Causes of Stability of Aggression from Early Childhood to Adolescence: A Longitudinal Genetic Analysis in Dutch Twins

This study investigated the contribution of genetic and environmental influences on the stability of aggressive behavior from early childhood to adolescence. Two developmental models, the simplex model and the common factor model, were tested to study the underlying processes of stability and change. Measures of aggressive behavior (AGG) were obtained from maternal CBCL data as part of a large ongoing longitudinal study of the Netherlands Twin Registers (NTR) and included data from 6488 three-year-old twin pairs, 5475 seven-year-old twin pairs, 2983 ten-year-old twin pairs, and 1509 twelve-year-old twin pairs. AGG showed moderate to high stability during childhood. The stability coefficients ranged from 0.41 to 0.77 across varying intervals. Averaged across boys and girls, genetic factors accounted for approximately 65% of the total stability. Longitudinal genetic analysis indicated a simplex model for genetic effects, which suggests a dynamic development process consisting of transmission of existing genetic effects interacting with new genetic influences. This is especially true at age 7, when the influence of new genetic factors was large. Shared environmental factors accounted for approximately 25% of phenotypic stability, and it seemed that a stable set of the same shared environmental factors underlay the development of AGG. Nonshared environmental factors, when important, are age specific. Sex-specific differences for stability were identified. For boys, genetic influences were greater, whereas for girls shared environmental factors were more important. These data support the idea that both genetic and environmental influences play a role in the stability of AGG from age 3 to 12.     

The mutational spectrum of brachydactyly type C

Growth/differentiation factor-5 (GDF5), also known as cartilage-derived morphogenetic protein-1 (CDMP-1), is a secreted signaling molecule that participates in skeletal morphogenesis. Heterozygous mutations in GDF5, which maps to human chromosome 20, occur in individuals with autosomal dominant brachydactyly type C (BDC). Here we show that BDC is locus homogeneous by reporting a GDF5 frameshift mutation segregating with the phenotype in a family whose trait was initially thought to map to human chromosome 12. We also describe heterozygous mutations in nine additional probands/families with BDC and show nonpenetrance in a mutation carrier. Finally, we show that mutant GDF5 polypeptides containing missense mutations in their active domains do not efficiently form disulfide-linked dimers when expressed in vitro. These data support the hypothesis that BDC results from functional haploinsufficiency for GDF5.     

Partial trisomy 1q. A nonrandom primary chromosomal abnormality in myelodysplastic syndromes?

Cytogenetic and clinical data of 11 patients with de novo myelodysplastic syndromes and partial or total trisomy of the long arm of chromosome 1 are presented. In eight of these patients trisomy 1q was the sole karyotypic change and therefore can be classified as a primary chromosome anomaly. A remarkably young median age of 36.5 years was noticed in this patient group.     

Subacute thyroiditis (de Quervain) presenting as a painless "cold" nodule

A 49-yr-old woman presented with a solid, painless, nontender nodule in the left thyroid lobe. Thyroid scintigraphy revealed a solitary "cold" area in the left lobe and a slightly decreased 24-hr radioactive iodine thyroid uptake (9%). Although there were no specific clinical or biochemical signs suggesting thyroiditis needle aspiration cytology showed the presence of a subacute thyroiditis. Approximately 1 mo later the entire thyroid gland was affected leading to a completely suppressed thyroid radioiodine uptake and elevated serum thyroid hormone concentrations. This case illustrates that in the early phase of the disease, subacute thyroiditis may present as a solitary, painless, "cold" nodule and should be considered in the differential diagnosis of such lesions.     

Development and evaluation of an enzyme-linked immunoassay for the prostate: specific antigen utilizing two monoclonal antibodies

Summary PSA is an important tumor-marker for prostatic cancer disease. We developed a sensitive, simple and inexpensive Sandwich ELISA for PSA with two monoclonal antibodies. The precision and reliability of the assay are reflected in the low inter-and intraassay coefficient of variation. PSA was not detectable in sera from normal females (n=50). Sera from males with different serum levels of PSA (normal males, patients with prostate hypertrophy, prostate cancer patients, n=79) and 15 prostate cancer patients treated with Zoladex were measured by our ELISA and by a commercially available RIA. The correlation coefficient between these both testsystems was close to 1 (r=0.97).     

Surgical approach and histoanatomical aspects of the oculomotor nerve in rats

The surgical approach and some histoanatomical characteristics of the intracavernous portion of the oculomotor nerve are described. Moreover, some perioperative precautions for intracranial surgical procedures in the rat are reported and the suitability of the rat as a model for studying intracranial nerve regeneration is discussed. With the data provided, this model of oculomotor nerve approach can be used to study various aspects of intracranial nerve regeneration.     

Decreased β2-adrenoceptor density and decreased isoproterenol induced c-AMP increase in juvenile type I diabetes mellitus: An additional cause of severe hypoglycaemia in childhood diabetes?

Little is known about the receptor and post receptor mechanisms of sympathoadrenal signal transmission in type I diabetes mellitus. Therefore, we examined the maximum binding of granulocyte ₂-adrenoceptors and the in vitro c-AMP accumulation in lymphocytes of 24 children and adolescents with diabetes mellitus and 14 similarly aged healthy subjects. The number of high affinity ₂-adrenoceptors on granulocytes correlated significantly with unstimulated (r=0.6,P<0.004) and with isoproterenol stimulated c-AMP values in lymphocytes (r=0.68,P<0.0007) showing the proportional changes of ₂-adrenoceptors and c-AMP in two different cells. The number of ₂-adrenoceptors on granulocytes was significantly reduced in diabetic as compared to healthy children (median 1397, range 599–3405 vs. 2205, 825–3200 ₂-adrenoceptors per granulocyte,P=0.014). Moreover, the percentage in vitro stimulation of c-AMP by isoproterenol in lymphocytes was significantly reduced in diabetic children as compared to healthy individuals (120%, 39%–278% vs. 225%, 66%–500%,P=0.012). These results indicate a decreased sympathoadrenergic signal transmission in peripheral blood cells as a model for the liver probably contributing to severe hypoglycaemia in diabetic children.