Gravity outweighs the contribution of structure to passive ventilation-perfusion matching in the supine adult human lung

Gravity and matched airway/vascular tree geometries are both hypothesized to be key contributors to ventilation-perfusion (V̇/Q̇) matching in the lung, but their relative contributions are challenging to quantify experimentally. We used a structure-based model to conduct an analysis of the relative contributions of tissue deformation (the “Slinky” effect), other gravitational mechanisms (weight of blood and gravitational gradient in tissue elastic recoil), and matched airway and arterial tree geometry to V̇/Q̇ matching and therefore to total lung oxygen exchange. Our results showed that the heterogeneity in V̇ and Q̇ were lowest and the correlation between V̇ and Q̇ was highest when the only mechanism for V̇/Q̇ matching was either tissue deformation or matched geometry. Heterogeneity in V̇ and Q̇ was highest and their correlation was poorest when all mechanisms were active (that is, at baseline). Eliminating the contribution of matched geometry did not change the correlation between V̇ and Q̇ at baseline. Despite the much larger heterogeneities in V̇ and Q̇ at baseline, the contribution of in-common (to V̇ and Q̇) gravitational mechanisms provided sufficient compensatory V̇/Q̇ matching to minimize the impact on oxygen transfer. In summary, this model predicts that during supine normal breathing under gravitational loading, passive V̇/Q̇ matching is predominantly determined by shared gravitationally induced tissue deformation, compliance distribution, and the effect of the hydrostatic pressure gradient on vessel and capillary size and blood pressures. Contribution from the matching airway and arterial tree geometries in this model is minor under normal gravity in the supine adult human lung. NEW & NOTEWORTHY We use a computational model to systematically analyze contributors to ventilation-perfusion matching in the lung. The model predicts that the multiple effects of gravity are the predominant mechanism in providing passive ventilation-perfusion matching in the supine adult human lung under normal gravitational loads, while geometric matching of airway and arterial trees plays a minor role.

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Effect of aging alone on mechanical properties of the normal adult human lung

Journal of Applied Physiology ◽

10.1152/jappl.1977.43.6.1054 ◽

1977 ◽

Vol 43 (6) ◽

pp. 1054-1062 ◽

Cited By ~ 131

Author(s):

R. J. Knudson ◽

D. F. Clark ◽

T. C. Kennedy ◽

D. E. Knudson

Keyword(s):

Respiratory Mechanics ◽

Human Lung ◽

Age Groups ◽

The Elderly ◽

Elastic Recoil ◽

Lung Volumes ◽

Men And Women ◽

Maximum Expiratory Flow ◽

Alpha1 Antitrypsin ◽

Adult Human Lung

For plethysmographic studies of respiratory mechanics, we selected, from a general population, 51 subjects, aged 25–75 yr, who had never smoked, had no present or past cardiorespiratory symptoms or disease, were alpha1-antitrypsin MM phenotypes, and were normal by physical examination, vectorcardiography, and chest roentgenography. Approximately equal numbers of men and women were represented in each of three age groups; 25–35, 36–64, and 65–75. Both sexes demonstrated loss of lung elastic recoil with age, most significant at high lung volumes, but the rate of loss was less than previously reported. Males had higher lung recoil than females of comparable age, but if lung size was taken into account, there were no sex differences in bulk elastic properties. Maximum expiratory flow diminished with age only at low volumes, suggesting that equal pressure points are more centrally located at low lung volumes in the elderly.

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Branching pattern of airways and air spaces of a single human terminal bronchiole

Journal of Applied Physiology ◽

10.1152/jappl.1975.38.6.983 ◽

1975 ◽

Vol 38 (6) ◽

pp. 983-989 ◽

Cited By ~ 53

Author(s):

J. E. Hansen ◽

E. P. Ampaya ◽

G. H. Bryant ◽

J. J. Navin

Keyword(s):

Young Adult ◽

Polyurethane Foam ◽

First Generation ◽

Human Lung ◽

Branching Pattern ◽

Serial Sections ◽

Adult Human ◽

Three Generations ◽

Terminal Bronchiole ◽

Adult Human Lung

A polyurethane-foam enlarged reconstruction was made from serial sections of a portion of young adult human lung parenchyman. Study of the progeny of a terminal bronchiole disclosed three generations of respiratory bronchioles and an irregular branching pattern of eight generations of alveolar ducts. Sacs and alveoli arose from the lateral and distal aspects of all generations of ducts. There were an average of 3.5 alveoli per sac. Considering the terminal bronchiole as the first generation branch of the acinus, over 60 per cent of the alveoli counted and predicted were members of the 10–12th generations. The acinus contained one terminal bronchiole and approximately 14 respiratory bronchioles, 1,200–1,500 ducts, 2,500–4,500 sacs, and 14,000–20,000 alveoli.

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Characterization of the human pH- and PKA-activated ClC-2G(2 alpha) Cl- channel

AJP Cell Physiology ◽

10.1152/ajpcell.1997.273.2.c384 ◽

1997 ◽

Vol 273 (2) ◽

pp. C384-C393 ◽

Cited By ~ 38

Author(s):

A. M. Sherry ◽

K. Stroffekova ◽

L. M. Knapp ◽

E. Y. Kupert ◽

J. Cuppoletti ◽

...

Keyword(s):

Human Lung ◽

Single Channel ◽

Reversal Potential ◽

Fetal Lung ◽

Northern Analysis ◽

Adult Human ◽

Cl Channel ◽

Voltage Curve ◽

Current Voltage Curve ◽

Adult Human Lung

A ClC-2G(2 alpha) Cl- channel was identified to be present in human lung and stomach, and a partial cDNA for this Cl- channel was cloned from a human fetal lung library. A full-length expressible human ClC-2G(2 alpha) cDNA was constructed by ligation of mutagenized expressible rabbit ClC-2G(2 alpha) cDNA with the human lung ClC-2G(2 alpha) cDNA, expressed in oocytes, and characterized at the single-channel level. Adenosine 3',5'-cyclic monophosphate-dependent protein kinase (PKA) treatment increased the probability of opening of the channel (Po). After PKA activation, the channel exhibited a linear (r = 0.99) current-voltage curve with a slope conductance of 22.1 +/- 0.8 pS in symmetric 800 mM tetraethylammonium chloride (TEACl; pH 7.4). Under fivefold gradient conditions of TEACl, a reversal potential of +21.5 +/- 2.8 mV was measured demonstrating anion-to-cation discrimination. As previously demonstrated for the rabbit ClC-2G(2 alpha) Cl- channel, the human analog, hClC-2G(2 alpha), was active at pH 7.4 as well as when the pH of the extracellular face of the channel (trans side of the bilayer; pHtrans) was asymmetrically reduced to pH 3.0. The extent of PKA activation was dependent on pHtrans. With PKA treatment, Po increased fourfold with a pHtrans of 7.4 and eightfold with a pHtrans of 3.0. Effects of sequential PKA addition followed by pHtrans reduction on the same channel suggested that the PKA- and pH-dependent increases in channel Po were separable and cumulative. Northern analysis showed ClC-2G(2 alpha) mRNA to be present in human adult and fetal lung and adult stomach, and quantitative reverse transcriptase-polymerase chain reaction showed this channel to be present in the adult human lung and stomach at about one-half the level found in fetal lung. The findings of the present study suggest that the ClC-2G(2 alpha) Cl- channel may play an important role in Cl- transport in the fetal and adult human lung.

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The Secondary Lobule in the Adult Human Lung, with Special Reference to its Appearance in Bronchograms

Thorax ◽

10.1136/thx.13.2.110 ◽

1958 ◽

Vol 13 (2) ◽

pp. 110-115 ◽

Cited By ~ 26

Author(s):

L. Reid

Keyword(s):

Special Reference ◽

Human Lung ◽

Adult Human ◽

Adult Human Lung

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Gene transfer to adult human lung tissue ex vivo

Gene Therapy ◽

10.1038/sj.gt.3301146 ◽

2000 ◽

Vol 7 (8) ◽

pp. 675-678 ◽

Cited By ~ 10

Author(s):

S McBride ◽

D Rannie ◽

D J Harrison

Keyword(s):

Gene Transfer ◽

Lung Tissue ◽

Human Lung ◽

Ex Vivo ◽

Human Lung Tissue ◽

Adult Human ◽

Adult Human Lung

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CD105-Positive Cells in Pulmonary Arterial Blood of Adult Human Lung Cancer Patients Include Mesenchymal Progenitors

Stem Cells ◽

10.1634/stemcells.2008-0037 ◽

2008 ◽

Vol 26 (10) ◽

pp. 2523-2530 ◽

Cited By ~ 13

Author(s):

Haruki Chiba ◽

Genicihro Ishii ◽

Ta-Kashi Ito ◽

Kazuhiro Aoyagi ◽

Hiroki Sasaki ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Patients ◽

Human Lung ◽

Human Lung Cancer ◽

Mesenchymal Progenitors ◽

Lung Cancer Patients ◽

Adult Human ◽

Arterial Blood ◽

Pulmonary Arterial ◽

Adult Human Lung

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Extracellular Pneumococcal Serine Proteases Affect Nasopharyngeal Colonization

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2020.613467 ◽

2021 ◽

Vol 10 ◽

Author(s):

Murtadha Q. Ali ◽

Thomas P. Kohler ◽

Gerhard Burchhardt ◽

Andreas Wüst ◽

Nadin Henck ◽

...

Keyword(s):

Serine Proteases ◽

Bacterial Load ◽

Acute Infection ◽

Minor Role ◽

Extracellular Proteases ◽

Nasopharyngeal Colonization ◽

Invasive Diseases ◽

Pneumococcal Colonization ◽

A Minor ◽

The Impact

Streptococcus pneumoniae has evolved versatile strategies to colonize the nasopharynx of humans. Colonization is facilitated by direct interactions with host cell receptors or via binding to components of the extracellular matrix. In addition, pneumococci hijack host-derived extracellular proteases such as the serine protease plasmin(ogen) for ECM and mucus degradation as well as colonization. S. pneumoniae expresses strain-dependent up to four serine proteases. In this study, we assessed the role of secreted or cell-bound serine proteases HtrA, PrtA, SFP, and CbpG, in adherence assays and in a mouse colonization model. We hypothesized that the redundancy of serine proteases compensates for the deficiency of a single enzyme. Therefore, double and triple mutants were generated in serotype 19F strain EF3030 and serotype 4 strain TIGR4. Strain EF3030 produces only three serine proteases and lacks the SFP encoding gene. In adherence studies using Detroit-562 epithelial cells, we demonstrated that both TIGR4Δcps and 19F mutants without serine proteases or expressing only CbpG, HtrA, or PrtA have a reduced ability to adhere to Detroit-562 cells. Consistent with these results, we show that the mutants of strain 19F, which preferentially colonizes mice, abrogate nasopharyngeal colonization in CD-1 mice after intranasal infection. The bacterial load in the nasopharynx was monitored for 14 days. Importantly, mutants showed significantly lower bacterial numbers in the nasopharynx two days after infection. Similarly, we detected a significantly reduced pneumococcal colonization on days 3, 7, and 14 post-inoculations. To assess the impact of pneumococcal serine proteases on acute infection, we infected mice intranasally with bioluminescent and invasive TIGR4 or isogenic triple mutants expressing only CbpG, HtrA, PrtA, or SFP. We imaged the acute lung infection in real-time and determined the survival of the mice. The TIGR4lux mutant expressing only PrtA showed a significant attenuation and was less virulent in the acute pneumonia model. In conclusion, our results showed that pneumococcal serine proteases contributed significantly to pneumococcal colonization but played only a minor role in pneumonia and invasive diseases. Because colonization is a prerequisite for invasive diseases and transmission, these enzymes could be promising candidates for the development of antimicrobials to reduce pneumococcal transmission.

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Low incidence of Schmallenberg virus infection in natural cases of abortion in domestic ruminants in Hungary

Acta Veterinaria Hungarica ◽

10.1556/004.2020.00002 ◽

2020 ◽

Vol 68 (1) ◽

pp. 105-111

Author(s):

Levente Szeredi ◽

Ádám Dán ◽

Péter Malik ◽

Szilárd Jánosi ◽

Ákos Hornyák

Keyword(s):

Tissue Sample ◽

Schmallenberg Virus ◽

Minor Role ◽

Chain Reaction ◽

Domestic Ruminants ◽

Polymerase Chain ◽

Low Incidence ◽

A Minor ◽

The Impact

AbstractAn epizootic caused by a new orthobunyavirus called Schmallenberg virus (SBV) was recognised in European ruminants in 2011 and 2012. The re-emergence of the infection was reported in several countries in the subsequent years. Although the main clinical sign of SBV infection is abortion, the impact of SBV in natural cases of abortion in domestic ruminants had not been systematically examined before this study. The aim of the study was to investigate the role of SBV infection and to compare it to the importance of other causes of abortion by examining 537 natural cases of abortion that had occurred between 2011 and 2017 in Hungary. The cause of abortion was determined in 165 (31%) cases. An infectious cause was proved in 88 (16%) cases. SBV infection was found only in a total of four cases (0.8%) using real-time polymerase chain reaction. Three of them proved to be inapparent SBV infection, and one case was attributed to SBV-induced abortion by detecting non-purulent encephalitis and SBV nucleoprotein by immunohistochemistry in a brain tissue sample. According to the results, SBV played a minor role in natural cases of domestic ruminant abortion in Hungary during the 7-year period following the first SBV outbreak in 2011.

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Hope, Disillusion and Coincidence in Migratory Decisions by Senegalese Migrants in Brazil

Social Inclusion ◽

10.17645/si.v9i1.3721 ◽

2021 ◽

Vol 9 (1) ◽

pp. 268-277

Author(s):

Philipp Roman Jung

Keyword(s):

Minor Role ◽

Positive Outcomes ◽

Essential Characteristic ◽

New Destinations ◽

Onward Migration ◽

Decisions To Leave ◽

Restricted Mobility ◽

A Minor ◽

The Impact ◽

Do So

Uncertainty is an essential characteristic of our lives. However, by moving from one country to another, from a familiar context to an unfamiliar one, uncertainty becomes a key element of migrants’ decisions. In times of restricted mobility regimes, migrants often do not know if they will be able to reach the desired destination. Even if they manage to do so, it is still uncertain if they will be able to fulfil their aspirations. However, uncertainty also leaves room for hope. Departing from the conceptualisation of hope as the simultaneity of both potentiality and uncertainty and from the concept of circumstantial migration, this article analyses (1) retrospectively the decision of Senegalese migrants to move to Brazil and (2) the intentions of onward migration. Based on empirical data collected through ethnographic fieldwork in four Brazilian cities, this article shows how migration as a form of social hope is redirected to new destinations and that this redirection is a consequence of circumstances and coincidences, which enable or prevent movement. Potential positive outcomes of migration outweighed negative ones, which play a minor role and hardly affect decisions to leave Senegal. However, decisions to emigrate are often based on incomplete information and ill-informed expectations regarding the circumstances at the destination and can lead to feelings of disillusion. The impact of uncertainties shows a more differentiated picture in the context of onward migration intentions. While some migrants are willing to take big risks in onward migration, others try to minimize uncertainties.

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