Circulation of the airway mucosa

The major part of tracheobronchial blood flow is distributed to the mucosa. Its microvasculature comprises 10-20% of the subepithelial tissue volume, with blood flow ranging from 30 to 95 ml.min-1.100 g wet tissue-1 in different animal species. Mucosal blood flow is influenced by vascular and airway pressures, inspired air conditions, and autonomic neurotransmitters. Several inflammatory mediators and neuropeptides are capable of enhancing the permeability for macromolecules in postcapillary venules and of augmenting tissue water volume, often with a concomitant increase in perfusion. These microvascular responses of the lower airway mucosa have an important role under various conditions of physiological stress and in airway inflammation.     

Involvement of the phosphate regulon and the psiD locus in carbon-phosphorus lyase activity of Escherichia coli K-12.

Escherichia coli K-12 can readily mutate to use methylphosphonic acid as the sole phosphorus source by a direct carbon-to-phosphorus (C-P) bond cleavage activity that releases methane and Pi. The in vivo C-P lyase activity is both physiologically and genetically regulated as a member of the phosphate regulon. Since psiD::lacZ(Mu d1) mutants cannot metabolize methylphosphonic acid, psiD may be the structural gene(s) for C-P lyase.     

Indomethacin and FPL-57231 inhibit antigen-induced airway hyperresponsiveness in sheep

We compared the development of antigen-induced airway hyperresponsiveness (AHR) 24 h after challenge with Ascaris suum antigen in allergic sheep with acute (n = 7) and with dual (n = 7) airway responses and then attempted to modify this AHR. Cholinergic airway responsiveness was determined by measuring the carbachol dose required to increase specific lung resistance (sRL) 150% (i.e., PC150). Subsequently the sheep were challenged with antigen and sRL was measured at predetermined times to document the presence or absence of a late response. PC150 was redetermined 24 h later followed by bronchoalveolar lavage (BAL) to assess inflammation. Only dual responders developed AHR (PC150 decreased, P less than 0.05). There were no significant differences in BAL between the two groups. Six dual responders were then, on separate occasions (greater than or equal to 3 wk), pretreated with placebo, indomethacin (2 mg/kg iv), or a leukotriene antagonist, FPL-57231 (30 mg inhaled). Neither agent significantly affected the acute response to antigen. Only FPL pretreatment blocked the late response, but both agents blocked the antigen-induced AHR 24 h later. BAL at 24 h showed no significant differences. These results indicate that only dual responders develop AHR 24 h after antigen challenge. This AHR appears independent of the late increase in sRL or the severity of pulmonary inflammation. AHR appears to be sensitive to agents that interfere with the early release or actions of cyclooxygenase and lipoxygenase metabolites in dual responders.     

Overlapping and separate controls on the phosphate regulon in Escherichia coli K12

The physiological and genetic controls operating on phosphate-regulated promoters were studied in greater detail. This was done by defining the control for three phosphate-regulated genes: phoA, psiE, and psiO. Each is highly inducible by phosphate starvation. Individually, these phosphate-starvation-inducible, psi, genes at the same time show common and differing features in their molecular control. The phoA gene, encoding alkaline phosphatase, is specifically induced by phosphate starvation. It is negatively controlled by phoR as well as by the phosphate-specific transport (PST) system in Escherichia coli. phoA induction is positively controlled by the phoB, M, and R products; it is unaffected by the cAMP and CAP system. The psiE and psiO genes were studied by using strains with lacZ fused to their respective promoters. psiE-lacZ is induced by phosphate-, carbon- or nitrogen-limited growth. Genetically, psiE-lacZ induction is partially phoB and phoR-dependent. However, its expression is phoM-independent. This implies that phoB/phoR coupled control differs from phoB/phoM coupled control. Repression of psiE-lacZ is substantially altered in only some PST mutants, such as phoT. In addition, psiE-lacZ is negatively controlled by the cAMP and CAP system. psiO-lacZ is induced by phosphate-, carbon- or nitrogen-limited growth or by anaerobiosis. Its expression is unaffected by any pho mutation that has been previously described. A cell density-dependent induction of psiO-lacZ is observed in lon mutants. Also, psiO-lacZ is negatively controlled by the cAMP-CAP system. In summary, these results demonstrate that co-ordinately regulated promoters can have some common regulatory elements while, at the same time, not sharing other controlling factors.     

Über den Einfluß von Kinetin auf den Coffeingehalt der Blätter von Coffea arabica L.

Summary Kinetin induces an increase in the caffeine content of Coffea leaves of up to 40% of the normal level. The effect is most pronounced in young leaves; it is, however, transient. After six days in old leaves and after 12 days in young leaves, the caffeine content has decreased to its normal level.The results are discussed in relation to the recently discovered fact that cytokinins kinins are constituents of rare nucleotides of seryl-t-RNA. It seems plausible that the methylations necessary in the synthesis of caffeine are linked with this primary function of cytokinins.     

Bacterial pneumonia stimulates macromolecule secretion and ion and water fluxes in sheep trachea

In vivo instillation of Pasteurella haemolytica (greater than or equal to 10(7) colony-forming units/kg) into a lobar bronchus of sheep produced bacterial pneumonia by 7 days postinoculation. Infection was verified bacteriologically and histologically. Macromolecule secretion and ion and water fluxes were subsequently measured in tracheal tissues in vitro and were compared with values from sham-infected sheep. Macromolecules were radiolabeled with 35SO4 and [3H]threonine, and we measured the secretion of macromolecule-bound radiolabel onto the mucosa. Unidirectional fluxes of Cl-, Na+, and water were measured with radioactive tracers under open-circuit and short-circuit conditions. Lung infection increased basal secretion of bound 35SO4 (by 189%) and bound [3H]-threonine (by 110%). It significantly increased net Na+ absorption under open- and short-circuit conditions and induced open-circuit net absorption of Cl- and water (16 +/- 29 microliters X cm-2 X h-1). These changes were associated with specific recruitment of neutrophils and elevated levels of arachidonate metabolites (thromboxane B2 and leukotriene B4) in the airways. Thus the bacterial pneumonia-induced changes in tracheal mucus secretion may be the result of airway inflammation.     

Effect of osmolarity on LDL binding and internalization in hepatocytes

The present study has been performed to elucidate a possiblerole of cell volume in low-density lipoprotein (LDL) binding andinternalization (LDL_b+i). Asshown previously, increase of extracellular osmolarity (OSMe) andK⁺ depletion, both known to shrinkcells, interfere with the formation of clathrin-coated pits and thuswith LDL_b+i. On the other hand,alterations of cell volume have been shown to modify lysosomal pH,which is a determinant of LDL_b+i.LDL_b+i have been estimated fromheparin-releasable (binding) or heparin-insensitive (internalization)uptake of ¹²⁵I-labeled LDL. OSMewas modified by alterations of extracellular concentrations of ions,glucose, urea, or raffinose. When OSMe was altered by varying NaClconcentrations, LDL_b+i decreased (by 0.5 ± 0.1%/mM) with increasing OSMe andLDL_b+i increased (by 1.2 ± 0.1%/mM) with decreasing OSMe, an effect mainly due to alteredaffinity; the estimated dissociation constant amounted to 20.6, 48.6, and 131.6 µg/ml at 219, 293, and 435 mosM, respectively. A 25%increase of OSMe increased cytosolic (by 0.46 ± 0.03) and decreasedlysosomal (by 0.14 ± 0.02) pH. Conversely, a 25% decrease of OSMedecreased cytosolic (by 0.28 ± 0.02) and increased lysosomal (by0.17 ± 0.02) pH. Partial replacement of extracellularNa⁺ withK⁺ had little effect onLDL_b+i, although it swelledhepatocytes and increased lysosomal and cytosolic pH. Hypertonicglucose, urea, or raffinose did not exert similar effects despite ashrinking effect of hypertonic raffinose. Monensin, which completelydissipates lysosomal acidity, virtually abolishedLDL_b+i. In conclusion, theobservations reveal a significant effect of ionic strength onLDL_b+i. The effect is, however,not likely to be mediated by alterations of cell volume or alterationsof lysosomal pH.