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Biomedical subjects

R R Howell

Publications and source records attributed to R R Howell.

At least 37 records · Page 2Linked to original sources
PubMed1981

Neurotransmitter defects and treatment of disorders of hyperphenylalaninemia.

The disordered biosynthesis of dopamine, norepinephrine, and serotonin in brain in untreated PKU is corrected by dietary restriction of phenylalanine. Low levels of biogenic amine metabolites were measured in cerebrospinal fluid from three patients with classical PKU; metabolite concentrations increased after dietary treatment. In a variant of hyperphenylalaninemia caused by deficiency of dihydropteridine reductase, there is defective metabolism of biogenic amines despite dietary restriction of phenylalanine. Two siblings with DHPR deficiency had low amine metabolite values in CSF; in one patient the metabolic defect was corrected by administration of hydroxylated amino acid precursors. Defective biosynthesis of biogenic amines in brain in disorders associated with hyperphenylalaninemia and evaluation of specific dietary treatments can be determined by analysis of neurotransmitter metabolites in CSF.

Brain↗
PubMed1981

The Sabinas syndrome.

We have defined a new autosomal recessive disorder in patients stemming from a small community in northern Mexico. Diagnosable at birth, its major symptoms include brittle hair, mental retardation, and nail dysplasia. Structural hair abnormalities are seen by both light and electron microscopy. Hair cystine content is reduced while the copper/zinc ratio in hair is increased.

Adolescent↗
PubMed1980

CSF neurotransmitter studies. An infant with ascorbic acid-responsive tyrosinemia.

A female newborn infant with Marfan-like habitus experienced lethargy and hypothermia associated with tyrosinemia that was not corrected by the administration of ascorbic acid at 50 mg/day but that subsequently responded to ascorbic acid at 500 mg/day. Cerebrospinal fluid analysis for neurotransmitter metabolites showed elevated concentrations of homovanillic acid and 5-hydroxyindoleacetic acid when the child was symptomatic and normal concentrations after successful ascrobic acid therapy. These observations suggest that a high level of tyrosine in serum can affect the metabolism in the brain of dopamine and serotonin.

Ascorbic Acid↗
PubMed1979

Familial recurrent rhabdomyolysis due to carnitine palmityl transferase deficiency.

Muscle carnitine palmityltransferase (CPT) activity was very low (0 to 14 per cent of controls) in two brothers with a syndrome of recurrent rhabdomyolysis and myoglobulinuria. In isolated muscle mitochondria the majority (87.5 per cent) of total measurable CPT enzyme activity could be attributed to external membrane CPT with severe deficiency of inner membrane CPT. By contrast, control mitochondria demonstrated a 1:1 distribution of external membrane CPT to inner membrane CPT. Thus, myoglobinuria may be due to a genetic defect of lipid metabolism in skeletal muscle, with inner membrane CPT deficiency presenting the same clinical features as external membrane CPT deficiency.

Acyltransferases↗
PubMed1977

Genetic evidence for the common identity of glucose-6-phosphatase, pyrophosphate-glucose phosphotransferase, carbamyl phosphate-glucose phosphotransferase and inorganic pyrophosphatase.

We demonstrate that glucose-6-phosphatase, pyrophosphate-glucose phosphotransferase, carbamyl phosphate-glucose phosphotransferase and inorganic pyrophosphatase activities are deficient in livers of patients with type I glycogen storage disease. This provides strong genetic evidence that these enzymatic activities reside in a single protein or share a common polypeptide chain.

Carbamyl Phosphate↗
PubMed1977

Morquio-like syndrome with beta galactosidase deficiency and normal hexosamine sulfatase activity: mucopolysacchariodosis IVB.

A 14-year-old white girl with mild dysostosis multiplex, odontoid hypoplasia, short stature, cloudy corneas, keratansulfaturia, but without detectable central nervous system abnormalities was referred with the diagnosis of Morquio syndrome. Clinical and roentgenographic findings were minimal compared to those of typical patients with the Morquio syndrome, MPS IV. Beta-Galactosidase activity in extracts of the patient's cultured fibroblasts was deficient, while that of galactosamine-6-sulfate sulfatase was normal. Conjunctival biopsy revealed intracytoplasmic vacuoles typical of lysosomal storage diseases. It is postulated that in this patient the deficiency of a beta-galactosidase is responsible for inadequate degradation of keratan sulfate and the appearance of a mild form of the Morquio syndrome (MPS IVB).

Adolescent↗
PubMed1976

Hepatic adenomata with type 1 glycogen storage disease.

In older patients with glucose-6-phosphatase deficiency adenomatous nodules develop within the liver parenchyma. Investigation of eight such patients, age 3 to 28 years, using radioisotopic scans, has demonstrated areas of depressed isotope uptake in the liver in all except the one preteenaged child. Three patients were further studied with hepatic angiograms and liver biopsy specimens. A diffuse nodularity, more widespread than apparent on isotopic scans, was demonstrated on angiograms. Although initial histologic study in each case showed adenomatous tissue without evidence of neoplasm, the development of hepatocellular carcinoma in one of our patients and in others from the literature suggests that the nodules may be premalignant.

Adolescent↗
PubMed1976

Computerized data analysis of amino acids in physiologic fluids.

A Fortran IV computer program is described which identifies, computes, and statistically evaluates amino acid concentrations determined by an automatic amino acid analyzer in physiologic fluids. The program accepts retention time and intergrated peak areas from two calibration standards for identification and computational reference. Two internal standards are used to compensate for variations in injector performance and ninhydrin decay. Calibration standard responses are statistically treated to assist in detection of equipment malfunction. The statistical data base is automatically explanded through inclusion of data from normal patients. Amino acid concentrations are printed with appropriate mean and standard deviation values in a format acceptable as a final report.

Amino Acids↗
PubMed1976

Ocular findings in mannosidosis.

Three patients with typical features of mannosidosis and deficiency of alpha-mannosidase activity, who were examined ophthalmologically, had similar lenticular opacities. Corneal opacities were absent. Chamber angle and striking ophthalmoscopic anomalies occurred in two young patients who had normal electroretinograms. Two patients had strabismus. Conjunctival biopsy specimens morphologically confirmed the lysosomal nature of this disorder.

Carbohydrate Metabolism, Inborn Errors↗
PubMed1976

Development of gluconeogenic enzymes in fetal sheep liver and kidney.

In the sheep, the system of enzymes necessary for conversion of nonhexose substrates to glucose becomes active during late fetal life. Glucose-6-phosphatase and fructose-1,6-diphosphatase, two of the four key gluconeogenic enzymes, appear in significant amounts between 100 and 120 days gestation. Phosphoenolpyruvate carboxykinase activity is comparable to mature animals as early as 45 days gestation. Two aminotransferases, necessary to allow amino acid access to the gluconeogenic pathway, likewise have substantial activity as early as 45 days gestation. Hence, the surge of glucose-6-phosphatase and fructose-1,6-diphosphatase at 100-120 days gestation makes possible the endogenous production of new glucose by fetal sheep at a time when the amount of glucose transferred from the maternal circulation is less than the total aerobic substrate utilized by the fetus. Both renal cortex and liver have similar developmental patterns for the gluconeogenic enzymes, although renal cortex generally shows greater activity than liver. This observation holds true for tissue from both fetal and mature animals.

Animals↗
PubMed1976

Myophosphorylase deficiency (McArdle's disease): report of a family.

The clinical and biochemical findings are presented of two brothers suffering from McArdle's Disease (Myophosphorylase Deficiency). Tissue enzyme estimations and lactate levels were done in affected and non-affected members of the family. Affected members showed absence of phosphorylase enzyme by histochemical and quantitative estimation. No quantitative abnormalities were found in other enzyme systems of glycolytic pathways in the family investigated. Various other aspects of clinical features, biochemical abnormalities and inheritance are discussed.

Adult↗
PubMed1976

Menkes disease: a biochemical abnormality in cultured human fibroblasts.

Cultured skin fibroblasts from patients with Menkes disease, an X-linked disorder involving a defect in copper metabolism, were analyzed for copper concentration by means of atomic absorption spectrophotometry. These cultures consistently exhibited elevated copper concentrations (mean = 335.5 ng of copper per mg of protein) when compared to control fibroblast cultures (mean = 59.2 ng of copper per mg of protein). External factors that could influence the copper content of cultures were found not to affect the differences in copper concentration between control and Menkes cells. Furthermore, Menkes cells could be differentiated from cultured fibroblasts of controls, of presumed heterozygotes, and of Wilson's disease patients by copper concentration. These observations led to the conclusion that the increased copper content of cultured Menkes cells was characteristic of Menkes disease, resulting from the expression of the genetic abnormality. This provides a genetic marker, a defect in metal metabolism demonstrated in human fibroblasts, that should prove valuable in both the diagnosis of Menkes disease and in the study of the fundamental defect of this genetic disorder.

Brain Diseases↗
PubMed1976

Type IV glycogen-storage disease. Light-microscopic, electron-microscopic, and enzymatic study.

The case of a 14-month-old Latin American girl with the diagnosis of Type IV glycogen-storage disease is reported. The diagnosis was reached on the basis of the typical clinical manifestations, the light- and electron-microscopic findings, and the demonstration of absence of the branching enzyme alpha-1,4-glucan:alpha-1,4-glucan 6-glucosyl transferase in the liver and in the cultured skin fibroblasts.

1,4-alpha-Glucan Branching Enzyme↗
PubMed1976

The iduronidase-deficient mucopolysaccharidoses: clinical and roentgenorgraphic features.

Hurler and Scheie syndromes, two of the six clinically distinct mucopolysaccharidoses, are deficient in the same lysosomal enzyme, alpha-L-iduronidase. A third group of iduronidase-deficient patients can now be identified during the pediatric years using clinical and radiographic criteria. Based on inferential evidence for allelism between the Hurler and Scheie genes, the occurrence of genetic compounds which simultaneously carry both mutant alleles may be predicted to occur. This can be considered analogous to the structural gene mutations leading to hemoglobin SC disease. Four patients with phenotypes intermediate between Hurler and Scheie syndromes are flet to represent genetic compounds of this type. Both clinical and roentgenographic features are helpful in distinguishing these patients from those with Hurler syndrome or Scheie syndrome. Fibroblast correction characteristics identical to those of Hurler syndrome and Scheie syndrome and absence of consanguinity are additional features which favor classification as genetic compounds. The possibility of a third mutant allele at the Hurler-Scheie locus or of extreme phenotype variation are not considered likely alternative explantations. Depending on the frequency of the Scheie syndrome and the Hurler syndrome, genetic compounds may occur with an intermediate frequency or may be more common than either homozygous condition.

Adolescent↗