Extra-alveolar vessel fluid filtration coefficients in excised and in situ canine lobes

We continuously weighed fully distended excised or in situ canine lobes to estimate the fluid filtration coefficient (Kf) of the arterial and venous extra-alveolar vessels compared with that of the entire pulmonary circulation. Alveolar pressure was held constant at 25 cmH2O after full inflation. In the in situ lobes, the bronchial circulation was interrupted by embolization. Kf was estimated by two methods (Drake and Goldberg). Extra-alveolar vessels were isolated from alveolar vessels by embolizing enough 37- to 74-micron polystyrene beads into the lobar artery or vein to completely stop flow. In excised lobes, Kf's of the entire pulmonary circulation by the Drake and Goldberg methods were 0.122 +/- 0.041 (mean +/- SD) and 0.210 +/- 0.080 ml X min-1 X mmHg-1 X 100 g lung-1, respectively. Embolization was not found to increase the Kf's. The mean Kf's of the arterial extra-alveolar vessels were 0.068 +/- 0.014 (Drake) and 0.069 +/- 0.014 (Goldberg) (24 and 33% of the Kf's for the total pulmonary circulation). The mean Kf's of the venous extra-alveolar vessels were similar [0.046 +/- 0.020 (Drake) and 0.065 +/- 0.036 (Goldberg) or 33 and 35% of the Kf's for the total circulation]. No significant difference was found between the extra-alveolar vessel Kf's of in situ vs. excised lobes. These results suggest that when alveolar pressure, lung volume, and pulmonary vascular pressures are high, approximately one-third of the total fluid filtration comes from each of the three compartments.     

Effects of particle concentration and season on the filtration rates of the freshwater clam,Sphaerium striatinum Lamarck (Bivalvia: Pisidiidae)

The effects of particle concentration and season on the filtration rates of the freshwater clamSphaerium striatinum Lamarck were assessed by measuring clearance rates of small (2.02 μm) latex beads from dilute suspensions. Filtration rates decreased as particle concentration increased over a range of 2–64 mg 1⁻¹, with rates decreasing in similar proportion for clams of all sizes. For a 1-mg clam, rates decreased from approximately 8.4 to 0.57 ml clam⁻¹ h⁻¹. Seasonal filtration rates for adult clams peaked during periods of greatest reproduction. The patterns for smaller clams are similar, though proportional changes in filtration rates differ for various sizes of clams. It is estimated that clams occupying 1 m² of stream substrate removed about 3.67 gCa⁻¹. This is equivalent to 0.0004% of the carbon that flows past them annually. Filter-feeding provided only 24% of the calculated energy needs of the population, suggesting that another mode of feeding (e.g. deposit-feeding) may provide an important energy source for these forms. Funded in part by a grant-in-aid to D. J. Hornbach from Sigma-Xi, The Research Society. Funded in part by a grant-in-aid to D. J. Hornbach from Sigma-Xi, The Research Society.     

Relationship of thyrotropin-releasing hormone-induced spike and plateau phases in cytosolic free Ca2+ concentrations to hormone secretion. Selective blockade using ionomycin and nifedipine

In clonal rat pituitary cells (GH cells), thyrotropin-releasing hormone (TRH) induced a pattern of changes in cytosolic free calcium concentrations [( Ca2+]i) composed of two phases: an acute spike phase to micromolar levels which decayed (t1/2 = 8 s) to a near-basal concentration and then rose to a prolonged plateau phase of elevated [Ca2+]i (as measured using Quin 2). Closely following these changes in [Ca2+]i, TRH stimulated a rapid "spike phase" of pronounced, but brief, enhancement of the rate of prolactin and growth-hormone secretion and then a "plateau phase" of prolonged enhancement. These two phases were dissociated using two classes of pharmacologic agents: the ionophore ionomycin, and a calcium channel antagonist nifedipine. Ionomycin (100 nM) specifically blocked (less than 90%) the spike phase of TRH action by rapidly emptying the TRH-regulated reservoir of cellular Ca2+ to generate a TRH-like spike in [Ca2+]i; nifedipine inhibited (less than 50%) the plateau phase of TRH-induced changes in [Ca2+]i and hormone secretion by preventing Ca2+ influx through voltage-dependent Ca2+ channels. These agents demonstrated that the TRH-induced spike in [Ca2+]i in GH cells is caused by release of an ionomycin-sensitive pool of cellular Ca2+ with a small component (10%) due to influx of extracellular Ca2+. The TRH-induced plateau in [Ca2+]i is due to influx of extracellular Ca2+, about half of which enters through voltage-dependent calcium channels and half of which enters via nifedipine/verapamil-insensitive influx. The TRH-induced spike in [Ca2+]i led to a burst in hormone secretion, and the plateau in [Ca2+]i produced a prolonged enhancement of secretion; the spike and plateau phases were generated independently by TRH. A spike in [Ca2+]i is necessary, but not sufficient, to induce burst release of hormone, while the prolonged rate of hormone secretion is intimately related to the steady-state [Ca2+]i.     

Continuity of arterial and venous extra-alveolar interstitium in excised rabbit lungs

We studied the interdependence of arterial and venous extra-alveolar vessel (EAV) leakage on the rate of pulmonary vascular fluid filtration (measured as the change in lung weight over time). Edema was produced in continually weighed, excised rabbit lungs kept in zone 1 (alveolar pressure = 25 cmH2O) by increasing pulmonary arterial (Ppa) and/or venous (Ppv) pressure from 5 to 20 cmH2O (relative to the lung base) and continuing this hydrostatic stress for 3-5 h. Raising Ppa and Ppv simultaneously produced a lower filtration rate than the sum of the filtration rates obtained when Ppa and Ppv were raised separately, while the lung gained from 20 to 95% of its initial weight. When vascular pressure was elevated in either EAV segment, fluid filtration always decreased rapidly as the lung gained up to 30-45% of its initial weight. Filtration then decreased more slowly. The lungs became isogravimetric at 60 and 85% weight gain when the Ppa or Ppv was elevated, respectively; when Ppa and Ppv were raised simultaneously substantial fluid filtration continued even after 140% weight gain. We conclude that the arterial and venous EAV's share a common interstitium in the zone 1 condition, this interstitium cannot be represented as a single compartment with a fixed resistance and compliance, and arterial and venous EAV leakage influences leakage from the other segment.     

Lung endothelial and epithelial permeability after platelet-activating factor

We investigated whether platelet-activating factor (PAF) increased epithelial or endothelial permeability in isolated-perfused rabbit lungs. PAF was either injected into the pulmonary artery or instilled into the airway of lungs perfused with Tyrode's solution containing 1% bovine serum albumin. The effect of adding neutrophils or platelets to the perfusate was also tested. Perfusion was maintained 20-40 min after adding PAF and then a fluid filtration coefficient (Kf) was determined to assess vascular permeability. At the end of each experiment, one lung was lavaged, and the lavagate protein concentration (BALP) was determined. Wet weight-to-dry weight ratios (W/D) were determined on the other lung. PAF added to the vascular space increased peak pulmonary arterial pressure (Ppa) from 13.5 +/- 3.1 (mean +/- SE) to 24.2 +/- 3.3 cmH2O (P less than 0.05). The effect was amplified by platelets [Ppa to 70.8 +/- 8.0 cmH2O (P less than 0.05)] but not by neutrophils [Ppa to 22.0 +/- 1.4 cmH2O (P less than 0.05)]. Minimal changes in Ppa were observed after instilling PAF into the airway. The Kf, W/D, and BALP of untreated lungs were not increased by injecting PAF into the vasculature or into the air space. The effect of PAF on Kf, W/D, and BALP was unaltered by adding platelets or neutrophils to the perfusate. PAF increases intravascular pressure (at a constant rate of perfusion) but does not increase epithelial or endothelial permeability in isolated-perfused rabbit lungs.     

Interaction of bradykinin with sodium dodecyl sulfate and certain acidic lipids

The striking change in the circular dichroism (CD) of bradykinin (BK) occasioned by its interaction with sodium dodecyl sulfate (SDS) is evidently due in large part to a change in the conformation of the C-terminal tetrapeptide moiety of the hormone. The full change in CD is induced by the binding of two molecules of monomeric SDS per peptide molecule, the complex being aggregated. Formation of the 1:2 BK-SDS complex apparently proceeds via intermediates of stoichiometry 1:1 and 2:1. The cooperative nature of the interaction is attributed to the SDS-promoted aggregation of BK. Electrostatic interactions with the Arg residues appear important for the binding reaction per se. CD reveals that BK also interacts with acidic lipids which bear a net electrical charge (e.g., cerebroside sulfate and phosphatidyl inositol) but not with lipids bearing no net charge (e.g., cerebroside and phosphatidyl choline). The interactions are with particular mixed micelles of the lipid and the nonionic surfactant used for their solubilization, micellar size and structure being examined by surface tensiometry and electron microscopy.     

Cytoarchitectonic localization of foci of electrocortical activity accompanying focused attention in cats

Beta electrocorticographic rhythms (30-45 Hz) develop during focused immobile attention within two distinct foci in cats. A multiple electrode exploration was performed, followed by post-mortem histological analysis, to determine the precise localization of these foci. Electrode tips recording beta rhythms in the waking attentive cat were located: in motor areas (Brodmann's areas 4 and 6), in a band extending from the postcruciate cortex to the walls of the presylvian sulcus, crossing the frontal pole (anterior beta focus); in the posterior parietal associative area 5a, along the divisions of the ansate sulcus (posterior beta focus). The two foci are separated by somatic areas 3, 2 and 1, where beta rhythms were never recorded. The location of the posterior focus may suggest that area 5 is, in the cat as it is in the monkey, involved in motor control.     

Tryptophan feeding adversely influences pregnancy

Additional tryptophan during pregnancy reduces embryo and neonate survival in the golden hamster, $\text{Mesocricetus auratus}$.Relatively small doses of exogenous serotonin have been reported to cause abortions in several vertebrate species (1, 2, 3, 4, 5). Smaller doses reduce litter sizes, increase still births and neonate abnormalities, and otherwise influence pregnancy adversely. These effects are produced by serotonin throughout pregnancy, beginning at implantation (6).The availability of tryptophan is probably the most important rate limiting factor in serotonin synthesis (7). Inasmuch as tryptophan is an essential amino acid and is not synthesized by the body, the diet is the sole source; studies have shown that increases (8) or decreases (9) in dietary tryptophan lead to concomitant changes in serotonin content. Because tryptophan is employed in humans to promote sleep (10, 11, 12) and to decrease appetite (13) we felt it might be important to test whether increased amounts of diet tryptophan can adversely influence pregnancy.     

Characterization of a 45-kDa polypeptide as the precursor of subunit 1 of cytochrome c oxidase in Neurospora crassa

In a previous paper (Van 't Sant, P., Mak, J.F.C. and Kroon, A.M. (1981) Eur. J. Biochem. 121, 21–26) we showed the existence of three elongated precursor proteins (45, 36 and 25 kDa) of mitochondrial translation products in Neurospora crassa. We presented some indications that the largest precursor could be related to subunit 1 of cytochrome c oxidase. Here we present conclusive evidence that the 45-kDa polypeptide is indeed this precursor by demonstrating that an immunodetectable 45-kDa polypeptide displays the same behaviour as the labeled 45-kDa precursor; both accumulate after long incubation with cycloheximide or by decreasing the temperature and both are not tightly membrane bound. Moreover the antibody against subunit 1 of cytochrome c oxidase also recognizes, in immunoadsorption experiments, besides subunit 1, the 45-kDa polypeptide accumulated by cycloheximide incubation. Furthermore, we developed a small scale purification of antibodies against subunit 1 of cytochrome c oxidase. By means of these purified antibodies it is demonstrated that the 45-kDa polypeptide and subunit 1 have corresponding antigenic determinants. Under the various conditions tested, all three precursors are less firmly membrane-bound than the mature subunits. Finally, it is observed that in short incubations in vivo, chloramphenicol inhibits the processing of the mitochondrially synthesized precursors, under conditions where mitochondrial translation is only partially inhibited.