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Biomedical subjects

C R Miller

Publications and source records attributed to C R Miller.

At least 55 records · Page 3Linked to original sources
PubMed1987

Effect of different levels and periods of lead exposure on tissue levels and excretion of lead, zinc, and calcium in the rat.

Influence of lead on tissue content and urinary excretion of lead, zinc, and calcium in rats was studied following various exposure periods. Weanling male rats were fed a trace mineral-sufficient diet with either 0, 200, 500, or 1000 ppm lead (as acetate) in drinking water for 4, 8, or 12 weeks. Blood lead ranged from 40 to over 100 micrograms/dl; kidney lead was highest at 4 weeks. Urinary lead excretion was highest at 4 weeks and declined with longer exposure. Urinary zinc excretion correlated positively with lead excretion at the lower excretion rates but plateaued at higher lead excretion rates. After 12 weeks exposure at each lead dose employed, decrease zinc concentration was observed in testes, bone, and brain. Plasma, erythrocyte, and kidney zinc were not affected, while pancreas and liver zinc were slightly elevated. Urine calcium was increased significantly only in rats exposed to 1000 ppm, possibly reflecting renal cell damage as determined by elevated renal calcium levels. These results indicate that lead dose is more important than exposure period for determining kidney lead levels, while urinary lead excretion rate is both dose and time dependent. Blood lead clearance values are relatively independent of dose and fall as exposure continues. Essential trace metal balance for zinc, especially, and to a lesser extent for calcium, is affected by the dose and length of chronic lead exposure.

Animals↗
PubMed1986

Partitioning of renal zinc between metallothionein and ethylenediaminetetraacetic acid (EDTA) after treatment of rats with Ca(Na)2EDTA.

Calcium disodium edtate (EDTA) is a widely used chelator in the treatment of lead poisoning, although it also mobilizes other trace metals such as zinc. We have found that daily injection of 400 mg EDTA/kg body wt ip to rats results in an increase in the concentration of zinc (Zn) in the kidney when measured by atomic absorption spectroscopy. This increase is not associated with an induction of metallothionein (MT), a protein normally involved in the homeostasis of zinc. In fact, separation of kidney homogenate on a column of Sephadex G-75 demonstrates that virtually no Zn-MT remains in the kidney 24 hr after an EDTA injection, although after 3 days, Zn-MT levels appear to return to normal. Instead, increased renal Zn is found associated with residual EDTA. False high measurements of MT can be obtained from the Cd-saturation/hemoglobin assay due to the presence of residual EDTA in the kidney. Although nearly all of an injected dose of radiolabeled EDTA is rapidly excreted, 0.2 to 0.1% is retained in the kidney 1 day later; this is sufficient to account for the additional Zn. We propose that the small proportion of EDTA incorporated by pinocytosis into lysosomes in the renal cortical cells binds with all free Zn and subsequently depletes the MT concentration. Although the concentration of Zn measured in the kidney is elevated, there is actually less available for Zn-dependent activity.

Animals↗
PubMed1986

Purification and characterization of a peptidyl glycine monooxygenase from porcine pituitary.

A peptide alpha-amidating enzyme was purified to apparent homogeneity from porcine pituitary. This enzyme is a glycoprotein with a mol wt of 64,000, a metal prosthetic group, and a dependence upon ascorbate and molecular oxygen. The purified enzyme has a strong preference for peptides ending in glycine. It also catalyzes the oxidation of valylglycine bonds more rapidly than prolylglycine bonds, and demonstrates a primary isotope effect greater than 5 when the alpha-hydrogens of glycine are replaced by deuterium. Kinetic analysis is consistent with a ping-pong or double displacement catalytic mechanism in which both the peptide substrate and ascorbate are competitive inhibitors with respect to each other. With respect to its kinetic properties, catalytic mechanism, and cofactor requirements, the purified amidating enzyme is very similar to dopamine beta-hydroxylase, a finding which supports the previous suggestion that the peptide alpha-amidating enzyme be classified as a peptidyl glycine monooxygenase.

Animals↗
PubMed1986

Essential trace metal excretion from rats with lead exposure and during chelation therapy.

Urinary excretion of lead, zinc, calcium, magnesium, iron, copper, sodium, and potassium was measured in rats daily for 1 week after a 6-week exposure to 10,000 micrograms/ml lead in drinking water. Beginning on the third day, half of the lead-exposed and control rats were injected intraperitoneally with calcium disodium ethylenediaminetetraacetate (EDTA) daily for 3 days. Whole blood, plasma, and kidney metal concentrations were determined from samples obtained at the end of the experiment. Exposure to lead increased urinary excretion, not only of lead, but also of calcium, magnesium, zinc, copper, and iron. Excretion of sodium and potassium was not altered. Chelation therapy further increased excretion of lead, zinc, copper, and iron, but not magnesium. The increase in calcium excretion during chelation treatment (beyond that resulting from lead exposure per se) was accounted for by the Ca content of CaNa2-EDTA. EDTA treatment increased renal concentration of zinc but lowered renal concentration of lead, copper, and iron. These multimetal alterations may have implications for essential metal supplementation, particularly zinc, in persons being given chelation agents for excess lead exposure and in infants and children with low-level lead exposure not necessarily requiring chelation therapy.

Animals↗
PubMed1985

A rapid, sensitive assay for glycine-directed amidating enzymes.

Current assays for glycine-directed, peptide-amidating enzymes have several shortcomings. In this report, we describe a rapid, sensitive microassay for amidating activity which overcomes these disadvantages. Tissue homogenates are incubated in the presence of D-Tyr-Val-Gly-OH and the product, D-Tyr-Val-NH2, is measured by radioimmunoassay using an antiserum with an affinity for the product, D-Tyr-Val-NH2 (Kaff 2 X 10(8) L/M), 4 orders of magnitude higher than for the substrate, D-Tyr-Val-Gly-OH (Kaff 4 X 10(4) L/M), and 3 orders of magnitude higher than for the deamidated product D-Tyr-Val-OH (Kaff 8 X 10(5) L/M). Addition of N-ethylmaleimide (0.5 mM) to the enzyme incubates prevents the degradation of D-Tyr-Val-NH2 and permits the measurement of enzymatic activity in crude homogenates. This assay is sensitive enough to permit the measurement of amidating activity in crude rat brain homogenates containing as little as 4-8 micrograms protein.

Animals↗
PubMed1985

The relationship of congenital heart disease and respiratory infection mortality in patients with Down's syndrome.

Is respiratory infection mortality in Down's syndrome (DS) individuals due mainly to their congenital heart disease (CHD) or to other factors which subject most mentally retarded persons to risk? Detailed clinical and autopsy records of 137 institutionalized DS patients and 480 non-DS controls over 31 years yielded 42 DS subjects and 13 non-DS controls with congenital heart disease. These were compared to 20 DS patients and 20 controls without CHD. The DS and non-DS patients were matched for age, sex and IQ. DS patients had more CHD; controls had more pulmonary oedema. In neither group was there association between heart disease and death from respiratory infection. Nor did pulmonary oedema contribute importantly to such deaths. Such mortality, however, was associated with young age, short institutionalization and bedridden status. We conclude that respiratory infection death in DS individuals is due not primarily to heart disease but to factors which lead to mortality in the general population of retarded people.

Adolescent↗
PubMed1984

Lead accumulation by rat renal brush border membrane vesicles.

Pb++ accumulation by rat renal cortical brush border membrane vesicles was evaluated by in vitro incubation with rapid filtration technique. Pb++ uptake was time- and concentration-dependent, with apparent saturation of binding sites at 100 to 200 microM (5 sec initial rate experiments). Equilibrium binding studies (60-min incubation) showed that the ratio of bound Pb++ to free Pb++ was constant at 1.25 +/- 0.07 between 0.01 to 10 microM Pb, with decreasing bound to free ratios at higher concentrations. Osmotic experiments showed that Pb++ uptake was due primarily to membrane binding rather than intravesicular accumulation. Electrochemical gradients of NaCl, KCl or protons did not increase vesicle uptake of Pb++. Incubation of vesicles with a number of amino acids did not stimulate Pb++ uptake although two (cysteine and glutathione) and the chelators EDTA or ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid) completely blocked this process. Competition studies with a number of other metals (at 10 microM and 1 mM) showed that only Sn++ or Sn +, La , Fe++ or Fe and Cu++ produced significant reductions in Pb++ uptake whereas Mg++, Ca++, Zn++, Cd++ and Hg++ were without effect on this process. Release of 203Pb from preloaded vesicles was accelerated in the presence of either cysteine or Sn +. Prior in vivo exposure to Pb (3 mg of Pb/kg i.v.) reduced Pb uptake to 70% of that of vesicles prepared from control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Postgraduate pharmacy fellowships (1983-1984).

During June and July 1983, the Pharmacy Services Department of the Brigham and Women's Hospital conducted its third annual national survey by mail questionnaire regarding postgraduate pharmacy fellowships. There was a total response of 76 percent to the questionnaire. Eighty-three fellowships are offered at 31 fellowship sites. Information regarding type of specialty fellowship, fellowship characteristics, fellowship location and contact person, and qualifications of applicants is reported.

Directories as Topic↗
PubMed1982

Effect of morphine on 3H-thymidine incorporation in the subependyma of the rat: an autoradiographic study.

Following morphine treatment, an autoradiographic study investigated the uptake of 3H-thymidine by the subependymal cells in the rat brain. 3H-thymidine was administered subcutaneously to adult, male Sprague-Dawley rats 30 minutes after saline or morphine (19 mg/kg) injection. The animals were sacrified 1 hour after 3H-thymidine administration. In some experiments the opioid antagonist, naloxone, was given alone 45 minutes before 3H-thymidine or 125 minutes before morphine treatment. Three areas of the subependyma were evaluated in terms of the percentage labeled cells and number of grains per nucleus, and a dorsal-to-ventral gradiant was described. Morphine treatment significantly increased the number of 3H-thymidine labeled subependymal cells and number of grains/nucleus within labeled cells. Examination of the distribution of grains/nucleus showed that morphine-treated animals had significantly more cells labeled with 30 or more grains than did saline-injected controls. Prior administration of naloxone blocked the increased 3H-thymidine uptake in morphine-treated animals but had no significant influence on cell proliferation when administered alone. The data are discussed in terms of morphine's possible dual influence on mechanisms which enhance cell transition from G to S phase and/or which accelerate DNA synthesis once these cells have entered the S phase of cell replication.

Animals↗
PubMed1980

Perceived control: bogus pulse rate feedback and reported symptom reduction for individuals with accumulated stressful life events.

The present investigation tested the hypothesis that perceived control reduces reported symptom incidence for individuals with stressful life events. Subjects (undergraduate psychology students from an urban university) were divided into two groups, high and low in stress, based on their life change unit scores as measured by the Schedule of Recent Events (Holmes & Rahe, 1967). Subjects participated in a study in which they attempted to reduce pulse rate (PR) and were informed of their successes (i.e., PR reductions) through bogus feedback. High and low stress subjects were assigned randomly to one of the following conditions: bogus ascending success feedback (AS), wherein successes were concentrated more in the later stage of a PR reduction period; bogus equally distributed success feedback (EDS), wherein successes were equally distributed in the early and later stages of a PR reduction period; or no feedback (NF). The study consisted of three sessions held on 3 consecutive days. Each session consisted of a 3-minute baseline (nonfeedback) period followed by a 10-minute PR reduction period. Self-reports on 13 symptom items were measured 2 weeks before the study (pretest), after the final session of the study (posttest), and 3 weeks after the study (follow-up). Results indicated that on 5 of the 13 symptom items, the AS condition produced a significant reduction in reported symptom incidence for high-stress subjects only, and this effect was maintained for 3 weeks after the experiment. Results are discussed in terms of the effect perceived control may have on perceptions of physical health. Suggestions are made regarding the use of biofeedback treatment as a method by which perceptions of symptom distress may be reduced for individuals exposed to cumulative stressful experiences.

Adult↗
PubMed1979

Comparison of respiratory mortality in the profoundly mentally retarded and in the less retarded.

Autopsy records of 600 profoundly retarded and 405 less retarded were examined for a thirty-one-year period at Pacific State Hospital. The profoundly retarded were found to have more respiratory infections at autopsy, and more deaths of such infections. Profound retardation was a particularly outstanding risk when in combination with epilepsy, inability to ambulate, and developmental cranial anomalies. Non-infectious respiratory morbidity and mortality are more common in the less retarded, apparently because of their living longer to develop these complications.

Adolescent↗
PubMed1977

Toxicologic and teratologic studies of oxibendazole in ruminants and laboratory animals.

Acute toxicity of oxibendazole was assessed with single oral doses given to mice (4 to 32 g/kg of body weight), sheep (230 to 600 mg/kg), and cattle (600 mg/kg); there were no ill effects. Subacute toxicity did not occur with multiple doses given 5 days to cattle (30 to 75 mg/kg/day) and to sheep (10 to 50 mg/kg/day). Chronic effects did not occur with daily doses of 3 to 30 mg/kg given 98 days to rats and dogs. Teratogenicity of the compound was studied in mice, rats, and sheep medicated at a dose level of 30 mg of oxibendazole/kg and in cattle given 75 mg/kg on selected dates during pregnancy. Microscopically, rodent fetuses seemed normal, and on gross physical examination, lambs and calves were free of malformations and ossification variations.

Abnormalities, Drug-Induced↗