A new missense mutation of fibrillin in a patient with Marfan syndrome.

A patient with Marfan syndrome was shown to be heterozygous for a G to A transition at nucleotide 3952 of the FBNI gene. This would result in a cysteine to tyrosine substitution at amino acid 1223 in the fibrillin protein.     

Serum and plasma from patients with Lambert-Eaton myasthenic syndrome reduce depolarization-dependent uptake of Ca into rat cortical synaptosomes

The reduction in nerve-evoked release of transmitter at the neuromuscular jkunction of patients with Lamber-Eaton Myasthenic Syndrome (LEMS) is thought to be caused by a circulating autoantibody to calcium channels of presynaptic motor nerve terminals. Studies were undertaken to determine whether acute application of plasma and serum from patients with LEMS or small cell carcinoma (SCC) would reduce depolarization-dependent uptake of ⁴⁵Ca²⁺ into isolated nerve terminals of the central nervous system (CNS). Net potassium-stimulated influx was reduced by sera and plasma from patients with LEMS but not by sera from patients with SCC. Lactate dehydrogenase (LDH) release from synaptosome incubated with plasma or serum from patients with LEMS was not increased over control. These results are significant because: (1) they demonstrate that acute exposure to a circulating factor in sera/plasma from a patient with LEMS is sufficient to inhibit Ca²⁺ channel activity in isolated nerve terminals, as opposed to chronic regimens used on other models for the disease; (2) they indicate that the existence of SCC alone is insufficient to trigger a LEMS-like autoimmune response; (3) they suggest that Ca²⁺ channels of nerve terminals secreting different transmitters may share common epitopes recognized by the LEMS autoantibody; and (4) they suggest that synaptosomes will be useful determining the neurochemical site and specificity of the LEMS autoantibody.     

Renin and renin substrate in primary adrenal insufficiency: contrasting effects of glucocorticoid and mineralocorticoid deficiency.

Overactivity of the renin-angiotensin system has recently been shown to be important in circulatory homeostasis in adrenocortical failure. However, renin substrate levels decrease in experimentally induced glucocorticoid deficiency, and this can impair both the function of the renin-angiotensin system and its accurate assessment by measurement of renin activity. In order to define the effects of spontaneous steroid deficiency, renin concentration activity and renin substrate were assessed before and after treatment in seven patients with Addison's disease who showed varying degrees of aldosterone and cortisol deficiency.Severe adrenocortical failure, affecting both aldosterone and cortisol, resulted in a gross increase in renin concentration with substrate levels reduced to less than 10 per cent of the mean normal level. Renin excess was poorly reflected by measurement of renin activity when substrate depletion was severe. Substrate deficiency was closely related to the degree of cortisol lack, i.e., renin substrate showed a positive correlation with the level of plasma cortisol before treatment (r = 0.94, p < 0.005). In severe glucocorticoid deficiency, with preservation of normal aldosterone secretion, substrate was very low without renin excess, indicating that severe substrate depletion can occur without increased utilization. With marked renin excess in predominant mineralocorticoid deficiency and in untreated diabetic ketoacidosis, substrate remained normal, indicating that renin excess per se does not lead to substrate depletion.These findings indicate that although mineralocorticoid failure stimulates renin release, adequate glucocorticoid production is crucial in preventing substrate depletion. The homeostatic role of the renin-angiotensin system may be impaired in severe adrenal failure despite an appropriate renin response to mineralocorticoid deficiency. Depletion of substrate may be a factor which contributes to circulatory failure in glucocorticoid deficiency.