The effect ofβ-adrenergic stimulation and blockade on the efflux of PGE1-like material from the isolated perfused rabbit heart

Summary Prostaglandin (PG) release was measured from the isolated perfused rabbit heart. The effects of -adrenergic stimulation and blockade suggest that PG synthesis is regulated in part by adrenergic mechanisms.     

Impaired amylase release from the parotid gland of rats treated with reserpine.

Using an automated system for the analysis of amylase, the release of this enzyme was compared in superfused parotid gland segments from control and reserpine treated rats. Stimulant-evoked amylase release was delayed and of smaller magnitude in the glands of the treated animals and a reduction of the transmembrane K+ gradient caused a smaller and short lasting reduction in Ach-evoked release of amylase in the glands from these animals.     

The effect of acidic polysaccharides and prostaglandin-like substances isolated from Propionibacterium acnes on granulocyte chemotaxis.

Three acidic polysaccharide (AP) fractions and the prostaglandin-like substances (PLS) isolated from P. acnes were investigated regarding their chemotactic activities on polymorphonuclear leukocytes. Both AP's and PLS induced a significant chemotatic response, which suggests their involvement in inflammatory acne vulgaris.     

Effect of insulin on immunological phagocytosis by macrophages.

It was shown that, in physiological concentrations, insulin enhances, in vitro, the immunological phagocytosis of sensitized sheep erythrocytes by cultured mouse peritoneal macrophages. Insulin seems to stimulate macrophage phagocytosis as a cholinomimetic agonist by increasing the intracellular levels of cyclic GMP.     

Multiplicity of monoamine oxidase in chick brain

Summary The substrate- and inhibitor-related characteristics of monoamine oxidase (MAO) were studied on chick brain mitochondria. It was found that neither 5-hydroxytryptamine nor -phenylethylamine is the specific substrate for type A and type B MAO in chick brain.     

An assessment of the effect of hormone and neurotransmitters on adenine and gluanine derivatives simultaneously in rat brain cortical slices

Summary A 2-dimensional thin-layer method has been developed for the separation on cellulose of adenine and guanine derivatives. Using incubated rat cerebral cortex slices it was shown that noradrenaline and acetylcholine stirnulated cAMP and cGMP production respectively but glutamate and -aminobutyric acid stimulated production of both cyclic nucleotides.     

Reciprocal changes in serum free thyroxine fraction and thyrotropin level after administration of thiocyanate to rats

Summary The administration of thiocyanate to rats caused a significant increase of serum free thyroxine fraction, which coincided with the significant decrease of TSH level. The other components (AFT₄, T₄, T₃) in serum at this time were decreased or unchanged. The finding suggests the role of free thyroxine fraction in feed-back regulation of TSH secretion.Acknowledgment. We thank Dr A. Parlow and the NIAMDD, Rat Pituitary Hormone Distribution Program, for material for rat TSH immunoassay; Dr J. Nauman (Inst. Postgrad. Med., Warsaw, Poland) for T₃ antibody, and to Ing. J. Sadlo, Mrs M. t'astná and Miss R Fajkoová for technical assistance.     

Trak1 mutation disrupts GABA(A) receptor homeostasis in hypertonic mice

Hypertonia, which results from motor pathway defects in the central nervous system (CNS), is observed in numerous neurological conditions, including cerebral palsy, stroke, spinal cord injury, stiff-person syndrome, spastic paraplegia, dystonia and Parkinson disease. Mice with mutation in the hypertonic (hyrt) gene exhibit severe hypertonia as their primary symptom. Here we show that hyrt mutant mice have much lower levels of gamma-aminobutyric acid type A (GABA(A)) receptors in their CNS, particularly the lower motor neurons, than do wild-type mice, indicating that the hypertonicity of the mutants is likely to be caused by deficits in GABA-mediated motor neuron inhibition. We cloned the responsible gene, trafficking protein, kinesin binding 1 (Trak1), and showed that its protein product interacts with GABA(A) receptors. Our data implicate Trak1 as a crucial regulator of GABA(A) receptor homeostasis and underscore the importance of hyrt mice as a model for studying the molecular etiology of hypertonia associated with human neurological diseases.     

Genome-wide genetic association of complex traits in heterogeneous stock mice

Difficulties in fine-mapping quantitative trait loci (QTLs) are a major impediment to progress in the molecular dissection of complex traits in mice. Here we show that genome-wide high-resolution mapping of multiple phenotypes can be achieved using a stock of genetically heterogeneous mice. We developed a conservative and robust bootstrap analysis to map 843 QTLs with an average 95% confidence interval of 2.8 Mb. The QTLs contribute to variation in 97 traits, including models of human disease (asthma, type 2 diabetes mellitus, obesity and anxiety) as well as immunological, biochemical and hematological phenotypes. The genetic architecture of almost all phenotypes was complex, with many loci each contributing a small proportion to the total variance. Our data set, freely available at http://gscan.well.ox.ac.uk, provides an entry point to the functional characterization of genes involved in many complex traits.