Preliminary Evidence on the Diagnostic and Molecular Role of Circulating Soluble EGFR in Non-Small Cell Lung Cancer

Assessment of biological diagnostic factors providing clinically-relevant information to guide physician decision-making are still needed for diseases with poor outcomes, such as non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) is a promising molecule in the clinical management of NSCLC. While the EGFR transmembrane form has been extensively investigated in large clinical trials, the soluble, circulating EGFR isoform (sEGFR), which may have a potential clinical use, has rarely been considered. This study investigates the use of sEGFR as a potential diagnostic biomarker for NSCLC and also characterizes the biological function of sEGFR to clarify the molecular mechanisms involved in the course of action of this protein. Plasma sEGFR levels from a heterogeneous cohort of 37 non-advanced NSCLC patients and 54 healthy subjects were analyzed by using an enzyme-linked immunosorbent assay. The biological function of sEGFR was analyzed in vitro using NSCLC cell lines, investigating effects on cell proliferation and migration. We found that plasma sEGFR was significantly decreased in the NSCLC patient group as compared to the control group (median value: 48.6 vs. 55.6 ng/mL respectively; p = 0.0002). Moreover, we demonstrated that sEGFR inhibits growth and migration of NSCLC cells in vitro through molecular mechanisms that included perturbation of EGF/EGFR cell signaling and holoreceptor internalization. These data show that sEGFR is a potential circulating biomarker with a physiological protective role, providing a first approach to the functional role of the soluble isoform of EGFR. However, the impact of these data on daily clinical practice needs to be further investigated in larger prospective studies.     

Measurements of single chain form factors by small-angle neutron scattering from polystyrene blends containing high concentrations of labelled molecules

A series of small angle neutron scattering measurements on blends of normal polystyrene (PSH) and labelled (deuterated) polystyrene (PSD) have been made with concentrations of PSD from 5 to 50 mol %. It is shown that the single chain form factor of the polymer in bulk can be obtained from a single concentration measurement for any concentration of labelled molecules, providing the molecular weights of the parent and labelled molecules are the same and the molecular weight distributions are narrow.     

Bacillary angiomatosis and bacillary peliosis in patients infected with human immunodeficiency virus: clinical characteristics in a case-control study

Clinical characteristics associated with bacillary angiomatosis and bacillary peliosis (BAP) in patients with human immunodeficiency virus (HIV) infection were evaluated in a case-control study; 42 case-patients and 84 controls were matched by clinical care institution. Case-patients presented with fever (temperature, > 37.8 degrees C; 93%), a median CD4 lymphocyte count of 21/mm3, cutaneous or subcutaneous vascular lesions (55%), lymphadenopathy (21%), and/or abdominal symptoms (24%). Many case-patients experienced long delays between medical evaluation and diagnosis of BAP (median, 4 weeks; range, 1 day to 24 months). Case-patients were more likely than controls to have fever, lymphadenopathy, hepatomegaly, splenomegaly, a low CD4 lymphocyte count, anemia, or an elevated serum level of alkaline phosphatase (AP) (P < .001). In multivariate analysis, a CD4 lymphocyte count of < 200/mm3 (matched odds ratio [OR], 9.9; P < .09), anemia reflected by a hematocrit value of < 0.36 (OR, 19.7; P < .04), and an elevated AP level of > or = 2.6 mukat/L (OR, 23.9; P < .05) remained associated with disease after therapy with zidovudine was controlled for. BAP should be considered an AIDS-defining opportunistic infection and should be included in the differential diagnosis for febrile, HIV-infected patients with cutaneous or osteolytic lesions, lymphadenopathy, abdominal symptoms, anemia, or an elevated serum level of AP.     

Misinterpretation of body sensations in panic disorder

Cognitive accounts of panic predict that panic disorder patients will be particularly prone to misinterpret autonomic sensations. Several studies have produced results consistent with this prediction, but each is open to alternative interpretation. To clarify matters, 2 studies administered the Body Sensations Interpretation Questionnaire (BSIQ) to panic patients and controls. Panic patients were more likely to interpret ambiguous autonomic sensations as signs of immediately impending physical or mental disaster and were more likely than other anxiety disorder patients and nonpatients to believe these interpretations. In a 3rd study, a brief version of the BSIQ was shown to have satisfactory test-retest reliability, to change with treatment, and to discriminate treatments that varied in their effects on panic.     

Fluorescene in situ hybridization establishes homology between human and silvered leaf monkey chromosomes, reveals reciprocal translocations between chromosomes homologous to human Y/5, 1/9, and 6/16, and delineates an X1X2Y1Y2/X1X1X2X2 sex-chromosome system

The adhesive core of the desmosome is composed of cadherin-like glycoproteins of 2 families, desmocollins and desmogleins. The desmosomal cadherins show distinct patterns of expression in adult epidermis, and we have suggested that the desmocollins have a functional role in regulating the differentiation and/or morphogenesis of that epithelium (North et al. [1996] Proc. Natl. Acad. Sci. USA 93:7701-7705.). To examine this hypothesis, we cloned murine desmocollins and examined the induction patterns of desmocollins 1 and 3 during skin and skin appendage development. Desmocollins 3 and 1 were first expressed in epidermis in highly regional patterns at embryonic days 13.0 and 13.5, respectively, and both were up-regulated in general body epidermis at day 14.5. At this stage, epidermis is undifferentiated and the desmocollins showed an unexpected expression pattern. However, by day 18.5 when skin had undergone terminal differentiation, desmocollin 1 and 3 expression resembled that found in the adult. Thus, the establishment of the adult pattern of desmocollin expression corresponds to the adult pattern of epidermal stratification. We suggest that it is the ratio of desmocollin 1 to desmocollin 3 expression at different levels in the epidermis that is fundamental in establishing this pattern of differentiation.     

Regional and cellular expression of glial (GLT1) and neuronal (EAAC1) glutamate transporter proteins in ovine fetal brain

Glutamate transport is a primary mechanism for regulating extracellular levels of glutamate which can have either neurotrophic or neurotoxic effects in the developing brain, depending on its concentration. Using immunoblotting and immunocytochemistry, we tested the hypotheses that expression of neuronal and glial glutamate transporter proteins was regionally and temporally regulated in the developing ovine brain and that expression of the glial isoform early in development was not cell-type specific. Immunoblots for the neuronal glutamate transporter EAAC1 revealed a major band of immunoreactivity at 69,000 nmol. wt, whereas glial glutamate transporter-1 (GLT1) immunoreactivity was observed as 73,000 and 146,000 mol. wt proteins. EAAC1 and GLT1 are regulated differently during development, with EAAC1 immunoreactivity being most abundant at 60 and 71 days completed gestation (term=145 days) and dissipating thereafter, while GLT1 immunoreactivity was most abundant at 136 days gestation. By immunocytochemistry EAAC1 expression is neuronal throughout gestation with intense labelling of dendrites within the telencephalon evident at 60 days. Neuropil, neuronal cell bodies and processes are EAAC1-immunoreactive throughout gestation with no evidence of astrocytic or oligodendroglial immunoreactivity. In contrast, GLT1 is expressed by neuronal and non-neuronal cell types during midgestation with astrocyte selectivity developing by 136 days. During midgestation, GLT1 is transiently expressed in neurons of the subplate, cranial nerve nuclei, basal ganglia, and cerebellar cortex. The major finding of this study, that GLT1 is transiently expressed in various neuronal populations at midgestation demonstrates that the cell-type specificity of the GLT1 phenotype is developmentally regulated and depends on brain maturity.     

Lithium disilicate glass produced at high pressure: Characterization of structural,thermal and mechanical properties

In this work, high-density lithium disilicate (LS₂) vitreous systems were produced by melting and quenching under high pressure (7.7 GPa) following two distinct experimental routes. In the first case, LS₂ glass was remelted at 7.7 GPa and 1600°C and, then, quenched. In the second case, a stoichiometric mixture of precursor oxides (Li₂O and SiO₂) was melted at 1600°C and 7.7 GPa before quenching. A reference LS₂ glass sample was produced at atmospheric pressure using conventional melting and quenching procedure. The samples were characterized by X-ray diffraction, differential thermal analysis, and instrumented ultramicro hardness measurements. X-ray diffraction confirmed that all samples were amorphous and thermal analysis suggests that different glassy structures were produced depending on the route of synthesis. Hardness and elastic modulus of the glasses produced under high pressure were higher than those of the reference glass, reflecting the irreversible densification effect induced by the high-pressure processing.