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Biomedical subjects

A Garland

Publications and source records attributed to A Garland.

12 recordsLinked to original sources
PubMed1992

Hyperoxia-induced airway hyperresponsiveness and remodeling in immature rats.

We exposed 21-day-old rats to either normoxia or hyperoxia (greater than 95% O2) for 8 days and assessed in vivo airway responsiveness to aerosolized and intravenous methacholine (MCh) and airway architecture. Airway responsiveness was determined using a plethysmographic method. Hyperoxia increased airway cholinergic responsiveness, as reflected in a decreased mean ED200 (concentration of MCh required to increase respiratory system resistance by 100%) for both aerosolized MCh [air exposed, 5.94 +/- 2.50 vs. O2 exposed, 0.29 +/- 3.34 (SD) mg/ml, P = 0.0013, unpaired t test] and intravenous MCh (air, 1.40 x 10(-8) vs. O2, 2.45 x 10(-10) mol/kg, P = 0.0002). Airway morphometry was studied in a separate cohort of animals. After fixation by distension with Formalin at 25 cmH2O pressure, each airway cross section was photographed, and airway circumference, epithelial area, and smooth muscle layer area were determined by means of contour tracing using a digitizing pad and microcomputer. For the small airways (circumference less than 1,000 microns), hyperoxia increased both mean epithelial thickness (air, 4.88 +/- 0.53; O2, 8.64 +/- 0.90 microns) and mean smooth muscle layer thickness (air, 2.69 +/- 0.11; O2, 4.79 +/- 0.56 microns; P less than 0.0001 for each). O2 had similar effects on the larger (1,000-3,000 microns) central airways (P less than 0.0001 for both layers). We conclude that chronic hyperoxic exposure induces both airway hyperresponsiveness and airway wall thickening in immature rats.

Aerosols↗
PubMed1992

Direct effects and augmentation of airway smooth muscle contraction caused by phospholipase A2.

We examined the effect of phospholipase A2 (PLA2; Naja naja) on isometric tracheal smooth muscle force generation in guinea pig trachealis in situ. Direct application of PLA2 to the surface of the trachea caused dose-related contraction of tracheal smooth muscle. In seven guinea pigs, a dose/density of 100 micrograms/cm2 PLA2 caused active tension (AT) that began immediately and was maximum (1.32 +/- 0.13 g/cm) at 5 min (p less than 0.01 versus baseline tension). PLA2 also augmented the contractile response to intravenously administered acetylcholine (ACh); AT caused by 3 x 10(-7) mol/kg ACh was 0.98 +/- 0.13 g/cm after PLA2 versus 0.64 +/- 0.09 g/cm in control animals (p = 0.003). PLA2 inactivated with bromophenacyl bromide (BPB) prior to topical application neither caused contraction (-0.18 +/- 0.18 g/cm AT, p = NS versus baseline tension) nor altered muscarinic responsiveness to 3 x 10(-7) mol/kg ACh. Contraction caused by 100 micrograms/cm2 PLA2 was greater after epithelium removal (2.73 +/- 0.40 g/cm AT versus 1.32 +/- 0.13 g/cm AT in epithelium-intact animals, p less than 0.005). However, epithelium removal (confirmed histologically) attenuated completely augmentation of muscarinic contraction caused by PLA2. Augmentation of muscarinic contraction also was blocked with 15 mg/kg 3-amino-1-(3-trifluoromethylphenyl)-2-pyrazoline hydrochloride (BW 755c), an inhibitor of eicosanoid synthesis, administered intravenously 30 min prior to topical application of 100 micrograms/cm2 PLA2. In contrast, contraction of tracheal smooth muscle caused by PLA2 was not affected significantly by blockade of eicosanoid synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1992

Endogenous sensory neuropeptide release enhances nonspecific airway responsiveness in guinea pigs.

To test whether endogenous sensory neuropeptide release results in airway hyperresponsiveness to exogenous bronchoconstrictor stimuli, male Camm-Hartley guinea pigs were exposed either to capsaicin aerosol for 10 min (CAP-AER) or to saline aerosol (SAL-AER) as a control condition. The following day, animals were anesthetized, tracheostomized, and beta-adrenergically blocked with propranolol, and their bronchoconstrictor responses to intravenously administered acetylcholine (ACh), neurokinin A (NKA), or capsaicin were measured. The bronchoconstriction induced by isocapnic dry gas hyperpnea also was assessed. Compared with the SAL-AER control group, the CAP-AER-treated animals exhibited augmented bronchoconstrictor responses to ACh and NKA. In contrast, the SAL-AER and CAP-AER groups had equivalent bronchoconstrictor responses to dry gas hyperpnea and to intravenously administered capsaicin. CAP-AER treatment caused neutrophilic airway inflammation, as reflected in increased numbers of neutrophils in bronchoalveolar lavage fluid obtained from CAP-AER-treated animals. Ablation of airway c-fiber neuron function (by chronic pretreatment with capsaicin prior to capsaicin aerosol inhalation) eliminated the ACh hyperresponsiveness observed in the CAP-AER-treated animals, demonstrating that sensory nerve products play a key role in the development of this nonspecific hyperresponsiveness. Our results demonstrate that sensory nerve stimulation with capsaicin aerosol leads to nonspecific bronchoconstrictor hyperresponsiveness and cellular airway inflammation, and thus disclose another potentially important role of sensory nerves in regulating airway function.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1992

Hyperoxia-induced airway remodeling in immature rats. Correlation with airway responsiveness.

We recently found that exposure of 21-day-old rats to hyperoxia (> 95% O2 for 8 days) significantly increased in vivo airway cholinergic responsiveness and that O2 exposure also increased airway epithelial and smooth muscle layer thicknesses in a separate cohort of animals. There was substantial variation in the magnitude of both the functional and structural responses to hyperoxia. The present study was designed to test whether the magnitude of O2-induced airway remodeling could account for individual differences in airway responsiveness after O2 exposure, as well as for the difference in responsiveness between air- and O2-exposed animals. We assessed in vivo airway responsiveness to aerosolized acetylcholine (ACh) and airway architecture in 14 O2- and 5 air-exposed, immature rats. Total respiratory system resistance was determined using a plethysmographic method. The mean thicknesses and fractional areas of the airway epithelial and smooth muscle layers were determined by contour tracing using a digitizing pad and microcomputer. Both the small (circumference < 1,000 microns) and central (circumference 1,000 to 4,000 microns) airways were studied. For O2-exposed rats, individual values of EC200 ACh correlated negatively with small airway smooth muscle layer thickness (r = -0.59, p < 0.05; ANOVA), small airway smooth muscle layer fractional area (r = -0.75, p < 0.01), small airway epithelial thickness (r = -0.54, p < 0.05), small airway epithelial fractional area (r = -0.69, p < 0.01), and central airway smooth muscle layer thickness (r = -0.53, p < 0.05). When both air- and O2-exposed animals were considered, EC200 ACh correlated negatively with all eight parameters of airway layer thickness and fractional area.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1992

Measurement of proliferative index in squamous cell carcinoma by flow cytometry.

Squamous cell carcinoma of the upper aerodigestive tract presents significant problems in determining appropriate treatment regimens. Staging aided by sophisticated investigations allows for planning of treatment, but there is a definite need for a specific and reproducible marker to quantify biological aggressiveness. For some classes of tumors the DNA ploidy of cells, as determined by flow cytometry, has shown good correlation to pathologic grading and prognosis. Using a mathematical model, it is possible to calculate the S-phase fraction, which is indicative of proliferative activity and may reflect tumor aggressiveness. However, this parameter is often difficult to determine reliably in squamous cell carcinoma. An optimal marker would be a measureable protein related to proliferation. An attempt was made to use flow cytometry to measure the nuclear enzyme topoisomerase II to assess proliferation in cultured cell lines. Although the antibody was specific to the extracted protein, constituents of the rabbit serum bound non-specifically throughout fixed cells. Further purification of this antibody preparation could realize its diagnostic potential. Antibody against proliferating cell nuclear antigen was more specific, resulting in good correlation flow cytometrically with the S-phase fraction of the cultured cell lines. The results obtained with these protein markers deems further investigation into their use as prognostic indicators. The protocol has been established to apply this technology to tumor samples and establish a meaningful parameter of biological behavior of tumors, upon which treatment regimens can be confidently based.

Antigens, Neoplasm↗
PubMed1991

The impact of curriculum-based suicide prevention programs for teenagers.

The impact of three school-based suicide prevention programs was assessed by comparing attitudes and knowledge of 758 9th and 10th graders with those of 680 control pupils, matched on age, ethnicity, and socioeconomic status at the school level, who did not receive the programs. Evaluations were conducted before exposure to the programs and again 1 month later. A large majority of students knew and subscribed to some of the more important program goals before exposure to the program. There was little evidence of program impact among the minority that did not. Most students were interested by the programs, and positive reactions were more common among female and minority students.

Adolescent↗
PubMed1991

Role of tachykinins in hyperpnea-induced bronchovascular hyperpermeability in guinea pigs.

Isocapnic dry gas hyperpnea causes bronchoconstriction in guinea pigs that is mediated by release of tachykinins from airway sensory nerves. Exogenous neuropeptides can induce microvascular leak. Therefore we tested whether dry gas hyperpnea also elicits bronchovascular hyperpermeability by measuring Evans blue-labeled albumin extravasation along the airways of mechanically ventilated guinea pigs. We found that 1) room temperature dry gas hyperpnea increased Evans blue extravasation in extrapulmonary and intrapulmonary airways as a specific consequence of local airway heat/water losses, 2) capsaicin pretreatment ablated the bronchoconstrictor response to dry gas hyperpnea and reduced bronchovascular leak only in intrapulmonary airways, 3) phosphoramidon given to capsaicin-pretreated animals partially restored dry gas hyperpnea-induced bronchoconstriction and increased the vascular hyperpermeability response to hyperpnea in intrapulmonary airways, and 4) propranolol administration had no important effects on any of these airway responses. We conclude that dry gas hyperpnea causes bronchovascular hyperpermeability in guinea pigs. Tachykinins have a dominant role in this response in the intrapulmonary airways, although another mechanism may also contribute to the microvascular leak in the extrapulmonary airways.

Animals↗
PubMed1991

Time course of bronchoconstriction induced by dry gas hyperpnea in guinea pigs.

We examined the effects of hyperpnea duration and abrupt changes in inspired gas heat and water content on the magnitude and time course of hyperpnea-induced bronchoconstriction (HIB) in anesthetized mechanically ventilated male Hartley guinea pigs. In 12 animals subjected to 5, 10, and 15 min (random order) of dry gas isocapnic hyperpnea [tidal volume (VT) 4-6 ml, 150 breaths/min) followed by quiet breathing of humidified air (VT 2-3 ml, 60 breaths/min), severe bronchoconstriction developed only after the cessation of hyperpnea; the magnitude of respiratory system resistance (Rrs) increased with the duration of dry gas hyperpnea [peak Rrs 1.0 +/- 0.2, 1.8 +/- 0.3, and 2.3 +/- 0.3 (SE) cmH2O.ml-1.s, respectively]. Seven other guinea pigs received, in random order, 10 min of warm humidified gas hyperpnea, 10 min of room temperature dry gas hyperpnea, and 5 min of dry gas hyperpnea immediately followed by 5 min of warm humidified gas hyperpnea. After each hyperpnea period, the animal was returned to quiet breathing of humidified gas. Rrs rose appreciably after the 10 min of dry and 5 min of dry-5 min of humidified hyperpnea challenges (peak Rrs 1.3 +/- 0.2 and 0.7 +/- 0.2 cmH2O.ml-1.s, respectively) but not after 10 min of humidified hyperpnea (0.2 +/- 0.04 cmH2O.ml-1.s). An additional five animals received 10 min of room temperature dry gas hyperpnea followed by quiet breathing of warm humidified air and 10 min of room temperature dry gas hyperpnea followed by 30 min of warm humidified gas hyperpnea in random order.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗
PubMed1991

The impact of curriculum-based suicide prevention programs for teenagers: an 18-month follow-up.

In a long-term follow-up of a study designed to assess the impact of school-based suicide prevention curricula on high school students, a group of 174 students from two high schools who were exposed to a prevention program were compared with a group of 207 control students from two additional high schools who were not exposed to the curriculum. A questionnaire, designed to measure the effects of the prevention program on actual help-seeking behaviors and suicide morbidity during the follow-up period, was administered 18 months after delivery of the program. The study failed to find convincing evidence of any program effect.

Adolescent↗
PubMed1990

Adolescent suicide attempters. Response to suicide-prevention programs.

As part of a controlled evaluation of three suicide-prevention curricula delivered to 1438 ninth- and 10th-grade students, 63 adolescents were identified as having made a suicide attempt. Their attitudes about suicide and help seeking were compared with those of 910 nonattempters drawn from the same population. Reaction to the prevention program was assessed by comparing the responses of the 35 attempters exposed to the programs with responses of 524 exposed nonattempters. The impact of the programs was assessed by comparing 35 exposed attempters with 28 attempters from a control group. Self-identified attempters were less likely to endorse views consistent with the curricula at baseline, but there was little evidence that the programs were successful in influencing these views. There was some evidence that previous attempters were more upset by the programs than their nonattempter peers. The prevalence of suicide attempts as defined in this study by self-report was higher than that reported in studies using interview techniques.

Adolescent↗
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In a panic.

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Adult↗