Somatic mosaicism in a patient with neurofibromatosis type 1

Using loss of heterozygosity analysis, a method designed to detect moderate to large gene deletions, we have identified a new-mutation neurofibromatosis type 1 (NF1) patient who is somatically mosaic for a large maternally derived deletion in the NF1 gene region. The deletion extends at least from exon 4 near the 5' end of the gene to intron 39 near the 3' end. The gene-coding region is, therefore, mostly or entirely deleted, encompassing a loss of > or = 100 kb. We hypothesize that the deletion occurred at a relatively early developmental timepoint, since signs of NF1 in this patient are not confined to a specific body region, as seen in "segmental" NF, and since both mesodermally and ectodermally derived cells are affected. This report provides the first molecular evidence of somatic mosaicism in NF1 and, taken together with a recent report of germ-line mosaicism in NF1, adds credence to the concept that mosaicism plays an important role in phenotypic and genetic aspects of NF1 and may even be a relatively common phenomenon.     

An approximate model and empirical energy function for solute interactions with a water-phosphatidylcholine interface

An empirical model of a liquid crystalline (L alpha phase) phosphatidylcholine (PC) bilayer interface is presented along with a function which calculates the position-dependent energy of associated solutes. The model approximates the interface as a gradual two-step transition, the first step being from an aqueous phase to a phase of reduced polarity, but which maintains a high enough concentration of water and/or polar head group moieties to satisfy the hydrogen bond-forming potential of the solute. The second transition is from the hydrogen bonding/low polarity region to an effectively anhydrous hydrocarbon phase. The "interfacial energies" of solutes within this variable medium are calculated based upon atomic positions and atomic parameters describing general polarity and hydrogen bond donor/acceptor propensities. This function was tested for its ability to reproduce experimental water-solvent partitioning energies and water-bilayer partitioning data. In both cases, the experimental data was reproduced fairly well. Energy minimizations carried out on beta-hexyl glucopyranoside led to identification of a global minimum for the interface-associated glycolipid which exhibited glycosidic torsion angles in agreement with prior results (Hare, B.J., K.P. Howard, and J.H. Prestegard. 1993. Biophys. J. 64:392-398). Molecular dynamics simulations carried out upon this same molecule within the simulated interface led to results which were consistent with a number of experimentally based conclusions from previous work, but failed to quantitatively reproduce an available NMR quadrupolar/dipolar coupling data set (Sanders, C.R., and J.H. Prestegard. 1991. J. Am. Chem. Soc. 113:1987-1996). The proposed model and functions are readily incorporated into computational energy modeling algorithms and may prove useful in future studies of membrane-associated molecules.     

A-IMilano apoprotein. Decreased high density lipoprotein cholesterol levels with significant lipoprotein modifications and without clinical atherosclerosis in an Italian family

Significant hypertriglyceridemia with a very marked decrease of high density lipoproteins (HDL)-cholesterol levels (7-14 mg/dl) was detected in three members (father, son, and daughter) of an Italian family. The three affected individuals did not show any clinical signs of atherosclerosis, nor was the atherosclerotic disease significantly present in the family. Lipoprotein lipase and lecithin:cholesterol acyltransferase activites were normal or slightly reduced. Morphological and compositional studies of HDL in the subjects showed a significant enlargement of the lipoprotein particles (approximately 120 vs. approximately 94 A for control HDL) and a concomitant increase in the triglyceride content. Analytical isoelectric focusing of HDL apoproteins provided evidence for multiple isoproteins in the apoprotein(apo)-A-I range, with nine different bands being detected instead of the usual four bands observed in normal subjects. Two-dimensional immunoelectrophoresis against apo-A antiserum indicated a clear reduction of apo-A in the alpha electrophoretic region, with splitting of the protein "peak." The observation in otherwise clinically healthy subjects of hypertriglyceridemia, reduced HDL-cholesterol, and marked apoprotein abnormalities, without a significant incidence of atherosclerotic disease in the family suggests this is a new disease entity in the field of lipoprotein pathology, very probably related to an altered amino acid composition of the apo-A-I protein (see Weisgraber et al. 1980. J. Clin. Invest. 66: 901-907).     

Autoantibodies to the insulin receptor. Effect on the insulin-receptor interaction in IM-9 lymphocytes

The serum of some patients with insulin-resistant "diabetes" contains antibodies that bind to and block the cell membrane receptors for insulin. In this report, we have characterized the effects of the antireceptor antibodies on the interaction of (125)I-insulin with its receptor on the human lymphoblastoid cell line IM-9. Up to 95% of specific insulin binding can be inhibited by pretreatment of the cells with these immunoglobulins. The onset of the inhibitory effect is time- and temperature-dependent, and the effect is reversed extremely slowly if the cells are suspended in a large excess of antibody-free buffer. These features of antibody binding can be easily distinguished from those for insulin binding to its receptor. The inhibitory effect of the antibodies can be reversed by exposure of the cells to conditions known to elute surface immunoglobulins. The three antireceptor sera studied appear to alter the insulin-receptor interaction in different ways. Two antisera markedly reduce receptor affinity through combined effects on the insulin association and dissociation rates, and, additionally, have smaller effects on available receptor number. A third antiserum primarily affects available receptor number and has little effect on receptor affinity. All three antisera inhibit the capacity of insulin to promote negatively cooperative site-site interactions among insulin receptors. The data suggest that these autoantibodies to the insulin receptor bind to different determinants on the receptor and may therefore be useful as unique probes of insulin receptor structure and function.     

Experimental automobile-pedestrian injuries

Fifteen fresh cadaver impacts were conducted in simulation of pedestrian-automobile accidents. The test sled configuration simulated an automobile bumper and hood in "standard" and "nosedive" situations as well as "hard" and "soft" impact surfaces. Instrumentation and film demonstrated large axial compression forces in the struck leg and considerable angular velocity of the torso in all modes. Dissection revealed primary injury at the impact site at low velocities with added remote injury at high velocities. Fracture of the lateral tibial plateau was most common. Lowering the bumper height offered the greatest protection against injury at moderate impact velocities.     

Childhood Sexual and Physical Abuse and the 1-Year Prevalence of Medical Problems in the National Comorbidity Survey.

In a population sample (N = 5,877; ages 15 to 54), the authors found childhood sexual and physical abuse to be associated with the 1-year prevalence of serious health problems for both men and women. The authors also found that participants' psychiatric disorders partially mediated the effects of physical and sexual abuse on adult health. However, childhood abuse continued to independently influence health status after the authors controlled for psychiatric disorders. Contrary to expectations, individuals who experienced a combination of sexual and physical abuse did not have a higher frequency of health problems than those who experienced either type of abuse alone. Implications for these findings are discussed, including possible mechanisms that may account for the association between childhood abuse and adult health problems. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Advances in selective wet oxidation of AlGaAs alloys

We review the chemistry, microstructure, and processing of buried oxides converted from AlGaAs layers using wet oxidation. Hydrogen is shown to have a central role in the oxidation reaction as the oxidizing agent and to reduce the intermediate predict As₂O₃ to As. The stable oxide is amorphous (Al_xGa_1-x) ₂O₃ which has no defects along the oxide/semiconductor interfaces but can exhibit strain at the oxide terminus due to volume shrinkage. The influence of gas flow, gas composition, temperature, Al-content, and layer thickness on the oxidation rate are characterized to establish a reproducible process. Linear oxidation rates with Arrhenius activation energies which strongly depend upon AlAs mole fraction are found. The latter produces strong oxidation selectivity between AlGaAs layers with slightly differing Al-content. Oxidation selectivity to thickness is also shown for layer thickness <60 nm. Differences between the properties of buried oxides converted from AlGaAs and AlAs layers and the impact on selectively oxidized vertical cavity laser lifetime are reported     

Reductionin Listeria monocytogenes,Salmonella enterica and Escherichia coli O157:H7 in vitro and on tomato by sophorolipid and sanitiser as affected by temperature and storage time

Increased consumption of produce by consumers has been attributed to perceived health benefits of postharvest produce. Pathogen control is crucial because periodic occurrences and contamination of tomato and leafy greens have exacerbated food safety risks for consumers. We investigated the effects of temperatures (5 and 25 °C), storage time (30 min and 24 h) for inactivation of Listeria monocytogenes, Salmonella enterica and Escherichia coli O157:H7 by sophorolipid (SL‐p) produced fermentatively using palmitic acid as a co‐substrate at different concentrations in vitro. Reduction in pathogenic bacteria on grape tomato by SL‐p, sanitiser (Lovit) and combinations of SL‐p and sanitiser was determined. Temperature and storage time significantly (P < 0.05) affected pathogen inactivations by SL‐p as pathogen reductions were greater at 25 °C and 24 h than at 5 °C and 30 min of storage. L. monocytogenes was the most sensitive to SL‐p treatment as reductions of 5 log relative to untreated controls were attained at 0.12% of SL‐p. Significant reductions in S. enterica (1.91–3.85 logs) and E. coli O157:H7 (0.87–4.09 logs) were recorded at 2–5% of SL‐p. Lower populations of Salmonella and E. coli O157:H7 were inactivated than L. monocytogenes. On grape tomato, pathogen populations inactivated increased at higher SL‐p levels at 25 °C. Sanitiser and sanitiser + SL‐p reduced bacterial populations on tomato by 5.29–5.76 logs and 0.71–3.3.66 logs, respectively. These results imply the interactions of temperature, storage time and SL‐p significantly (P < 0.05) affected pathogen strain reductions. The combination of SL‐p with sanitiser led to synergistic effect on E. coli O157:H7, but not L. monocytogenes and S. enterica.