Search PubMed⌕ Search

Biomedical subjects

G O'Connor

Publications and source records attributed to G O'Connor.

At least 55 records · Page 3Linked to original sources

Analysis of dose-response curves to methacholine. An approach suitable for population studies.

Dose-response curves to methacholine were examined in 9 normal and 10 asthmatic volunteers to determine whether the relationship between dose and response can be adequately summarized by means of a single, continuous measure that is not censored at lower levels of bronchial responsiveness. Subjects underwent a standard methacholine challenge test. There was a strong linear relationship between percent decline FEV1 and cumulative dose methacholine. We summarized each dose-response curve by the slope of a line extending from the origin to the last data point obtained. This summary dose-response slope effectively separated asthmatic from normal subjects, and there was a greater than 3,000-fold difference between the least and most responsive subjects. There was a high degree of correlation between the dose-response slope determined by the standard methacholine challenge protocol and that determined by an abbreviated protocol currently being used to examine nonspecific airway responsiveness in a large, longitudinal study of aging. Among the participants of the latter study, there is a unimodal, skewed distribution of dose-response slope. Dose-response slope is proposed as a quantitative measure of nonspecific airway responsiveness that avoids censoring and that may be particularly useful in epidemiologic studies.

Aging↗

The relationship of nonspecific bronchial responsiveness to the occurrence of respiratory symptoms and decreased levels of pulmonary function. The Normative Aging Study.

Nonspecific bronchial responsiveness was assessed by an abbreviated methacholine challenge test in 458 male participants of the Normative Aging Study, who also completed a respiratory questionnaire and spirometry. A positive response to the methacholine challenge test was defined as a greater than or equal to 20% decline in FEV1 during the test. Cigarette smoking was significantly associated with a positive methacholine response (p less than 0.001). Logistic regression analyses indicated that there was a significant association between a positive response to methacholine and both any wheeze (p = 0.002) and persistent wheeze (p less than 0.001) after taking into account smoking status and age; an association between responsiveness and chronic cough was of borderline significance (p = 0.06). Multiple linear regression analyses indicated that positive methacholine responsiveness was independently associated with lower levels of FEV1 (p less than 0.001) and FEF25-75 (p less than 0.001). Using the log of the dose-response slope rather than a dichotomous variable to characterize responder status yielded very similar results in the linear and logistic models. The findings of this cross-sectional study suggest that increased level of nonspecific responsiveness is significantly associated with wheeze and cough symptoms and decreased levels of pulmonary function in adult men. Longitudinal follow-up of these men should shed light on the importance of nonspecific responsiveness as a risk factor for the subsequent development of chronic obstructive pulmonary disease.

Adult↗

Toxofactor associated with Toxoplasma gondii infection is toxic and teratogenic to mice.

A toxin associated with Toxoplasma gondii infection was obtained from the trophozoites and culture medium used to propagate the parasite in cell cultures. The toxin, named Toxofactor (TF), administered parenterally or nonparenterally in adult mice, produces transient symptoms of lethargy, ruffled fur, and body weight loss. Organ changes which accompanied the outward symptoms included hepatosplenomegaly and involuted thymus. TF activity was detected in extracts of the blood, peritoneal fluid, liver, and spleen of infected mice. Severe damage to embryonal and fetal development was induced when TF was administered during pregnancy. Resorption, abortion, and congenital abnormalities were produced, dependent upon the stage of development at the time of exposure. Adult mice which had reacted to and recovered from an initial intraperitoneal injection to TF were protected against a secondary challenge from TF. Fetal development was also protected from damage when TF was used to challenge adults previously exposed to TF. Mouse and rabbit anti-TF sera neutralized TF activity in the adult. In no instance did control mice show any deleterious effect when exposed to soluble cell lysate from the uninfected cell line (BHK-21) used to propagate the organism plus the used medium from these same uninfected cells. TF activity was not attributed to bacterial, myocoplasmal, or viral contamination. TF toxic activity is labile to elevated temperature and high or low pH, which also destroy its protective properties. TF activity was sensitive to trypsin and was obtained in the elution fraction (alpha-methyl-D-mannoside) from affinity chromatography (concanavalin A-Sepharose 4B). Ultrafiltration indicated the molecular weight to be between 50,000 and 100,000. TF, apparently a glycoprotein, was quantitated for activity by a weight loss assay. A unit of activity was defined as the minimum quantity of TF (highest dilution) which produced at least a 10% average body weight loss in adult Nya:NYLAR female mice between days 7 and 12 post-intraperitoneal injection.

Abnormalities, Drug-Induced↗

Central mechanisms in DOC-salt hypertensive rats.

These experiments were intended to elucidate the role of central mechanisms in the maintenance of high blood pressure produced by deoxycorticosterone (DOC) and salt in rats. We investigated the central effect of angiotensin (AII) on systemic arterial blood pressure and plasma arginine vasopressin (AVP) in DOC-salt and control rats. There was a pronounced augmentation of the pressor responsiveness to centrally injected AII in DOC-salt hypertensive rats; but there was no difference in AII induced AVP release in DOC-salt hypertensive rats compared to sham controls. The increase in vascular resistance of the perfused hindquarters induced by stimulation of the lumbar sympathetic chains did not change in DOC-salt hypertensive rats although the increases induced by norepinephrine (NE) were potentiated at the higher doses. Pressor responsiveness of the DOC-salt hypertensive rats to i.v. administration of AII, AVP and NE was shown to be augmented by factors of 3.6, 2.5 and 1.8 respectively in DOC-salt rats. Reflex bradycardia to these pressor responses was attenuated indicating impairment of baroreflex function. The potentiation of pressor responses to centrally injected AII in DOC-salt hypertensive rats was greater than could be explained by augmented pressor responsiveness to iv NE and AVP. Neither baroreflex dysfunction, facilitated release of NE at sympathetic terminals, nor augmented release of AVP into the circulation could explain the potentiation. Therefore, our data suggested that selective central amplification of sympathetic vasomotor responses to centrally injected AII stimuli may play a role in the hypertension after 3 weeks of DOC-salt treatment in rats.

Angiotensin II↗

Double-contrast arthrotomography of the shoulder.

We have used double-contrast arthrotomography to assess the glenoid labrum, as plain radiographs and single-contrast arthrograms are unsatisfactory for this purpose. Establishing the clinical diagnosis of a torn glenoid labrum may be difficult, as not all patients with such tears have a history of a previous shoulder dislocation. The glenoid labrum is seen distinctly on double-contrast arthrotomography, and tears are manifested by truncation or blunting of the anteroinferior lip. We compared the anatomy of the normal shoulder as seen in double-contrast arthrotomography with that seen in patients with surgically proved tears of the glenoid labrum. Double-contrast arthrotomography is an accurate method of assessing the integrity of the glenoid labrum, and it has important implications for the operative management of patients with trauma to the shoulder.

Humans↗

Urinary kallikrein in postobstructive diuresis.

We studied urinary kallikrein excretion in the rat during unilateral release of 24-hr bilateral ureteral ligation (BUL). In six rats studied after 24 hr of BUL, the glomerular filtration rate was 20 per cent of that in the five sham-operated controls. In the BUL group, the urine flow rate was 5 fold greater, fractional sodium excretion 100 times greater, and fractional potassium excretion 5 times greater than in controls. Urinary kallikrein excretion in the BUL group was one-half that of the controls. However, urinary kallikrein excretion per functioning nephron was increased 3 fold in the BUL group. Five of six BUL rats with increased fractional sodium and water excretion also showed increased urinary kallikrein excretion/GFR when compared to controls. Our study suggests that after 24 hr of BUL in the rat, urinary kallikrein excretion is increased in relation to the remaining, functioning nephrons and suggests a role for the kallikrein-kinin system in the postobstructive salt and water losses.

Animals↗