A new hot spot for mutations in the ret protooncogene causing familial medullary thyroid carcinoma and multiple endocrine neoplasia type 2A.

One hundred and eighty-one families with multiple endocrine neoplasia type 2A (MEN-2A) or familial medullary thyroid carcinoma (FMTC) have been investigated for mutations in the ret protooncogene in Germany. In 8 families with FMTC or MEN-2A, no mutation could be detected in the cysteine-rich domain encoded in exons 10 and 11 of the ret protooncogene. DNA sequencing of additional exons (no. 13-15) revealed rare noncysteine mutations in 3 families (codons 631, 768, and 844). In contrast to these rare events, heterozygous missense mutations in exon 13, codons 790 and 791, were found in 5 families (4 with MTC only; 1 family with MTC and pheochromocytoma) and 11 patients with apparently sporadic tumors. Two different mutations in codon 790 (TTG-->TTT, TTG-->TTC; Leu790Phe) and one mutation in codon 791 (TAT-->TTT; Tyr791Phe) created a phenylalanine residue. We conclude that codons 790 and 791 of the ret protooncogene represent a new hot spot for FMTC/MEN-2A causing mutations. With the discovery of these considerably common mutations in codons 790 and 791 and the identification of some rare mutations, 100% of the German FMTC/MEN-2A families could be characterized by a mutation in the ret protooncogene.

[Determination of lean body mass by skin fold measurements (author's transl)]. / Untersuchungen zur Bestimmung der Hautfaltendicke mit verschiedenen Kalipern

Skin folds were measured on 12 different body sites of 32 boys, aged 9--12, by using the calipers of Best, Lange, Harpenden and Holtain successively. We compared the measurements of the biceps, triceps, scapula, suprailiaca, abdominal and thigh skin folds. The results depended on body sites as well as on the type of caliper used. Therefore, conversion is recommendable only when absolute values of body fat must be taken into consideration, as when investigating population parameters in terms of functional performance capacity. Moreover conversion is necessary when using those nomograms which are built up mainly by measurements with an unusual caliper. Conversions must be omitted when comparing data by means of rank-correlations.

[Studies on the influence of various mathematical formulations on the determination of the proportion of fat in relation to bodyweight by means of skin fold measurements (author's transl)]. / Untersuchungen über den Einfluss verschiedener Rechenansätze auf die Ermittlung des relativen Fettanteils am Körpergewicht mit Hilfe von Hautfaltenmessungen.

The paper reports on investigations on the influence of various mathematical formulations on the determination of the proportion of fat in relation to body-weight by means of skin fold measurements. For this purpose, the various equations derived from Archimedes' law, as well as the densities of various body fractions as determined by different authors, are discussed. This is followed by a discussion of the deliberations on the methods to be employed for estimating the density of the body by means of skin fold measurements. The various formulations differ from each other mainly by the location and number of measuring points. It was shown by means of comparative studies that for children aged between 9 and 16, independent of their sex, it will be sufficient to employ two skin folds (triceps and scapula). The existence of a very close correlation between the measured data of these points of measurement was found when using different calipers and the relevant conversion factors. In this manner it becomes possible to use a nomogram which has already been determined by Parízková and which was converted into a matrix for easier calculation. The determination of the relative proportion of fat'via skin fold measurements cannot replace the determination of individual body density by weighing under water. However, in mass examinations it is very well suited for differentiating between various groups of children (e.g. overweight, underweight, trained, and untrained) in respect of their relative proportion of fat.

Maximum aerobic power and body composition during the puberty growth period: similarities and differences between children of two European countries.

This report gives results of a longitudinal study of two cohorts of school children in Norway and West-Germany. The rate of growth in body size and composition is identical for the two samples, but different for the two sexes, and follows closely the trend of growth which has been found for North-Europeans in general. Despite of this similarity in growth of anatomical variables the Norwegian children appeared to be superior in their maximum aerobic power at all comparable ages and in both sexes. The differences between means in maximal oxygen uptake varies somewhat with age and sex and are in the range of 5-10%. It is suggested that the mean differences between Norwegian and German children in their exercise and cardio-vascular fitness are brought about by a more physically active behavioural pattern of living in Norway.

The growth of lung volumes affected by physical performance capacity in boys and girls during childhood and adolescence.

The paper concerns a longitudinal study of the relationship between growth in lung functions in terms of forced vital capacity and forced expiratory volume in 1 s, and the development of maximal aerobic power during the age span from 8-18 years of age. The growth curves of anatomical dimensions for boys and girls were similar to those previously established for Northern European children. The growth in lung volume ended later than the growth in body height. It was found that the growth in lung volume was entirely due to growth in body dimensions, with no additional effect of changes in the development of physical performance capacity.

Leisure time sport activities and maximal aerobic power during late adolescence.

The pattern of leisure time sport activity was estimated by retrospective recalls and expressed in terms of an annual sport activity score. The activity score was related to the development of maximal aerobic power during the period of late adolescence in German children. Both girls and boys reduced their activity pattern from 14 to 18 years of age, boys more than girls. At each age boys were more active than girls. A slight tendency towards better fitness with increased habitual physical activity was noticed, but many sedentary children exhibited a good performance capacity and some children with a high level of leisure time sport activity were characterized by a low level of maximal aerobic power. A statistical analysis revealed that the observed tendency to better fitness with increased habitual physical activity could be explained by an age factor with no additional effect of variation in sport activity score.

Lack of MEN1 gene mutations in 27 sporadic insulinomas.

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant familial cancer syndrome characterized by tumours of the parathyroids, anterior pituitary gland and endocrine pancreas. Since the cloning of the MEN1 gene (encoding menin) on chromosome 11q13 by Chandrasekharappa et al. in 1997, it has become possible to identify mutations that are responsible. We examined whether MEN1 gene mutations are present in sporadic insulinomas, a rare sporadic tumour that is seen more frequently in patients with the MEN 1 syndrome. PATIENTS AND METHODS: We sequenced the coding part of the MEN1 gene (exons 2-10) in tumour tissue of 27 patients suffering from an insulinoma (24 benign, three malignant). To validate our methods we also examined tumour tissue from five patients with primary hyperparathyroidism (HPT) at a younger age and/or multiple gland disease, with increased risk of MEN 1. RESULTS: We found no mutations in the nine coding exons of the MEN1 gene in the insulinoma tissues. We could confirm three benign polymorphisms (S145S, R171Q, D418D) reported previously. In the control patients we found two new point mutations (one mis-sense, one non-sense mutation) and one deletion. CONCLUSION: Mutations of the MEN1 gene do not play an important role in the pathogenesis of sporadic insulinomas. Therefore genetic screening is not cost effective in sporadic insulinoma patients without other indicators of MEN 1. Patients with primary HPT at a younger age and/or multiple gland disease should be screened for MEN1 gene mutations.