über 50% mehr Absenzen auf als Nichtrauchende (p<0,001). Zunehmende Bedeutung des Joggingmotivs «als Ausgleich zum Berufsalltag» korreliert invers mit Absentismus (p<0,001), hohe Bedeutung wettkampforientierter Beweggründe für Jogging ist jedoch positiv mit Absentismus assoziiert (p<0,001). Eine multiple Regressionsanalyse mit insgesamt 8 Faktoren vermag lediglich 11% der Varianz der Arbeitsplatzabsenzen zu erklären, was auf die Komplexität der untersuchten abhängigen Variable hindeutet. Die Frage nach der Kausalität der Beziehung zwischen aktivem, regelmässigem (nicht übermässigem) Jogging und erniedrigtem Absentismus bleibt offen. Erst Interventions-studien würden eine bessere Beurteilung des vermuteten Potentials von Bewegung und Sport zur Reduktion von Absentismus erlauben.

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Jogging is related to reduced absenteeism (the Berne Grand-prix study'84)

Summary 4358 male runners over age 16, competitors of the 16 km race Grand-prix of Berne 1984, represent the study population of a cross-sectional survey. As a part of it, relationships between jogging and absenteeism were investigated. 16 km running time was positively associated with the number of missed work days (p<0,001); training activity (kilometers run per week, one-year's average) and absenteeism were related in an inverse way, but only up to a training distance of not more than 50 km/wk. Runners who smoked cigarettes missed over 50% more work days than nonsmokers (p<0,001). The relative importance of the motive for jogging as a balance to work was associated with decreased absenteeism (p<0,001), whereas relative importance of competition-orientated motives was associated with increased absenteeism (p<0,001). A multiple regression analysis involving 8 factors was not able to explain more than 11% of the observed variance in missed work days, which underlines the complexity of this dependent variable. The question concerning a possible causal relationship between active, regular, moderate jogging and reduced absenteeism remains unanswered.

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Le jogging est associé à un absentéisme réduit (Berner Läuferstudie '84)

Résumé 4358 coureurs agés de 16 ans et plus, participants à la course de 16 km «Grand-Prix de Berne» en 1984, forment l'échantillon d'une étude transversale, à l'occasion de laquelle les relations entre le jogging et l'absentéisme ont également été analysées. Il existe une corrélation positive entre le chronométrage des 16 km et le nombre de jours de travail manqués (p<0,001); en plus, la distance parcourue (moyenne des kilomètres de jogging par semaine) et l'absentéisme sont correlés de façon inverse, mais seulement jusqu'à 50 km d'entraînement hebdomadaire. Les coureurs fumeurs de cigarettes ont plus de 50% d'absences de plus que les coureurs non-fumeurs (p<0,001). L'importance relative du motif pour le jogging «comme compensation au travail journalier» est associée de manière inverse à l'absentéisme (p<0,001), tandis que le contraire est le cas pour l'importance des motifs axés vers la compétition (p<0,001). Une analyse multivariée basée sur un total de 8 facteurs peut expliquer que 11% de la variance de l'absentisme, soulignant ainsi le caractère complexe de la variable dépendente analysée. La question visant la relation causale entre le jogging actif et régulier (mais non exagéré) et un absentisme diminué reste ouverte. Seule des études avec intervention permetteraient de mieux juger le potentiel supposé du sport et de l'activité physique en loisir de réduire l'absentisme.

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Der Autor dankt René Rehmann für die Durchführung sämtlicher Datenanalysen, Horst Noack für die kritische Durchsicht des Manuskripts sowie Theres Bietenholz und Christine Vauclair-Liniger für die sekretarielle Hilfe.