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Biomedical subjects

R L Clancy

Publications and source records attributed to R L Clancy.

At least 91 records · Page 5Linked to original sources
PubMed1993

Effector mechanisms of intestinally induced immunity to Pseudomonas aeruginosa in the rat lung: role of neutrophils and leukotriene B4.

This paper investigates the effector mechanisms of immune clearance in the lungs of rats immunized against mucoid Pseudomonas aeruginosa. After the gut-associated lymphoid tissue was primed and after a subsequent pulmonary challenge with live bacteria, significantly accelerated bacterial clearances from the lung and raised levels of anti-P. aeruginosa antibodies in sera (immunoglobulin G [IgG], IgA, and IgM) and bronchoalveolar lavages (IgG and IgA) were observed for all immune animals. These changes were associated with enhanced recruitment, chemotaxis, chemokinesis, phagocytic indices, and chemiluminescence of pulmonary polymorphonuclear neutrophils (PMN). In the alveolar spaces of immune animals, an increase in the level of PMN recruitment was not associated with higher levels of leukotriene B4 (LTB4). In contrast, in nonimmune animals that were intratracheally infected with P. aeruginosa, the levels of recruitment and activity of alveolar PMN were lower than those in immune rats but PMN infiltration correlated with a significant increase in the synthesis of LTB4 in the alveolar space. In pulmonary tissue, LTB4 synthesis for both groups was elevated. These findings suggest that accelerated clearance of mucoid P. aeruginosa from the lungs of intestinally immunized rats is due at least in part to factors that induce the enhancement of PMN recruitment and activity in the alveolar space. The mediators that regulate this enhanced response remain unknown but do not seem to include LTB4. The high levels of LTB4 measured in the bronchoalveolar lavages and pulmonary tissues from nonimmune animals infected with live bacteria implicate LTB4 as an important amplifier of the inflammatory response during acute pulmonary infections with mucoid P. aeruginosa in unimmunized hosts.

Animals↗
PubMed1993

Determinants of maximal oxygen uptake in rats acclimated to simulated altitude.

The effect of acclimation to hypoxia on maximal O2 uptake (VO2max), maximal cardiac output (Qmax), and arteriovenous O2 concentration difference (a-vCO2) was studied in male Sprague-Dawley rats acclimated for 3 wk to a barometric pressure of approximately 380 Torr (A rats). Nonacclimated control animals were pair-fed littermates maintained at an ambient barometric pressure of approximately 740 Torr (NA rats). Both A and NA rats exercised maximally on a treadmill with inspired PO2 maintained at either approximately 72 or 145 Torr. Arterial blood O2 concentration was significantly higher in A than in NA rats (16.0 +/- 0.6 vs. 12.4 +/- 0.3 ml/dl in hypoxia and 28.4 +/- 1.5 vs. 20.1 +/- 0.9 ml/dl in normoxia, respectively; both P < 0.05). During hypoxic exercise VO2max was slightly but significantly higher in A than in NA subjects (55.3 +/- 1.3 vs. 48.8 +/- 1.1 ml STPD.min-1 x kg-1; P < 0.05). In hypoxia a-vCO2 was 16.6 +/- 0.6 and 12.4 +/- 0.4 ml/dl and Qmax was 401 +/- 17 and 489 +/- 9 ml.min-1 x kg-1 in A and NA subjects, respectively (both P < 0.05). A rats showed both lower maximal heart rate and lower maximal stroke volume during hypoxic exercise. In normoxia there was no significant difference in VO2max between A and NA rats (71.8 +/- 2.7 vs. 73.9 +/- 3.1 ml.min-1 x kg-1). As with hypoxia, in normoxia a-vCO2 was significantly higher and Qmax was significantly lower in A than in NA animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Acclimatization↗
PubMed1993

Mucosal immune response in a case of sudden infant death syndrome.

A prospective study to define the normal patterns of development of mucosal immunity in 263 children provided a unique opportunity to study the mucosal immune response in an infant who unexpectedly died from sudden infant death syndrome. The subject initially had a normal pattern of mucosal immune function, which was perturbed after a transient mild upper respiratory tract infection at 3 1/2 wk of age. After the upper respiratory tract infection, there was an increase in mucosal permeability and the appearance of IgA and IgM in saliva. The unusual features in this case were the degree and the duration of the increases in salivary IgA and IgM after resolution of the illness. The marked abnormalities suggested a persistent stimulation of the mucosal immune response. The case provides informative data on potential mechanisms of sudden infant death syndrome and supports a role for involvement of upper respiratory tract infection.

Albumins↗
PubMed1992

Measurement of lysozyme by an enzyme-linked immunosorbent assay.

In this study an enzyme-linked immunosorbent assay has been developed for the determination of lysozyme in saliva, serum and urine. The assay relies on the detection of specific protein rather than lytic activity, a property which has been shown to be most suitable for the quantitation of lysozyme in mucin containing substances. Our results indicate that no pretreatment is necessary for the immunochemical method. The assay is sensitive to concentrations as low as 1 microgram lysozyme/l. The intra-assay and inter-assay coefficients of variation were 5.9% and 15.8% respectively. The lysozyme level in whole saliva was 55.53 +/- 30.35 mg/l, in serum the level was 0.64 +/- 0.15 mg/l and in urine it was 0.17 +/- 0.22 mg/l. Comparisons between immunochemical determination and lytic assays showed a good correlation (serum, r = 0.79, P less than 0.01; saliva, r = 0.85, P less than 0.005; treated saliva, r = 0.96, P less than 0.001).

Adult↗
PubMed1992

Mechanism of the effect of alkalosis on maximum oxygen uptake in hypoxic exercise.

Maximum oxygen uptake (VO2max) of rats is increased in alkalosis; this increase is larger in hypoxic than in normoxic exercise (Gonzalez et al. (1991b). J. Appl. Physiol., 71: 1050-1056). The objective of the present experiments was to determine the mechanism of this phenomenon. NaHCO3 (0.3 M, 9 mmol/kg) was given 15 min before exercise to rats acclimated to PB 380 Torr for 3 weeks (HxBic) and to normoxic rats (NxBic). Additional groups of acclimated and normoxic rats received 0.3 M NaCl (HxNaCl and NxNaCl, respectively). Hx rats exercised at PIO2 approximately 70 Torr; Nx rats at PIO2 approximately 140 Torr. VO2max was higher after NaHCO3 than after NaCl; this effect was larger in hypoxia. The increase in VO2max was mediated through an increased arterio-venous oxygen concentration difference ((Ca - Cv)O2), due, in turn, to a higher CaO2 without changes in CvO2. (Ca - Cv)O2 after NaHCO3 was larger in hypoxia because a change in pH results in a larger change in HbO2 saturation at the values prevalent in arterial blood of the hypoxic rats (i.e. PO2 approximately 40-50 Torr, SO2 50-60%), than at either the values of normoxic arterial blood or of venous blood during maximum exercise. These results suggest that an increase in hemoglobin-oxygen affinity improves oxygen uptake in the lungs during hypoxia, without hindering its release in the tissues, and therefore has a beneficial effect in hypoxic exercise.

Acid-Base Equilibrium↗
PubMed1992

Biotypes of Haemophilus parainfluenzae from the respiratory secretions in chronic bronchitis.

A total of 2401 isolates of Haemophilus parainfluenzae was isolated from respiratory secretions of 36 healthy adults and 128 patients with chronic bronchitis over a period of 1 year. The isolates were allocated to eight biotypes, by their production of indole, urease and ornithine decarboxylase. Biotypes I and II constituted most of the isolates of H. parainfluenzae from the oropharynx of controls (75%) and chronic bronchitics (c. 90%). Among the patients, there was no difference in the isolation rate between oropharyngeal swabs and sputum specimens. Biotypes III, IV, VI, VII and VIII were isolated less frequently, as was a new taxon defined here as biotype V which does not produce indole, urease or ornithine decarboxylase. Biotype III was isolated significantly less frequently from cases of chronic bronchitis than from controls, whereas biotype II was isolated somewhat more frequently from the patients, especially during acute episodes.

Adult↗
PubMed1992

A novel particulate influenza vaccine induces long-term and broad-based immunity in mice after oral immunization.

The immunogenicity of a novel particulate oral influenza vaccine was examined in terms of antibody response and protection in mice. Oral immunization with chicken erythrocytes (CRBC) adsorbed with gamma-irradiated influenza A virus induced high levels of immunoglobulin G antibodies and protection in the lung compared with gamma-irradiated virus administered alone or CRBC. Immunoglobulin A antibodies were the predominant antibodies in nasal washings, and their presence did not correlate with protection as well as immunoglobulin G antibodies. Immunity was not specific for the immunizing virus subtype, as antibodies and enhanced lung clearance of virus were demonstrated with different virus subtypes. However, mice were not protected when challenged with live influenza B virus. The antibody response and the degree of protection were dependent on both the concentration of virus adsorbed to CRBC and number of CRBC adsorbed to virus. Virus-adsorbed CRBC given subcutaneously failed to induce antibodies or protection. Oral immunization with A/Qld/6/72 (H3N2) virus gave a high level of protection over 12 weeks, which could be demonstrated with different subtypes. Protection correlated with antibody levels in the lung determined by both enzyme-linked immunosorbent and hemagglutination inhibition assays, although the levels detected by the latter declined over time.

Animals↗
PubMed1991

The variability of immunoglobulins and albumin in salivary secretions of children.

The variation of concentrations of immunoglobulins and albumin in consecutive daily collections of saliva was studied in 33 infants, aged 6 months to 5 years, for periods ranging from 16 to 26 days. The concentration and the within-child variability of IgA and albumin and the detection of IgG and IgM in saliva increased with age. Between-child variances were greater than the within-child variances by a factor of 2.8 for log (IgA) and 1.3 for log (albumin). The geometric mean IgA levels were consistently higher and IgG was detected more frequently during upper respiratory tract infections compared with periods of non-infection. There were no changes in albumin levels between infection and non-infection periods, suggesting a local immune response rather than serum leakage. There were significant within-child correlations (autocorrelations) between levels of IgA in saliva collected on consecutive days and samples collected up to 3 days apart. The autocorrelations between levels of albumin were significant for samples collected up to 2 days apart. The autocorrelation for IgA was significantly greater during infection periods compared with non-infection periods for samples collected on consecutive days.

Age Factors↗
PubMed1991

Wheat dust-associated respiratory disease in a farming community.

Sixty-six volunteers who considered themselves to have wheat dust-related respiratory disease, were reviewed from a farming community. A spectrum of disease was described ranging from a mild allergic rhinitis limited to periods of wheat dust exposure through to perennial asthma in which wheat dust was but one of several precipitating factors. Approximately half of those with asthma had symptoms limited to times of wheat dust exposure. Results of a limited survey of farmers showed patterns of symptoms similar to those in the volunteer group. Most subjects were atopic with elevated IgE levels, and had positive skin prick tests to environmental allergens. All but one of 65 subjects tested had a positive RAST test to wheat dust antigen. It is concluded that wheat dust associated respiratory tract disease is a significant problem in Australian farming communities, that a particular pattern of asthma can be described, and that IgE mediated reactions contribute to this disease pattern.

Adolescent↗
PubMed1991

Maximum oxygen uptake and arterial blood oxygenation during hypoxic exercise in rats.

The objectives of these experiments were 1) to describe the effect of maximum treadmill exercise on gas exchange, arterial blood gases, and arterial blood oxygenation in rats acclimated for 3 wk to simulated altitude (SA, barometric pressure 370-380 Torr) and 2) to determine the contribution of acid-base changes to the changes in arterial blood oxygenation of hypoxic exercise. Maximum O2 uptake (VO2max) was measured in four groups of rats: 1) normoxic controls run in normoxia (Nx), 2) normoxic controls run in acute hypoxia [AHx inspiratory PO2 (PIO2) approximately 70 Torr], 3) SA rats run in hypoxia (3WHx, PIO2 approximately 70 Torr), and 4) SA rats run in normoxia (ANx). VO2max (ml STPD.min-1.kg-1) was 70.8 +/- 0.9 in Nx, 46.4 +/- 1.9 in AHx, 52.6 +/- 1.1 in 3WHx, and 70.0 +/- 2.4 in ANx. Exercise resulted in acidosis, hypocapnia, and elevated blood lactate in all groups. Although blood lactate increased less in 3WHx and ANx, pH was the same or lower than in Nx and AHx, reflecting the low buffer capacity of SA. In AHx and 3WHx, arterial PO2 increased with exercise; however, O2 saturation of hemoglobin in arterial blood (SaO2) decreased. In vitro measurements of the Bohr shift suggest that SaO2 decreased as a result of a decrease in hemoglobin O2 affinity. The data indicate that several features of hypoxic exercise in this model are similar to those seen in humans, with the exception of the mechanism of decrease in SaO2, which, in humans, appears to be due to incomplete alveolar-capillary equilibration.

Acclimatization↗
PubMed1991

Effect of alkalosis on maximum oxygen uptake in rats acclimated to simulated altitude.

The objective of the present experiments was to determine whether prevention or moderation of exercise acidosis would influence arterial blood oxygenation and exercise capacity in hypoxia. The effect of administration of 0.3 M NaHCO3 (3 ml/100 g) on maximum O2 uptake (VO2max) and arterial blood oxygenation was determined in rats acclimated to simulated altitude (370-380 Torr barometric pressure) for 3 wk (HxBic) and in normoxic littermates (NxBic). Controls were simulated-altitude (HxNaCl) and normoxic rats (NxNaCl) given 0.3 M NaCl. Inspiratory PO2 during treadmill exercise was approximately 70 Torr for hypoxic rats and 140-145 Torr for normoxic rats. VO2max was 18% higher in HxBic than in HxNaCl (62.8 + 1.6 vs. 53.1 + 1.0 ml STPD.min-1.kg-1, respectively, P less than 0.05) and only 8% higher in NxBic than in NxNaCl (74.0 + 1.1 vs. 68.7 + 1.5 ml STPD.min-1.kg-1, respectively, P less than 0.05). Exercise in HxNaCl resulted in a decrease in arterial O2 concentration (CaO2), which was largely due to a pH-induced decrease in O2 saturation of arterial blood, and occurred despite an increase in arterial PO2. NaHCO3 moderated the acidosis of exercise and largely attenuated the decrease in CaO2. The effects of acidosis and bicarbonate on CaO2 were much less evident in the normoxic controls. There was an almost linear relationship between VO2max and the corresponding CaO2 for all four groups, suggesting that the effect of NaHCO3 on VO2max may be related to moderation of the decrease in CaO2.

Acclimatization↗
PubMed1991

Reduction in the incidence of acute bronchitis by an oral Haemophilus influenzae vaccine in patients with chronic bronchitis in the highlands of Papua New Guinea.

Following the administration of a standardized questionnaire, 62 adult patients with chronic bronchitis were enrolled into a double-blind controlled trial of an oral killed Haemophilus influenzae vaccine in the highlands of Papua New Guinea. A 3-day course of vaccine or placebo was given monthly for 3 consecutive months. Participants were monitored weekly over 12 months for acute exacerbations; early morning sputum specimens were collected monthly and during acute exacerbations. Density of colonization by H. influenzae and H. parainfluenzae was determined by standard quantitative and semiquantitative techniques, and the latter method (quadrant score) was used to determine the density of growth of pneumococci. A total of 30 patients received vaccine and 32 placebo. The incidence rate of acute bronchitis in the vaccine group (0.011 episodes/person-weeks) was significantly lower than that in the placebo group (0.021 episodes/person-weeks), but there was no difference between the two groups in the incidence rates of more severe disease. Vaccine efficacy was maximal at times of peak incidence of disease. There was no evidence of a decline in vaccine efficacy for acute bronchitis over the 12-month follow-up period. The number of viable H. influenzae in the sputum declined in both vaccine and placebo groups over the 12-month follow-up period. The average concentration of H. influenzae in the vaccine group fell below that in the placebo group within 1 to 2 months after first immunization and remained so for 12 months, although the difference between the two groups narrowed during the follow-up period.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1991

Cellular electrolyte and volume changes induced by acidosis in the rabbit proximal straight tubule.

Cellular acidosis induced either by high Pco2 or by low HCO3- concentrations has been shown to cause cell swelling in isolated, lumen-collapsed, S2 segments of the rabbit proximal tubule (Sullivan et al., Am J Physiol 1990; 258: F831-F839). The swelling is not followed by a volume regulatory response. The ionic basis of the swelling has been investigated by measurement of the cellular K+, Na+, and Cl- content (electron probe) and HCO3- concentration (pH-sensitive fluorescent dye). Cell content of K+, Na+, and Cl- was expressed as a ratio to P content. Exposure to 15% CO2 increased K/P from 0.98 to 1.16, Cl/P from 0.14 to 0.20, and Na/P from 0.09 to 0.11. Cell (HCO3-) increased from 22 to 32 mM. Reduction in bath (HCO3-) from 25 to 5 mM reduced cell (HCO3-) from 24 to 8 mM and increased K/P from 0.75 to 0.90. Na/P fell from 0.13 to 0.09, and Cl/P fell from 0.15 to 0.12. Thus, swelling resulting from acidosis induced by high CO2 was accompanied by an accumulation of K+, Cl-, and HCO3-; that resulting from acidosis induced by a fall in (HCO3-) was combined with an accumulation of K+ and an unidentified anion. To determine if the swelling induced by a fall in pH might be coupled with depolarization of the basolateral membrane, the effect of 1 mM barium was tested. Barium caused cell volume to increase 10.2%. Cell pH rose from 7.38 to 7.56, K/P increased from 0.63 to 0.73, Na/P did not change, and Cl/P rose from 0.17 to 0.20. Cell (HCO3-) increased 10.4 mM. When the pH of the barium-treated tissue was reduced to 7.02 by raising Pco2, additional cell swelling and accumulation of K+ occurred. The effect on cell volume of a reduction of bath (HCO3-) from 25 to 5 mM at constant bath pH was determined. Cell pH was not altered. Cell volume decreased 3% initially and then returned to the control level. When the bath (HCO3-) was restored to 25 mM, cell volume increased 3.9% and then returned to the baseline. Thus, volume regulation was not impaired. It was concluded that a fall in cell pH induces swelling, and this is coupled with an accumulation of K+. This is probably the result of a pH effect on barium-sensitive and barium-insensitive K+ conductance pathways. The nature of the anions that balance the gain in K+ depends on the means used to induce acidosis.

Acidosis, Renal Tubular↗
PubMed1991

A role for intestinal T lymphocytes in bronchus mucosal immunity.

Rats immunized by intra-Peyer's patch (IPP) injection with non-typable Haemophilus influenzae (NTHI) have been shown to clear this organism from the respiratory tract faster than non-immunized rats. We therefore performed a series of experiments in order to determine the mechanism of action of the enhanced pulmonary clearance. The experiments show that homing of intestinal T cells to the respiratory tract is an important component in the observed immunity, while specific antibody adsorbed to bacteria does not influence pulmonary bacterial clearance rate. Mucosally derived lymphocytes were collected from the thoracic duct of rats primed by IPP inoculation with NTHI, and intravenously transfused to recipient rats. These rats were shown to clear bacteria from bronchial spaces faster than non-transfused rats, or rats transfused with non-immune lymphocytes. Lymphocytes collected from the spleens of immunized rats were also capable of conferring the ability to accelerate pulmonary clearance. When thoracic duct lymphocytes (TDL) purified for T lymphocytes were transferred to recipients, the NTHI clearance rate was accelerated. In experiments to evaluate the activity of specific antibody, it was demonstrated that NTHI opsonized with antibody from bronchial washings of immunized rats was not cleared from the respiratory tract of naive rats faster than non-opsonized controls. These data indicate that immune clearance of NTHI from the respiratory tract following gut immunization is dependent upon antigen-primed lymphocytes, that primed T cells are capable of conferring this protection, and that a primary role for specific antibody in the process cannot be established.

Animals↗
PubMed1990

Protection against recurrent acute bronchitis after oral immunization with killed Haemophilus influenzae.

Subjects prone to recurrent acute bronchitis were admitted to a six-month double-blind clinical study, in which the value of oral immunization with a preparation of killed Haemophilus influenzae was tested. Most subjects had early smoking-related chronic lung disease, unrecognized by either the patient or his/her doctor. Subjects taking the active agent had a 41% reduction in the total number of episodes of acute bronchitis (P = 0.16), a 60% reduction in the number of episodes of acute wheezy bronchitis (P = 0.02) and a 58% reduction in antibiotic use (P = 0.07). The power of analysis was restricted by the small study group. Parameters of episode severity favoured the test group, suggesting that individual episodes of acute bronchitis in subjects taking an oral preparation of killed H. influenzae were less severe than in those taking placebo tablets. Oral immunization with H. influenzae selectively reduced the increase in colonization of the oropharynx with H. influenzae which occurred in the group taking placebo. This is the first demonstration that the common mucosal system can be activated to modify a colonization pattern at a distant site.

Acute Disease↗