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Biomedical subjects

T Lyons

Publications and source records attributed to T Lyons.

At least 19 recordsLinked to original sources

The copper transport protein Atox1 promotes neuronal survival.

Atox1, a copper transport protein, was recently identified as a copper-dependent suppressor of oxidative damage in yeast lacking superoxide dismutase. We have previously reported that Atox1 in the rat brain is primarily expressed in neurons, with the highest levels in distinct neuronal subtypes that are characterized by their high levels of metal, like copper, iron, and zinc. In this report, we have transfected the Atox1 gene into several neuronal cell lines to increase the endogenous level of Atox1 expression and have demonstrated that, under conditions of serum starvation and oxidative injury, the transfected neurons are significantly protected against this stress. This level of protection is comparable with the level of protection seen with copper/zinc superoxide dismutase and the anti-apoptotic gene bcl-2 that had been similarly transfected. Furthermore, neuronal cell lines transfected with a mutant Atox1 gene, where the copper binding domain has been modified to prevent metal binding, do not afford protection against serum starvation resulting in apoptosis. Therefore, Atox1 is a component of the cellular pathways used for protection against oxidative stress.

Amino Acid Sequence↗

Simulating ozone detoxification in the leaf apoplast through the direct reaction with ascorbate.

This paper presents a mathematical model which enables the semi-quantification of ozone (O3) detoxification, based upon the direct reaction of the pollutant with ascorbate (ASC) located in the aqueous matrix associated with the cell wall (i.e. the apoplast). The model describes the uptake of ozone into the leaf and its direct reaction with ASC, taking into consideration the regeneration of dehydroascorbic acid in the cytosol, the rate of replenishment of cell wall ASC and the distribution of ASC between sub-cellular compartments based upon the permeability of biomembranes to the neutral species, ascorbic acid and the pH of various sub-cellular compartments. The importance of various physico-chemical characteristics (e.g. stomatal conductance, mesophyll cell wall thickness and tortuosity, chloroplast volume, apoplast pH, ASC:O3 reaction stoichiometry) in mediating the flux of ozone to the plasmalemma is analysed. Model simulations, supported by experimental observations, suggest that the ASC concentration in the leaf apoplast is high enough to scavenge a significant proportion of the O3 taken up into the leaf interior, under environmentally relevant conditions. However, there is considerable variation between taxa in the potential degree of protection afforded by apoplastic ASC, emphasizing the need for an improved understanding of the reaction chemistry of O3 in the cell wall.

Ascorbic Acid↗

Proximal tibia--extensor mechanism composite allograft for revision TKA with chronic patellar tendon rupture.

Rupture of the patellar tendon following TKA is fortunately an uncommon complication with an incidence of 0.2-4% (Abril et al. 1995). Numerous options have been reported for treating this complication, including primary suture into a bone trough (Abril et al. 1995), autogenous tendon transfer (Cadambi and Engh 1992), and use of an artificial ligament (Fujikawa et al. 1994). Allograft patellar tendon has also been utilized either retaining the host patella and using a bone-tendon-bone graft or excising the host patella and using a quadriceps tendon-patella-patellar tendon-tibial tubercle graft (Emerson et al. 1990, Emerson et al. 1994, Zanotti et al. 1995, Booth et al. 1999). All of these techniques require structural integrity of the proximal tibia in the area of the tibial tubercle in order to attach the repair or graft to restore continuity of the extensor mechanism. When there is massive osteolysis and bone loss involving the proximal tibia, the situation becomes more complex and the previously described techniques are not advisable. In such cases, function can be obtained with a composite allograft of proximal tibia-patellar tendon-patella-quadriceps tendon. We describe a technique for dealing with this difficult clinical situation.

Arthroplasty, Replacement, Knee↗

Interaction of chemical defense clothing and high terrestrial altitudes on lift/carry and marksmanship performance.

BACKGROUND: The increased metabolic energy requirement imposed by a chemical defense uniform (CDU) and the lower maximal aerobic capacity associated with increased altitude should produce greater demands on the cardiopulmonary system during the performance of a given work task at increasing altitudes. We hypothesized that: a) relative to sea level, the decrements in physical work performance caused by ascending to high terrestrial altitudes would be greater in a CDU compared with a standard fatigue uniform (U.S. Army, BDU); b) the aversive subjective reactions to the CDU would be accentuated with increasing altitude; and c) that staging at moderate altitude, to induce acclimatization, would restore work performance at higher altitudes to sea level norms. METHODS: The physiological and subjective responses of 8 male soldiers to work (10-min lift-and-carry task and rifle marksmanship) were measured. Subjects wore the BDU and a CDU ensemble (U.S. Army, BDO) at sea level, intermediate (2743 m) and high (4,300 m) altitudes following rapid and staged (3 d at 1,830 m) ascents to the higher altitudes. RESULTS: Lift/carry task performance tended to be lower (p = 0.076) in the CDU vs. the BDU at altitude. The cardiopulmonary responses to the lift/carry task increased at altitude and were greater in the CDU. The subjects' perception of their ability to perform the lift/carry task at altitude was adversely impacted more in the CDU than the BDU. Rapid ascent to intermediate altitude degraded marksmanship in both uniforms. Following staged ascent, lift/carry task and marksmanship performance was restored to sea level norms. CONCLUSIONS: Personnel wearing CDU or equivalent protective clothing at intermediate to high terrestrial elevations should anticipate proportionally larger CDU-induced decrements of work performance and lower tolerance to working in a CDU than experienced near sea level. Staging at moderate altitude is an effective strategy for restoring work performance to sea level norms at higher altitudes.

Activities of Daily Living↗

Does ascorbate in the mesophyll cell walls form the first line of defence against ozone? Testing the concept using broad bean (Vicia faba L.).

Broad bean (Vicia faba L.) plants were exposed, in duplicate controlled environment chambers, to charcoal/Purafil-filtered air (CFA-grown plants) or to 75 nmol mol(-1) ozone (O(3)) for 7 h d(-1) (O(3)-grown plants) for 28 d, and then exposed to 150 nmol mol(-1) O(3 )for 8 h. The concentration of ascorbate (ASC) was determined in leaf extracellular washing fluid (apoplast) and in the residual leaf tissue (symplast) after 0, 4 and 8 h acute fumigation, and after a 16 h "recovery" period in CFA. Changes in stomatal conductance were measured in vivo in order to model pollutant uptake, while the light-saturated rate of CO(2) assimilation (A:(sat)) was recorded as an indicator of O(3)-induced intracellular damage. Measurements of A:(sat) revealed enhanced tolerance to 150 nmol mol(-1) O(3) in plants pre-exposed to the pollutant compared with equivalent plants grown in CFA, consistent with the observed reduction in pollutant uptake due to lower stomatal conductance. The concentration of ASC in the leaf apoplast (ASC(apo)) declined upon O(3)-treatment in both CFA- and O(3)-grown plants, consistent with the oxidation of ASC(apo) under O(3)-stress. Furthermore, the decline in ASC(apo) was reversible in O(3)-grown plants after a 16 h "recovery" period, but not in plants grown in CFA. No significant change in the level and/or redox state of ASC in the symplast (ASC(symp)) was observed in plants exposed to 150 nmol mol(-1) O(3), and there was no difference in the constitutive level of ASC(symp) between CFA- and O(3)-grown plants. Model calculations indicated that the reaction of O(3) with ASC(apo) in the leaves of Vicia faba is potentially sufficient to intercept a substantial proportion (30-40%) of the O(3)entering the plant under environmentally-relevant conditions. The potential role of apoplastic ASC in mediating the tolerance of leaves to O(3) is discussed.

Air Pollutants↗

Association of anti-Yo (type I) antibody with paraneoplastic cerebellar degeneration in the setting of transitional cell carcinoma of the bladder: detection of Yo antigen in tumor tissue and fall in antibody titers following tumor removal.

Anti-Yo (type I) autoantibodies reactive with Purkinje cell cytoplasmic antigens of 34 and 62 kd are found in the serum and cerebrospinal fluid of patients with paraneoplastic cerebellar degeneration associated with cancer of the ovary, uterus, adnexa, or breast. Anti-Yo antibody response is rarely associated with other tumors. Here, we present a patient who developed paraneoplastic cerebellar degeneration and anti-Yo antibody response in association with transitional cell carcinoma of the bladder. The presence of anti-Yo antibodies was confirmed by immunofluorescence assay and by Western blot analysis against both Purkinje cell lysates and the CDR62 fusion protein. Yo antigen was demonstrated in sections of the patient's tumor. Antibody titers fell after tumor removal. Transitional cell carcinoma should be considered in patients presenting with subacute cerebellar degeneration and anti-Yo antibody response in whom ovarian, adnexal, uterine, or breast cancer cannot be detected.

Autoantigens↗

Safety and efficacy of early extubation of elderly coronary artery bypass surgery patients.

OBJECTIVE: Early extubation and fast-track management protocols on younger, low-risk patients result in shorter hospital stays and decreased costs. The impact of such protocols on elderly patients undergoing coronary artery bypass graft (CABG) surgery is not presently known. DESIGN: A matched retrospective cohort study. SETTING: A university teaching hospital. PARTICIPANTS: Six hundred ninety-eight consecutive patients undergoing isolated CABG between January 1995 and September 1996. INTERVENTIONS: Three hundred seventy-seven patients underwent early extubation, defined as extubation within 8 hours of arrival in the intensive care unit. They were divided into groups of patients 70 years of age and younger (n = 263) and patients older than 70 years of age (n = 114). RESULTS: The mean length of stay (LOS) for all patients extubated within 8 hours or less was 5.5 days versus 8.4 days for patients who underwent later extubation (p < 0.0001). The percentage of patients undergoing early extubation was greater for the younger cohort (59% v 48%; p < 0.003) compared with the older cohort of patients. Analysis of demographics showed the older patients to have a greater incidence of peripheral vascular disease, congestive heart failure, and prior strokes (p < 0.05). Although the intensive care unit LOS was similar, postoperative LOS was 5.3 +/- 1.8 days for the younger patients versus 6.1 +/- 2.6 days for the older patients (p = 0.001). The overall surgical mortality rate was 2.6% (18/698), and there were no deaths among patients undergoing early extubation. Reintubation rate was negligible in both groups of patients. CONCLUSION: This study confirms the safety and efficacy of early extubation among elderly patients undergoing CABG. Elderly patients have more comorbid conditions, yet a significant number can be extubated early, with resultant shortened LOSs.

Adult↗

Transmission of two novel mutations in a pedigree with familial lecithin:cholesterol acyltransferase deficiency: structure-function relationships and studies in a compound heterozygous proband.

Two novel mutations were identified in a compound heterozygous male with lecithin:cholesterol acyltransferase (LCAT) deficiency. Exon sequence determination of the LCAT gene of the proband revealed two novel heterozygous mutations in exons one (C110T) and six (C991T) that predict non-conservative amino acid substitutions (Thr13Met and Pro307Ser, respectively). To assess the distinct functional impact of the separate mutant alleles, studies were conducted in the proband's 3-generation pedigree. The compound heterozygous proband had negligible HDL and severely reduced apolipoprotein A-I, LCAT mass, LCAT activity, and cholesterol esterification rate (CER). The proband's mother and two sisters were heterozygous for the Pro307Ser mutation and had low HDL, markedly reduced LCAT activity and CER, and the propensity for significant reductions in LCAT protein mass. The proband's father and two daughters were heterozygous for the Thr13Met mutation and also displayed low HDL, reduced LCAT activity and CER, and more modest decrements in LCAT mass. Mean LCAT specific activity was severely impaired in the compound heterozygous proband and was reduced by 50% in individuals heterozygous for either mutation, compared to wild type family members. It is also shown that the two mutations impair both catalytic activity and expression of the circulating protein.

Adult↗

Diabetes research in South Carolina: past, present, and future.

Medical investigators in South Carolina have been on the "cutting edge" of diabetes research for a number of decades. Despite this fact, our state ranks second in the nation in diabetes prevalence, and diabetes complications are more severe here than anywhere else. It is from the efforts of these investigators that our hope for a brighter future comes. Through a concerted effort toward prevention, improvements in care, and investigation of the pathophysiology of diabetes and its complications, researchers may reduce the substantial burden of diabetes in our state and throughout the world.

Diabetes Complications↗

Diabetes management: current diagnostic criteria, drug therapies, and state legislation.

The policies, standards, guidelines, and criteria that each member of the healthcare team uses to assist in the delivery of comprehensive healthcare are constantly being defined and redefined. This article has discussed many of those changes as they relate to diabetes management. The entire healthcare team must have a working knowledge of these changes so that they can continue to deliver the best possible care to patients with diabetes. Improvements in quality of life, decreases in mortality and morbidity, and subsequent declines in healthcare costs will benefit both individual patients and society. The profession of pharmacy has realized the need for additional education and training in managing the patient with diabetes. Many colleges of pharmacy, as well as companies in the pharmaceutical industry, are offering diabetes certification and diabetes disease management programs to pharmacists to enhance their ability to manage these patients (Lyons T, Gourley DR, unpublished data, 1997. Similar efforts in diabetes management have been made in other health professions as well, such as nursing.

Cost Control↗

Effects of erythrocyte infusion on VO2max at high altitude.

This study investigated whether autologous erythrocyte infusion would ameliorate the decrement in maximal O2 uptake (VO2max) experienced by lowlanders when they ascend to high altitude. VO2max was measured in 16 men (treadmill running) at sea level (SL) and on the 1st (HA1) and 9th (HA9) days of high-altitude (4,300 m) residence. After VO2max was measured at SL, subjects were divided into two matched groups (n = 8). Twenty-four hours before ascent to high altitude, the experimental group received a 700-ml infusion of autologous erythrocytes and saline (42% hematocrit), whereas the control group received only saline. The VO2max of erythrocyte-infused [54 +/- 1 (SE) ml.kg-1.min-1] and control subjects (52 +/- 2 ml.kg-1.min-1) did not differ at SL before infusion. The decrement in VO2max on HA1 did not differ between groups, averaging 26% overall, despite higher (P < 0.01) arterial hematocrit, hemoglobin concentration, and arterial O2 content in the erythrocyte-infused subjects. By HA9, there were no longer any differences in hematocrit, hemoglobin concentration, or arterial O2 content between groups. No change in VO2max occurred between HA1 and HA9 for either group. Thus, despite increasing arterial O2-carrying capacity, autologous erythrocyte infusion did not ameliorate the decrement in VO2max at 4,300-m altitude.

Acclimatization↗

Femoral shaft fractures treated by Ender nails using a trochanteric approach.

We describe the use of Ender nails for the internal fixation of femoral shaft fractures by a closed technique via the greater trochanter and report the treatment of 100 patients with 106 fractures, of which 88 were reviewed 12 months or more after operation. There was primary union in 85 fractures (96.6%) and significant angulation, rotation or leg length discrepancy in eight (9%). We discuss the principles of management which we have evolved.

Bone Nails↗