Transient Absorption of Inhaled Vapors into a Multilayer Mucus–Tissue–Blood System

Previous studies have approximated the absorption of vapors into the walls of the respiratory tract as a steady state process. However, non-dimensional analysis indicates that the absorption of vapors in the conducting airways is time-dependent over the timescale of a breathing cycle. The objective of this study was to evaluate the mass transport of sample chemical species through a simple multilayer system composed of mucus, tissue, and blood components on a transient basis. Individual multilayer models were considered that represent the wall dimensions of the nasal extrathoracic (ET₂), bronchial (BB), and bronchiolar (bb) airways. Sample vapors considered were acetaldehyde and benzene, which are highly soluble and moderately soluble in mucus, respectively. To determine absorption, mass transport was calculated based on an existing analytical steady state solution, a new analytical transient solution, and a numerical transient solution. Results indicated that concentrations within the mucus and tissue layers were highly time dependent in the ET₂ and BB regions and moderately time dependent in the bb airways over the timescale of an inhalation cycle, which is approximately 1–2 s. Fluxes of vapors into the tissue and blood varied with time for approximately 6–8 s in the BB region and 0.6–0.8 s in the bb model. The associated transient blood uptake of acetaldehyde and benzene in the upper ET₂ and BB regions varied from steady state values by a factor of approximately 30 after 1 s. Under similar conditions, transient uptake in the bb model varied from steady state conditions by a factor of approximately 1.3. Surprisingly, inclusion of chemical reactions in the mucus and tissue modified the transient uptake predictions only for very large values of reaction rate coefficients (K > 100 min⁻¹). In summary, transient effects significantly impact the absorption of vapors into the walls of the upper respiratory tract (ET₂ and BB regions) and may largely diminish the effects of chemical reactions over the timescale of an inhalation cycle. Furthermore, the transient analytical solution that was developed provides the basis for an improved boundary condition in future CFD simulations of air-phase transport and wall absorption.     

Fcgamma receptor transmembrane domains: role in cell surface expression,gamma chain interaction,and phagocytosis

We constructed chimeric receptors to dissect the role of the transmembrane (TM) domain in cell surface expression of and phagocytosis by the gamma chain-dependent Fcgamma receptors FcgammaRIIIA and FcgammaRI. FcgammaR chimeras containing the TM and cytoplasmic (CY) domains of the gamma chain were expressed on the cell surface and mediated an efficient phagocytic signal. In contrast, chimeras containing the FcgammaRIIIA TM were poorly expressed. Receptors containing the FcgammaRI TM and the gamma chain CY but lacking the gamma chain TM also were expressed efficiently and mediated phagocytosis, suggesting that a gamma chain dimer induced by the gamma chain TM is not required for efficient phagocytosis. Cotransfection of FcgammaRI or FcgammaRIIIA with the chimera CD8-gamma-gamma (EC-TM-CY) resulted in FcgammaR cell surface expression and phagocytosis, whereas CD8-CD8-gamma, whose TM does not associate with FcgammaR, allowed cell surface expression of (but not phagocytosis by) FcgammaRI. CD8-CD8-gamma also did not allow surface expression of FcgammaRIIIA. Exchanging FcgammaRI and CD8 TMs indicated that the C-terminal 11 amino acids of the FcgammaRI TM are essential for association of FcgammaRI with the gamma chain and phagocytosis. The data indicate that specific sequences in the FcgammaRIIIA and FcgammaRI TMs govern their different interactions with the gamma chain in cell surface expression and phagocytosis and that gamma chain TM sequences are not required for gamma chain-mediated phagocytosis. The data identify a specific region of the FcgammaRI TM and its asparagine as important for FcgammaRI cell surface expression in the absence of the gamma chain and for distinguishing the FcgammaRI and FcgammaRIIIA phenotypes.     

Failure of single-unit neuronal activity to differentiate globus pallidus internus and externus in Parkinson disease

OBJECT: The authors examine the validity of single-unit neuronal recordings as a method of differentiating the globus pallidus internus (GPi) from the GP externus (GPe) in Parkinson Disease. METHODS: One hundred twenty-eight recordings of apparent single-unit activity used to help guide final electrode placement in eight patients who underwent pallidotomy were analyzed using sophisticated spike sorting methods, and 185 neurons were characterized for mean firing frequency and percent of firing within bursts. In addition, the total spectral power was calculated on the full measured waveform for each of 128 samples without spike sorting. No correlation was identified between these measures of neuronal activity and depth within the GP. CONCLUSIONS: These results call into question the validity of relying on single-unit activity and microelectrode recordings in the operating room to localize lesion or electrode placement within the GPi during stereotactic pallidal surgery.     

Examination of motor fitness within the scope of The Child and Adolescent Health Survey

Several studies indicate that physical performance of children and young people is declining. However, actually available data on physical performance and physical activity of children and young people are not representative and hence no countrywide predictions can be made. The examination of motor fitness in association with development and health of children and young people is indispensable for the implementation of appropriate measures of intervention. The module 'Motoric' in the National Health Survey for Children and Adolescents shall remedy the deficiency of information. For the module, 6,000 children and adolescents, age 4-17 years, will be representatively drawn from the total survey sample. Their physical performance and physical activity will be comprehensively assessed. For this purpose, appropriate tests have been developed. In pilot studies, all methods were tested for practicability, objectivity, reliability, and validity. The application of methods was coordinated between the Robert Koch-Institute and the Institute of Sport and Science of Sports, University of Karlsruhe.     

Eradication of osteosarcoma lung metastases following intranasal interleukin-12 gene therapy using a nonviral polyethylenimine vector

The use of adenoviral vectors for therapeutic delivery of genes via pulmonary application poses several problems in terms of immune responses. The purpose of this study was to determine whether polyethylenimine (PEI), a polycationic DNA carrier, can be used to deliver the IL-12 gene into the lungs of mice having microscopic osteosarcoma (OS) lung metastases. Incubation of SAOS-LM6 cells in vitro with PEI containing the murine IL-12 (mIL-12) gene (PEI:IL-12) resulted in expression of both the p35 and p40 subunits of IL-12 mRNA and production of mIL-12 protein. Using our newly developed OS nude mouse model, we demonstrated that treatment of mice using intranasal PEI:IL-12 resulted in significant IL-12 mRNA expression in the lung but not the liver. Furthermore, plasma IL-12 was undetectable after up to 4 weeks of intranasal PEI:IL-12 therapy given twice weekly. No IL-12 expression was seen following intranasal PEI therapy alone. The number of lung metastases in animals that received intranasal PEI:IL-12 twice weekly for 4 weeks starting 6 weeks after tumor inoculation was significantly decreased (median, 11; range, 0-47) compared with those that received PEI alone (median, 89; range, 2 to >200; P=.012). Also, the size of the nodules was significantly smaller in the PEI:IL-12-treated animals, with 90% measuring < or =0.5 mm in diameter compared with 56% in the PEI-alone group. Animals that received PEI alone also had numerous large nodules (3-6 mm) throughout the lungs. Intranasal therapy is a noninvasive way to administer agents and has the advantage of targeting the pulmonary region, resulting in higher concentrations in the tumor area. Additionally, delivery of IL-12 to the lung via the airway using PEI may avoid systemic toxicity. Because OS metastasizes almost exclusively to the lung, this may be a novel approach to the treatment of pulmonary OS metastases.     

Transient leukemia with extreme basophilia in a phenotypically normal infant with blast cells containing a pseudodiploid clone, 46,XY i(21)(q10)

PURPOSE: Transient leukemia and extreme basophilia occurred in a phenotypically normal newborn with expression of isochromosome (21)(q10) in the blast population. PATIENTS AND METHODS: A newborn boy was found to have an elevated white blood cell count of 120,800 with 33% blasts. The peripheral blood also contained elevated numbers of basophils and neutrophils with unusual staining properties. The blasts, evaluated by flow cytometry and light and electron microscopy, had the properties of megakaryoblasts. Cytogenetic studies revealed 46,XY karyotype in peripheral blood lymphocytes; however, analysis of the blast cells from the bone marrow showed an abnormal chromosome 21. RESULTS: The blast cells in the peripheral blood disappeared by day 42 without chemotherapy. The red blood cell count and platelet count normalized by 2 months. Chromosomal analysis of skin fibroblasts and bone marrow after the disappearance of the blast cells in the peripheral blood showed a 46,XY phenotype. CONCLUSIONS: The leukemic cell of transient leukemia has the potential of forming cells of basophil and megakaryocyte lineages. Trisomy of the q arm of chromosome 21 contains sufficient genetic information for the development of transient leukemia in a phenotypically normal newborn.