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T J Lyons

Publications and source records attributed to T J Lyons.

At least 37 records · Page 2Linked to original sources
PubMed1998

The dark side of dioxygen biochemistry.

The cellular biochemistry of dioxygen is Janus-faced. The good side includes numerous enzyme-catalyzed reactions of dioxygen that occur in respiration and normal metabolism, while the dark side encompasses deleterious reactions of species derived from dioxygen that lead to damage of cellular components. These reactive oxygen species have historically been perceived almost exclusively as agents of the dark side, but it has recently become clear that they play beneficial roles as well.

Antioxidants↗
PubMed1998

Frequency of the "push-pull effect" in U.S. Air Force fighter operations.

BACKGROUND: Recent investigation into the push-pull effect (PPE), the reduction of +Gz tolerance when preceded by less than +1 Gz, has focused on centrifuge studies to demonstrate the presence of adverse cardiovascular responses. Maneuvers found to cause the Push-Pull Effect (PPEM) have not been studied previously in U.S. Air Force (USAF) fighter aircraft. The frequency of and extent to which PPEMs are performed in fighter aircraft are unknown. METHODS: Head-up display (HUD) videotapes from F-15 and F-16 air combat training missions were reviewed for the presence of PPEMs. The frequency of engagements containing PPEMs and the magnitude of the Gz profiles were noted. RESULTS: PPEMs were found in 11 to 67%, of engagements reviewed, depending on the nature of the training mission, with an overall average of 32%. The PPEMs that were observed contained segments of less than +1 Gz, ranging on average from 0.0 to 0.5 Gz for an average of 3.5 to 5 s duration. CONCLUSIONS: PPEMs are present in air combat training missions performed by today's USAF fighter aircraft and represent an operationally significant source of risk for accidents. These findings support continued research into the physiologic response to PPE and the development of countermeasures.

Acceleration↗
PubMed1998

The "push-pull effect" and G-induced loss of consciousness accidents in the U.S. Air Force.

BACKGROUND: A recent Canadian Forces CF-18 Hornet aircraft accident has focused interest on the push-pull effect (PPE). PPE has not previously been identified in U.S. Air Force (USAF) G-Induced Loss of Consciousness (G-LOC) Accidents. The presence of maneuvers known to cause the push-pull effect (PPEMs) that lead to G-LOC accidents suggests that PPE is operationally significant and is a potential cause of G-LOC accidents. METHODS: USAF accident reports where G-LOC was found to be causal were reviewed for indications of a PPEM immediately prior to the G-LOC. Terminology in the narratives was used to indicate a PPEM in the accident sequences. RESULTS: In 3 of 24 mishaps, the presence of a PPEM was highly probable, while another 4 mishaps were found to have a probable association with PPEMs. The probable presence of PPEMs represents a significant percentage (12.5-29%) of USAF G-LOC accidents. CONCLUSION: USAF G-LOC accident reports contained descriptions that indicated the presence of PPEMs in accident sequences. This finding suggests that the PPE is an operationally significant source of risk for accidents in USAF high-performance aircraft.

Acceleration↗
PubMed1997

Age-dependent increase in ortho-tyrosine and methionine sulfoxide in human skin collagen is not accelerated in diabetes. Evidence against a generalized increase in oxidative stress in diabetes.

The glycoxidation products Nepsilon-(carboxymethyl)lysine and pentosidine increase in skin collagen with age and at an accelerated rate in diabetes. Their age-adjusted concentrations in skin collagen are correlated with the severity of diabetic complications. To determine the relative roles of increased glycation and/or oxidation in the accelerated formation of glycoxidation products in diabetes, we measured levels of amino acid oxidation products, distinct from glycoxidative modifications of amino acids, as independent indicators of oxidative stress and damage to collagen in aging and diabetes. We show that ortho-tyrosine and methionine sulfoxide are formed in concert with Nepsilon-(carboxymethyl)lysine and pentosidine during glycoxidation of collagen in vitro, and that they also increase with age in human skin collagen. The age-adjusted levels of these oxidized amino acids in collagen was the same in diabetic and nondiabetic subjects, arguing that diabetes per se does not cause an increase in oxidative stress or damage to extracellular matrix proteins. These results provide evidence for an age-dependent increase in oxidative damage to collagen and support previous conclusions that the increase in glycoxidation products in skin collagen in diabetes can be explained by the increase in glycemia alone, without invoking a generalized, diabetes-dependent increase in oxidative stress.

Adolescent↗
PubMed1997

Carboxymethylethanolamine, a biomarker of phospholipid modification during the maillard reaction in vivo.

Nepsilon-(Carboxymethyl)lysine (CML) is a stable chemical modification of proteins formed from both carbohydrates and lipids during autoxidation reactions. We hypothesized that carboxymethyl lipids such as (carboxymethyl)phosphatidylethanolamine (carboxymethyl-PE) would also be formed in these reactions, and we therefore developed a gas chromatography-mass spectrometry assay for quantification of carboxymethylethanolamine (CME) following hydrolysis of phospholipids. In vitro, CME was formed during glycation of dioleoyl-PE under air and from linoleoylpalmitoyl-PE, but not from dioleoyl-PE, in the absence of glucose. In vivo, CME was detected in lipid extracts of red blood cell membranes, approximately 0.14 mmol of CME/mol of ethanolamine, from control and diabetic subjects, (n = 22, p >> 0.5). Levels of CML in erythrocyte membrane proteins were approximately 0.2 mmol/mol of lysine for both control and diabetic subjects (p >> 0.5). For this group of diabetic subjects there was no indication of increased oxidative modification of either lipid or protein components of red cell membranes. CME was also detected in fasting urine at 2-3 nmol/mg of creatinine in control and diabetic subjects (p = 0.085). CME inhibited detection of advanced glycation end product (AGE)-modified protein in a competitive enzyme-linked immunosorbent assay using an anti-AGE antibody previously shown to recognize CML, suggesting that carboxymethyl-PE may be a component of AGE lipids detected in AGE low density lipoprotein. Measurement of levels of CME in blood, tissues, and urine should be useful for assessing oxidative damage to membrane lipids during aging and in disease.

Adult↗
PubMed1997

Quantification of malondialdehyde and 4-hydroxynonenal adducts to lysine residues in native and oxidized human low-density lipoprotein.

Malondialdehyde (MDA) and 4-hydroxynonenal (HNE) are major end-products of oxidation of polyunsaturated fatty acids, and are frequently measured as indicators of lipid peroxidation and oxidative stress in vivo. MDA forms Schiff-base adducts with lysine residues and cross-links proteins in vitro; HNE also reacts with lysines, primarily via a Michael addition reaction. We have developed methods using NaBH4 reduction to stabilize these adducts to conditions used for acid hydrolysis of protein, and have prepared reduced forms of lysine-MDA [3-(N epsilon-lysino)propan-1-ol (LM)], the lysine-MDA-lysine iminopropene cross-link [1,3-di(N epsilon-lysino)propane (LML)] and lysine-HNE [3-(N epsilon-lysino)-4-hydroxynonan-l-ol (LHNE)]. Gas chromatography/MS assays have been developed for quantification of the reduced compounds in protein. RNase incubated with MDA or HNE was used as a model for quantification of the adducts by gas chromatography/MS. There was excellent agreement between measurement of MDA bound to RNase as LM and LML, and as thiobarbituric acid-MDA adducts measured by HPLC; these adducts accounted for 70-80% of total lysine loss during the reaction with MDA. LM and LML (0.002-0.12 mmol/ mol of lysine) were also found in freshly isolated low-density lipoprotein (LDL) from healthy subjects. LHNE was measured in RNase treated with HNE, but was not detectable in native LDL. LM, LML and LHNE increased in concert with the formation of conjugated dienes during the copper-catalysed oxidation of LDL, but accounted for modification of < 1% of lysine residues in oxidized LDL. These results are the first report of direct chemical measurement of MDA and HNE adducts to lysine residues in LDL. LM, LML and LHNE should be useful as biomarkers of lipid peroxidative modification of protein and of oxidative stress in vitro and in vivo.

Aldehydes↗
PubMed1997

Lipoprotein glycation and its metabolic consequences.

Glycation of lipoproteins is implicated in the development of the macro- and microvascular complications of diabetes, atherosclerosis in general, and other disease processes including aging. Enhanced glycation may have direct effects, and may also amplify the effects of oxidative stress on lipoproteins. Most studies have examined the effects of glycation of LDL, particularly with respect to its atherogenicity. Other lipoproteins are more difficult to study because their several apolipoproteins, being of varying age, are not uniformly exposed to glucose. Inhibition of the combined stresses of glycation and oxidation towards lipoproteins may have beneficial effects on health.

Animals↗
PubMed1997

Hospitals and managed care: catching up with the networks.

Although the growth of managed care is having a significant impact on hospitals, organizational response to managed care remains fragmented. We conducted a survey of 83 hospitals nationwide that indicated that most hospitals now have at least one person devoted to managed care initiatives. These individuals, however, often spend most of their time on current issues, such as contracting with managed care organizations and physician relations. Concerns for the future, such as network development and marketing, although important, receive less immediate attention form these individuals. Hospital managed care executives must take a more proactive role in long range managed care planning by collaborating with managed care organizations and pharmaceutical companies.

Administrative Personnel↗
PubMed1997

Assessment of the anti-G straining maneuver (AGSM) skill performance and reinforcement program.

Initial high-G centrifuge training of USAF fast jet pilots was instituted in 1985. Also, since the mid-1980's, pilot awareness of G-induced loss of consciousness (G-LOC) has been enhanced by briefings, videotapes, and safety articles. Aircraft accidents caused by an improperly performed anti-G straining maneuver (AGSM), however, continue to occur. Deficiencies in the AGSM of pilots in flight have not been systematically studied. A test program to reinforce the proper performance of the AGSM in flight was initiated in the United States Air Forces Europe (USAFE) in 1993. Head-up display videotapes (HUD tapes) were recorded during flight and critiqued during debrief by flight leads for AGSM technique and continuity. Questionnaires were completed by F-16, F-15C, and F-15E pilots assigned to USAFE: 78 surveys were completed out of 110 distributed (71%). There were 57 pilots (73%) who reported one or more problems with their AGSM: 33 noted that the timing of their breathing was too quick (< 2 s cycle), 11 that their breathing was too slow (> 4 s), 9 that inhalation was too long, 18 occasionally did not "get the jump on the Gs," and 34 frequently or occasionally talked during +Gz exposures. Of the 105 reported deficiencies, 67 (64%) were mostly or completely corrected: 30/33 (91%) if the timing of breathing was too quick, 8/11 (73%) if too slow, 5/9 (56%) if inhalation too long, 12/18 (67%) "jump on the Gs," and 12/34 (35%) if they talked. This program was most successful in remediating timing problems with the AGSM.

Aerospace Medicine↗
PubMed1997

East meets West: a comparison of eastern block/western aeromedical practices.

Under the auspices of the European Command (EUCOM) Military-to-Military Exchange Program, the authors participated in 13 trips to visit aeromedical facilities of nine Eastern European nations (Albania, Belarus, Bulgaria, Czech Republic, Hungary, Lithuania, Poland, Romania, and Slovakia). In addition, eight of these Eastern European nations visited United States Air Force (USAF) aeromedical facilities. This article highlights the similarities and differences noted between the USAF and Eastern Europe in the practice of aerospace medicine. Flight surgeons from both Eastern Europe and the USAF address issues such as physiologic stresses of flight (acceleration, hypoxia, etc.) and lifestyle stresses (rest, diet, alcohol, cigarettes, etc.). Eastern European Flight Surgeons do not regularly fly. The Eastern European approach to medical standards and screening for aviation applicants is much stricter and more comprehensive than ours. Several of the nations visited had active research programs at their central aeromedical institute emphasizing aircrew selection and retention standards. With the exception of the Czech Republic, Eastern European nations did not routinely grant waivers for chronic medical conditions such as hypertension in aircrew. Soviet-built aircraft had many unique features such as an outside-in attitude indicator and an auto-recovery system.

Aerospace Medicine↗
PubMed1996

Mutations in copper-zinc superoxide dismutase that cause amyotrophic lateral sclerosis alter the zinc binding site and the redox behavior of the protein.

A series of mutant human and yeast copper-zinc superoxide dismutases has been prepared, with mutations corresponding to those found in familial amyotrophic lateral sclerosis (ALS; also known as Lou Gehrig's disease). These proteins have been characterized with respect to their metal-binding characteristics and their redox reactivities. Replacement of Zn2+ ion in the zinc sites of several of these proteins with either Cu2+ or Co2+ gave metal-substituted derivatives with spectroscopic properties different from those of the analogous derivative of the wild-type proteins, indicating that the geometries of binding of these metal ions to the zinc site were affected by the mutations. Several of the ALS-associated mutant copper-zinc superoxide dismutases were also found to be reduced by ascorbate at significantly greater rate than the wild-type proteins. We conclude that similar alterations in the properties of the zinc binding site can be caused by mutations scattered throughout the protein structure. This finding may help to explain what is perhaps the most perplexing question in copper-zinc superoxide dismutase-associated familial ALS-i.e., how such a diverse set of mutations can result in the same gain of function that causes the disease.

Amyotrophic Lateral Sclerosis↗
PubMed1996

The advanced glycation end product, Nepsilon-(carboxymethyl)lysine, is a product of both lipid peroxidation and glycoxidation reactions.

Nepsilon-(Carboxymethyl)lysine (CML) is an advanced glycation end product formed on protein by combined nonenzymatic glycation and oxidation (glycoxidation) reactions. We now report that CML is also formed during metal-catalyzed oxidation of polyunsaturated fatty acids in the presence of protein. During copper-catalyzed oxidation in vitro, the CML content of low density lipoprotein increased in concert with conjugated dienes but was independent of the presence of the Amadori compound, fructoselysine, on the protein. CML was also formed in a time-dependent manner in RNase incubated under aerobic conditions in phosphate buffer containing arachidonate or linoleate; only trace amounts of CML were formed from oleate. After 6 days of incubation the yield of CML in RNase from arachidonate was approximately 0.7 mmol/mol lysine compared with only 0.03 mmol/mol lysine for protein incubated under the same conditions with glucose. Glyoxal, a known precursor of CML, was also formed during incubation of RNase with arachidonate. These results suggest that lipid peroxidation, as well as glycoxidation, may be an important source of CML in tissue proteins in vivo and that CML may be a general marker of oxidative stress and long term damage to protein in aging, atherosclerosis, and diabetes.

Arachidonic Acid↗
PubMed1996

Lipoxidation products as biomarkers of oxidative damage to proteins during lipid peroxidation reactions.

Oxidative stress is implicated in the pathogenesis of numerous disease processes including diabetes mellitus, atherosclerosis, ischaemia reperfusion injury and rheumatoid arthritis. Chemical modification of amino acids in protein during lipid peroxidation results in the formation of lipoxidation products which may serve as indicators of oxidative stress in vivo. The focus of the studies described here was initially to identify chemical modifications of protein derived exclusively from lipids in order to assess the role of lipid peroxidative damage in the pathogenesis of disease. Malondialdehye (MDA) and 4-hydroxynonenal (HNE) are well characterized oxidation products of polyunsaturated fatty acids on low-density lipoprotein (LDL) and adducts of these compounds have been detected by immunological means in atherosclerotic plaque. Thus, we first developed gas chromatography-mass spectrometry assays for the Schiff base adduct of MDA to lysine, the lysine-MDA-lysine diimine cross-link and the Michael addition product of HNE to lysine. Using these assays, we showed that the concentrations of all three compounds increased significantly in LDL during metal-catalysed oxidation in vitro. The concentration of the advanced glycation end-product N epsilon-(carboxymethyl)lysine (CML) also increased during LDL oxidation, while that of its putative carbohydrate precursor the Amadori compound N epsilon-(1-deoxyfructose-1-yl)lysine did not change, demonstrating that CML is a marker of both glycoxidation and lipoxidation reactions. These results suggest that MDA and HNE adducts to lysine residues should serve as biomarkers of lipid modification resulting from lipid peroxidation reactions, while CML may serve as a biomarker of general oxidative stress resulting from both carbohydrate and lipid oxidation reactions.

Aldehydes↗
PubMed1996

Cancer incidence in United States Air Force aircrew, 1975-89.

UNLABELLED: We compared the cancer incidence of male United States Air Force (USAF) aircrew (342 cancers, 532,980.97 man-years) with non-flying Air Force officers (827 cancers, 1,084,370.08 man-years) between 1975-89. METHODS: Incident cancer cases for both aviators and non-flying officers were obtained from USAF hospitalization records. Age-adjusted standardized incidence ratios (SIR's) were calculated for aircrew using data from the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) program. Aviator age-adjusted cancer rate ratios were also obtained using non-flying officers as an internal comparison group. RESULTS: We observed statistically significant excesses of aircrew cancers for all sites, testis, and urinary bladder. All other aviator cancer classifications were not significantly different from the comparison cohort; most notably, cancers of the colon and rectum, skin (both malignant melanoma and non-epithelial), brain and nervous system, Hodgkin's Disease and leukemias. CONCLUSION: Previous studies of commercial pilots that demonstrated excesses of these cancers may have been biased by the use of external comparison groups. We used an internal comparison population to reduce selection bias, information bias and confounding. From these data we detected notable excess aircrew cancer risk for cancers of the testis, urinary bladder, and all sites combined.

Adult↗
PubMed1996

Neuroendocrine carcinoma of the larynx.

Neuroendocrine carcinomas (NEC) of the larynx are rare. The key to diagnosis is therefore an increased awareness of such lesions amongst otolaryngologists and pathologists. A precise histological diagnosis is crucial, as the management is different for each NEC sub-type. Advances in immunohistochemistry have been a great help in this respect. We report a typical case of large cell NEC (atypical carcinoid) and highlight the clinical pointers to the histological diagnosis.

Carcinoma, Neuroendocrine↗