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Biomedical subjects

J P Loehr

Publications and source records attributed to J P Loehr.

10 recordsLinked to original sources
PubMed1993

Abnormal hepatic mitochondrial respiration and cytochrome C oxidase activity in rats with long-term copper overload.

BACKGROUND: Dietary copper overload in the rat is associated with morphological abnormalities and lipid peroxidation of hepatic mitochondria. This study was designed to determine if copper hepatotoxicity was associated with functional alterations in mitochondrial respiration in conjunction with lipid peroxidation. METHODS: Weanling male rats were pair-fed for 8 weeks on diets containing normal or high levels of copper in combination with sufficient vitamin E. Serum and liver samples were obtained, and hepatic mitochondria were isolated by differential centrifugation. RESULTS: Oxidant injury (decreased levels of hepatic glutathione and alpha tocopherol and increased levels of mitochondrial thiobarbituric acid-reacting substances) was present in the copper-overloaded rats. Serum aminotransferase levels correlated with concentrations of mitochondrial copper and thiobarbituric acid-reacting substances. Copper overload caused a decrease in state 3 respiration and the respiratory control ratio in hepatic mitochondria when several electron donors were used. Analysis of the oxidoreductase activities of the four mitochondrial electron transport protein complexes showed that complex IV (cytochrome C oxidase) activity was reduced by 60% in copper overload. CONCLUSIONS: Functional abnormalities of mitochondria accompany lipid peroxidation and the morphological alterations caused by copper overload, supporting the hypothesis that the mitochondrion is one of the major intracellular targets in copper hepatotoxicity.

Animals↗
PubMed1993

Cardiopulmonary function in men with sickle cell trait who reside at moderately high altitude.

Sickle cell trait has been associated with an unexplained increased risk of sudden death during military basic training. Previous studies of cardiopulmonary function in persons with sickle cell trait at sea level or after brief exposure to moderately high altitude have not shown significant abnormalities. To determine whether cardiopulmonary function is impaired in men with sickle cell trait who chronically reside at moderately high altitude, we prospectively studied 17 men with sickle cell trait and 25 men with normal hemoglobin. All subjects had resided at > or = 1609 m above sea level for at least 10 years. Resting pulmonary function and cardiopulmonary performance during exercise to exhaustion were evaluated. No statistically significant differences were observed between subjects with sickle cell trait and controls for any of the resting pulmonary function variables measured. All parameters of exercise performance were not statistically different between the groups. Increasing age was associated with a similar decrease in work capacity and oxygen consumption in both groups. Electrocardiogram findings were not statistically different between groups. We conclude that chronic exposure to moderately high altitude does not impair cardiopulmonary function in men with sickle cell trait.

Adult↗
PubMed1991

Tryptophan fluorescence in electron-transfer flavoprotein:ubiquinone oxidoreductase: fluorescence quenching by a brominated pseudosubstrate.

We have studied the intrinsic fluorescence of the 12 tryptophan residues of electron-transfer flavoprotein:ubiquinone oxidoreductase (ETF:QO). The fluorescence emission spectrum (lambda ex 295 nm) showed that the fluorescence is due to the tryptophan residues and that the contribution of the 22 tyrosine residues is minor. The emission maximum (lambda m 334 nm) and the bandwidth (delta lambda 1/2 56 nm) suggest that the tryptophans lie in hydrophobic environments in the oxidized protein. Further, these tryptophans are inaccessible to a range of ionic and nonionic collisional quenching agents, indicating that they are buried in the protein. Enzymatic or chemical reduction of ETF:QO results in a 5% increase in fluorescence with no change of lambda m or delta lambda 1/2. This change is reversible upon reoxidation and is likely to reflect a conformational change in the protein. The ubiquinone analogue Q0(CH2)10Br, a pseudosubstrate of ETF:QO (Km = 2.6 microM; kcat = 210 s-1), specifically quenches the fluorescence of one tryptophan residue (Kd = 1.6-3.2 microM) in equilibrium fluorescence titrations. The ubiquinone homologue UQ-2 (Km = 2 microM; kcat = 162 s-1) and the analogue Q0(CH2)10OH (Km = 2 microM; kcat = 132 s-1) do not quench tryptophan fluorescence; thus the brominated analogue acts as a static heavy atom quencher. We also describe a rapid purification for ETF:QO based on extraction of liver submitochondrial particles with Triton X-100 and three chromatographic steps, which results in yields 3 times higher than previously published methods.

Acrylamide↗
PubMed1991

Hemodynamic effects of ketamine, hypoxia and hyperoxia in children with surgically treated congenital heart disease residing greater than or equal to 1,200 meters above sea level.

Little data are available on the hemodynamic effects of premedications and anesthetic agents on infants and children. Ketamine is the most frequently used anesthetic agent for cardiac catheterization procedures in pediatric patients with congenital heart disease. Previous reports both suggest and deny ketamine's pulmonary vasoreactive effects. Since the advent of sophisticated noninvasive equipment, one of the few indications for cardiac catheterization is to obtain accurate pressure data. If ketamine alters pulmonary vascular resistance, it would negate the primary reason for the procedure. Because the patient population studied herein resides greater than or equal to 1,200 meters above sea level, concerns about pharmacologic effects on pulmonary vascular resistance are enhanced. Simultaneous pulmonary artery and aortic pressures, thermodilution cardiac outputs, and blood gases were measured in room air (16% oxygen) and with ketamine infusion in 14 patients at cardiac catheterization. Reaction to hypoxia identified 3 groups: normal, intermediate and hyperresponders. The normal responders had normal resistance ratios (0.11) in room air and had little resistance ratio response to hypoxia (+0.02), hyperoxia (-0.03) or ketamine (+0.01). The intermediate responders had a slightly higher but normal resistance ratio (0.20) in room air, and a moderate reaction to hypoxia (+0.13), hyperoxia (-0.08) and ketamine (+0.11). The hyperresponders had an elevated resistance ratio (0.42) in room air and a striking reaction to hypoxia (+0.65), hyperoxia (-0.17) and ketamine (+0.49). Hypoxia and ketamine have a greater effect on resistance ratio than hypoxia alone in patients with reactive pulmonary vascular beds. Ketamine should not be used in children undergoing procedures to establish operability based on pulmonary vascular resistance or pulmonary vascular reactivity.

Altitude↗
PubMed1990

Glutaric acidemia type II: heterogeneity of clinical and biochemical phenotypes.

We have examined 23 fibroblast lines from patients with neonatal and late onset glutaric acidemia type II and fibroblasts from four parents of these patients. Fifteen of these patients are previously unreported. Results of these investigations show deficiency of electron transfer flavoprotein or electron transfer flavoprotein-ubiquinone oxidoreductase activity in all of the patients' fibroblasts. Immunoblots indicate that the steady state levels of the antigens is very low or undetectable in most of the neonatal onset patients; however, cross-reacting antigen without electron transfer activity is observed in several glutaric acidemia type II fibroblast lines. Assay of parental lines confirm the autosomal transmission of deficiencies of proteins. Of particular interest is the clinical heterogeneity among these patients. Patients may present with an extrapyramidal movement disorder as observed in glutaric aciduria type I, without the typical organic aciduria typical of glutaric acidemia type II even in the presence of severe enzyme deficiency, or with renal cystic dysplasia accompanying electron transfer flavoprotein deficiency. Renal cystic dysplasia had previously been reported only in patients with electron transfer flavoprotein-ubiquinone oxidoreductase deficiency.

Cell Line↗
PubMed1989

Glutaric aciduria type II: review of the phenotype and report of an unusual glomerulopathy.

A male infant with glutaric aciduria II secondary to electron transfer flavoprotein: ubiquinone oxidoreductase deficiency is compared to previously reported cases of glutaric aciduria II. A common pattern of anomalies in patients with malformations (8/16) includes macrocephaly, large anterior fontanelle, high forehead, flat nasal bridge, telecanthus, and malformed ears. Abnormalities such as hypotonia, cerebral gliosis, heterotopias, hepatomegaly, hepatic periportal necrosis, polycystic kidneys, and genital defects in glutaric aciduria II are reminiscent of those in Zellweger syndrome, whereas elevations of glutaric, ethylmalonic, adipic, and isovaleric acids are quite distinctive. A unique ultrastructural alteration of the glomerular basement membrane was observed in the proposita. This manifestation may represent an early stage in renal cyst formation and provide a diagnostic criterion for glutaric aciduria II when enzyme studies are unavailable.

Abnormalities, Multiple↗
PubMed1987

Recent progress in understanding glutaric acidemias.

Glutaric acidemia, which is due to inherited deficiency of glutaryl-CoA dehydrogenase, is characterized clinically by progressive dystonia and dyskinesia in childhood, and pathologically by degeneration of the caudate and putamen. Results using newer imaging techniques (computer tomography and magnetic resonance image scanning) suggest that neurological involvement in this condition begins before birth, and that gliosis of the basal ganglia is a relatively late event. Glutaric acidemia type II is usually due to inherited deficiency of electron transfer flavoprotein (ETF) or ETF:ubiquinone oxidoreductase, but some patients with typical disease may have another, to date undefined, abnormality. There may also be a clinical phenotype of glutaric acidemia type II which, like glutaryl-CoA dehydrogenase deficiency, is characterized by a movement disorder and by degeneration of the basal ganglia.

Child, Preschool↗
PubMed1986

Aortoventriculoplasty in a five-month-old infant: an alternative approach to the treatment of critical aortic stenosis in infancy.

A newborn with critical aortic stenosis and anular hypoplasia was treated with an aortic valvotomy using inflow occlusion. Five months later, important valvular insufficiency and residual stenosis necessitated aortic valve replacement. An aortoventriculoplasty using a 19 mm St. Jude Medical Valve was successfully performed with a good hemodynamic response.

Angiography↗
PubMedDate not supplied

Aortic root dilatation and mitral valve prolapse in the fragile X syndrome.

Forty patients with fragile X [fra(X)] or Martin-Bell syndrome, confirmed by chromosome analysis, underwent full cardiac evaluation including physical examination, chest film, electrocardiography (ECG), and M-mode and 2-dimensional echocardiography. Thirty-four males and six females were studied. Although all patients were asymptomatic, seven males were found to have mild aortic root dilatation. All seven also had evidence of mitral valve prolapse. Twenty-two (55%) of the study patients had mitral valve prolapse with either a click or murmur heard on physical examination and confirmation by M-mode echocardiography. The frequency of mitral valve prolapse was the same in males and females, but 80% of males older than 18 years had mitral valve prolapse. These findings support the hypothesis of a connective tissue dysplasia in the fra(X) syndrome.

Adolescent↗