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Biomedical subjects

M Phelps

Publications and source records attributed to M Phelps.

At least 19 recordsLinked to original sources
PubMed1992

Detection of coronary artery disease with positron emission tomography and rubidium 82.

Myocardial blood flow was evaluated in 31 subjects with not only visual but also, for the first time, circumferential profile analysis of rubidium 82 (82Rb) images acquired with positron emission tomography. Fifteen were control subjects and 16 subjects had significant coronary artery disease, defined as 50% or greater diameter stenosis in a major coronary artery or a first-order branch. Simultaneous 82Rb images at three myocardial levels were obtained before and after intravenous dipyridamole plus handgrip stress. In patients with significant coronary artery disease, visual analysis correctly identified significant disease in 26 (76%) of 34 arteries and its absence in 12 (86%) of 14 normal arteries. According to circumferential profile analysis, these numbers were 91% and 86%, respectively. Thus circumferential analysis of 82Rb images, obtained before and after intravenous dipyridamole plus handgrip stress, yielded improved sensitivity and comparable specificity compared with visual analysis.

Coronary Disease↗
PubMed1991

Late onset Krabbe's leukodystrophy: a report of four cases.

Four cases of late-onset Krabbe's leukodystrophy had varying clinical features. One sibling became wheelchair-bound while another leads an active working life. The computed tomography (CT) scan of a third patient showed occipital demyelination with contrast enhancement identical to that seen in an adrenoleucodystrophy. The fourth was the only patient with peripheral neuropathy. All patients had enzyme activity comparable to the classic infantile-onset form.

Adolescent↗
PubMed1989

Sustained nonoxidative glucose utilization and depletion of glycogen in reperfused canine myocardium.

Ischemically injured reperfused myocardium is characterized by increased 18F-fluorodeoxyglucose uptake as demonstrated by positron emission tomography. To elucidate the metabolic fate of exogenous glucose entering reperfused myocardium, D-[6-14C] glucose and L-[U-13C] lactate were used to determine glucose uptake, glucose oxidation and the contribution of exogenous glucose to lactate production. The pathologic model under investigation consisted of a 3 h balloon occlusion of the left anterior descending coronary artery followed by 24 h of reperfusion in canine myocardium. The extent and severity of myocardial injury after the ischemia and reperfusion were assessed by histochemical evaluation (triphenyltetrazolium chloride and periodic acid-Schiff stains). Thirteen intervention and four control dogs were studied. The glucose uptake in the occluded/reperfused area was significantly enhanced compared with that in control dogs (0.40 +/- 0.14 versus 0.15 +/- 0.10 mumol/ml, respectively). In addition, a significantly greater portion of the glucose extracted immediately entered glycolysis in the intervention group (75%) than in the control dogs (33%). The activity of the nonoxidative glycolytic pathway was markedly increased in the ischemically injured reperfused area, as evidenced by the four times greater lactate release in this area compared with the control value. The dual carbon-labeled isotopes showed that 57% of the exogenous glucose entering glycolysis was being converted to lactate. Exogenous glucose contributed to greater than 90% of the observed lactate production. This finding was confirmed by the histochemical finding of sustained glycogen depletion in the occlusion/reperfusion area. The average area of glycogen depletion (37%) significantly exceeded the average area of necrosis (17%). These data demonstrate enhanced and sustained activity of the nonoxidative glycolytic pathway after a prolonged occlusion with reperfusion in canine myocardium. Because glycogen stores remain depleted, exogenous glucose becomes an important myocardial substrate under these pathologic conditions.

Animals↗
PubMed1988

The plasma binding protein for vitamin D is a site of discrimination against vitamin D-2 compounds by the chick.

The binding of 25-hydroxy-[26,27-3H]vitamin D-3 and 25-hydroxy-[26,27-3H]vitamin D-2 to the vitamin D binding protein in the plasma of both rats and chicks has been studied. In the case of rats, sucrose density gradient analysis, competitive displacement, and Scatchard analysis demonstrate that 25-hydroxyvitamin D-3 and 25-hydroxyvitamin D-2 are bound equally well to the vitamin D binding protein. In contrast, 25-hydroxyvitamin D-2 is poorly bound, while 25-hydroxyvitamin D-3 is tightly bound to the vitamin D binding protein in chick plasma. On the other hand, the chick intestinal receptor binds 1,25-dihydroxyvitamin D-2 and 1,25-dihydroxyvitamin D-3 equally well with a KD of 7.10(-11) M for both compounds. These results strongly suggest that the failure of the plasma transport protein in chicks to bind the vitamin D-2 compounds may be responsible for their relative ineffectiveness in these animals.

25-Hydroxyvitamin D 2↗
PubMed1988

Cerebral correlates of depressed behavior in rats, visualized using 14C-2-deoxyglucose autoradiography.

14C-2-Deoxyglucose (2DG) was used to investigate changes in the rate of cerebral metabolism in 3 rat models of depressed behavior. The models had already been established in the literature and were induced by injections of alpha-methyl-para-tyrosine, withdrawal from chronic amphetamine, or stress. We verified that exploratory behaviors were depressed in each model and that an antidepressant drug, tranylcypromine, prevented the depressed behavior in each model. 2DG studies revealed that the rate of regional glucose metabolism was elevated bilaterally in the lateral habenula of each of the 3 models. Regional metabolic rates were reduced in each model in the dorsal medial prefrontal cortex, anterior ventral nucleus of the thalamus, and inferior colliculus. Forebrain global metabolic rates were also reduced in each of the models. Tranylcypromine prevented the elevated rate of lateral habenula metabolism seen in each of the models alone but did not significantly affect the rates of global metabolism. Our findings of identical metabolic changes in each of the models indicate that these changes are not idiosyncratic to a particular model; rather, they correlate with a generalizable state of depressed exploratory behavior in rats.

Amphetamine↗
PubMed1987

Synthesis of 25-hydroxy-[26,27-3H]vitamin D2, 1,25-dihydroxy-[26,27-3H]vitamin D2 and their (24R)-epimers.

Synthesis of a C-24-epimeric mixture of 25-hydroxy-[26,27-3H]vitamin D2 and a C-24-epimeric mixture of 1,25-dihydroxy-[26,27-3H]vitamin D2 by the Grignard reaction of the corresponding 25-keto-27-nor-vitamin D2 and 1 alpha-acetoxy-25-keto-27-nor-vitamin D3 with tritiated methyl magnesium bromide is described. Separation of epimers by high-performance liquid chromatography afforded pure radiolabeled vitamins of high specific activity (80 Ci/mmol). The identities and radiochemical purities of 25-hydroxy-[26,27-3H[vitamin D2 and 1,25-dihydroxy-[26,27-3H]vitamin D2 D2 were established by cochromatography with synthetic 25-hydroxyvitamin D2 or 1,25-dihydroxyvitamin D2. Biological activity of 25-hydroxy-[26,27-3H]vitamin D2 was demonstrated by its binding to the rat plasma binding protein for vitamin D compounds, and by its in vitro conversion to 1,25-dihydroxy-[26,27-3H]vitamin D2 by kidney homogenate prepared from vitamin D-deficient chickens. The biological activity of 1,25-dihydroxy-[26,27-3H]vitamin D2 was demonstrated by its binding to the chick intestinal receptor for 1,25-dihydroxyvitamin D3.

25-Hydroxyvitamin D 2↗
PubMed1986

Assay and properties of rat yolk sac 25-hydroxyvitamin D3 1 alpha-hydroxylase.

An in vitro assay has been developed for the rat yolk sac 25-hydroxyvitamin D3 1 alpha-hydroxylase (1 alpha-hydroxylase). The subcellular location and some properties of the enzyme are described. 1,25-Dihydroxyvitamin D3 produced from incubations of yolk sac homogenates was extracted, purified by Sephadex LH-20 chromatography and straight- and reverse-phase high-performance liquid chromatography (HPLC), and measured by a competitive binding assay using chick intestinal receptor. The reaction is linear with time for up to 45 min at a substrate concentration of 80 microM and 4-6 mg/mL microsomal protein. The enzyme, located in the microsomes, requires molecular oxygen and NADPH. Metyrapone (1 X 10(-3) M) was found to inhibit 1-hydroxylation, but a 90% carbon monoxide-10% oxygen atmosphere did not, leaving open the question of involvement of cytochrome P-450. Diphenyl-p-phenylenediamine, a lipid peroxidase inhibitor, inhibited 1 alpha-hydroxylation.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1986

Reversibility of cardiac wall-motion abnormalities predicted by positron tomography.

Positron emission tomography (PET) can be used with nitrogen-13-ammonia (13NH3) to estimate regional myocardial blood flow, and with fluorine-18-deoxyglucose (18FDG) to measure exogenous glucose uptake by the myocardium. We used PET to predict whether preoperative abnormalities in left ventricular wall motion in 17 patients who underwent coronary-artery bypass surgery were reversible. The abnormalities were quantified by radionuclide or contrast angiography or both, before and after grafting. PET images were obtained preoperatively. Abnormal wall motion in regions in which PET images showed preserved glucose uptake was predicted to be reversible, whereas abnormal motion in regions with depressed glucose uptake was predicted to be irreversible. According to these criteria, abnormal contraction in 35 of 41 segments was correctly predicted to be reversible (85 percent predictive accuracy), and abnormal contraction in 4 of 26 regions was correctly predicted to be irreversible (92 percent predictive accuracy). In contrast, electrocardiograms showing pathological Q waves in the region of asynergy predicted irreversibility in only 43 percent of regions. We conclude that PET imaging with 13NH3 to assess blood flow and 18FDG to assess the metabolic viability of the myocardium is an accurate method of predicting potential reversibility of wall-motion abnormalities after surgical revascularization.

Ammonia↗
PubMed1986

Magnetic resonance imaging in intractable partial epilepsy: correlative studies.

A study was performed evaluating magnetic resonance imaging (MRI) in 35 patients with intractable complex partial seizures in whom computed tomographic (CT) scans showed no focal abnormalities. These results were correlated with positron emission tomography evaluation (PET), the electroencephalographic ictal onset, and findings during pathological examination. Seven patients had structural lesions that were epileptogenic, detected by MRI; the lesions were tuberous sclerosis, astrocytomas, or hamartomas. Three of these 7 patients underwent PET scanning, which was normal in all. Of 18 patients with mesial temporal sclerosis, 10 were shown by PET to have temporal lobe hypometabolism, though all 18 had normal MRI findings. The results indicate that MRI contributes information to that provided by CT and PET, by detecting nonsclerotic epileptogenic lesions of the temporal lobe.

Astrocytoma↗
PubMed1986

An outbreak of candidiasis in a special care baby unit: the use of a resistogram typing method.

An outbreak of candida infections involving 12 neonates in a special care baby unit is reported. An investigation of colonization of all the babies in the unit was made together with the sampling of the environment and hands of staff. Resistogram typing of isolates indicated the presence of several strains with probable cross-infection. Transmission was possibly by the hands of staff, but multiple antibiotic therapy may have played a role in the increased incidence of infection in the unit.

Candida albicans↗
PubMed1985

Metabolism and pharmacokinetics of 24,25-dihydroxyvitamin D3 in the vitamin D3-replete rat.

The time course of in vivo metabolism of 24,25-dihydroxyvitamin D3 in rats has been examined. Several tissues were surveyed in an effort to discover new metabolites of 24,25-dihydroxyvitamin D3 and to estimate the concentrations of previously identified metabolites. Rapidly growing male rats were dosed with 24,25-dihydroxyvitamin D3 orally until plasma concentrations of 24,25-dihydroxyvitamin D3 were at steady state. 24,25-Dihydroxyvitamin [3-3H]D3 was then administered. At 10 min and 1, 6, 15, 24, 96, and 192 h after dosing, the animals were killed, and plasma, liver, intestine, and bones were analyzed with a newly developed gradient straight-phase high performance liquid chromatography system. The high performance liquid chromatography system is capable of base-line resolution of most of the major vitamin D metabolites. 24,25-Dihydroxyvitamin D3 clearance from plasma, liver, and kidney but not intestine followed a two-compartment model. 24,25-Dihydroxyvitamin D3 disappeared from plasma with a half-life of 0.55 h (fast phase) and 73.8 h (slow phase). Only two lipid-soluble metabolites of 24,25-dihydroxyvitamin D3 were detected: 24-oxo-25-hydroxyvitamin D3 and 1,24,25-trihydroxyvitamin D3. These compounds circulate at very low concentrations in the plasma (50 pg/ml of plasma).

24,25-Dihydroxyvitamin D 3↗
PubMed1985

Elevated serum calcitriol concentrations do not fall in response to hyperphosphatemia in familial tumoral calcinosis.

Five affected members in two branches of a Druze Arab kindred presented with calcified deposits in or about the hips and knees, indicating the diagnosis of tumoral calcinosis. Serum vitamin D metabolite concentrations, immunoreactive parathyroid hormone, and the tubular reabsorption of phosphate were measured in three affected siblings, as well as in their parents and an unaffected sibling. Normocalcemia and hyperphosphatemia with an elevated tubular maximum for phosphate per glomerular filtration rate were found in the affected patients. Levels of serum immunoreactive parathyroid hormone were normal, and the calcitriol value (1,25-dihydroxyvitamin D) was normal or elevated in the three affected patients. A trial of a low-phosphorus diet and oral aluminum hydroxide gel did not lower serum phosphate levels or improve the calcified deposits. These findings suggest that serum calcitriol values do not decline in response to hyperphosphatemia in tumoral calcinosis and that hyperphosphatemia with elevated tubular reabsorption of phosphate is a constant feature of this disorder because the kidney fails to excrete the increased filtered load of phosphate.

Adult↗
PubMed1984

Renal tubular acidosis does not alter circulating values of calcitriol.

In 10 patients with renal tubular acidosis, seven with type I and three with Fanconi syndrome, simultaneous measurements of vitamin D metabolites and electrolytes were made. No marked abnormalities of calcidiol2, calcidiol3, 24,25(OH)2D, or calcitriol were found in these patients, whose mean serum HCO3 was 18 +/- 3 mM/L (SD). Further, no relationship between serum HCO3 and calcitriol could be found. These results suggest that either vitamin D deficiency may be required before any alterations in the production of calcitriol are seen, or that the effects of acidosis in animals may not be reflected in humans. Further, it appears less likely that the bone disease found in renal tubular acidosis is related to abnormalities in vitamin D metabolism resulting from systemic acidosis, but that bone disease is more likely related to the acidosis and hypercalcuria prevalent in this disorder.

Acidosis, Renal Tubular↗
PubMed1984

Multiple-radionuclide autoradiography in evaluation of cerebral function.

We have developed the mathematical model and experimental technique for quantitative simultaneous multiple-radionuclide autoradiography. The technique is an extension of previously described dual-tracer methods and offers the advantage of a general approach in which any two or more radionuclides with different half-lives can be used to measure multiple parameters of cerebral function. The model allows the selection of nuclide doses and exposure times to balance cross-contamination of the multiple images with nuclide requirements. The technique was validated with homogeneous tissue sections containing combinations of 123I, 124I , 131I, 18F, 99mTc , 68Ga, and 14C, and then used in qualitative and quantitative investigations of interrelationships of local cerebral blood flow, glucose metabolism, and protein synthesis in normal and several pathological conditions in rats.

Animals↗
PubMed1983

Structural teratogenicity evaluation of methyl chloride in rats and mice after inhalation exposure.

One hundred bred Fischer-344 female rats were exposed daily for 6 hours to atmospheres containing 0, 100, 500, or 1,500 ppm methyl chloride, 25 females per exposure concentration, from gestation day (gd) 7 through gd 19. On gd 20, the females were sacrificed for evaluation of maternal reproductive and fetal parameters. Maternal and fetal toxicity was apparent at the highest exposure concentration. There were no methyl chloride-induced external, skeletal, or visceral abnormalities seen in the fetuses. One hundred thirty-two C57BL/6 female mice bred to C3H males to produce B6C3F1 offspring were exposed daily for 6 hours to atmospheres containing 0, 100, 500, or 1,500 ppm methyl chloride, 33 females per exposure concentration, from gd 6 through gd 17. Exposure to the entire 1,500-ppm group was terminated on gd 10-14, with the animals killed in extremis. Selective necrosis of neurons in the internal granular layer of the cerebellum, ranging from individual cell involvement to focal areas comprising large numbers of neurons, was found in all females. On gd 18, the females from the other treatment groups, all of which survived, were killed for evaluation of maternal reproductive and fetal parameters. No evidence was seen of maternal or fetal toxicity in these exposure groups. There were no significant alterations in external appearance in fetuses from any of the exposure groups. Visceral examination of mouse fetuses revealed a small, but statistically significant, incidence of heart defects in litters of the 500-ppm group. The anomaly, a reduction or absence of the atrioventricular valve, chordae tendineae, and papillary muscle, was observed on the left side (bicuspid valve) in three fetuses and the right side (tricuspid valve) in six fetuses: three males and six females. It is concluded that methyl chloride inhalation exposure in pregnant rats, during critical periods of embryo and fetal development, is not teratogenic at concentrations which elicit maternal and fetal toxicity. In pregnant mice, methyl chloride was severely toxic to dams following 4 days or more of exposure to 1,500 ppm in air. Methyl chloride, at 500, but not 100 ppm, was teratogenic in mice, leading to a malformation in the heart. No embryo-fetal toxicity or teratogenicity was associated with exposure of mice, during critical periods of embryo and fetal development, to 100 ppm of ethyl chloride.

Air↗
PubMed1983

Evaluation of heart malformations in B6C3F1 mouse fetuses induced by in utero exposure to methyl chloride.

C57BL/6 female mice impregnated by C3H males mice to produce B6C3F1 fetuses were exposed daily for six hr to atmospheres containing 0, 250, 500, or 750 ppm methyl chloride, from gestation day 6 to gestation day 18. There were 74 to 77 females with copulation plugs per exposure concentration. Females exposed to 750 ppm ethyl chloride exhibited ataxia commencing on the seventh day of exposure (gestation day 12). They also showed hypersensitivity to touch or sound, tremors and convulsions. Six females in the 750 ppm group died and one was euthanized in extremis prior to scheduled sacrifice. On gestation day 18, all other females were euthanized for evaluation. Only dams exposed to 750 ppm exhibited significant decrease in body weight by gestation day 18, weight gain during the gestation period, and absolute weight gain (weight gain minus gravid uterine weight) versus controls. There were no treatment related-effects on these parameters in the other exposure groups. None of the groups exhibited exposure-related differences in pregnancy rate, gravid uterine weight, or maternal liver weight. There were no differences in the numbers of implantations, resorption, dead fetuses, nonlive (dead plus resorbed) fetuses, live fetuses, sex-ratio, or mean fetal body weight per litter. There was a significant exposure-related increase in the number and percentage of affected (nonlive plus malformed) fetuses per litter with the incidence of affected fetuses in the 750 ppm group significantly higher than controls. There was a statistically significant increase in the incidence of heart defects in the 500 and 750 ppm group relative to controls. Of the 37 fetuses in the study with heart defects, 23 were females, 14 were males. The heart defects observed included: absent or abnormal tricuspid valve, reduced number of papillary muscles and/or chordae tendineae on the right side, small right ventricle, globular heart, and white spots in the left ventricular wall. Multiple malformations were observed in one fetus from the 500 ppm group and in three fetuses in the 750 ppm group. It is concluded that methyl chloride inhalation exposure to pregnant C57BL/6 mice from gestation day 6 through gestation day 17 resulted in maternal toxicity only at the 750 ppm exposure concentration and was teratogenic to B6C3F1 conceptuses at exposure concentrations of 750 and 500 ppm, leading to fetal heart malformations. No evidence of embryo or fetotoxicity other than teratogenicity was seen at any of the exposure concentrations employed. No maternal, embryo or fetotoxicity or teratogenicity was associated with exposure of mice, during critical periods of embryo and fetal development, to 250 ppm of methyl chloride.

Abnormalities, Drug-Induced↗