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Biomedical subjects

W N McKenzie

Publications and source records attributed to W N McKenzie.

At least 19 recordsLinked to original sources
PubMed1991

Pulmonary perivascular and interstitial inflammation in MRL/MpJ-lpr/lpr mice. III. Modulation by cyclophosphamide and sex hormones in 4- and 6-month-old animals.

Estradiol (E) abolished clearing of pulmonary inflammation in 2-month-old male MRL/MpJ-lpr/lpr (MRL/l) mice treated with cyclophosphamide (CY). To determine if this effect persisted in animals with advanced disease, we studied male and female MRL/l mice, aged 4 and 6 months (4M, 6M, 4F, and 6F, respectively). Mice were treated, beginning at 1 month of age, with saline, CY (12 mg/kg/day), CY + castration, CY + castration + testosterone (T) in females, and CY + castration + E in males. CY had no effect on pulmonary inflammation in 4M, possibly because of the development of relatively mild lesions. However, CY was highly effective in 6M. CY + castration + T significantly reduced overall inflammation in 6F and showed a trend in 4F. CY alone had a variable effect on bronchoalveolar lavage fluid (BALF) cells and BALF IgG in both males and females. However, concurrent treatment with T was required for histologic changes of pulmonary inflammation to fully respond to a high dose of CY in female mice. E-treated males had reduced responsiveness to CY.

Aging↗
PubMed1989

A comparison of the effect of ipratropium and albuterol in the treatment of chronic obstructive airway disease.

Twenty-five subjects with moderate to severe chronic obstructive airway disease were studied to compare the effect of ipratropium bromide, albuterol, and placebo on the forced expiratory volume in 1 s, (FEV1), forced vital capacity, heart rate, and blood pressure during six hours. Ipratropium produced a significantly greater improvement than albuterol in the FEV1 at 30 minutes and at 3, 4, and 5 hours and in the forced vital capacity at one through six hours. Fifteen subjects did not demonstrate a 15% improvement and at least a 200-mL increase in the FEV1, 15 minutes after metaproterenol sulfate aerosol. All 15 did improve after ipratropium therapy during the study. Ipratropium was effective significantly longer than albuterol. Subjects with better peak responses to ipratropium had a lower FEV1 percent predicted and a greater pack-year smoking history. In patients with chronic obstructive airway disease, ipratropium produces a longer duration of action than albuterol. It is more effective than albuterol in treating severely obstructed individuals and those not responding to metaproterenol. It is equally effective in treating others.

Administration, Inhalation↗
PubMed1988

Sex hormones modulate the response of pulmonary perivascular inflammation to cyclophosphamide therapy in MRL/MpJ-lpr/lpr mice.

Responses of pulmonary perivascular infiltrates to immunosuppressive therapy with cyclophosphamide (CY) were evaluated in the MRL/MpJ-lpr/lpr (MRL/1) mouse, a model for the study of systemic lupus erythematosus. Male and female mice were divided into the following groups: controls injected with saline; intact mice receiving CY; castrated CY-treated mice; castrated, hormone implanted, CY-treated mice. CY treatment began at 30 days of age and animals were killed at 60 days of age. Lungs were fixed-inflated to 26 cm H2O pressure with glutaraldehyde-formaldehyde fixative. The pulmonary perivascular response to immunosuppressive therapy was graded depending on the extent of infiltrates surrounding 15 pulmonary vessels per animal. Intact males treated with CY alone had almost complete clearing of perivascular infiltrates, whereas intact females did not respond to therapy. Castrated CY-treated males showed a decreased response to CY compared to intact CY-treated males. Castrated, estradiol-implanted males had no response to CY therapy. Estradiol interfered with the therapeutic response to CY in male MRL/1 mice.

Animals↗
PubMed1986

Pulmonary inflammation in autoimmune MRL/Mp-lpr/lpr mice. Histopathology and bronchoalveolar lavage evaluation.

Early detection of lupus pneumonitis is difficult because it requires lung biopsy. The authors describe here in detail the age-related histologic changes in pulmonary inflammation, the age-related changes in bronchoalveolar lavage (BAL), and the effect of cyclophosphamide (8 mg/kg) on pulmonary inflammation and bronchoalveolar lavage in MRL/Mp-lpr/lpr mouse, an animal model of systemic lupus erythematosus. To assess the evolution of pulmonary inflammation and response to cyclophosphamide therapy, they compared the age-related progression of pulmonary inflammation with sequential changes in BAL cell populations in this autoimmune mouse model. A striking similarity was noted between age-related changes in pulmonary inflammation and lymphocyte counts in BAL. A trend to reduction in histologic evidence of inflammation was reflected by lymphocytes in BAL in cyclophosphamide-treated (8 mg/kg/day) males but not in females. There was a striking sex-related difference in that the histologic evidence of pulmonary inflammation and bronchoalveolar lavage lymphocyte count in cyclophosphamide-treated males was significantly lower than cyclophosphamide-treated females of the same age.

Aging↗
PubMed1984

Milk production and lactation curve of guinea pigs.

Milk was collected daily from 65 albino English guinea pigs throughout the first 21 days of lactation. Mean milk yield was 21.7 +/- .38 g per day per animal. Production on the 1st day of lactation was 10.8 +/- .44 g. It peaked on days 6 and 7 at 40.1 +/- 1.17 g and then decreased. It was 18.7 +/- .93 g on day 14 and 2.9 +/- 2.5 g on day 21. Total milk production for 21 days varied from 223 to 787 g with a mean of 455 +/- 13.2 g. Predictive equations for lactation curves included linear, quadratic, cubic, linear-, quadratic-, cubiccum-log, and several exponential models. The equation chosen was Y(g) = 10.23D .913e-.00984D2 where Y was milk production per day and D was day of lactation. This equation had a coefficient of determination of .812 for an individual response. Alternately, three lines could be used to fit the lactation curve. These were: Y = .739 + 10.35D - .625D2 for days 1 to 6, Y = 61.9 - 3.10D for days 7 to 18, and Y = 25.5 - 1.08D for days 18 to 21.

Animals↗
PubMed1983

The effect of terbutaline on cardiac function in patients with stable chronic obstructive lung disease.

The effect of 0.25 mg of terbutaline sulfate, a beta 2-adrenergic agent, on the right and left ventricular ejection fractions (RVEF and LVEF, respectively) was studied in 30 patients with severe stable chronic obstructive pulmonary disease (COPD) with a mean forced expiratory volume in 1 s of 0.79 +/- 0.06 L. All bronchodilator therapy was withdrawn 48 hours before the study. The ECG-synchronized gated equilibrium radionuclide ventriculography showed decreased RVEF in 27 patients and LVEF in 16 patients. Both the RVEF and LVEF significantly increased after the terbutaline injection; this increase was noted both in patients with normal and decreased ejection fractions. We conclude that the increase in ejection fractions after terbutaline injection may contribute to the good clinical response to this drug seen in patients with severe stable COPD even though the bronchodilator effect may be minimal.

Adult↗
PubMed1982

Cell culture of rat gastric fundic mucosa.

The purpose of this study was to develop a primary cell culture system of rat gastric fundic epithelial cells. The cells, isolated enzymatically, were cultured in Coon's modified Ham's F-12 medium supplemented with 10% fetal bovine serum, 15 mM HEPES buffer, fibronectin, and antibiotics. The inoculated cells started to grow rapidly on day 1 (doubling time, 26 h). The cells reached confluency on day 3. On phase contrast microscopy, over 90% of cells possessed epithelial characteristics. Histochemical studies showed (a) 90% of the epithelial cells contained PAS positive granules, (b) 5% of the cells gave a strong reaction for succinic dehydrogenase activity (presumably parietal cells), and (c) immunohistochemical localization of pepsinogen was negative. Ultrastructurally, microvilluslike structures, junctional complexes, Golgi apparatus, mitochondria, rough-surfaced endoplasmic reticulum, and mucous granules were observed. Mitotic figures were clearly observed on Giemsa staining and the mitotic index was maximum on day 2. Autoradiographic and biochemical studies showed these cells possessed the capability to synthesize deoxyribonucleic acid and this ability was maximum on day 2. These cells were able to synthesize and to secrete glycoprotein and this function was significantly increased by 16,16-dimethyl prostaglandin E2. Cyclic adenosine monophosphate produced by the cultured cells was enhanced by addition of 16,16-dimethyl prostaglandin E2 (p less than 0.01). This in vitro system provides a valuable model for studies of cellular functions of gastric mucosa.

16,16-Dimethylprostaglandin E2↗
PubMed1982

Arachidonic acid protection of rat gastric mucosa against ethanol injury.

AA, an essential dietary fatty acid, is a precursor for synthesis of prostaglandins. The ability of prostaglandins to protect the gastric mucosa against ethanol injury prompted us to investigate the possibility of AA providing similar protection in the rat. AA or its solubilizer were instilled intragastrically 60 min prior to absolute ethanol. The gastric lining was examined at 3 and 15 hr after the administration of ethanol. The extent of damage was assessed both macroscopically and histologically. AA administration 30 or 60 min prior to ethanol ingestion protected the gastric mucosa against macroscopic and histological damage for 3 to 15 hr. The intragastric concentration of prostaglandin E2 was 5,000 to 13,000 times higher in the animals pretreated with AA than in the controls. The protective action of AA was markedly diminished by indomethacin pretreatment. Intrajejunal administration of AA did not protect the gastric mucosa. These experiments demonstrate that a dietary constitutent--arachidonic acid--can protect the gastric mucosa against alcohol injury by inducing the synthesis of prostaglandins by the gastric mucosa.

Animals↗
PubMed1981

Endotoxin induced migration of leukocytes from blood to milk.

Guinea pigs were separated from young on days 5 to 7 of lactation. They were anesthetized with ether and were infused intramammary via the teat canal with either sterile saline (.5 ml) or Escherichia coli endotoxin (026:B6:500 microgram/.5 ml). Each animal served as its own control by having sterile saline in one gland and endotoxin in the other. Animals were sacrificed 4, 6, 8, and 12 h later to determine the time of maximum migration of polymorphonuclear leukocytes from blood to milk. A control group of animals having had no intramammary infusion was sacrificed. Tissues were prepared for observation by light and electron microscopy. Five fields per slide, five slides per animal, and three animals per period were examined by light microscopy, and numbers of polymorphonuclear leukocytes per field were categorized for presence a) in the capillary, b) in interstitial space, c) touching the basal lamina, d) between epithelial cells of an alveolus, and e) in the lumen of an alveolus. Polymorphonuclear leukocytes were in small numbers in the lumen by 4 h and peaked at about 8 h after intramammary infusion of endotoxin. By 12 h numbers had decreased from 8 h. Polymorphonuclear leukocytes were observed by electron microscopy in the intercellular spaces of the alveolar epithelium. A time sequence model using the guinea pig to study mechanisms of leukocyte migration into milk based upon tissue studies may be used in research aimed at controlling mastitis.

Animals↗
PubMed1981

Endotoxin dose-related leukocytosis in milk of guinea pigs.

Objectives were to determine minimum and maximum doses of Escherichia coli endotoxin that would stimulate leukocytosis in the mammary gland of the guinea pig. Endotoxin concentrations of .005, .05, .5, 5.0, and 50.0 microgram/ml in 1 ml were used to stimulate migration of polymorphonuclear leukocytes in milk of guinea pigs at five times (2, 4, 6, 8, and 12 h postinjection with endotoxin). There were three animals in each experimental group per endotoxin concentration. Each animal served as its own control by having sterile saline injected into one mammary gland and endotoxin into the other. A control group of three animals had no saline or endotoxin injected. Guinea pigs were milked with a modified milking apparatus. Leukocyte numbers in the uninjected mammary gland did not differ from those in saline injected glands. The difference in mean leukocyte numbers between saline injected and .005 microgram/ml endotoxin injected glands approached significance at 5%. There was no difference between mean numbers recruited by the 5.0 and 50.0 microgram/ml endotoxin doses at 4, 6, 8, and 12 h. The chemotactic effect and, therefore, the rate of polymorphonuclear leukocyte recruitment was maximal at the 5 microgram/ml endotoxin dose.

Animals↗
PubMed1979

A modified device for collecting milk from guinea pigs.

A modified device for milking small animals is discussed. The advantage of these modifications are 1) quiet operation, 2) ease of operation in animal room, and 3) quick change to allow the same device to be used on different animals. This device can be tailored to the test size as well as milk volume expected. Construction is simple, and materials are inexpensive.

Animals↗
PubMed1978

The lung of the copper-deficient rat. A model for developmental pulmonary emphysema.

Based on the hypothesis that cross-linked elastin is critical for normal lung structure, lung tissue from copper-deficient rats was studied. Copper deficiency was induced in the second generation by feeding dams a milk-based diet low in copper (less than 1 ppm) during gestation and lactation. The weanlings were fed the same diet until they showed severe signs of deficiency between 6 and 10 weeks of age. Controls animals received the basal diet supplemented with 10 ppm copper. Liver cytochrome oxidase activity, which served as the chief index of deficiency, decreased from a normal level of approximately 80 to 15 mumole/min/g. The lungs of the deficient animals contained 17% less elastin and had 35% larger alveolar spaces (34.7 vs 47.7 intercepts), as determined by the mean alveolar intercept method. The ultrastructure of elastin in the bronchi, arterioles, and alveolar ducts had a "washed out" appearance. To determine the reversibility of the pathology, deficient animals, 5 to 10 weeks of age, were repleted by feeding a copper-supplemented diet for 1, 2, and 3 months. During this period growth resumed, anemia disappeared, and liver cytochrome oxidase returned to normal. There was no improvement in lung structure with regard to alveolar size (28.4 intercepts compared with 43.6 in controls and 35.1 in deficient littermates killed at the start of repletion). The ultrastructure and electron density of pulmonary elastin was restored to near normal. The lung of the copper-deficient rat is proposed as a model for developmental pulmonary emphysema.

Animals↗
PubMed1978

Leukocyte recruitment to airways by aldehyde-carbon combinations that mimic cigarette smoke.

Exposure of Syrian golden hamsters to formaldehyde (3 to 250 p.p.m.) evaporated onto carbon (21 to 805 mg. per cu. m.) recruited polymorphonuclear (PMN) leukocytes to the epithelium of tracheas and intrapulmonary airways which peaked at 24 to 48 hours. Acrolein (less than 6 p.p.m.) on carbon (593 mg. per cu. m.) caused PMN recruitment which was maximal at 12 hours. The vapor phase of cigarette smoke produced PMN leukocyte recruitment of the same magnitude and with the same time course. In contrast, exposure to formaldehyde at doses of 2 to 250 p.p.m. and acrolein at 6 p.p.m. was cytotoxic to airway cells and caused prompt and delayed exfoliation but no recruitment of PMN leukocytes. There was no difference in cytotoxicity when carbon was present. Leukocyte recruitment occurred only when carbon was present, either given simultaneously wiht aldehydes or with adsorbed aldehydes. Thus, aldehyde vapor simulates the cytotoxic effects of particle-free cigarette smoke vapor. Of greater significance is the finding that an aldehyde, formaldehyde or acrolein, inhaled adsorbed on carbon or simultaneously with carbon to hamster airways is chemotactic for PMN leukocytes just as is the vapor phase of cigarette smoke when given simultaneously with carbon particles.

Acrolein↗
PubMed1977

Granulocyte recruitment to airways exposed to endotoxin aerosols.

Guinea pigs were exposed to aerosols of 0.1 mg of Salmonella typhosa endotoxin per ml for 2 or 4 hours, and white cells in blood and in bronchopulmonary lavage were counted at 2, 4, and 6 hours. The lungs of a second group of guinea pigs and hamsters exposed in the same manner were fixed in inflation with osmium tetroxide in fluorocarbon, which retains cells on luminal surfaces of airways. The polymorphonuclear leukocyte counts in cardiac blood were significantly increased, and lymphocyte counts were decreased at 6 hours (P less than 0.05). The number of cells obtained by bronchopulmonary lavage, which were mostly polymorphonuclear leukocytes, increased at 4 hours to 28 million, and at 6 hours, was 26.5 million (P less than 0.01), compared to 5 million cells at the same times in air and in water aerosol control preparations. The polymorphonuclear cell counts on airway cross sections, i.e., (polymorphonuclear cells/epithelial cells) x 100, showed a mean +/- SD peak of 53.9 +/- 10.9 after 4 hours in guinea pigs and a peak of 99.7 +/- 11.0 after 6 hours in hamsters. Alveoli showed no cell recruitment. Platelets were aggregated on surfaces of arterioles facing bronchioles, although counts in blood were unchanged. Neither leukocytes nor airway cells showed damage to their ultrastructure. The time course for airway recruitment and leukocytosis matches that for symptoms after exposure of workers to dusts from natural fodder or fibers. This suggests that leukocyte recruitment to airways by inhaled endotoxin may be part of the mechanism for the fever and chest tightness in occupational disorders.

Aerosols↗
PubMed1975

Responses to cotton dust.

Twelve cotton textile workers were studied: (1) to compare standard measures of volume and expiratory flow, maximal expiratory flow volume (MEFV) curves, closing volume (CV), and closing capacity (CC) in detection of airway narrowing with cotton dust exposure; (2) to evaluate the response of arterial blood gases to exposure; (3) to measure changes in leukocytes in peripheral blood and airway secretions; and (4) to assess the temporal relationships and correlations between measures. Change in expiratory flow (FEV) most consistently and significantly discriminated between the control and cotton dust exposures. Vmax50%FVC was a more sensitive indicator, but variance was increased proportionately. CV and CC changed inconsistently with relatively large variances. The PaO-2 decreased overall and two subjects had large decrements. Peripheral blood and polymorphonuclear cell counts increased with exposure to cotton dust and polymorphonuclear leukocytes were recruited to the nasal mucosa. Chest tightness and decreased flow were temporally correlated with leukocyte recruitment that may be important in respiratory disease among cotton textile workers and therefore deserves further investigation.

Adult↗