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Human Lung (human + lung)
Terms modified by Human Lung Selected AbstractsRed Cell Pulmonary Transit Times Through the Healthy Human LungEXPERIMENTAL PHYSIOLOGY, Issue 2 2003G. S. Zavorsky It has previously been postulated that rapid red cell capillary transit through the human lung plays a role in the mechanism of diffusion limitation in some endurance athletes. Methodological limitations currently prevent researchers from directly measuring pulmonary capillary transit times in humans during exercise; however, first pass radionuclide cardiography allows direct measurement of red blood cell (RBC) transit times through the whole lung at various exercise intensities. We examined the relationship between mean whole lung red cell pulmonary transit times (cardiopulmonary transit times or CPTT) and different levels of flow in 88 healthy humans (76 males, 12 females) from several studies (mean age 31 years). The pooled data suggest that the relationship between CPTT and cardiac index (CI), beginning at rest and progressing through to maximum exercise demonstrates that CPTT reaches its minimum value when CI is about 8.1 l m2 min,1 (2.5-3 times the CI value at rest), and does not significantly change with further increases in CI. Cardiopulmonary blood volume (CPBV) index also does not change significantly until CI reaches 2.5 to 3 times the CI value at rest and then increases roughly linearly after that point. Consequently, the systematic increase in CPBV index with increasing pulmonary blood flow between 8.1 and 20 l m2 min,1 displays an adaptive response of the cardiopulmonary system by augmenting CPBV (and perhaps pulmonary capillary blood volume through distension and recruitment) to offset the reduction in CPTT, as no significant difference in mean CPTT is observed between these levels of flow (P > 0.05). Therefore, these data demonstrate that CPBV does not reach maximum capacity during strenuous or maximum exercise. This does not support the principle of quarter-power allometric scaling for flow when explaining modifications during exercise. Therefore, we speculate that the observed relationships between CPTT, CBPV index and flow may prevent mean CPTT (and perhaps mean pulmonary capillary transit times) from decreasing below the threshold time required for oxygenation. [source] Molecular characterization of a human scavenger receptor, human MARCOFEBS JOURNAL, Issue 3 2000Nabil A. Elshourbagy Murine MARCO has been identified recently in subsets of macrophages located in the peritoneum, marginal zone of the spleen, and the medullary cord of lymph nodes, where it has been proposed that it serves as a bacteria-binding receptor. A scavenger receptor family member with an extended collagenous domain, murine MARCO has also been demonstrated in atherosclerotic lesions of susceptible mice. We report here the identification, tissue and chromosomal localization, and pharmacological characterization of human (h)MARCO. hMARCO was identified from a macrophage cDNA library by electronic screening with the murine MARCO sequence. Nucleotide sequence analysis confirmed that the full-length hMARCO clone encoded a 519-amino acid protein sharing 68.5% identity with murine MARCO. RNA blot analysis indicated that the hMARCO transcript is 2.0 kb in length and is predominantly expressed in human lung, liver, and lymph nodes. Radiation hybrid mapping localized hMARCO to chromosome 2q14. Ligand-binding studies of COS cells expressing hMARCO demonstrated significant specific binding of both Escherichia coli and Staphylococcus aureus. In contrast, the hMARCO receptor expressed in COS cells did not specifically bind the scavenger receptor ligand acetylated low-density lipoprotein (LDL), despite its similarity to the elongated collagen-like binding domain of the macrophage scavenger receptor. In addition, acetylated (Ac)LDL and oxidized (Ox)LDL did not inhibit E. coli binding to hMARCO. These data suggest that hMARCO may play an important role in host defense, but it has no obvious role in the accumulation of modified lipoproteins during atherogenesis. [source] Secondary Metabolites from the Fungus Chaetomium brasilienseHELVETICA CHIMICA ACTA, Issue 1 2008Guo-You Li Abstract Two new depsidones, mollicellins I and J (1 and 2, resp.), and a new chromone, 2-(hydroxymethyl)-6-methylmethyleugenin (3), along with six known compounds, 4,9, were isolated from the ethyl acetate extract of a solid-state fermented culture of Chaetomium brasiliense. Their structures were elucidated based on spectroscopic analysis. Mollicellins I and H (5) exhibited significant growth inhibitory activity against human breast cancer (Bre04), human lung (Lu04), and human neuroma (N04) cell lines with GI50 values between 2.5,8.6,,g/ml. [source] Quantitative contrast-enhanced perfusion measurements of the human lung using the prebolus approachJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 1 2009Markus Oechsner MS Abstract Purpose To investigate dynamic contrast-enhanced MRI (DCE-MRI) for quantification of pulmonary blood flow (PBF) and blood volume (PBV) using the prebolus approach and to compare the results to the global lung perfusion (GLP). Materials and Methods Eleven volunteers were examined by applying different contrast agent doses (0.5, 1.0, 2.0, and 3.0 mL gadolinium diethylene triamine pentaacetic acid [Gd-DTPA]), using a saturation-recovery (SR) true fast imaging with steady precession (TrueFISP) sequence. PBF and PBV were determined for single bolus and prebolus. Region of interest (ROI) evaluation was performed and parameter maps were calculated. Additionally, cardiac output (CO) and lung volume were determined and GLP was calculated as a contrast agent,independent reference value. Results The prebolus results showed good agreement with low-dose single-bolus and GLP: PBF (mean ± SD in units of mL/minute/100 mL) = single bolus 190 ± 73 (0.5-mL dose) and 193 ± 63 (1.0-mL dose); prebolus 192 ± 70 (1.0,2.0-mL dose) and 165 ± 52 (1.0,3.0-mL dose); GLP (mL/minute/100 mL) = 187 ± 34. Higher single-bolus resulted in overestimated values due to arterial input function (AIF) saturation. Conclusion The prebolus approach enables independent determination of appropriate doses for AIF and tissue signal. Using this technique, the signal-to-noise ratio (SNR) from lung parenchyma can be increased, resulting in improved PBF and PBV quantification, which is especially useful for the generation of parameter maps. J. Magn. Reson. Imaging 2009;30:104,111. © 2009 Wiley-Liss, Inc. [source] Non-contrast-enhanced perfusion and ventilation assessment of the human lung by means of fourier decomposition in proton MRIMAGNETIC RESONANCE IN MEDICINE, Issue 3 2009Grzegorz Bauman Abstract Assessment of regional lung perfusion and ventilation has significant clinical value for the diagnosis and follow-up of pulmonary diseases. In this work a new method of non-contrast-enhanced functional lung MRI (not dependent on intravenous or inhalative contrast agents) is proposed. A two-dimensional (2D) true fast imaging with steady precession (TrueFISP) pulse sequence (TR/TE = 1.9 ms/0.8 ms, acquisition time [TA] = 112 ms/image) was implemented on a 1.5T whole-body MR scanner. The imaging protocol comprised sets of 198 lung images acquired with an imaging rate of 3.33 images/s in coronal and sagittal view. No electrocardiogram (ECG) or respiratory triggering was used. A nonrigid image registration algorithm was applied to compensate for respiratory motion. Rapid data acquisition allowed observing intensity changes in corresponding lung areas with respect to the cardiac and respiratory frequencies. After a Fourier analysis along the time domain, two spectral lines corresponding to both frequencies were used to calculate the perfusion- and ventilation-weighted images. The described method was applied in preliminary studies on volunteers and patients showing clinical relevance to obtain non-contrast-enhanced perfusion and ventilation data. Magn Reson Med, 2009. © 2009 Wiley-Liss, Inc. [source] Assessment and compensation of susceptibility artifacts in gradient echo MRI of hyperpolarized 3He gasMAGNETIC RESONANCE IN MEDICINE, Issue 2 2003Jim M. Wild Abstract The effects of macroscopic background field gradients upon 2D gradient echo images of inhaled 3He in the human lung were investigated at 1.5 T. Effective compensation of in-slice signal loss in 3He gradient echo images was then demonstrated using a multiple acquisition interleaved single gradient echo sequence. This method restores signal dephasing through a combination of separate images acquired with different slice refocusing gradients. In vivo imaging of volunteers with the sequence shows substantial restoration of signal at the lung periphery and close to blood vessels. The technique presented may be useful when using 3He MRI for volumetric measurements of lung ventilation and in studies using 3He combined with intravenous contrast as a means of assessing lung ventilation/perfusion (V/Q). Magn Reson Med 50:417,422, 2003. © 2003 Wiley-Liss, Inc. [source] Cell-specific expression of manganese superoxide dismutase protein in the lungs of patients with respiratory distress syndrome, chronic lung disease, or persistent pulmonary hypertension,PEDIATRIC PULMONOLOGY, Issue 3 2001Tiina M. Asikainen MD Abstract The developmental profile of manganese superoxide dismutase (MnSOD) and its regulation in hyperoxia vary between species. We hypothesized that MnSOD increases in human lung in response to oxygen treatment, although this response could be restricted to certain cell types and depend on gestational age. Therefore, the cell-specific expression of pulmonary immunoreactive MnSOD protein was investigated during development, and in patients with respiratory distress syndrome (RDS), chronic lung disease (CLD), or persistent pulmonary hypertension (PPHN). Throughout ontogenesis, all cell types expressed MnSOD, but the most intense positivity was found in bronchiolar epithelium and (pre-) type-II pneumocytes. MnSOD protein did not increase during development. The MnSOD staining pattern in arterial endothelium was more intense in RDS patients than in age-matched controls, but this may be related to induction of MnSOD by increased blood flow rather than by oxygen. MnSOD expression in other cell types of RDS, CLD, or PPHN patients did not differ from that in age-matched controls. We conclude that, in terms of mitochondrial enzymatic superoxide scavenging capacity, preterm infants are not more vulnerable than term infants to oxygen-induced lung injury at physiological oxygen concentrations. However, the inability to induce MnSOD in response to oxygen treatment may result in a poor outcome. Pediatr Pulmonol. 2001; 32:193,200. © 2001 Wiley-Liss, Inc. [source] Reference gene selection for real-time polymerase chain reaction in human lung cells subjected to cyclic mechanical strainRESPIROLOGY, Issue 7 2008Liao PINHU Background and objective: The respiratory system is constantly exposed to mechanical forces that influence cellular phenotype in health and disease. Quantitative real-time PCR (qPCR) is widely used to determine gene expression. The validity of qPCR depends on using stable reference genes for normalization. The effect of cyclic mechanical strain on reference gene expression by lung epithelial, fibroblast and endothelial cells has not been studied systematically. Methods: The stability of expression of fourteen potential reference genes in response to six different regimens of cyclic mechanical strain was ranked using the geNorm tool in human lung epithelial cell lines (A549 and H441), human fetal lung fibroblasts (HFL-1), human lung microvascular endothelial cells, primary human lung fibroblasts and primary human alveolar type 2 (hAT2) cells. The expression variation of these reference genes was also screened in unstimulated whole human lung. Results: The stability of the selected reference genes varied within and between cell types, the variation in expression being greatest in primary cultures of hAT2. Correspondingly, the effect of expressing message for the stretch responsive gene IL-8 normalized to the 14 reference genes was greatest in the hAT2 cells, there being an almost fivefold difference in mRNA relative change comparing different reference genes in the same samples. The minimum number of genes required to derive a reliable normalization factor for experiments on single lung cell types undergoing mechanical strain was two and for whole human lung it was four. Conclusions: These results demonstrate that the optimal reference genes for lung cells subjected to CMS are cell type specific. [source] Herpes simplex virus-induced, death receptor-dependent apoptosis and regression of transplanted human cancersCANCER SCIENCE, Issue 12 2004Hironaga Kamiyama Inoculation of a live attenuated herpes simplex virus (HSV) vector, bH1, into human U87MG glioblastoma cells transplanted into athymic nude mice induced complete regression of tumors. The infected cells underwent histochemically confirmed apoptosis without lymphocyte infiltration after expressing CD30, CD30 ligand (CD30L), tumor necrosis factor (TNF)-a, TNF receptor 1 (TNF-R1), FAS, and FAS ligand (FAS-L) with activation of caspases 3 and 8. Induction of the transcripts of these receptors and ligands in inoculated tumors was confirmed by quantitative RT-PCR. To examine the specificity of apoptosis in the transplanted tumor, we inoculated bH1 into transplanted human lung, breast, gastric, and colon cancer tumors, and similar tumor regression with apoptosis was observed in all tumors. We analyzed the roles of expression of CD30, CD30L, TNF-a, TNF-R1, FAS, and FAS-L in the tumors, and found that HSV-induced apoptosis was suppressed by the respective antibodies. These findings indicate that the CD30/CD30L, TNF-a/TNF-R1, and FAS/FAS-L interactions resulted in apoptosis and tumor regression in immunocompromised mice. In addition to the death receptor-dependent apoptosis induced by HSV, the expressed ligands and receptors might enhance the susceptibility of tumor cells to cell-mediated cyto-toxicity and augment the activation of tumor-killing lymphocytes in immunocompetent models. [source] Mycobacterium tuberculosis possesses a functional enzyme for the synthesis of vitamin C, L -gulono-1,4-lactone dehydrogenaseFEBS JOURNAL, Issue 19 2006Beata A. Wolucka The last step of the biosynthesis of l -ascorbic acid (vitamin C) in plants and animals is catalyzed by l -gulono-1,4-lactone oxidoreductases, which use both l -gulono-1,4-lactone and l -galactono-1,4-lactone as substrates. l -Gulono-1,4-lactone oxidase is missing in scurvy-prone, vitamin C-deficient animals, such as humans and guinea pigs, which are also highly susceptible to tuberculosis. A blast search using the rat l -gulono-1,4-lactone oxidase sequence revealed the presence of closely related orthologs in a limited number of bacterial species, including several pathogens of human lungs, such as Mycobacterium tuberculosis, Pseudomonas aeruginosa, Burkholderia cepacia and Bacillus anthracis. The genome of M. tuberculosis, the etiologic agent of tuberculosis, encodes a protein (Rv1771) that shows 32% identity with the rat l -gulono-1,4-lactone oxidase protein. The Rv1771 gene was cloned and expressed in Escherichia coli, and the corresponding protein was affinity-purified and characterized. The FAD-binding motif-containing Rv1771 protein is a metalloenzyme that oxidizes l -gulono-1,4-lactone (Km 5.5 mm) but not l -galactono-1,4-lactone. The enzyme has a dehydrogenase activity and can use both cytochrome c (Km 4.7 µm) and phenazine methosulfate as exogenous electron acceptors. Molecular oxygen does not serve as a substrate for the Rv1771 protein. Dehydrogenase activity was measured in cellular extracts of a Mycobacterium bovis BCG strain. In conclusion, M. tuberculosis produces a novel, highly specific l -gulono-1,4-lactone dehydrogenase (Rv1771) and has the capacity to synthesize vitamin C. [source] Factors affecting the deposition of inhaled porous drug particlesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2002Cynthia J. Musante Abstract Recent findings indicate that the inhalation of large manufactured porous particles may be particularly effective for drug delivery. In this study, a mathematical model was employed to systematically investigate the effects of particle size, particle density, aerosol polydispersity, and patient ventilatory parameters on deposition patterns of inhaled drugs in healthy human lungs. Aerodynamically similar particles with densities of 0.1, 1.0, and 2.0 g/cm3 were considered. Particle size distributions were defined with mass median aerodynamic diameters (MMADs) ranging from 1 to 3 ,m and geometric standard deviations ranging from 1.5 to 2.5, representing particles in the respirable size range. Breathing rates of 30 and 60 L/min with tidal volumes of 500 to 3000 mL were assumed, simulating shallow to deep breaths from a dry powder inhaler. Particles with a high density and a small geometric diameter had slightly greater deposition fractions than particles that were aerodynamically similar, but had lower density and larger geometric size (typical of manufactured porous particles). This can be explained by the fact that particles with a small geometric diameter deposit primarily by diffusion, which is a function of geometric size but is independent of density. As MMAD increased, the effect of density on deposition was less pronounced because of the decreased efficiency of diffusion for large particles. These data suggest that polydisperse aerosols containing a significant proportion of submicron particles will deposit in the pulmonary airways with greater efficiency than aerodynamically similar aerosols comprised of geometrically larger porous particles. © 2002 Wiley-Liss Inc. and the American Pharmaceutical Association J Pharm Sci 91:1590,1600, 2002 [source] | |||||||||||||||||||||||||