Use of liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) for routine identification of enzymatically digested proteins separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis

A distinct form of aplasia cutis congenita presenting as linear facial skin defects has been described under a variety of names as Xp deletion syndrome. MIDAS (microphthalmia, dermal aplasia and sclerocornea) syndrome, MLS (microphthalmia and linear skin defects) and Gazali-Temple syndrome. The syndrome is lethal in males, and its severity in females varies from a relatively mild residual facial scarring with short stature to lethal developmental organ malformations. A new case with peculiar ultrastructural findings is presented. A review of the literature suggests that these associations represent a series of contiguous-gene syndromes.     

Chronic relapsing brachial plexus neuropathy with persistent conduction block

Idiopathic brachial plexus neuropathy (BPN) is an immune-mediated disorder characterized by an acute onset of painful weakness in one or both upper extremities. The course is usually monophasic with gradual improvement over months; however, occasionally BPN can recur. Electrophysiologic studies suggest the pathogenesis is primarily axonal in the majority of cases. We describe an unusual case of BPN in which the patient had a chronic and relapsing course of painless weakness associated with conduction blocks and other electrophysiologic features of demyelination across the brachial plexus. The patient improved following treatment with intravenous immunoglobulin. The neuropathy falls within the spectrum of chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy.     

Syllabic effects in word processing: evidence from the structural induction paradigm

Spoken words have a rich structural organization in memory, consisting of syllabic and subsyllabic representations. A phoneme monitoring paradigm, in which the target phoneme occurs more frequently in one syllabic position than another (e.g., onset of the 2nd syllable vs. the coda of the 1st syllable: neu-tral vs. nut-meg; C. Pallier, N. Sebastian-Galles, T. Felguera, A. Christophe, & J. Mehler, 1993) was used to explore the formation of syllabic structure during word processing. Experiment 2 investigated how a recognition system that uses syllabic structure processes words with unclear syllable boundaries (e.g., pa-lace or pal-ace?). Two methodological issues were explored: The importance of a baseline condition for measuring effects of induction (Experiment 1) and the form of the representation used in the induction paradigm (Experiment 3). Findings suggest that syllabic structure begins to form early in word processing, and they demonstrate the adequacy of the induction procedure for measuring such processes.     

Health promotion ideology and nursing education

Nursing has been concerned primarily with the visible aspects of health promotion and has shown little regard for what is invisible. Yet the hidden ideology powerfully shapes current approaches to health promotion. This paper examines and makes visible the ideology of individual responsibility which is embedded in individualistic health promotion, the primary orientation to health promotion. Ways in which this ideology is perpetuated within nursing curricula are described. Concrete strategies are proposed that may be considered by nurse educators as they seek to prepare students in health promotion, with particular emphasis on strategies that highlight its ideological underpinnings.     

Patient-centered care and today''s dental practice

Certain constitutional chromosomal abnormalities increase the risk of malignancy and/or decrease treatment tolerance. We identified two patients with the XYY syndrome among a total of 444 male children with acute lymphoblastic leukemia who had complete cytogenetics studies. In both cases, the leukemic cell karyotype suggested a constitutional XYY abnormality that was confirmed in studies of lymphocytes obtained during remission. The incidence rate in our series is higher than that of the XYY syndrome in the general population (0.0045 vs. 0.001), but not significantly so. This finding and a literature review failed to confirm an increased frequency of the XYY syndrome among children with acute lymphoblastic leukemia. Both of our patients remain in remission 24 and 28 months, respectively, postdiagnosis. Their tolerance of intensive treatment, including high-dose methotrexate, suggests that the untoward treatment toxicity seen in patients with chromosomal abnormalities such as trisomy 21 does not extend to the XYY syndrome.     

Approval of new drugs in the United States. Comparison with the United Kingdom, Germany, and Japan

In a study reported herein, the marketing approval dates of 214 drugs newly introduced into the world market from January 1990 through December 1994 were compared in 4 countries. The analysis reveals that the United States and the United Kingdom have similar patterns of drug availability, although the United States has a number of therapies with significant public health benefits that are not yet available in the United Kingdom. The findings also show that the United States outpaces both Germany and Japan in approving important new drugs. Various strategies adopted by the Food and Drug Administration to expedite its pharmaceutical review process, including the use of industry user fees, are described.     

Assembly of the human neutrophil NADPH oxidase involves binding of p67phox and flavocytochrome b to a common functional domain in p47phox

The human neutrophil NADPH oxidase is a multi-component complex composed of membrane-bound and cytosolic proteins. During activation, cytosolic proteins p47(phox), p67(phox), Rac2, and possibly p40(phox) translocate to the plasma membrane and associate with flavocytochrome b to form the active superoxide-generating system. To further investigate the role of p67(phox) in this complex assembly process, experiments were performed to identify possible regions of interaction between p67(phox) and other NADPH oxidase proteins. Using random sequence peptide phage-display library analysis of p67(phox), we identified a novel region in p47(phox) encompassing residues 323-332 and a previously identified SH3 binding domain encompassing p47(phox) residues 361-370 as p67(phox) binding sites. Synthetic peptides mimicking p47(phox) residues 323-332 inhibited the p47(phox)-p67(phox) binding interaction in an affinity binding assay; however, peptides mimicking flanking regions were inactive. Surprisingly, this same region of p47(phox) was found previously to represent a site of binding interaction for flavocytochrome b (DeLeo, F. R., Nauseef, W. M., Jesaitis, A. J., Burritt, J. B., Clark, R. A., and Quinn, M. T.(1995) J. Biol. Chem. 270, 26246-26251), and this observation was confirmed in the present report using two different in vitro assays that were not evaluated previously. Using affinity binding assays, we also found that p67(phox) and flavocytochrome b competed for binding to p47(phox)after activation, suggesting that prior to full NADPH oxidase assembly the 323-332 region of p47(phox) is associated with p67(phox) and at some point in the activation process is transferred to flavocytochrome b. Thus, taken together our data demonstrate that both p67(phox) and flavocytochrome b utilize a common binding site in p47(phox), presumably at distinct stages during the activation process, and this p47(phox) region plays a key role in regulating NADPH oxidase assembly.     

The role of ErbB receptor signaling in cell fate decisions by cortical progenitors: evidence for a biased, lineage-based responsiveness to different ligands

We recently identified the required collaborative signaling of TGFalpha and collagen type IV to regulate cell fate choice in the cerebral cortex, measured by the expression of the limbic system associated membrane protein (LAMP) by nonlimbic, sensorimotor progenitors. We show that activation of different members of the erbB receptor family can similarly modulate the specification of cortical area fate. The region of the cerebral wall from which progenitor cells arise does not influence the response to the neuregulin-1 or TGFalpha, but a subpopulation of progenitors is not competent to express LAMP in response to neuregulin-1. The heterogeneity in the responsiveness by progenitors to the two growth factors is reflected in the expression of different repertoires of erbB receptors. Using clonal analysis, we demonstrate that there may be a lineage-dependent mechanism regulating the ability of neuronal progenitors to respond to specific inductive cues that control cell fate.