Body fat distribution reference standards in Spanish adolescents: the AVENA Study.

OBJECTIVE: To present body fat patterning reference standards to identify children with a predominant distribution of body fat in the abdominal or truncal region of the body. DESIGN: Cross-sectional study in a representative sample of Spanish adolescents aged 13-18 years. SUBJECTS: A total of 2160 adolescents with a complete set of anthropometric measurements (1109 males and 1051 females). MEASUREMENTS: Weight, height, body mass index, skinfold thickness (biceps, triceps, subscapular, suprailiac, thigh, calf) and waist and hip circumferences. RESULTS: In the majority of the age groups, subscapular/triceps skinfolds ratio, trunk-to-total skinfolds percent (TTS%)and waist circumference values were significantly higher in males than in females; hip circumference was higher in females than in males, except at 15.5 years. In males, age showed a significant effect for all the body fat distribution indices; however, in females, the effect was only significant for triceps skinfold, waist and hip circumferences and waist-to-hip ratio. Smoothed age- and sex-specific triceps skinfold, subscapular skinfold, subscapular/triceps skinfolds ratio, TTS%, waist circumference and hip circumference, waist-to-hip and waist-to-height ratio percentile values for male and female adolescents have been established. CONCLUSION: These reference data for waist circumference and the other fat patterning indices, together with data from other countries, will help to establish international central obesity criteria for adolescents. The presented percentile values will give the possibility to estimate the proportion of adolescents with high or low regional adiposity amounts.

Anthropometric body fat composition reference values in Spanish adolescents. The AVENA Study.

OBJECTIVE: To determine reference values for body mass index (BMI), sum of six skinfolds (sigma6 skinfolds) and body fat percentage (BF%) in Spanish adolescents aged 13-18 years, included in the AVENA Study (Alimentación y Valoración del Estado Nutricional en Adolescentes: Food and Assessment of the Nutritional Status of Adolescents). DESIGN: Multicentre cross-sectional study. SETTING: Representative sample of Spanish adolescents. SUBJECTS: The population was selected by means of a multiplestep, simple random sampling. The final number of subjects included in the AVENA Study was 2859 adolescents; 2160 adolescents had a complete set of anthropometric measurements and were then included in this study (1109 males and 1051 females). INTERVENTIONS: Weight, height and six skinfold thicknesses were measured. As indices of total adiposity, we calculated BMI, summation sigma6 skinfolds and BF% with the formulas described by Slaughter et al. RESULTS: Sigma6 skinfolds and BF% in each age group were significantly higher in females than in males. In males, age showed a significant effect for BMI, sigma6 skinfolds and BF%; however, in females, the effect was only significant for BF%. The percentile distribution was more disperse towards higher sigma6 skinfolds and BF% values in males when compared with females. CONCLUSIONS: The presented percentile values will help us to classify adolescents in comparison with a well-established reference population, and to estimate the proportion of adolescents with high or low adiposity amounts. SPONSORSHIP: The AVENA-Study was supported by the Spanish Ministry of Health (FIS 00/0015), and grants from Panrico SA, Madaus SA and Procter and Gamble SA. This study was also supported by Instituto de Salud Carlos III (Spain), RCESP (C03/09) and Spanish Ministry of Education (AP2003-2128).

[Mycophenolate mofetil in lupus nephritis]. / Micofenolato mofetil en la nefritis lúpica.

The treatment of severe lupus nephritis is based on the combination of steroids and cytotoxic drugs. Intravenous cyclophosphamide administered in "pulses" is effective in the induction of remission but other therapeutic alternatives are sought in refractory cases or severely relapsing patients. Mycophenolate mofetil, used in renal transplantation, also can be useful in severe lupus nephritis. We describe the evolution of 6 patients (5 women and 1 man; age 17-45 years) with severe lupus nephropathy who after achieving remission with intravenous cyclophosphamide and steroids (5 cases) or cyclosporin A (1 case) showed relapse of proteinuria and were treated with mycophenolate mofetil (dose 1000-2000 mg/day). Two patients have completed 24 months, 1 patient two cycles of 12 months, 2 patients 18 months and 1 patient 6 months. After this treatment, all patients have achieved remission (3 partial and 3 complete). There was no treatment failure and no one patient discontinued medication; however 1 case relapsed. There were no changes in leucocytes, haemoglobin, serum creatinine and serum albumin. ANA and alpha DNA antibodies decreased. Proteinuria (measured as protein/creatinine urine ratio: initial 3 and final 0.3) and dose of steroids (initial: 17.5 mg/d and final 5 mg/d) decreased significantly (p < 0.05 Wilcoxon t-test). The most common side effects were nausea and abdominal discomfort that improved without discontinuation of treatment. We conclude that mycophenolate mofetil is effective and a safe drug in severe relapsing lupus nephritis.

Micofenolato mofetil en la nefritis lúpica / Mycophenolate mofetil in lupus nephritis

El tratamiento de la nefritis lúpica grave se basa en la asociación de esteroides e inmunosupresores. La ciclofosfamida parenteral administrada en 'bolus' es eficaz en la inducción de remisión, pero en casos refractarios o recidivantes son necesarias otras alternativas. El micofenolato mofetil, eficaz para prevenir el rechazo en el trasplante renal, puede ser útil en estas ocasiones. Describimos la evolución de 6 pacientes (5 mujeres y 1 varón; edad 17-45 años) y nefritis lúpica grave que tras responder al tratamiento con ciclofosfamida iv y esteroides orales (5 pacientes) o ciclosporina A (1 paciente) presentaron recidiva e iniciaron tratamiento con micofenolato a dosis de 1.000-2.000 mg/día. Dos pacientes han completado 24 meses, 1 paciente 2 ciclos de 12 meses, 2 pacientes 18 meses y 1 paciente 6 meses. Tras este tratamiento, 3 de ellos han entrado en remisión completa y 3 en remisión parcial. No existió fracaso terapéutico ni abandono del tratamiento, si bien un paciente presentó una recidiva. Globalmente no encontramos modificaciones de leucocitos, creatinina ni albúmina sérica. Los anticuerpos DNA y ANA descendieron y apreciamos una disminución significativa (p < 0,05) de la proteinuria (relación proteína/creatinina en orina inicial 3 y final 0,3) y de la dosis de prednisona (inicial 17,5 mg/d y final 5 mg/d). Los únicos efectos secundarios fueron náuseas y molestias digestivas que desaparecieron sin suspender el tratamiento. Concluimos que el micofenolato puede ser un fármaco eficaz en las formas recidivantes de nefritis lúpica (AU)

Cloning and gene defects in microsomal triglyceride transfer protein associated with abetalipoproteinaemia.

The microsomal triglyceride transfer protein (MTP), which catalyses the transport of triglyceride, cholesteryl ester and phospholipid between phospholipid surfaces, is a heterodimer composed of the multifunctional protein, protein disulphide isomerase, and a unique large subunit with an apparent M(r) of 88K (refs 1-3). It is isolated as a soluble protein from the lumen of the microsomal fraction of liver and intestine. The large subunit of MTP was not detectable in four unrelated subjects with abetalipoproteinaemia, a rare autosomal recessive disease characterized by a defect in the assembly or secretion of plasma lipoproteins that contain apolipoprotein B (ref. 6). We report here the isolation and sequencing of complementary DNA encoding the large subunit of MTP. A comparison of this sequence to corresponding genomic sequences from two abetalipoproteinaemic subjects revealed a homozygous frameshift mutation in one subject and a homozygous nonsense mutation in the other. The results indicate that a defect in the gene for the large subunit of MTP is the proximal cause of abetalipoproteinaemia in these two subjects, and that MTP is required for the secretion of plasma lipoproteins that contain apolipoprotein B.

Porcine pancreatic phospholipase A2 isoforms: differential regulation by heparin.

Isoforms of porcine pancreatic phospholipase A2 (PLA2) can be differentially regulated by heparin. The major isoform of PLA2 can bind to heparin-Affigel and its catalytic activity can be inhibited by heparin. The interaction between this PLA2 isoform and heparin does not require calcium ion or a functional active site. The sensitivity to heparin inhibition depends on the pH, with optimum sensitivity at pH 5-7 and greatly diminished sensitivity as the pH is increased from 7 to 10. A minor isoform of porcine pancreatic PLA2 cannot bind to heparin and is resistant to heparin inhibition. The resistant isoform appears to be iso-pig PLA2. Heparin affinity chromatography therefore offers a convenient route to the isolation of structurally and functionally distinct classes of PLA2 enzymes. The existence of classes of PLA2 that can be differentially regulated by heparin may have important physiological consequences.

Purification and characterization of apolipoprotein J.

Apolipoprotein J (apoJ), a unique 70-kDa component of high density lipoproteins in human plasma, consists of two disulfide-linked subunits designated apoJ alpha (34-36 kDa), and apoJ beta (36-39 kDa) which share pI values of 4.9-5.4 and which are recognized by a monoclonal antibody (mAb) 11. ApoJ and its subunits were purified to homogeneity from plasma by a combination of immunoaffinity chromatography, using mAb11 linked to Affi-Gel, and reverse-phase high performance liquid chromatography. ApoJ alpha and apoJ beta are both glycoproteins. When deglycosylated, the molecular mass of apoJ alpha is 24 kDa and that of apoJ beta is 28 kDa, suggesting that approximately 30% of the mass of each subunit is carbohydrate. The amino acid compositions of apoJ alpha and apoJ beta are very similar; however, the sequences of the first 30-amino acid residues are distinct. A comparison of peptide maps suggests that apoJ alpha and apoJ beta are not identical but share limited regions of homology. This possibility is supported by immunochemical data. Five additional mAb specific for apoJ were characterized. One of the mAb, like mAb11, reacts with both apoJ alpha and apoJ beta; the others react with apoJ alpha only. All mAb, including those which recognize both apoJ alpha and apoJ beta and those which recognize apoJ alpha only, immunoprecipitate a approximately 50-kDa protein synthesized from a liver mRNA template translated in a rabbit reticulocyte lysate. We propose that the apoJ alpha and apoJ beta subunits, which have limited homology, are derived by proteolytic cleavage of a common precursor.

Apolipoprotein J: structure and tissue distribution.

The primary structure of apolipoprotein J (apoJ) was deduced by the combined strategies of protein sequencing and cDNA cloning and sequencing. ApoJ, an apolipoprotein associated with discrete subclasses of high-density lipoproteins, is encoded by a single gene in both the human and mouse genomes. ApoJ is synthesized as a 427 amino acid polypeptide that is posttranslationally cleaved at an internal bond between Arg-205 and Ser-206. The subunits of apoJ are designated apoJ alpha, corresponding to residues 1-205, and apoJ beta, corresponding to resides 206-427. The subunits are associated through disulfide bonds. Analysis of the primary structure of apoJ predicts the existence of amphiphilic helices, which may account for the association of apoJ with lipoproteins, and heparin-binding motifs in both subunits. ApoJ appears to be the human analogue of a rat protein present in high concentrations in the testis, sulfated glycoprotein 2. ApoJ mRNA (1.9 kb) is expressed in all but one tissue examined. The mRNA is present in relatively high levels in brain, ovary, testis, and liver, is less abundant in heart, spleen, lung, and breast, and is absent in T-lymphocytes. ApoJ is unique among previously characterized human apolipoproteins in its structure and tissue distribution.