Familial jejunal atresia with renal dysplasia

Although jejunal atresia occasionally may occur with a familial pattern, an association with renal disease has not been described. The authors report on three family members treated over two generations, all of whom had both proximal jejunal atresia and renal dysplasia. This association was most likely inherited as an autosomal dominant trait.     

Net glutamate release from astrocytes is not induced by extracellular potassium concentrations attainable in brain

Elevated extracellular potassium concentration ([K+]e) has been shown to induce reversal of glial Na+-dependent glutamate uptake in whole-cell patch clamp preparations. It is uncertain, however, whether elevated [K+]e similarly induces a net glutamate efflux from intact cells with a physiological intracellular milieu. To answer this question, astrocyte cultures prepared from rat and mouse cortices were incubated in medium with elevated [K+]e (by equimolar substitution of K+ for Na+), and glutamate accumulation was measured by HPLC. With [K+]e elevations to 60 mM, medium glutamate concentrations did not increase during incubation periods of 5-120 min. By contrast, 45 min of combined inhibition of glycolytic and oxidative ATP production increased medium glutamate concentrations 50-100-fold. Similar results were obtained in both rat and mouse cultures. Studies were also performed using astrocytes loaded with the nonmetabolized glutamate tracer D-aspartate, and parallel results were obtained; no increase in medium D-aspartate content resulted from [K+]e elevation up to 90 mM, whereas a large increase occurred during inhibition of energy metabolism. These results suggest that a net efflux of glutamate from intact astrocytes is not induced by any [K+]e attainable in brain.     

VRCTC-310--a novel compound of purified animal toxins separates antitumor efficacy from neurotoxicity

Two purified animal venom toxins, crotoxin and cardiotoxin, have been combined to produce a unique natural product (VRCTC-310) currently under investigation as an antitumor agent by the National Cancer Institute. In vitro, it has demonstrated cytotoxic disease specificity and a unique mechanism of action when submitted to COMPARE analysis. In vivo, tolerance was developed to the neurotoxic properties of crotoxin which allowed comparison of several schedules of fixed and escalating daily i.m. doses to mice bearing s.c. Lewis Lung carcinoma. An 83% inhibition of tumor growth was achieved using an escalating dose schedule starting at 1.8 mg/kg and reaching 6.3 mg/kg/day on day 20. Although some irritation around the sites of i.m. injection was noted, animal weight loss was negligible and there were no other signs of adverse toxicity. This natural product represents a new, membrane interactive anticancer agent which produces a unique spectrum of cytotoxicity in vitro and which has demonstrated interesting in vivo antitumor efficacy.     

Centurion syndrome. Idiopathic anterior displacement of the medial canthus

Bone marrow transplantation (BMT) using HLA-partially matched family donors has produced disappointing results (25-30% of long-term survivors) in patients with severe aplastic anemia. We describe two children affected by severe aplastic anemia, not responsive to immunosuppressive therapy, who underwent allogeneic bone marrow transplantation using a HLA-partially matched family donor. Both cases presented 2 first class HLA-antigens (A and B) disparity between donor and recipient. The pretransplant conditioning regimen consisted of cyclophosphamide, thoracoabdominal irradiation, cytosine-arabinoside, and antilymphocyte globulin. As graft versus host disease (GVHD) prophylaxis, Cyclosporine-A was administered at usual dosages for 6 months. A full marrow engraftment was observed in both cases. Only grade I acute GVHD, promptly responsive to corticosteroid therapy, developed with no chronic GVHD. Five months after transplant, both children progressively developed hypertension, renal function impairment, thrombocytopenia, and severe normochromic anemia, with erythropoietin serum levels lower than expected for the haematocrit. After antihypertension treatment and supportive therapy, the clinical picture progressively improved, while treatment with recombinant human erythropoietin completely corrected the long-lasting anemia. The two children are alive and well 28 months after the transplant, with a Karnofsky score of 100% and a normal peripheral blood count. The authors suggest that, once immunosuppressive therapy has failed, BMT from donors other than HLA-identical sibling is a feasible approach in children affected by severe aplastic anemia, not having an HLA-identical donor.     

Nanoindentation mapping of mechanical properties of cement paste and natural rocks

This paper reports a study to assess nanoindentation mapping of mechanical properties of cement paste and natural rocks. Initial work seems to show that mechanical property mapping by nanoindentation is feasible and can be related to microscopic information. Further work is however required on the effect of indent size and spacing. Such a testing technique can be very useful for materials with different phases to study the intrinsic properties of each component, and also the interaction and properties of the interfacial regions of different phases. The values of Young's modulus and hardness of the individual mineral phases were also determined by statistically analysing a large number of experimental data.     

Optical Splitting Trees for High-Precision Monocular Imaging

In this article, we consider the design of monocular multiview optical systems that form optical splitting trees, where the optical path topology takes the shape of a tree because of recursive beam splitting. Designing optical splitting trees is challenging when it requires many views with specific spectral properties. We introduce a manual design paradigm for optical splitting trees and a computer-assisted design tool to create efficient splitting-tree cameras. The tool accepts as input a specification for each view and a set of weights describing the user's relative affinity for efficiency, measurement accuracy, and economy. An optimizer then searches for a design that maximizes these weighted priorities. Our tool's output is a splitting-tree design that implements the input specification and an analysis of the efficiency of each root-to-leaf path. Automatically designed trees appear comparable to those designed by hand; we even show some cases where they are superior. With the help of the optimizer, the system demonstrates high dynamic range, focusing, matting, and hybrid imaging implemented on a single, reconfigurable camera containing eight sensors     

Sites of alcohol and volatile anaesthetic action on GABA(A) and glycine receptors

Volatile anaesthetics have historically been considered to act in a nonspecific manner on the central nervous system. More recent studies, however, have revealed that the receptors for inhibitory neurotransmitters such as gamma-aminobutyric acid (GABA) and glycine are sensitive to clinically relevant concentrations of inhaled anaesthetics. The function of GABA(A) and glycine receptors is enhanced by a number of anaesthetics and alcohols, whereas activity of the related GABA rho1 receptor is reduced. We have used this difference in pharmacology to investigate the molecular basis for modulation of these receptors by anaesthetics and alcohols. By using chimaeric receptor constructs, we have identified a region of 45 amino-acid residues that is both necessary and sufficient for the enhancement of receptor function. Within this region, two specific amino-acid residues in transmembrane domains 2 and 3 are critical for allosteric modulation of both GABA(A) and glycine receptors by alcohols and two volatile anaesthetics. These observations support the idea that anaesthetics exert a specific effect on these ion-channel proteins, and allow for the future testing of specific hypotheses of the action of anaesthetics.