Symptomless hypoglycaemia

We report an unusual case of hypoglycaemia, in which a pregnant woman with a Rh-negative problem and random blood glucose levels of less than 10 mg/100 ml was found to have no clinical symptoms of hypoglycaemia. The patient, who had a blood glucose concentration of 7 mg/100 ml, behaved as normally as a person with the expected average physiological value. This finding did not seem to be connected in any way with the patient's serious Rh-ve problem. We have been unable to find reports of a similar situation in the literature available to us.     

A new technique for radiotherapy planning using quadratic programming

Previous attempts at optimization of radiotherapy planning are described and criticized, and consideration of these attempts has resulted in the development of a new technique using quadratic programming. Uniformity of tumour dose is selected as the most important feature of any plan, and this is achieved by minimizing the variance of the dose to preselected points within the tumour. The dose to vulnerable regions can be constrained not to exceed a given percentage of the mean tumour dose. Optimization of field weight and field type is possible. The operation of the system is described and some typical results are given.     

Systemic lupus erythematosus with a protein-losing enteropathy

Anasarca with pronounced hypoalbuminemia developed in a young woman 15 months after the onset of a mild, arthralgic type of systemic lupus erythematosus (SLE) without evidence of active nephritis. Investigation indicated a gastrointestinal rather than a renal site for protein loss. A full clinical remission was achieved with low-dose corticosteroid therapy.     

Synthesis of 2'(3')-O-DL-alanyl hexainosinic acid using T4 RNA ligase: suppression of the enzymic reverse transfer reaction by alkaline phosphatase

2'(3')-O-DL-Alanyl (Ip)5I was synthesized by a new method. An alanine ortho ester of inosine 5'-phosphate was added to (Ip)4I using the ATP-independent reaction of T4 RNA ligase, and the product was converted smoothly to the desired ester. The enzymic reverse transfer reaction was conveniently suppressed by the dephosphorylation of the adenosine 5'-phosphate coproduct, catalyzed in situ by alkaline phosphatase.     

Amphotericin B-induced changes in K+ content, viability, and ultrastructure of yeast-phase Histoplasma capsulatum

Yeast-phase cells of Histoplasma capsulatum were challenged with amphotericin B, and membrane perturbation was monitored by K+ efflux. Suspensions of washed cells readily absorbed about 1.12 microgram of amphotericin B per mg (dry weight) and further nonspecific sites were also apparent. The dose-response curve for initial rate of K+ efflux was sigmoidal within the range 0.1 to 1.0 microgram of amphotericin B per ml. A fungistatic concentration of amphotericin B (0.3 microgram/ml) evoked an efflux of 85 to 90% K+ from the cells within 15 min, but cell viability decreased only 13% (yeast phase) or 33% (transformed to mycelial units). Ultrastructural changes in treated cells were detected within 5 min, and the hallmark was expansion of vacuoles during the 1-h monitoring period. In contradistinction to a previous report, the appearance of the protoplasmic membrane was not altered by fungistatic concentration. When treated cells were returned to a fresh growth medium, there was a pronounced lag (20 h). During this apparent recovery phase, the large vacuoles fragmented and returned to normal size. It is proposed that vacuoles of H. capsulatum act as a spatial buffer of considerable survival value to stressed cells.     

A comparison of the rates of methylation of mercury(II) species in aquatic media by various organotin and organosilicon moieties

Metals can be methylated in environmental aqueous media by a variety of organotin and organosilicon compounds. Main group metals and metalloids were surveyed for the identification of species that can either donate or accept methyl groups. The methylation of mercury(II) by trimethyltin cation was found to be a bimolecular reaction, the reaction rate of which decreased with increasing chloride concentration. Kinetic investigations using NMR techniques showed that the most important pairs of reactants were (CH3)3Sn+ + HgCl2, (CH3)3SnCl + HgCl2, and (CH3)3SnCl + HgCl-3. Sodium 2,2,3,3-tetradeutero-3-(trimethylsilyl)propionate (TSP) and sodium 2,2-dimethyl-2-silapentane-5-sulfonate (DSS) were found to methylate mercury(II). Organylsilatranes were found to transfer their organic groups readily to mercury(II) to produce organomercury compounds.     

Mutations in the carboxyl terminus of the agouti protein decrease agouti inhibition of ligand binding to the melanocortin receptors

Several mutations that cause ectopic expression of the agouti gene result in obesity, hyperinsulinemia, and yellow coat color. A candidate pathway for agouti induced obesity and hyperinsulinemia is through altered signaling by melanocortin receptors, as agouti normally regulates coat coloration through antagonism of melanocortin receptor 1. Furthermore, melanocortin peptides mediate functions including steroidogenesis, lipolysis, and thermoregulation. We report apparent inhibition dissociation constants for mouse and human agouti protein inhibition of ligand binding to the melanocortin receptors, to determine which of these receptors might be involved in agouti induced diabetes. The similarity in the apparent K(I) values for agouti inhibition of ligand binding to the brain melanocortin receptors 3 and 4 (mouse: K(I) app = 190 +/- 74 and 54 +/- 18 nM; human: K(I) app = 140 +/- 56 and 70 +/- 18 nM, respectively) suggests that the MC3-R is a potential candidate for a receptor mediating the effects of agouti protein overexpression. Agouti residues important for melanocortin receptor inhibition were identified through the analysis of deletion constructs and site-specific variants. Val83 is important for inhibition of binding to MC1-R (K(I) app for Val83Ala agouti increased 13-fold relative to wild-type protein). Arg85, Pro86, and Pro89 are important for selective inhibition of binding between MC1-R and MC3-R and MC4-R as their apparent K(I) values are essentially unchanged at MC1-R, while they have increased 6-10-fold relative to wild-type protein at MC3-R and MC4-R.