Molecular fingerprints resolve affinities of Rhynie chert organic fossils.

The affinities of extinct organisms are often difficult to resolve using morphological data alone. Chemical analysis of carbonaceous specimens can complement traditional approaches, but the search for taxon-specific signals in ancient, thermally altered organic matter is challenging and controversial, partly because suitable positive controls are lacking. Here, we show that non-destructive Fourier Transform Infrared Spectroscopy (FTIR) resolves in-situ molecular fingerprints in the famous 407 Ma Rhynie chert fossil assemblage of Aberdeenshire, Scotland, an important early terrestrial Lagerstätte. Remarkably, unsupervised clustering methods (principal components analysis and K-mean) separate the fossil spectra naturally into eukaryotes and prokaryotes (cyanobacteria). Additional multivariate statistics and machine-learning approaches also differentiate prokaryotes from eukaryotes, and discriminate eukaryotic tissue types, despite the overwhelming influence of silica. We find that these methods can clarify the affinities of morphologically ambiguous taxa; in the Rhynie chert for example, we show that the problematic "nematophytes" have a plant-like composition. Overall, we demonstrate that the famously exquisite preservation of cells, tissues and organisms in the Rhynie chert accompanies similarly impressive preservation of molecular information. These results provide a compelling positive control that validates the use of infrared spectroscopy to investigate the affinity of organic fossils in chert.

Bone density and body composition in children with growth hormone insensitivity syndrome receiving recombinant IGF-I.

OBJECTIVE: There are few reports of the metabolic action of insulin-like growth factor 1 (IGF-I) in vivo. Growth hormone insensitivity syndrome is a good model to examine the effects of IGF-I deficiency. This study was designed to assess body composition and bone density in children with growth hormone insensitivity syndrome before and after receiving treatment with recombinant IGF-I. DESIGN: A prospective longitudinal study. PATIENTS: Four prepubertal boys age 6.1-9.8 years with short stature due to growth hormone insensitivity syndrome. MEASUREMENTS: Assessment of body fat by skinfold thickness measurements and dual energy X-ray absorptiometry (DXA) was made during the first 6 months of recombinant IGF-I treatment. Assessment of lumbar spine bone density by DXA was performed prior to IGF-I treatment and during the subsequent five years. RESULTS: Each child showed a significant reduction in fat mass (0.26-1.22 kg) after 6 weeks of IGF-I treatment. Bone density prior to treatment was reduced in comparison to age-matched controls but calculated volumetric bone density was within the normal range. Volumetric bone density progressively improved over the 5-year treatment period. CONCLUSIONS: Children with growth hormone insensitivity syndrome exhibit a metabolic response to IGF-I within 6 weeks analogous to that seen in GH-deficient children receiving GH. Bone density when corrected for body size is within normal limits and demonstrates a response to IGF-I, confirming the anabolic action on bone.

A homozygous splice site mutation affecting the intracellular domain of the growth hormone (GH) receptor resulting in Laron syndrome with elevated GH-binding protein.

Laron syndrome (LS) is a severe autosomal recessive form of GH resistance resulting from molecular defects in the GH receptor (GHR). Affected individuals have extreme short stature and a typical facial phenotype. The point mutations in the GHR gene identified in this condition have until now been confined to the region encoding the extracellular domain of the receptor. We report here the first homozygous point mutation within the intracellular domain of the GHR in two LS cousins distinguishable from classical LS patients only by the presence of elevated GH-binding protein (GHBP) in their serum. A G to C transversion at the vital - 1 position in the splice donor site of exon 8 disrupts normal splicing, resulting in the complete skipping of exon 8, producing a mutant GHR protein lacking transmembrane and intracellular domains. We predict that this mutant protein would not be anchored in the cell membrane and would be measurable in the circulation as GHBP, hence explaining the phenotype of severe GH resistance combined with elevated circulating GHBP.

Clonidine is a better test for growth hormone deficiency than insulin hypoglycaemia.

The oral clonidine test was compared with the standard intravenous insulin hypoglycaemia test in 41 children and adolescents with short stature. In those without growth hormone deficiency clonidine provoked a significantly higher mean plasma growth hormone response and gave fewer false subnormal responses (apparent growth hormone deficiency) than insulin. Children with psychosocial deprivation had poorer responses to both tests. In view of these findings and the absence of unacceptable side effects with clonidine it is concluded that the oral administration of this alpha-adrenergic stimulant is a safe and reliable alternative test of growth hormone release.

Accidental poisoning deaths in British children 1958-77.

In the 20 years 1958-77 598 deaths were registered as due to accidental poisoning in British children under the age of 10-343 boys and 255 girls. Drugs caused 484 deaths, non-medicinal products 111, and plants three. The annual number of deaths reached a peak in 1964 but fell steadily thereafter; 16 deaths occurred in 1977. After 1970 tricyclic antidepressants replaced salicylates as the most commonly fatal poison. The next ten drugs most often recorded in 1970-7 were, in order, opiates (including diphenoxylate/atropine (Lomotil)), barbiturates, digoxin, orphenadrine (Disipal), quinine, potassium, iron, fenfluramine (Ponderax), antihistamines, and phenothiazines. In 20 years paracetamol caused one death, and before 1976 deaths caused by aspirin had fallen to fewer than two a year. Thus the introduction in 1976 and 1977 of safety packaging of these drugs can be expected to have little impact on the mortality from them in childhood.