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Biomedical subjects

P A Robbins

Publications and source records attributed to P A Robbins.

At least 19 recordsLinked to original sources
PubMed1992

Effects of different levels of end-tidal PO2 on ventilation during isocapnia in humans.

The purpose of this investigation was to examine how the ventilatory decline observed during sustained, eucapnic hypoxia (HVD) is affected by different levels of hypoxia. Six subjects were each studied 3-6 times at each of 5 different levels of isocapnic hypoxia (end-tidal PO2 equal to 45, 50, 55, 65 and 75 Torr) in random order. The following variables were linearly related to saturation: (1) the rapid increase in ventilation at the onset of hypoxia; (2) the decline in ventilation over the period of hypoxia; and (3) the undershoot in ventilation below the pre-hypoxic control values at the relief of hypoxia. The rapid decrease in ventilation at the relief of hypoxia, however, was not linearly related to saturation. The mean time to peak ventilation was 2.13 +/- 0.07 min (+/- SE) at the onset of hypoxia, which was significantly longer (P less than 0.05) than the time to minimum ventilation at the relief of hypoxia of 1.23 +/- 0.18 min. The recovery from the undershoot in ventilation was 95% +/- 3% complete after 5 min, whereas the recovery in sensitivity to hypoxia was only 35% +/- 13% complete after 5 min of euoxia.

Adult↗
PubMed1991

Immune recognition of HLA molecules downmodulates CD8 expression on cytotoxic T lymphocytes.

An HLA-A2+ cytotoxic T lymphocyte (CTL) line restricted by HLA-A2 in recognition of an influenza B virus nucleoprotein (BNP) peptide uses the CD8 coreceptor in the recognition of this viral peptide. Incubation of these CTL with BNP peptide in the absence of antigen-presenting cells downmodulates CD8 alpha and CD8 beta expression and reduces their ability to lyse target cells without inducing self-lysis. CD8 downmodulation was dependent on peptide concentration, time of exposure, and T cell receptor specificity. Another viral peptide from the influenza A virus matrix protein interacting with HLA-A2 had no effect on CD8 expression. Upon further investigation, an anti-HLA class I monoclonal antibody (mAb), anti-HLA class II mAb, and HLA alloantisera were found to downmodulate CD8 alpha and CD8 beta expression and induce CTL nonresponsiveness without causing degranulation. When CD8 alpha and CD8 beta expression was modulated by viral peptide or anti-HLA mAbs, other cell surface molecules were unchanged. Finally, incubation of peripheral blood lymphocytes with these anti-HLA mAbs induced no change in CD8 expression on resting cells but did downmodulate it on mitogen-activated cells. These results suggest that T cell recognition of the HLA-A2-BNP peptide complex on neighboring CTL may be the mechanism for CD8 downmodulation induced by the BNP viral peptide. This mechanism may be important in clonal anergy.

Antibodies, Monoclonal↗
PubMed1991

Effects of dopamine and domperidone on ventilation during isocapnic hypoxia in humans.

In order to investigate the role of dopamine in the ventilatory response to sustained, isocapnic hypoxia six subjects were studied three times in each of three pharmacological conditions: (1) in the absence of any drug administration, (2) during i.v. infusion of dopamine (3 micrograms.kg-1.min-1), and (3) after pretreatment with domperidone. Otherwise the experimental protocol was identical on each day and consisted of holding the subjects' end-tidal PO2 at 100 Torr for 10 min, then 50 Torr for 20 min and finally at 100 Torr again for 5 min. End-tidal PCO2 was held constant 2-3 Torr above normal throughout the experiment. Domperidone increased, and dopamine decreased the magnitudes of both the fast on- and off-responses, but neither drug affected the magnitude of the hypoxic ventilatory decline (HVD). The results of this study suggests: (1) that a peripheral dopaminergic mechanism is not involved in the genesis of HVD, and (2) the peripheral chemoreflex may be modulated peripherally to produce HVD.

Adult↗
PubMed1991

The ventilatory effects of sustained isocapnic hypoxia during exercise in humans.

To investigate how the ventilatory response to isocapnic hypoxia is modified by steady-state exercise, five subjects were studied at rest and performing 70 W bicycle exercise. At rest, isocapnic hypoxia (end-tidal PO2 50 Torr) for 25 min resulted in a biphasic response: an initial increase in ventilation was followed by a subsequent decline (HVD). During exercise, an end-tidal PO2 of 55-60 Torr was used. The magnitude of the initial ventilatory response to isocapnic hypoxia was increased from a mean +/ SE of 1.43 +/- 0.323 L/min per % arterial desaturation at rest to 2.41 +/- 0.424 L/min per % during exercise (P less than 0.05), but the magnitude of the HVD was reduced from 0.851 +/- 0.149 L/min per % at rest to 0.497 +/- 0.082 L/min per % during exercise (P less than 0.05). The ratio of HVD to the acute hypoxia response was reduced from 0.696 +/- 0.124 at rest to 0.202 +/- 0.029 during exercise (P less than 0.01). We conclude that while exercise augments the ventilatory sensitivity to hypoxia, it also has a direct effect on the mechanisms by which sustained hypoxia depresses peripheral chemosensitivity.

Adult↗
PubMed1990

Changes in peripheral chemoreflex sensitivity during sustained, isocapnic hypoxia.

One hypothesis concerning the origin of hypoxic ventilatory decline is that hypoxia acts centrally to depress peripheral chemoreflex loop activity. To investigate possible changes in peripheral chemoreflex loop activity during sustained, isocapnic hypoxia, the ventilatory responses to four one minute pulses of either extra hypoxia (45 Torr) or carbon dioxide (8 Torr above resting levels) were measured in man at minutes 2, 7, 12, and 17 of a 23 min isocapnic, hypoxic period (50 Torr). For hypoxia, the first pulse response (130%) was significantly greater (P less than 0.05) than the fourth response (74%). For CO2, pulse responses 2 and 3 (101 and 103%, respectively) were significantly greater (P less than 0.05) than the fourth response (91%). A central depression of peripheral chemoreflex loop activity should affect peripheral sensitivities to CO2 and hypoxia equally. Our results suggest that the peripheral sensitivity to hypoxia declined more than that to CO2, implying a peripheral chemoreceptor origin for hypoxic ventilatory decline.

Adult↗
PubMed1990

Hypoxic depression of ventilation in humans: alternative models for the chemoreflexes.

The ventilatory responses of 5 volunteers to three protocols were determined. In protocol A, PETCO2 was held at 1-2 Torr above resting; and PETO2 at 100 Torr for 10 min, 50 Torr for 20 min, and 100 Torr again for 10 min. In protocol B, PETCO2 was held at 8 Torr above resting, and PETO2 varied as in protocol A. Protocol C formed a control. Each protocol was repeated at least 6 times on each subject. The data were used to evaluate four different models (models 2-5) for incorporating the depressant effect of hypoxia into a standard model (model 1) of the chemoreflex responses. In model 2, hypoxic depression was incorporated as an additive term independent of the central and peripheral chemoreflexes; in model 3 it affected the central chemoreflex gain; in model 4 it affected the peripheral chemoreflex gain; and in model 5 it affected the gain of both reflexes. From this, it was concluded only model 4 was consistent with the data; all other models were inconsistent.

Adult↗
PubMed1990

Changes in arterial K+ and ventilation during exercise in normal subjects and subjects with McArdle's syndrome.

1. We have examined the relationship between ventilation (VE), lactate (La) and arterial plasma K+ concentrations [( K+]a) during incremental exercise in six normal subjects and in four subjects with McArdle's syndrome (myophosphorylase deficiency) who do not become acidotic during exercise. 2. In normal subjects, [K+]a rose to ca 7 mM at the point of exhaustion. The time courses of the increases in VE, La and [K+]a were all similar during the exercise period. La reached its peak concentration during the recovery from exercise when both VE and [K+]a were returning to resting levels. 3. McArdle's subjects, like normal subjects, had a non-linear ventilatory response during incremental exercise. Their [K+]a was closely related to VE throughout exercise and recovery. 4. The arterial pH of McArdle's subjects, rather than remaining constant, actually rose from the onset of exercise. 5. For a given level of exercise, the levels of VE and [K+]a were greater in the McArdle's subjects than in normal subjects. 6. These findings are consistent with the idea that hyperkalaemia may contribute significantly to the drive to breathe, especially during heavy exercise.

Adult↗
PubMed1990

A comparison of indirect methods for continuous estimation of arterial PCO2 in men.

Four different measures (PETCO2, PACO2, PADCO2, and PJCO2) for indirectly estimating arterial PCO2 (PaCO2) from respired gas at the mouth have been investigated. PETCO2 was the end-tidal PCO2. PACO2 was calculated using a reconstruction of the alveolar oscillation of PCO2 obtained from the end-tidal "plateau" in PCO2. PADCO2 was calculated as for PACO2 except that the effects of dead space were incorporated. PJCO2 was calculated from an empirical relationship involving PETCO2 and tidal volume. Six subjects were studied at rest and during cycle ergometry at 50 and 100 W while breathing a variety of gas mixtures. Arterial samples were drawn for determination of true PaCO2. The differences for each method between estimated and true PaCO2 at rest and at 50 and 100 W were as follows: PETCO2, -1.35 +/- 2.64, 1.67 +/- 2.31, and 2.67 +/- 2.02 (SD) Torr; PaCO2, -2.15 +/- 2.73, -0.80 +/- 2.18, and -0.35 +/- 2.31 (SD) Torr; PADCO2, -1.55 +/- 2.54, 0.25 +/- 2.16, and 0.63 +/- 2.26 (SD) Torr; and PJCO2, -1.41 +/- 2.30, 0.12 +/- 1.79, and 0.08 +/- 1.96 (SD) Torr. It is concluded that, at rest, all methods significantly underestimate true PaCO2 and during exercise PETCO2 significantly overestimates PaCO2, but no bias was detected for any of the other methods.

Adolescent↗
PubMed1989

Comparison between two peptide epitopes presented to cytotoxic T lymphocytes by HLA-A2. Evidence for discrete locations within HLA-A2.

An influenza B virus nucleoprotein (BNP) peptide, residues 82-94, defined by limited sequence homology with an HLA-A2-restricted peptide from influenza A matrix protein, was recognized by HLA-A2-restricted CTL. Reciprocal inhibition of T cell recognition by the two peptides suggest that the BNP peptide may have lower avidity for HLA-A2 molecules than the matrix peptide. The interaction between this peptide and HLA-A2 was explored by studying the CTL recognition of BNP 82-94 presented by mutant HLA-A2 molecules. Mutations at residues 9, 99, 70, 74, 152 and 156 were found to abolish T cell recognition of the BNP peptide. These results were compared with results previously obtained with the influenza A matrix peptide and suggest that the two peptides bind differently in the peptide binding site.

Amino Acid Sequence↗
PubMed1989

The ventilatory response to lowering potassium with dextrose and insulin in subjects with hyperkalaemia.

Arterial plasma potassium concentration ([ K+]a) is increased during exercise. This change is sufficient to excite arterial chemoreceptors and stimulate ventilation (VE) in the anaesthetized cat. Moreover, changes in [K+]a and VE are highly correlated during exercise, however the contribution that [K+]a makes to the control of breathing in man is not yet known. Four otherwise relatively healthy male hyperkalaemic renal patients had their VE measured before, during and after an intravenous infusion of dextrose and insulin to lower their [K+]a. Thirty-six minutes after the infusion began [K+]a had been reduced by ca. 2 mM. Ventilation was virtually unchanged throughout the experiment. These results suggest that [K+]a does not significantly affect VE in this group of subjects. The assumptions that would need to be made to extrapolate this conclusion to the general population are discussed.

Adult↗
PubMed1989

Changes in arterial plasma potassium and ventilation during exercise in man.

We have investigated the relationship between arterial plasma potassium ( [K+]a) and ventilation (VE) in man because hyperkalaemia has been shown to increase VE in the anaesthetized cat by direct stimulation of the arterial chemoreceptors. Six healthy male volunteers undertook about of sub-maximal (100 W) and maximal (sprint ca. 350 W) exercise on a cycle ergometer. VE was measured breath-by-breath and arterial blood was sampled at regular intervals from a catheter inserted into a brachial artery for measurement of [K+]a and base excess. Changes in [K+]a closely mirrored changes in VE during exercise and recovery. At 100 W [K+]a increased from 4 mM to 5 mM, and during the sprint [K+]a increased to ca. 7 mM. Base excess did not mirror VE in that it reached its nadir 1-3 min after exercise had stopped, when [K+]a and VE were both falling. The increases in [K+]a seen here are probably sufficient to enhance the arterial chemoreceptor drive during exercise. Furthermore, the close temporal relationship between [K+]a and VE suggests that it is possible that exercise hyperkalaemia may contribute to the control of breathing in exercise.

Arteries↗
PubMed1988

Activated T cells and monocytes have characteristic patterns of class II antigen expression.

The expression of human histocompatibility class II Ag was measured on activated T cells and monocytes by quantitative mAb binding in direct two-color immunofluorescence. Monocytes activated by IFN-gamma bound an average of 2 x 10(6) DR-specific mAb, 3 x 10(5) DQ-specific mAb, and 7 x 10(5) DP-specific mAb per cell. For T cells activated by anti-CD3, a subpopulation bound 1 x 10(5) DR-specific mAb, 5 x 10(4) DQ-specific mAb and 5 x 10(4) DP-specific mAb per cell. These measurements were obtained after establishing a base line of class II Ag expression on resting B cells and monocytes. Resting B cells and those monocytes that were positive for class II Ag bound identical amounts of mAb; 3 x 10(4) DR-specific mAb, 3 x 10(3) DQ-specific mAb and 2 x 10(4) DP-specific mAb. However, most resting monocytes (75%) expressed only DR Ag. In the process of studying the expression of class II Ag on T cells, it was necessary to define and analyze the activated T cell state. Cell cultures activated with 0.3 ng/ml anti-CD3 had the highest expression of class II Ag on T cells, whereas those activated with 3.0 ng/ml anti-CD3 had the highest expression of IL-2R on T cells. Addition of IL-2 had no further effect on DR Ag expression on T cells but did up-regulate IL-2R expression. Reducing the initial monocyte concentration before activating T cells increased class II Ag expression on T cells without affecting IL-2R expression. The results obtained on T cell activation suggest that perhaps a lymphokine may be made by CD3-activated T cells which induces class II Ag expression on T cells.

Antibodies, Monoclonal↗
PubMed1988

Evidence for interaction between the contributions to ventilation from the central and peripheral chemoreceptors in man.

1. The question of whether there is any interaction between the peripheral and central chemoreceptor contributions to ventilation in man has been addressed. 2. Subjects were exposed to an end-tidal PCO2 of ca. 10 Torr above resting for 8 min at an end-tidal PO2 of 100 Torr. The end-tidal PCO2 was then reduced to near eucapnia. This provided a period of time when the PCO2 at the peripheral chemoreceptors would be near eucapnia, but would still be raised at the central chemoreceptors. 3. Against the background above, the effect of an hypoxic end-tidal step from a PO2 of 100 Torr to a PO2 of 50 Torr was studied, and compared with the effect of the same step when both sets of chemoreceptors were near eucapnia. 4. Three subjects were studied, each contributing twelve sets of data to each of the three protocols required for the comparisons. 5. In two of the three subjects, the ventilatory response to hypoxia was augmented when central PCO2 was high. 6. The results support the idea that there is an interaction between the central and peripheral chemoreceptors in man. The consequences of this and other possible interpretations of the results are discussed.

Adult↗
PubMed1987

Monoclonal antibodies that distinguish between class II antigens (HLA-DP, DQ, and DR) in 14 haplotypes.

The specificity of three commonly used monoclonal antibodies (MoAbs) reacting with human class II histocompatibility antigens, was analyzed to determine whether these MoAbs would distinguish between HLA-DP, DQ, and DR in a large number of haplotypes. The reactivity of these MoAbs (L243, Anti-Leu 10, and B7/21) was compared by serial immunoprecipitation of class II antigens from 11 B-cell lines. The cell lines examined expressed a total of five DP, three DQ, and nine DR types, which together represent most of the well-defined class II specificities. This is the first demonstration that one of these antibodies, B7/21. binds to at least five DP specificities, and does not bind to DR or DQ molecules as defined by reactivity with the two other MoAbs. Within the scope of these experiments, the B7/21 antibody was shown to react with a monomorphic DP determinant. A variant clone of the B7/21 hybridoma was isolated that secretes IgG1 antibody with the same specificity as the original IgG3 antibody. The two other antibodies studied have been previously shown to react with DR molecules (L243) or DQ molecules (Anti-Leu 10). Here, their lack of cross-reaction with DP molecules is demonstrated. Thus, each of the three MoAbs reacts exclusively with a distinct class II molecule in all haplotypes studied, and therefore should be useful for comparing the independent expression and function of DP, DQ, and DR molecules.

Antibodies, Monoclonal↗
PubMed1984

The ventilatory response of the human respiratory system to sine waves of alveolar carbon dioxide and hypoxia.

Sine waves of alveolar CO2 at constant high alveolar O2, and sine waves of alveolar hypoxia (1/(PA, O2 -C), C congruent to 32 torr) at constant alveolar CO2 have been administered to three subjects in each case. Sine waves of six different periods were studied, ranging between 900 and 30 s for the CO2 sine waves and 300 and 20 s for the hypoxic sine waves. The sinusoidal variations in ventilation produced by these manoeuvres, expressed as amplitudes and phase shifts, were compared with values predicted from the dynamic responses to alveolar steps of gas tension already to be found in the literature. For the CO2 sine waves, the amplitudes of response agreed well with those predicted at the higher frequencies, but were less than predicted at the lower frequencies. For the hypoxic sine waves, the amplitude of response varied less with frequency than was predicted. For both the CO2 and the hypoxic sine waves, the phase shift of response was less than expected at the higher frequencies. An attempt was made to fit parameters to a simple model, based on the wash-in and wash-out of respiratory gases into and out of a tissue compartment, and used in the literature for describing the responses to step changes. No satisfactory fit was found. It is concluded that the simple model is unsatisfactory by itself for describing the responses to sinusoidal chemical stimulation; features additional to those included in the model are required to explain fully the responses seen. The possibilities for chemoreception at the higher frequencies are discussed in the light of the low phase shifts.

Carbon Dioxide↗
PubMed1984

The pattern of breathing in man in response to sine waves of alveolar carbon dioxide and hypoxia.

Sine waves of alveolar CO2 at constant high alveolar O2, and sine waves of alveolar hypoxia (1/(PA, O2 -C) where C congruent to 32 torr) at constant alveolar CO2 have been administered to three subjects in each case. Six different periods of the sine waves were studied, ranging between 900 and 30 s for the CO2 sine waves and 300 and 20 s for the hypoxic sine waves. The sinusoidal variations in inspiratory and expiratory volumes (VT, I, VT, E), durations (TI, TE) and mean flows (vI, vE) produced by these manoeuvres were calculated, and the results analysed from the phase shifts of the responses. For the CO2 sine-wave results, the peak in the TI oscillation generally appeared after the minima for VT, I and vI, but before their maxima. The peak in the TE oscillation was variable. For the hypoxic sine-wave results, the peak in the TI oscillation showed no over-all tendency to lead or lag the peaks of VT, I and vI. The peak in the TE oscillation generally appeared after the maxima for VT, E and vE but before their minima. For the CO2 sine-wave results, expiratory mean flow led inspiratory mean flow, with the volumes showing no significant difference. For the hypoxic sine-wave results expiratory volumes and mean flows led inspiratory volumes and mean flows. The results are discussed in relation to the transient responses of the components of breathing pattern obtained from other perturbations of chemical drive.

Carbon Dioxide↗