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Biomedical subjects

T J Lyons

Publications and source records attributed to T J Lyons.

At least 73 records · Page 4Linked to original sources
PubMed1993

Maillard reaction products and their relation to complications in insulin-dependent diabetes mellitus.

Glycation, oxidation, and browning of proteins have all been implicated in the development of diabetic complications. We measured the initial Amadori adduct, fructoselysine (FL); two Maillard products, N epsilon-(carboxymethyl) lysine (CML) and pentosidine; and fluorescence (excitation = 328 nm, emission = 378 nm) in skin collagen from 39 type 1 diabetic patients (aged 41.5 +/- 15.3 [17-73] yr; duration of diabetes 17.9 +/- 11.5 [0-46] yr, [mean +/- SD, range]). The measurements were related to the presence of background (n = 9) or proliferative (n = 16) retinopathy; early nephropathy (24-h albumin excretion rate [AER24] > or = 20 micrograms/min; n = 9); and limited joint mobility (LJM; n = 20). FL, CML, pentosidine, and fluorescence increased progressively across diabetic retinopathy (P < 0.05, P < 0.001, P < 0.05, P < 0.01, respectively). FL, CML, pentosidine, and fluorescence were also elevated in patients with early nephropathy (P < 0.05, P < 0.001, P < 0.01, P < 0.01, respectively). There was no association with LJM. Controlling for age, sex, and duration of diabetes using logistic regression, FL and CML were independently associated with retinopathy (FL odds ratio (OR) = 1.06, 95% confidence interval (CI) = 1.01-1.12, P < 0.05; CML OR = 6.77, 95% CI = 1.33-34.56, P < 0.05) and with early nephropathy (FL OR = 1.05, 95% CI = 1.01-1.10, P < 0.05; CML OR = 13.44, 95% CI = 2.00-93.30, P < 0.01). The associations between fluorescence and retinopathy and between pentosidine and nephropathy approached significance (P = 0.05). These data show that FL and Maillard products in skin correlate with functional abnormalities in other tissues and suggest that protein glycation and oxidation (glycoxidation) may be implicated in the development of diabetic retinopathy and early nephropathy.

Adolescent↗
PubMed1993

Aircrew fatigue during Desert Shield C-5 transport operations.

The metrics used to define U.S. Air Force crew rest and flight duty limitations were not designed to manage surge operations such as Operation Desert Shield. Desert Shield provided an opportunity to obtain inflight data on acute and cumulative fatigue and the effect of other stressors during over-the-shoulder observations on 24 C-5 airlift crew members. Findings emphasize how sleep history, recent duty day cycles, subjective fatigue, scheduling patterns, nutrition, and billeting facilities contribute to fatigue and lower levels of alertness. The results of this fairly insignificant observational study attempt to preserve some of the aeromedical lessons of Desert Shield. The flight surgeon authors integrate their experience to outline development of a fatigue management and alertness enhancement doctrine.

Aerospace Medicine↗
PubMed1993

New histological observations in spontaneously developing osteoarthritis in the STR/ORT mouse questioning its acceptability as a model of human osteoarthritis.

Naturally developing spontaneous osteoarthritis (OA) is seen in a number of small animals one of which is the STR/ORT mouse, an accepted model of human OA. A histological evaluation of the patello-femoral joints of 37 male STR/ORT mice has shown features that are inconsistent with the disease in human joints. These include the presence of a prominent acute and chronic synovial inflammatory infiltrate. Such findings call into question the proposed aetiology of the arthropathy in this strain of mouse and its acceptability as a model of human primary OA.

Acute Disease↗
PubMed1993

Falling out of bed: a relatively benign occurrence.

OBJECTIVE: To determine the likelihood of injuries occurring to infants and children who fall out of bed. METHODS: A review of hospital records where children were documented to have fallen from a crib or bed and where the children were immediately assessed and examined following the fall. PATIENTS: Two hundred seven children younger than 6 years of age. One hundred twenty-four falls were from cribs and 83 from beds. The heights of the falls were 25 inches from beds or 41 inches when the child climbed over the bed rails and then fell, and 32 inches from cribs or 54 inches for those who fell after climbing the crib rails. RESULTS: There were 29 superficial injuries such as contusions or minor lacerations. One simple skull fracture was noted incidentally on skull roentgenogram and there was one fractured clavicle. There were no serious, multiple, visceral, or life-threatening injuries. Calculation of the momentum of impact between the injured and noninjured showed no significant difference. CONCLUSIONS: Because falls from short distances are unlikely to produce serious injury, the reliability of the history should be questioned when a child has significant injuries said to have resulted from a short fall.

Accidental Falls↗
PubMed1992

Lipoprotein glycation and its metabolic consequences.

In people with diabetes, glycation of apolipoproteins correlates with other indices of recent glycemic control, including HbA1. For several reasons, increased glycation of apolipoproteins may play a role in the accelerated development of atherosclerosis in diabetic patients. Recognition of glycated LDL by the classical LDL receptor is impaired, whereas its uptake by human monocyte-macrophages is enhanced. These alterations may contribute to hyperlipidemia and accelerated foam-cell formation, respectively. Glycation of LDL also enhances its capacity to stimulate platelet aggregation. The uptake of VLDL from diabetic patients by human monocyte-macrophages is enhanced. This enhancement may be due, at least in part, to increased glycation of its lipoproteins. Glycation of HDL impairs its recognition by cells and reduces its effectiveness in reverse cholesterol transport. Glycation of apolipoproteins may also generate free radicals, increasing oxidative damage to the apolipoproteins themselves, the lipids in the particle core, and any neighboring macromolecules. This effect may be most significant in extravasated lipoproteins. In these, increased glycation promotes covalent binding to vascular structural proteins, and oxidative reactions may cause direct damage to the vessel wall. Glycoxidation, or browning, of sequestered lipoproteins may further enhance their atherogenicity. Finally, glycated or glycoxidized lipoproteins may be immunogenic, and lipoprotein-immune complexes are potent stimulators of foam-cell formation.

Diabetes Mellitus↗
PubMed1992

Women in the fast jet cockpit--aeromedical considerations.

Historically, women have demonstrated the capacity to be successful aviators. A review of the scientific literature between 1966 and 1991 pertinent to the role of women in military aviation revealed only minor differences of questionable operational significance between men and women. Women may be more susceptible to motion sickness, radiation, and decompression sickness than men, but may be more resistant to cold water immersion and altitude sickness. Although men are on the average, larger, stronger, and more aerobically fit than women, there are large variations within each sex and a large overlap between the sexes. Gender differences in work performance, G tolerance, heat stress, and injury rate disappear when allowance is made for size, strength, and fitness. Aeromedical selection criteria can, thus, address individual characteristics without reference to gender. The possibility of fetal damage in the early stages of pregnancy (before diagnosis) appears to be perhaps the biggest single medical concern in allowing women access to all aviation and space careers.

Aerospace Medicine↗
PubMed1992

G-induced loss of consciousness accidents: USAF experience 1982-1990.

Discussion of acceleration protection measures should be based on analysis of relevant accident data, including determination of high risk aircraft, G profiles, and pilot descriptions. There were 18 accidents (14 fatalities) attributed to G-induced loss of consciousness (G-LOC) in the United States Air Force (USAF) from 1982 through 1990. All 18 accidents occurred during single crewmember sorties, for an average rate of 2.1 per million single-seat flying hours (pmfh). The average G-LOC accident rate for 1982-4 was 4.0 pmfh, decreasing significantly to 1.3 pmfh for 1985-90. This decrease is associated with the USAF initiation of an anti-G-LOC training program. We reviewed accident records for G-LOC cofactor data and compared them to normal data for USAF pilots for age, height, weight, systolic and diastolic blood pressures, heart rate, total flying time, and aircraft-specific flying hours. Only for systolic blood pressure (higher) and aircraft-specific flying hours (shorter) were the mishap pilots significantly different from other USAF pilots. We found no evidence to support weight training vs. aerobic training, missed meals, or heat in causing G-LOC accidents. Thus the mishap pilots appeared to be a representative cross section of USAF pilots with respect to personal variables. More significant factors appeared to be G duration, G magnitude, use of G trousers, and experience in assigned aircraft.

Accidents, Aviation↗
PubMed1991

Age-dependent accumulation of N epsilon-(carboxymethyl)lysine and N epsilon-(carboxymethyl)hydroxylysine in human skin collagen.

N epsilon-(Carboxymethyl)lysine (CML) is formed on oxidative cleavage of carbohydrate adducts to lysine residues in glycated proteins in vitro [Ahmed et al. (1988) J. Biol. Chem. 263, 8816-8821; Dunn et al. (1990) Biochemistry 29, 10964-10970]. We have shown that, in human lens proteins in vivo, the concentration of fructose-lysine (FL), the Amadori adduct of glucose to lysine, is constant with age, while the concentration of the oxidation product, CML, increases significantly with age [Dunn et al. (1989) Biochemistry 28, 9464-9468]. In this work we extend our studies to the analysis of human skin collagen. The extent of glycation of insoluble skin collagen was greater than that of lens proteins (4-6 mmol of FL/mol of lysine in collagen versus 1-2 mmol of FL/mol of lysine in lens proteins), consistent with the lower concentration of glucose in lens, compared to plasma. In contrast to lens, there was a slight but significant age-dependent increase in glycation of skin collagen, 33% between ages 20 and 80. As in lens protein, CML, present at only trace levels in neonatal collagen, increased significantly with age, although the amount of CML in collagen at 80 years of age, approximately 1.5 mmol of CML/mol of lysine, was less than that found in lens protein, approximately 7 mmol of CML/mol of lysine. The concentration of N epsilon-(carboxymethyl)hydroxylysine (CMhL), the product of oxidation of glycated hydroxylysine, also increased with age in collagen, in parallel with the increase in CML, from trace levels at infancy to approximately 5 mmol of CMhL/mol of hydroxylysine at age 80.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1991

The Maillard reaction in vivo.

The Maillard or browning reaction between reducing sugars and protein contributes to the chemical deterioration and loss of nutritional value of proteins during food processing and storage. This article presents and discusses evidence that the Maillard reaction is also involved in the chemical aging of long-lived proteins in human tissues. While the concentration of the Amadori adduct of glucose to lens protein and skin collagen is relatively constant with age, products of sequential glycation and oxidation of protein, termed glycoxidation products, accumulate in these long-lived proteins with advancing age and at an accelerated rate in diabetes. Among these products are the chemically modified amino acids, N epsilon-(carboxymethyl)lysine (CML), N epsilon-(carboxymethyl)hydroxylysine (CMhL), and the fluorescent crosslink, pentosidine. While these glycoxidation products are present at only trace levels in tissue proteins, there is strong evidence for the presence of other browning products which remain to be characterized. Mechanisms for detoxifying reactive intermediates in the Maillard reaction and catabolism of extensively browned proteins are also discussed, along with recent approaches for therapeutic modulation of advanced stages of the Maillard reaction.

Aging↗
PubMed1991

Decrease in skin collagen glycation with improved glycemic control in patients with insulin-dependent diabetes mellitus.

Glycation, oxidation, and nonenzymatic browning of protein have all been implicated in the development of diabetic complications. The initial product of glycation of protein, fructoselysine (FL), undergoes further reactions, yielding a complex mixture of browning products, including the fluorescent lysine-arginine cross-link, pentosidine. Alternatively, FL may be cleaved oxidatively to form N(epsilon)-(carboxymethyl)lysine (CML), while glycated hydroxylysine, an amino-acid unique to collagen, may yield N(epsilon)-(carboxymethyl)hydroxylysine (CMhL). We have measured FL, pentosidine, fluorescence (excitation = 328 nm, emission = 378 nm), CML, and CMhL in insoluble skin collagen from 14 insulin-dependent diabetic patients before and after a 4-mo period of intensive therapy to improve glycemic control. Mean home blood glucose fell from 8.7 +/- 2.5 (mean +/- 1 SD) to 6.8 +/- 1.4 mM (P less than 0.005), and mean glycated hemoglobin (HbA1) from 11.6 +/- 2.3% to 8.3 +/- 1.1% (P less than 0.001). These changes were accompanied by a significant decrease in glycation of skin collagen, from 13.2 +/- 4.3 to 10.6 +/- 2.3 mmol FL/mol lysine (P less than 0.002). However, levels of browning and oxidation products (pentosidine, CML, and CMhL) and fluorescence were unchanged. These results show that the glycation of long-lived proteins can be decreased by improved glycemic control, but suggest that once cumulative damage to collagen by browning and oxidation reactions has occurred, it may not be readily reversed. Thus, in diabetic patients, institution and maintenance of good glycemic control at any time could potentially limit the extent of subsequent long-term damage to proteins by glycation and oxidation reactions.

Arginine↗
PubMed1991

Effect of diabetes and aging on carboxymethyllysine levels in human urine.

Carboxymethyllysine (CML) has been identified as a modified amino acid that accumulates with age in human lens proteins and collagen. CML may be formed by oxidation of fructoselysine (FL), the Amadori adduct formed on nonenzymatic glycosylation of lysine residues in protein, or by reaction of ascorbate with protein under autoxidizing conditions. We proposed that measurements of tissue and urinary CML may be useful as indices of oxidative stress or damage to proteins in vivo. To determine the extent to which oxidation of nonenzymatically glycosylated proteins contributes to urinary CML, we measured the urinary concentrations of FL and CML in diabetic (n = 26) and control (n = 28) patients. The urinary concentration of FL correlated strongly with HbA1 measurements and was significantly higher in diabetic compared with control samples (9.2 +/- 6.5 and 4.0 +/- 2.8 micrograms/mg creatinine, respectively; P less than 0.0001). There was also a strong correlation between the concentrations of CML and FL in both diabetic and control urine (r = 0.67, P less than 0.0001) but only a weakly significant increase in the CML concentration in diabetic compared with control urine (1.2 +/- 0.5 and 1.0 +/- 0.3 micrograms/mg creatinine, respectively; P = 0.05). The molar ratio of CML to FL was significantly lower in diabetic compared with control patients (0.25 +/- 0.12 and 0.43 +/- 0.16, respectively; P less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Role of glycation in modification of lens crystallins in diabetic and nondiabetic senile cataracts.

To assess the significance of glycation, nonenzymatic browning, and oxidation of lens crystallins in cataract formation in elderly diabetic patients, we measured three distinct products of glycation, browning, and oxidation reactions in cataractous lens crystallins from 29 diabetic patients (mean +/- SD age 72.8 +/- 8.8 yr) and 24 nondiabetic patients (age 73.5 +/- 8.3 yr). Compounds measured included 1) fructoselysine (FL), the first stable product of glycation; 2) pentosidine, a fluorescent, carbohydrate-derived protein cross-link between lysine and arginine residues formed during nonenzymatic browning; and 3) N epsilon-(carboxymethyl)lysine (CML), a product of autoxidation of sugar adducts to protein. In diabetic compared with nondiabetic patients, there were significant increases (P less than 0.001) in HbA1 (10.2 +/- 3.1 vs. 7.1 +/- 0.7%), FL (7.6 +/- 5.4 vs. 1.7 +/- 1.2 mmol/mol lysine), and pentosidine (6.3 +/- 2.8 vs. 3.8 +/- 1.9 mumol/mol lysine). The disproportionate elevation of FL compared with HbA1 suggests a breakdown in the lens barrier to glucose in diabetes, whereas the increase in pentosidine is indicative of accelerated nonenzymatic browning of diabetic lens crystallins. CML levels were similar in the two groups (7.1 +/- 2.4 vs. 6.8 +/- 3.0 mmol/mol lysine), providing no evidence for increased oxidative stress in the diabetic cataract. Thus, although the modification of lens crystallins by autoxidation reactions was not increased in diabetes, the increase in glycation and nonenzymatic browning suggests that these processes may acclerate the development of cataracts in diabetic patients.

Aged↗
PubMed1991

Modafinil: the unique properties of a new stimulant.

Modafinil, a novel stimulant which has several remarkable features that distinguish it from other stimulants, has been developed by Lafon, a French pharmaceutical company. Unlike the amphetamines, for example, modafinil is reported to have minimal peripheral side effects at therapeutic doses. It also appears to have a low abuse potential, does not interfere with normal sleep, and does not seem to produce tolerance. It improves vigilance especially in sleep-deprived subjects. It has been used clinically for up to 3 years in the treatment of narcolepsy and idiopathic hypersomnia. It could be an ideal replacement for amphetamine in short-term operations in which fatigue might threaten the successful completion of a mission. We recommend that military laboratories experienced in studying sustained performance include modafinil or perhaps a more selective alpha 1 receptor agonist in their investigations.

Animals↗
PubMed1991

Medical causes of in-flight incapacitation: USAF experience 1978-1987.

In-flight incapacitation of a fully trained crewmember due to a serious underlying medical condition is a rather infrequent event. In order to delineate the extent and nature of the incapacitation problem we reviewed the data base at the Air Force Safety and Inspection Center for all incidents coded for incapacitation, preexisting disease, or other acute illnesses occurring during the 10 years between 1978 and 1987. During this period there were 23 in-flight incidents of incapacitation due to significant underlying medical conditions. In 11 of the incidents the incapacitation resulted in a loss of consciousness. Neurologic conditions were the most frequent cause followed by cardiovascular conditions. We calculated a rate of incapacitation as 0.19 per million aircrew flying hours.

Adult↗
PubMed1991

A test of thumb and index finger control in overcoming a visual analogue of the giant hand illusion.

Anecdotal evidence suggests that a thumb and index finger grip might facilitate recovery from the manifestation of spatial disorientation known as the giant hand phenomenon. Sixteen pilots volunteered as subjects in an experiment that compared the effectiveness of the thumb and index finger versus the whole hand technique to overcome a visually-induced analogue of the giant hand phenomenon. Thumb and index finger control produced greater stability overall, but did not overcome the specific tracking bias induced by a background visual roll stimulus. Various hypotheses are discussed as to why the thumb and index finger technique was ineffective in the present instance.

Adult↗