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Biomedical subjects

K L McNeill

Publications and source records attributed to K L McNeill.

9 recordsLinked to original sources
PubMed1999

Effects of vitamin C and of a cell permeable superoxide dismutase mimetic on acute lipoprotein induced endothelial dysfunction in rabbit aortic rings.

Low density lipoprotein (LDL) inhibits endothelium-dependent relaxation. The mechanism is uncertain, but increased production of superoxide anion O2- with inactivation of endothelium-derived NO and formation of toxic free radical species have been implicated. We investigated effects of the cell permeable superoxide dismutase mimetic manganese (III) tetrakis (1-methyl-4-pyridyl) porphyrin (MnTMPyP), the free radical scavenger vitamin C and arginine (which may reduce O2- formation) on acute LDL-induced endothelial dysfunction in rabbit aortic rings, using LDL prepared by ultracentrifugation of plasma from healthy men and aortic rings from New Zealand white rabbits. LDL (150 microg protein ml(-1) for 20 min) markedly inhibited relaxation of aortic rings (in Krebs' solution at 37 degrees C and pre-constricted to 80% maximum tension with noradrenaline) to acetylcholine 82+/-10% (mean percentage difference between sum of relaxations after each concentration of acetylcholine in the presence and absence of LDL, +/-s.e.mean, n=26, P<0.001) but not to the endothelium-independent agonist nitroprusside. MnTMPyP (10 microM) reduced inhibitory effects of LDL from 124+/-27 to 56+/-17% (n=6, P<0.05). Vitamin C (1 mM) reduced inhibitory effects of LDL from 59+/-8 to 22+/-5% (n=6, P<0.05). Inhibitory effects of LDL were similar in the absence or presence of arginine (84+/-12 vs 79+/-16%, n=14, P=0.55). Effects of L-arginine (10 mM) did not differ significantly from those of D-arginine (10 mM). Acute (20 min) exposure of aortic rings to LDL impairs endothelium-dependent relaxation which can be partially restored by MnTMPyP and vitamin C. This is consistent with LDL causing increased O2- generation.

Acetylcholine↗
PubMed1989

In vitro effects of fibrous and nonfibrous silicon nitride on bovine pulmonary macrophages.

Bovine pulmonary macrophages were exposed in vitro to 0.3, 0.1, 0.03, or 0.01 mg/ml of a fibrous silicon nitride, nonfibrous (milled) silicon nitride comminuted from the fibrous powder, alpha-quartz (an active control), or glass beads (an inert control). Functional evaluation of the exposed cells indicated that the fibrous silicon nitride was as cytotoxic as quartz, while the nonfibrous silicon nitride was relatively inert. To further evaluate the mechanisms of cytotoxicity, the cells were exposed to 1 mg/ml of the control and test materials and biochemical studies were performed. Quartz increased release of both the cytoplasmic enzyme, lactate dehydrogenase (LDH), and the lysosomal enzyme, acid phosphatase (AP), consistent with both cell membrane and lysosome lysis. In addition, total protein levels were significantly depressed, suggesting significant impairment of cellular synthetic processes. LDH, but not AP, values were increased with fibrous silicon nitride treatment, but not with the nonfibrous silicon nitride. In contrast to quartz, which increased LDH levels by 65%, the fibrous silicon nitride only increased LDH levels by 11%. Scanning electron micrographs further indicated that the fibrous silicon is cytotoxic and poorly tolerated by macrophages. These studies provide further evidence of morphology as a primary determinant of cytotoxicity since the milled powder test article was comminuted from the fibrous material.

Acid Phosphatase↗
PubMed1987

In vitro interactions between pulmonary macrophages and respirable particles.

Pulmonary alveolar macrophage cells (PAM) are an important component of the pulmonary response to particles deposited in the deep lung. To more fully characterize the interactions between macrophages and particulate materials, a correlative light and electron microscopic technique was developed that allowed light microscopic identification of individual cell viability after in vitro particle exposure, followed by scanning and transmission electron microscopic analyses of specific PAM, including surface morphology, X-ray microanalytic evaluation of particle content, and internal cellular structure. Individual cell viability, particle content, and morphologic alterations were evaluated for three particle types: Ni3S2, TiO2, and glass beads. Cell death and stages of cell disruption including bleb cluster formation, loss of surface features, formation of membrane tears and holes, and cell degranulation correlated with Ni3S2 and TiO2 content. Glass beads were not associated with cell disruption or viability reduction. Correlative microscopic techniques were essential in describing particle-dependent effects on an individual cell basis.

Animals↗
PubMed1986

Trace element interactions affecting pulmonary macrophage cytotoxicity.

Effluents from the smokestacks of powerplants contain respirable particles that are enriched with a variety of biologically active trace elements. To determine the relative toxicity of trace elements in coal fly ash, the effects of selected compounds, alone and in combination, were evaluated in cultures of pulmonary alveolar macrophages. The inorganic compounds studied were ZnO, Na2SeO3, V2O5, NaAsO2, Mn3O4, and Ni3S2. Vanadium pentoxide was the most cytotoxic compound while selenium was the least toxic (approximately 100-fold less toxic than vanadium). After dose-response curves for each element were established, interactions between various compounds were studied by coexposure to trace elements at different concentrations. Selenium was completely antagonistic to the toxic effects of vanadium and slightly antagonistic to arsenic. In contrast to selenite, sulfite, a moiety with a similar redox potential, was not antagonistic to vanadium toxicity. Zinc was weakly antagonistic to the in vitro effects of nickel. No other chemical combinations displayed antagonistic, synergistic or additive effects on the function of the cultured macrophages.

Air Pollutants↗
PubMed1983

Physical and biological studies of coal and oil fly ash.

Studies were performed to compare the physical and chemical characteristics and the in vitro macrophage cytotoxicity of oil and coal fly ash. Sampling methodology was developed to collect size-fractionated particulate matter from the smokestack of either a coal-fired or an oil-fired power plant. Morphological studies demonstrated particle heterogeneity, although most coal fly ash particles appeared to be spherical. Oil fly ash contained two major morphologies; nonopaque amorphous particles and opaque amorphous particles. Elemental analysis indicates that the coal ash is predominantly composed of aluminosilicate particles, while the oil ash is predominantly inorganic sulfates and carbonaceous particles. In vitro macrophage assays demonstrate that the finest coal fly ash particles are the most cytotoxic; the cytotoxicity is significantly less than that of alpha-quartz, the positive control particle. In contrast, the oil fly ash particles are more cytotoxic than quartz. The cytotoxicity of oil fly ash is due to soluble components, possibly vanadium salts.

Animals↗
PubMed1982

Functional evaluation of lung macrophages from cigarette smokers and nonsmokers.

The in vitro function of pulmonary alveolar macrophages (PAM) was compared for human smokers and nonsmokers. Initial studies demonstrated the feasibility of shipping lavaged cells on ice with storage up to 6 hr. Comparative studies were performed to evaluate ideal culture conditions including media composition, preincubation period, and phagocytic variables. Smokers had a six-fold enhancement in lavagable macrophages compared to nonsmokers. Macrophages from smokers demonstrated a decreased phagocytic capability compared to nonsmokers. The effects of cigarette smoking on phagocytosis were observed over a wide range of challenge periods using either fetal or newborn bovine serum (FBS or NBS). Regardless of smoking history, enhanced phagocytosis was observed with media containing NBS compared to FBS. No effects on in vitro viability, attachment, or adherence were observed.

Adult↗
PubMed1981

Serum copper and zinc levels in melanoma patients.

Serum copper levels (SCL) and serum zinc levels (SZL) were evaluated in malignant melanoma patients at various clinical stages. Copper levels were generally found to be elevated, reflecting the degree and extent of tumor activity. Zinc levels and, hence, SCL:SZL ratios did not reflect tumor activity. SCL appeared to prognosticate disease progression in that all patients whose values never declined below 150 micrograms/100 ml died during the course of the study. However, not all patients who died from tumor metastases displayed persistent elevations of SCL. Patients receiving BCG immunotherapy appeared to have higher SCL than untreated patients.

Adult↗
PubMed1979

Abnormal canine bone development associated with hypergravity exposure.

Chronic centrifugation of 85- to 92-day-old Beagles at 2.0 X g and 2.6 X g for 26 weeks during the time of active skeletal growth caused skeletal abnormalities in the radius and the ulna of ten of 11 dogs. The pattern of change mimicked that found in naturally occurring and experimentally induced premature distal ulnar physeal closure or delayed growth at this physis. Minimal changes in bone density were detected by sensitive photon absorptiometric techniques. Skeletal abnormalities also were found in five of the six cage-control dogs, although the run-control dogs were radiographically normal.

Animals↗