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Biomedical subjects

D A Applegarth

Publications and source records attributed to D A Applegarth.

At least 109 records · Page 6Linked to original sources
PubMed1977

Plasma arginine esterase activity in cystic fibrosis of the pancreas.

Using a micro-method for the determination of plasma arginine esterase activity, we have investigated the values for soybean trypsin inhibitor (STI)-inhibited arginine esterase activity in patients with cystic fibrosis, obligate heterozygotes and age matched control individuals. The mean of STI-inhibited activity is lowest for cystic fibrosis patients while the mean for normal controls is the highest. The mean of STI-inhibited activity for the heterozygotes is midway between the values of the patients and the normal individuals. The deficiency of arginine esterase activity was statistically significant for both cystic fibrosis patients and heterozygotes.

Adolescent↗
PubMed1977

Hyperprolinemia type II: identification of the glycine conjugate of pyrrole-2-carboxylic acid in urine.

The urinary organic acids were studied in two cases of hyperprolinemia Type II, using various combinations of chromatographic, electrophoretic and mass spectrometric techniques. In both cases N-(pyrrole-2-carboxylic acid) was idenfitied as a major urinary metabolite. While there was evidence for an additional conjugate of this pyrrolic acid, no free pyrrole-carboxylate could be detected in the urine from either case.

Carboxylic Acids↗
PubMed1977

Progressive cerebellar ataxia, spasticity, psychomotor retardation, and hexosaminidase deficiency in a 10-year-old child: juvenile Sandhoff disease.

During the course of investigating a 10-year-old boy because of progressive deterioration of intellectual functioning, ataxia, and hemiplegia, an absence of serum hexosaminidase activity was noted. A skin biopsy examined by electron microscopy showed axonal accumulations of dense osmiophilic deposits. Because of the patient's age at onset and the slowly progressive nature of his ilness, we are reporting an atypical juvenile case of Sandhoff disease.

Age Factors↗
PubMed1976

Type II hyperprolinemia. Delta1-pyrroline-5-carboxylic acid dehydrogenase deficiency in cultured skin fibroblasts and circulating lymphocytes.

Type II hyperprolinemia is an inherited abnormality in amino acid metabolism characterized by elevated plasma proline concentrations, iminoglycinuria, and the urinary excretion of delta1-pyrroline compounds. To define the enzymologic defect of this biochemical disorder, we developed a specific, sensitive radioisotopic assay for the proline degradative enzyme delta1-pyrroline-5-carboxylic acid dehydrogenase. Using this assay, we have shown an absence of delta1-pyrroline-5-carboxylic acid dehydrogenase activity in the cultured fibroblasts from three patients with type II hyperprolinemia. We confirmed this result on cultured cells by demonstrating a similar absence of delta1-pyrroline-5-carboxylic acid dehydrogenase activity in extracts prepared from the peripheral leukocytes of these patients. Additionally, we found significantly decreased levels of delta1-pyrroline-5-carboxylic acid dehydrogenase activity in the leukocyte extracts from five obligate heterozygotes for type II hyperprolinemia. We also demonstrated a reduction in leukocyte delta1-pyrroline-5-carboxylic acid dehydrogenase activity in three successive generations of a family. These results prove that an absence of delta1-pyrroline-5-carboxylic acid dehydrogenase is the enzymologic defect in type II hyperprolinemia and that this defect is inherited in an autosomal recessive fashion.

Amino Acid Metabolism, Inborn Errors↗
PubMed1976

Lactic acidosis in childhood.

Children with chronic metabolic acidosis should be investigated to determine the presence of an organic acid, especially when the plasma electrolyte profile shows a deficiency of anion. One of the organic acids that should be looked for in such a patient is lactic acid. Lactic acidosis due to tissue hypoxia is a well-known phenomenon (e.g., in shock and cardiopulmonary disease) and has not been discussed in this essay; nor has lactic acidosis due to exogenous causes like infusion of fructose or sorbitol, or admiministration of phenformin. Chronic lactic acidosis in infancy is a rare condition. It may be associated with glycogen storage disease Type 1, fructose diphosphatase deficiency, methylmalonic acidemia, propionic acidemia, pyruvate carboxylase or dehydrogenase deficiency and Leigh's subacute necrotizing encephalomyelopathy (SNE). Some patients with chronic lactic acidosis do not have nay of these diseases and comprise an "idiopathic" group. This is a heterogeneous group, probably having several different causes for the metabolic error. In Leigh's SNE, a metabolic block in the formation of thiamine triphosphate in brain has been demonstrated and has been attributed to the presence of an inhibitor of thiamine pyrophosphate-adenosine triphosphate (TPP-ATP) phosphoryl transferase in body fluids. The inhibitor has also been encountered in cases of intermittent cerebellar ataxia and of primary hypoventilation (Ondine's curse), which may represent variants of Leigh's disease. Increased blood levels of lactate, pyruvate and alanine frequently are encountered in SNE, but it still is not clear whether they are due to a primary or secondary disturbance in the catabolism of pyruvate. Disturbed lactate and pyruvate metabolism has also been encountered in isolated cases of mental retardation and growth failure, in mitochondrial myopathies and in polyneuropathies, and may be expected to occur in Wernicke's encephalopathy. Finally, it has been noted in malignancy and in association with other rare metabolic disorders.

Acidosis↗
PubMed1975

Interpretation of elevated blood glycine levels in children.

Recent experience with three children who had non-ketotic hyperglycinemia suggested that interpretation of blood glycine levels in children is complex. The elevations of blood glycine in these children were quite modest, and comparable to those of other children admitted to hospital with other diseases. Often we find elevations of blood glycine in children who have had some degree of starvation before blood was taken for amino acid analysis. In a "typical" patient, valine, leucine, isoleucine and occasionally threonine are depressed, while the glycine level is raised. As nutrition improves all of the amino acids return to normal. Our data suggest that blood glycine levels in children with an acute episode of a debilitating disease need to be interpreted with respect to the immediate state of nutrition of the children.

Adolescent↗
PubMed1975

Nonketotic hyperglycinemia. Glycine accumulation due to absence of glycerine cleavage in brain.

Glycine concentrations were measured in plasma and cerebrospinal fluid of five patients in different types of hyperglycinemia to determine why severe neurologic deterioration is confined to the so-called nonketotic form of hyperglycinemia. Glycine content and glycine-cleavage enzyme activity were also determined in brain obtained in autopsy from three of these patients. Spinal-fluid glycine concentrations were 15 to 30 times above normal in patients with nonketotic hyperglycinemia, but were normal in those with hyperglycinemias of undetermined type who had comparable elevations of plasma glycine. Glycine content was two to four times above normal in several brain regions, and brain glycine cleavage enzyme activity was absent in two patients dying of nonketotic hyperglycinemia. By contrast, glycine content was normal and glycine cleavage activity present in the brain of an infant who died of hyperglycinemia of unknown cause. These results suggest that elevated glycine levels may be harmless in blood, but lethal in brain.

Adult↗
PubMed1975

Analysis of urinary mucopolysaccharides using small ion exchange columns.

Methods are presented for the small scale column chromatography of urinary mucopolysaccharides. After isolation by cety pyridinium chloride mucopolysaccharides are applied to a small column of ion exchange resin and eluted by 2 M-sodium chloride. Colorimetric assays on this elutate allow clinically significant disease states to be detected.

Chemical Precipitation↗
PubMed1975

Metabolic studies of a family with massive formiminoglutamic aciduria.

We have described two siblings who excrete massive amounts (up to 3.89 mmol/24 hr) of N-formiminoglutamic acid (FIGLU) in their urine. This unusual compound was isolated from urine, purified, and firmly identified as FIGLU by combined gas chromatography-mass spectrometry. The patients presumably have a deficiency in activity of the hepatic enzyme, glutamate formiminotransferase, which carries out the fourth sequential step in the main pathway of histidine degradation. Unlike children reported previously with this disorder, our patients had normal serum folate levels, had no hematologic abnormalities, and were not mentally retarded. Very small amounts of FIGLU were present in the plasma of one of the patients, but FIGLU was not detectable in the cerebrospinal fluid of either patient. Administration of pharmacologic doses of folic or folinic acid produced a decrease in excretion of FIGLU in urine. Histidine loading caused a small and comparable urinary excretion of FIGLU in the children's parents and in control adult subjects.

Amino Acid Metabolism, Inborn Errors↗