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Biomedical subjects

G R Lee

Publications and source records attributed to G R Lee.

At least 37 records · Page 2Linked to original sources
PubMed1977

The anemia of vitamin E deficiency in swine: an experimental model of the human congenital dyserythropoietic anemias.

The ultrastructural and erythrokinetic characteristics of vitamin E deficiency in swine were investigated in an effort to evaluate the suitability of the swine disorder as a model of the human congenital dyserythropoietic anemias. The dominant erythrokinetic abnormality in vitamin E deficient pigs, as in the CDAs, is ineffective erythropoiesis. As in some patients with CDA, the activity of a number of erythrocyte enzymes was increased. Distinctive ultrastructual changes previously described in patients with CDA were found in normoblasts from vitamin E deficient pigs. The morphologic, erythrokinetic, biochemical and ultrastructural similarities between vitamin E deficiency in swine and the CDAs in man appear to justify the study of the animal disorder as a model of the human disease. A complete hematologic response was elicited by the administration not only of vitamin E, but also, as in the previous studies of vitamin E deficiency in monkeys, by hexahydrocoenzyme Q4. The partial hematologic response occurring after deletion of tocopherol stripped corn oil from the diet indicates that factors other than the dietary lack of vitamin E are important in the pathogenesis of this disorder.

Anemia↗
PubMed1977

Sampling in social gerontology: a method of locating specialized populations.

This paper describes a two-stage sampling design for obtaining probability samples of the elderly and other specialized populations. The first stage enumerates a sample of elderly individuals residing in a probability, sample of households; the second stage involves the mailing of a questionnaire to the eligible respondents located in the first stage. The results of this method for a study of noninstitutionalized elderly in Washington State are reported. These results indicate that (1) elderly individuals will respond in the two-stage sampling design does not appear to increase sample bias above that expected in normal mailed-questionnaire studies, and (3) the method is extremely inexpensive. Use of the two-stage design by social gerontologists is recommended.

Aged↗
PubMed1976

An inherited enzymatic defect in porphyria cutanea tarda: decreased uroporphyrinogen decarboxylase activity.

Uroporphyrinogen decarboxylase activity was measured in liver and erythrocytes of normal subjects and in patients with porphyria cutanea tarda and their relatives. In patients with porphyria cutanea tarda, hepatic uroporphyrinogen decarboxylase activity was significantly reduced (mean 0.43 U/mg protein; range 0.25-0.99) as compared to normal subjects (mean 1.61 U/mg protein; range 1.27-2.42). Erythrocyte uroporphyrinogen decarboxylase was also decreased in patients with porphyria cutanea tarda. The mean erythrocyte enzymatic activity in male patients was 0.23 U/mg Hb (range 0.16-0.30) and in female patients was 0.17 U/mg Hb (range 0.15-0.18) as compared with mean values in normal subjects of 0.38 U/mg Hb (range 0.33-0.45) in men and 0.26 U/mg Hb (range 0.18-0.36) in women. With the erythrocyte assay, multiple examples of decreased uroporphyrinogen decarboxylase activity were detected in members of three families of patients with porphyria cutanea tarda. In two of these families subclinical porphyria was also recognized. The inheritance pattern was consistant with an autosomal dominant trait. The difference in erythrocyte enzymatic activity between men and women was not explained but could have been due to estrogens. This possibility was supported by the observation that men under therapy with estrogens for carcinoma of the prostate had values in the normal female range. It is proposed that porphyria cutanea tarda results from the combination of an inherited defect in uroporphyrinogen decarboxylase and an acquired factor, usually siderosis associated with alcoholic liver disease.

5-Aminolevulinate Synthetase↗
PubMed1976

Role of copper in mitochondrial iron metabolism.

Heme synthesis by copper-deficient cells was investigated to elucidate the nature of the defect in intracellular iron metabolism. Iron uptake from transferrin by copper-deficient reticulocytes was 52% of normal, and the rate of heme synthesis was 33% of normal. Hepatic mitochondria isolated from copper-deficient animals were deficient in cytochrome oxidase activity and failed to synthesize heme from ferric iron (Fe III) and protoporphyrin at the normal rate. The rate of heme synthesis correlated with the cytochrome oxidase activity. Heme synthesis from Fe(III) and protoporphyrin by normal mitochondria was enhanced by succinate and inhibited by malonate, antimycin A, azide, and cyanide. It is proposed that an intact electron transport system is required for the reduction of Fe(III), thereby providing a pool of ferrous iron (Fe II) for protoheme and heme a synthesis.

Animals↗
PubMed1975

The role of iron in the pathogenesis of porphyria cutanea tarda. II. Inhibition of uroporphyrinogen decarboxylase.

Porphria cutanea tarda is characterized biochemically by excessive hepatic synthesis and urinary excretion of uroporphyrin I and 7-carboxylporphyrins. This pattern of excretion suggest an impaired ability to decarboxylate uroporphyrinogen to the paired ability to decarboxylate uroporphyringen to the 4-carboxyl porphyrinogen, coproporphyrinogen, a reaction catalyzed by the enzyme uroporphyringen decarboxylase. Because clinical evidence has implicated iron in the pathogenesis of porphyria cutanea tarda, these experiments were designed to study the effect of iron on uroporphyrinogen decarboxylase in procine crude liver extracts. Mitochondria-free crude liver extracts were preincubated with ferrous ion and aliquots were assayed for uroporphyrinogen decarboxylase activity. Uroporphyrinogens I and III, the substrates for the decarboxylase assay, were prepared enzymatically from (3H)porphobilinogen. The products of the decarboxylase reaction were identified and quantitated by three methods: (a) extraction into 1.5 N HCl and spectrophotometric quantitation; (b) adsorption onto talc, esterification, paper chromatographic identification, and quantitation by liquid scintillation counting; and (c) adsorption onto talc, esterification, thin-layer chromatographic identification on silica gel, and quantitation by liquid scintillation counting. The thin-layer scinllation method proved most sensitive as it was the only method which accurately identified and quantitated the 7-carboxyl porphyrin reaction product. Uroporphyrinogens I and III were decarboxylated at the same rate by porcine hepatic uroporphyrinogen decarboxylase, and the addition of iron induced marked inhibition of the decarboxylase activity. Ortholpehanthroline blocked the inhibitory effect of iron. The inhibition of uroporphyrinogen decarboxylase by ferrous ion, coupled with its previously reported inhibitory effect on uroporphyrinogen III cosynthetase, provides a possible biochemical explanation for the pattern of urinary porphyrin excretion observed in patients with porphyria cutanea tarda and the clinical association with disordered iron metabolism.

Animals↗
PubMed1975

Superoxide dismutase activity in copper-deficient swine.

These experiments demonstrate the dependency of cuprozinc superoxide dismutase activity in red cells and liver on an adequate dietary intake of copper. The superoxide dismutase activity in red cells decreased to 15% of control values and, therefore, these cells may be used as a convenient model for studying the physiologic consequences of free radicals

Animals↗
PubMed1975

Porphyria cutanea tarda associated with disinfectant misuse.

Porphyria cutanea tarda was detected in a 44-year-old janitress. The illness was probably caused by the unintentional synthesis of a polychlorinated phenol as a result of mixing commonly available household ingredients in toilet bowls and shower stalls. Although the evidence for this hypothesis is circumstantial, its likelihood and the wide-spread household use of these reagents justify calling attention to the innovative misuse of disinfectants as a potential source of toxic exposure.

Adult↗
PubMed1974

The role of superoxide anion radical in the reduction of ferritin iron by xanthine oxidase.

Superoxide dismutase exerted a pronounced inhibitory effect upon xanthine oxidase-mediated reduction of iron in ferritin, ferric chloride, or ferric ADP. Maximal inhibition was observed when the superoxide dismutase concentration was only about 1% of that found in normal porcine liver. These observations indicate that superoxide anion radical is an intermediate in the reduction of iron by xanthine oxidase in vitro but not in vivo.

Adenosine Diphosphate↗
PubMed1972

The role of iron in the pathogenesis of porphyria cutanea tarda. An in vitro model.

Porphyria cutanea tarda (PCT) is characterized biochemically by excessive hepatic synthesis and urinary excretion of uroporphyrin I. Clinical evidence has implicated iron in the pathogenesis of PCT. The synthesis of the normally occurring isomer of uroporphyrin, namely uroporphyrin III, from porphobilinogen (PBG) requires two enzymes; uroporphyrinogen I synthetase and uroporphyrinogen III cosynthetase (COSYN). In the absence of COSYN only uroporphyrinogen I is formed. These experiments were designed to study the effect of iron on porphyrin biosynthesis in porcine and human crude liver extracts and to measure COSYN activity in the presence of iron.Mitochondria-free crude liver extracts were prepared in 0.25 m sucrose at pH 7.4 by centrifugation at 37,000 g. Preparations were incubated with either 0.2 mm amino-levulinic acid (ALA) or 0.1 mm PBG. The addition of ferrous ion (either from ferritin iron [4 mug/ml] and cysteine [6.7 mm] or ferrous ammonium sulfate [0.3 mm Fe] and cysteine) significantly increased the rate of uroporphyrin synthesis from either ALA or PBG. The predominant porphyrin synthesized in the presence of ferrous ion was uroporphyrin I whereas coproporphyrin III predominated in its absence. Orthophenanthroline blocked these effects of ferrous ion.To investigate the effect of ferrous ion on COSYN, crude liver extracts were incubated with ferrous ammonium sulfate (0.3 mm Fe) and cysteine (6.7 mm) and the COSYN activity of the incubates was assayed directly. In both porcine and human extracts ferrous ion caused marked inhibition of COSYN activity. Orthophenanthroline blocked the inhibitory effect.Inactivation of COSYN by heating resulted in marked enhancement of porphyrin synthesis from PBG. The sole product was uroporphyrin I.Thus, inactivation of COSYN results in accelerated synthesis of uroporphyrin I. This effect of ferrous ion provides a possible biochemical explanation for the excess production and excretion of uroporphyrin I in patients with PCT and the reversal of this defect by phlebotomy.

Ammonia-Lyases↗