Biomedical subjects
Publications and source records attributed to D A Applegarth.
A patient is described who has Morquio syndrome (MPS IVA). He is a member of the Hutterite Brethren and genealogic analysis discloses a high inbreeding coefficient for the proband. The proband's sibship is segregating two autosomal recessive disorders, ie, MPS IVA and infantile hypophosphatasia. Two other families each have one or the other of these diseases but not both. The three families are distantly related.
The demonstration of low arylsulfatase-A (ASA) activity in leucocytes or fibroblasts is used often to establish the diagnosis of metachromatic leucodystrophy (MLD). However, low ASA activity is observed also in pseudo-ASA deficiency which may be as common as MLD. We report two patients with pseudo ASA deficiency who had abnormal neurological findings consistent with atypical MLD. Because the measurement of ASA activity is neither a sensitive nor specific method with which to establish a diagnosis of MLD, this diagnosis should be confirmed by nerve biopsy, measurement of urinary sulfatide or a cerebroside sulfate loading test, using cultured fibroblasts.
The putative involvement of alpha 2-macroglobulin (alpha 2M) in the pathogenesis of cystic fibrosis has long been a subject of controversy. Previous reports have indicated that there are alterations in the carbohydrate moieties of alpha 2M in the disease. In the present study the carbohydrate composition of alpha 2M isolated from the plasma of six patients with CF was compared to that of alpha 2M from six age- and sex-matched normal controls. The carbohydrate composition of CF alpha 2M expressed as mean mumol carbohydrate +/- SD per 100 mg protein was: fucose 0.70 +/- 0.12; mannose 14.07 +/- 1.31; galactose 6.72 +/- 0.65; glucosamine 15.38 +/- 1.59; sialic acid 5.52 +/- 0.33 while that of normal control alpha 2M was: fucose 0.69 +/- 0.11; mannose 14.42 +/- 1.21; galactose 6.91 +/- 0.52; glucosamine 16.13 +/- 1.77; sialic acid 5.58 +/- 0.31. Therefore, contrary to previous reports, this paper demonstrates that there is no difference in the carbohydrate composition of alpha 2M in cystic fibrosis.
Explore the source record for details and available documents.
Since the first observation in 1979 that CF infants have elevated blood IRT, studies in various centres have enabled us to more fully understand the importance of this phenomenon. There is increasing evidence to show that mass newborn screening for CF using the IRT assay is practical and is capable of detecting essentially all CF newborns at a cost comparable to existing screening programs for other disorders such as Hypothyroidism. Although the elevated IRT levels seen in infancy in CF soon decrease, IRT levels in older CF patients appear to quite closely reflect the capability of that patient to secrete pancreatic enzymes and can be helpful in separating CF patients whose ability to secrete enzymes is preserved, from those with diminished exocrine pancreatic function. In all CF patients there appears to be an altered relationship between pancreatic exocrine secretion and circulating IRT levels as compared to control patients. This is probably one further manifestation of a secretory obstructive defect which although not uniformly severe, is common to all CF patients.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
An infant with argininosuccinic aciduria was detected through the routine newborn screening program for inborn metabolic diseases and has been followed for over 7 years. Treatment consisting of restricted protein intake and arginine base supplementation was initiated at the age of 8 months and was continued intermittently. She maintained normal psychomotor development to the age of 3 years and currently at the age of 7.3 years, she has measured intelligence in the borderline range. She has had mild symptoms of cerebellar ataxia. Her physical growth has been below normal. Biochemical abnormalities are described. Special metabolic investigations and the effects of treatment are discussed.
We have reviewed evidence regarding the basic tissue involvement in cystic fibrosis (CF). CF is a disease almost exclusively confined to epithelial tissues, particularly those of endodermal origin. Exocrine glands containing such epithelium typically show both obstructive and electrolyte secretory defects. To date most basic CF research has centered on study of mesodermally-derived tissues in which little pathology is seen. The focus of CF research should be changed to concentrate on epithelial tissues.
We examined fasting levels of plasma ammonia, glutamine, glycine, and ornithine in patients taking three anticonvulsants - phenobarbital, carbamazepine and valproic acid. Contrary to previous reports no striking abnormalities were seen.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The interaction of alpha 2 macroglobulin (alpha 2M) with exogenous proteases has been reported by others to be abnormal in cystic fibrosis (CF). We have re-examined these claims. Four parameters were considered:(1) the molar protease binding of alpha 2M; (2) the interaction of bovine cationic trypsin (BCT), complexed to alpha 2M, with low molecular mass substrate, benzoyl arginine ethyl ester (BAEE); (3) the stability of formed alpha 2 M-BCT complexes; and (4) the subunit structure of alpha 2M. We have found CF alpha 2M to be similar to control alpha 2M in every respect studied.
Explore the source record for details and available documents.
We assayed more than 5000 blood spots dried on filter paper and approximately 1000 serum samples for immunoreactive trypsin, with commercial reagents (Behring and Sorin). The assay procedures were modified so that newborn screening is technically feasible. Both kits are satisfactory for serum assay, but the Sorin materials are better adapted for blood spot analysis. Immunoreactive trypsin in blood spots rapidly decreases with specimen age, but is stable in frozen serum. Values for premature infants do not differ significantly from those for full-term babies. Children with cystic fibrosis were readily distinguished from those without, up to at least one year of age.
Explore the source record for details and available documents.