Ear oximetry during combined hypoxia and exercise

Ear oximetry is widely used to detect arterial O2 desaturation during exercise in patients with cardiopulmonary disease. Although oximeters have been evaluated for accuracy, response time, and the influence of skin pigmentation, tests of their reliability have not been reported during strenuous exercise. Accordingly, we compared arterial O2 saturation (Sao2) measurements obtained by Hewlett-Packard (HP, model 47201A) and Biox II oximeters with those determined directly from arterial blood in six healthy volunteers during progressive exercise while rebreathing hypoxic gas mixtures. The relationship between the HP oximeter value and blood Sao2 was described by the equation: HP = 0.93 (Sao2) + 5.37 and for the Biox II: Biox = 0.55 (Sao2) + 38.97. With these equations, at a blood Sao2 value of 90%, the underestimation by both oximeters was less than 2%. At a blood value of 70%, the HP oximeter overestimated blood Sao2 by 0.7%, whereas the Biox II showed an overestimation of 10.7%. Below blood Sao2 of 83%, the Biox II tended to overestimate blood Sao2 by an amount greater than the error of the instrument, whereas the HP estimations were within the error of the instrument over all levels of blood Sao2 studied. We conclude that the HP oximeter provides valid estimates of Sao2 during exercise but that the Biox II oximeter, although reflecting qualitative changes in oxygenation that occur during exercise, does not provide accurate records of the degree of desaturation.     

Radiographic visualization of airway wall movement during oscillatory flow in dogs

It has been suggested that radial movement of the central airway walls during oscillatory flow might contribute to the increased frequency dependence of compliance seen in chronic obstructive pulmonary disease (COPD) (J. Appl. Physiol. 26: 670-677, 1969). Radial airway wall motion has also been invoked to explain the frequency-dependent decreases in the efficiency of gas exchange during low-volume high-frequency ventilation (HFV) in histamine-bronchoconstricted dogs and in patients with respiratory insufficiency. To test the possibility that airway wall motion increases with bronchoconstriction, we measured central airway diameters using cinebronchoradiography in anesthetized tracheostomized dogs during oscillatory HFV [50 and 100 ml tidal volume (VT) at frequencies (f) of 2, 6, and 12 Hz], under control conditions, during electrical stimulation of the vagi, and after exposure to histamine aerosol. Cineradiobronchograms from two dogs were evaluated quantitatively for tracheal diameter and for lengths and diameters of a number of major airways. Under control conditions, the diameter of the airways fluctuated 7-9% of the mean with VT of 50 ml and 9-18% with VT of 100 ml in the range of frequencies studied. Bronchoconstriction produced by aerosolized histamine increased radial airway wall movement to 10-47% with VT of 50 ml, and during vagal stimulation diameters changed 7-20% at VT of 50 ml. After histamine, the central airways displayed large diameter changes during HFV, whereas more peripheral airways were markedly constricted and did not change in diameter.(ABSTRACT TRUNCATED AT 250 WORDS)     

Assessment of maximal expiratory pressure in healthy adults

Maximal static expiratory pressure developed at the mouth (PEmax) provides a useful clinical index of expiratory muscle function; however, the range of normal values among laboratories shows considerable variation. We examined the hypothesis that the wide variability could be attributable to the differences in technique among laboratories. We measured PEmax at functional residual capacity (PEmax FRC) in 28 healthy subjects using the following five techniques: 1) using a scuba-type mouthpiece with the cheeks supported by the hands ("hands on"), 2) without supporting the cheeks ("no hands"), 3) using a rigid, circular mouthpiece (2.8 cm ID, "tube"), 4) using the scuba-type mouthpiece but with the cheeks supported by an observer ("other hands"), and 5) using a large-bore circular mouthpiece (4.1 cm ID, "new tube"). Mean PEmax FRC obtained with hands on was significantly higher than no-hands and tube methods. PEmax FRC values obtained by the other-hands and new-tube maneuvers were similar to the hands-on maneuver. We conclude that the technique used to measure PEmax FRC can significantly affect the results and suggest that it should be measured using a large-bore circular mouthpiece or a scuba-diving mouthpiece with the cheeks supported.     

Gas transport during oscillatory flow in a network of branching tubes

A transport coefficient was measured for a range of oscillatory flow conditions in a branching network of tubes. Measurements were made both across the first generation of a three-generation network and the second generation of a four-generation network. The results for these two series of tests were similar, indicating that there was no significant effect due to the system boundaries. The results are cast in terms of an effective axial diffusion coefficient of the form (Formula: see text) where kappa is the molecular diffusivity, Vt is the local stroke volume (cc); and f is the oscillation frequency (Hz). These results are compared to those obtained by other investigators in branching systems of similar geometry. At low frequency, this result is found to be in approximate agreement with the steady flow result of Scherer, et al. [15]. This expression differs from the oscillatory flow results of Tarbell, et al. [19] for liquids, primarily in terms of the effects of oscillation frequency.     

Organization of fusicoccin receptor in higher plant plasma membrane: relationship between affinity and molecular mass

Higher plant plasma membranes carry receptors of different affinity for the phytotoxin fusicoccin. Reception of fusicoccin involves proteins belonging to the highly conserved 14-3-3 family, but the complete structure of the fusicoccin receptor (FCR) is unknown. Using radiation inactivation analysis, we estimated the molecular masses of low-affinity and high-affinity FCR at 63 +/- 7 and 130 +/- 15 kD, respectively. The dose dependences of receptor inactivation indicate that microsomal specimens contain "silent" FCRs of 420 +/- 90 kD in amounts commensurate with that of the active FCRs. Both low- and high-affinity FCRs are inactivated by hydrolytic enzymes from the outer surface of the plasma membrane, and impairment of protoplast integrity causes an irreversible transition of the low-affinity binding site into the high-affinity one. A scheme is proposed for the organization of different types of FCR in the plasma membrane, implying that the membrane affinity for fusicoccin reflects the interaction between proteins in the FCR complex.     

Andrenocorticotropin and β-lipotropin in the hypothalamus

Adrenocorticotropin and β-lipotropin (β-LPH) have been localized by immunoperoxidase methods in nerve cells and fibers of the hypothalamus and brain stem of the ewe. 6-μm sections were immunostained first for either ACTH or β-LPH. The reaction products and the antibody complexes were then eluted completely from the tissue, and the same section was immunostained for the second peptide. Absorption of the primary antisera with a variety of peptide fragments of ACTH and β-LPH demonstrated, immunocytochemically as well as by radioimmunoassay, that the ACTH and β-LPH antisera were directed to the COOH- and NH(2)-termini of the peptides, respectively. Neither antiserum recognized any portion of the heterologous peptide. In the sequential staining procedure on the same tissue section, preincubation of the antisera with the homologous peptide abolished the staining, whereas preincubation with the heterologous peptide did not affect it, regardless of the order followed. Every nerve cell in the arcuate nucleus that contained ACTH also contained β-LPH, but β-LPH cells appeared, probably falsely, to be twice as numerous as ACTH cells. β-LPH-positive fibers in and beyond the hypothalamus were also more numerous and stained more intensively than ACTH fibers. The salient exception was fibers in the infundibular zona externa, where the opposite was true. Our observations establish that ACTH and β-LPH are contained in the same nerve cells They stongly favor biosynthesis in brain, probably from a common precursor molecule, as has been demonstrated in the pituitary gland. The complexity of the cytologic distribution pattern described suggests that the two peptides are not processed in the same manner by the nerve cell.     

Production via good manufacturing practice of exofucosylated human mesenchymal stromal cells for clinical applications

Background

The regenerative and immunomodulatory properties of human mesenchymal stromal cells (hMSCs) have raised great hope for their use in cell therapy. However, when intravenously infused, hMSCs fail to reach sites of tissue injury. Fucose addition in α(1,3)-linkage to terminal sialyllactosamines on CD44 creates the molecule known as hematopoietic cell E-/L-selectin ligand (HCELL), programming hMSC binding to E-selectin that is expressed on microvascular endothelial cells of bone marrow (BM), skin and at all sites of inflammation. Here we describe how this modification on BM-derived hMSCs (BM-hMSCs) can be adapted to good manufacturing practice (GMP) standards.