Around 15-20 hereditary disorders associated with impaired DNA damage response mechanisms have been previously described. The range of clinical features associated with these disorders attests to the significant role that these pathways play during development. Recently, three new such disorders have been reported extending the importance of the damage response pathways to human health. LIG4 syndrome is conferred by hypomorphic mutations in DNA ligase IV, an essential component of DNA non-homologous end-joining (NHEJ), and is associated with pancytopaenia, developmental and growth delay and dysmorphic facial features. Radiosensitive severe combined immunodeficiency (RS-SCID) is caused by mutations in Artemis, a protein that plays a subsidiary role in non-homologous end-joining although it is not an essential component. RS-SCID is characterised by severe combined immunodeficiency but patients have no overt developmental abnormalities. ATR-Seckel syndrome is caused by mutations in ataxia telangiectasia and Rad3 related protein (ATR), a component of a DNA damage signalling pathway. ATR-Seckel syndrome patients have dramatic microcephaly and marked growth and developmental delay. The clinical features of these patients are considered in the light of the function of the defective protein.

Ataxia Telangiectasia Mutated Proteins↗

PubMedDate not supplied

High resolution PET, SPECT and projection imaging in small animals.

Positron emission tomography, single photon emission computed tomography and planar projection imaging of radioactive tracers have long been in use for detecting and diagnosing disease in human subjects. More recently, advanced versions of these same technologies have begun to be used across the breadth of modern biomedical research to study non-invasively small laboratory animals in a myriad of experimental settings. In this report, we describe some of the new instruments and techniques that make these measurements possible and illustrate, with a few examples, the potential power of these methods in modern biomedical research.

Animals↗

PubMedDate not supplied

[Interdisciplinary treatment of early-onset ornithine transcarbamylase (OTC) deficiency. Two case reports and a review].

PATIENT REPORTS: We report on a male preterm infant (gestational age 31 weeks, birth weight 1420 g) and a male term infant (gestational age 38 weeks, birth weight 3680 g) with ornithine transcarbamylase (OTC) deficiency. After inconspicuous cardiopulmonary adjustment, both entered a state of metabolic crisis with respiratory insufficiency and ventilatory requirement at the 2nd and 4th day of life, respectively. Diagnosis of hyperammonemia (NH(3) > 1000 micromol/l) was followed by the detection of a plasma amino acid pattern that is typical for OTC-deficiency and an excessive orotic aciduria. Beside intravenous treatment (insulin-glucose-infusion, lipid infusion, sodium benzoate, arginine, L-carnitine), the preterm infant received an exchange transfusion and was supplied with central venous catheters, hemofiltration and hemodialysis. He died after severe disturbances of circulation and coagulation at the 14th day. The male term infant tolerated the effective hemofiltration and was dicharged home with specific therapy at day 26. CONCLUSIONS: Time of diagnosis and influence of additional risk factors are decisively for the prognosis of OTC-deficiency. The immediate aims of therapy (stabilization of vital functions, reduction of plasma ammonium, control of nutrition) can only be realized in cooperation between neonatology, division of metabolism, pediatric nephrology and pediatric surgery.

Exchange Transfusion, Whole Blood↗

PubMedDate not supplied

Some histochemical and electrophysiological effects of isatin.

Qualitative and semiquantitative histochemical investigations of acetylcholinesterase after a single or repeated administration of isatin, 160 mg/kg ip once or daily for 8 consecutive days have revealed a significant decrease of the histochemical reaction for acetylcholinesterase in chronically treated rats. The cholinergic effect of isatin was tested in the electrophysiological experiment after a single dose of 160 mg/kg isatin and was partially antagonized by atropine.

Acetylcholinesterase↗