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Biomedical subjects

C R Scriver

Publications and source records attributed to C R Scriver.

At least 217 records · Page 12Linked to original sources
PubMed1980

Abnormalities of carbohydrate metabolism in idiopathic Fanconi syndrome.

Various metabolic studies were performed in a patient with the idiopathic Fanconi syndrome in whom constant ketonuria suggested that organic acidemia might contribute to the metabolic acidosis. Glucose intolerance with a diminished insulin release was found after PO or IV glucose loads and after glucagon administratio. An insulinopenic "diabetes-like" state has not previously been described in such patients. The patient had impaired galactose-glucose interconversion, elevated blood lactate levels, reduced pyruvate levels, and an increased lactate:pyruvate ratio. Hepatomegaly and hypoglycemia were not present, and liver and muscle biopsies revealed no enzymatic evidence of glycogenosis. The erythrocyte UDP galactose transferase activity was normal. The patient failed to convert fructose to glucose and had a rise in blood lactate after ethanol administration. Further studies revealed no production of glucose after alanine or glycerol administraion, each test being associated with elevated blood lactate levels and, after alanine, an increased lactate:pyruvate ratio. The lactate:pyruvate ratio was elevated after glucagon administration with increased lactate and reduced pyruvate concentrations.

Carbohydrate Metabolism↗
PubMed1980

Effect of calciotropic hormones and cyclic nucleotides on aminoaciduria and phosphaturia.

Parathyroid extract (PTE), dibutyrylcyclic AMP (dbcAMP), adenosine cyclic 3':5'-monophosphate (cAMP). calcitonin (CT), and calcium chloride were infused separately into anesthetized, sham-operated, or TPTX vitamin D-fed adult rats to examine the effect of these calciotropic agents on fractional excretion (FE) of alpha-aminoisobutyric acid (AIB), and phosphate anion (Pi). AIB is a nonmetabolizable amino acid. Inulin clearance, FEAIB, and FEPi were stable in the intact (n = 10) and TPTX rat (n = 10). TPTX decreased FEAIB, and FEPi significantly (P less than 0.001 for both). PTE and dbcAMP both increased FEAIB in the intact rat (P less than 0.001); failure to obtain this response in the TPTX animal was a key finding. PTE and dbcAMP increased FEPi (P less than 0.001) in both the intact and TPTX animal. CT was the only agent (versus PTE, dbcAMP, adenosine cyclic 3':5'-monophosphate, and CaCl2) to increase FEAIB (P less than 0.001) in the TPTX rat; furthermore, it was the only agent that did not increase FEPi in the TPTX rat although it had hypocalcemic and hypophosphatemic effects. Changes in inulin clearance or plasma concentration of AIB, following infusion of calciotropic agents, do not explain the unique responses in FEAIB in the TPTX rat. Our findings suggest that hyperaminoaciduria induced by parathyroid hormone and cyclic nucleotide in the intact animal may be mediated by CT. Hyperphosphaturia is not a necessary response to small-dose (25 milliunits/kg.hr) infusions of CT.

Aminoisobutyric Acids↗
PubMed1979

Taurine transport in renal brush-border-membrane vesicles.

Taurine transport in isolated brush-border-membrane vesicles from rat kidney is concentrative and it is driven by the Na+ gradient and transmembrane potential difference; binding is not a significant component of net uptake. The Na+-dependent component of net uptake is saturable with an apparent Km of 17 microM. The taurine-transport mechanism is selective for beta-amino compounds.

Amino Acids↗
PubMed1979

Observations on the composition of milk-substitute products for treatment of inborn errors of amino acid metabolism. Comparisons with human milk. A proposal to rationalize nutrient content of treatment products.

We tabulated and compared the stated compositions of four milk-substitute products, now in wide use for the treatment of various inborn errors of amino acid metabolism, and the known composition of human milk. Variations between the treatment products is great not only in the content of amino acids but also in minerals and vitamins, for example. Different source materials and rationales for their manufacture appear to explain these differences. All four products deviate in many ways from the composition of human milk. Although the existing treatment products are quite effective clinically, we propose that a more rational approach to the feeding of young infants whose nutrition is compromised by inborn errors of metabolism would begin with a synthetic product based on the composition of human milk that could be modified specifically to fit the needs and tolerance of the individual patient.

Amino Acid Metabolism, Inborn Errors↗
PubMed1979

Ontogeny of amino acid reabsorption in human kidney. Evidence from the homozygous infant with familial renal iminoglycinuria for multiple proline and glycine systems.

Seven infants (two French Canadian, four Ashkenazi Jewish, and one Greek) with massive selective hyperiminoglycinuria (proline, hydroxyproline, and glycine) were detected by urine screening in the second week of life. Follow-up investigations and family studies revealed that each subject had a benign condition, familial renal iminoglycinuria, an autosomal recessive condition. The family studies (Table 1 and Fig. 1) indicate the presence of at least two different mutant alleles segregating in this small group of probands. Hmozygotes of two forms and one genetic compound were identified. Quantitative studies revealed normal concentrations of proline and glycine in plasma (Fig. 2), normal maturation of creatinine clearance (as an index of glomerular filtration rate) (Fig. 3), and elevated renal clearance of proline and glycine (Table 2). Fractional excretion (CAA/CCR) of both proline and glycine in the probands was far in excess of that expected for the normal postnatal infant; FFPro and FEGly approached 100% of the filtered load on occasion (Fig. 4). A schedule of maturing tubular reabsorptive activity was apparent in the proband group. Proline reabsorption matured earlier than glycine reabsorption in the homozygotes (and the genetic compound) as it does in the normal infants (Fig. 5). Our findings suggest that three gene products serve net tubular reabsorption of imino acids and glycine in human kidney. One, affected by mutation in our patients, is responsible for a shared transport activity; a second with preference for proline, and not affected by the mutation, has an "early" schedule of postnatal maturation; and a third with preference for glycine, also not affected by the mutation, has a "late" schedule of maturation.

Amino Acid Metabolism, Inborn Errors↗
PubMed1978

Serum 1,25-dihydroxyvitamin D levels in normal subjects and in patients with hereditary rickets or bone disease.

The serum concentration of 1,25-dihydroxylvitamin D (1,25-[OH]2D) in normal children and in children with inherited diseases of bone was compared by use of a competitive binding assay. Observed values were: in 12 normal children and adolescents, 37.1 +/- 1.9 pg per milliliter (mean +/- S.D.); in 14 patients with X-linked hypophosphatemic rickets treated with vitamin D2 and phosphate supplements, 15.6 +/- 7.8 (P less than 0.01 versus control); in six patients with autosomal recessive vitamin D dependency treated with vitamin D2, 9.5 +/- 2.9 (P less than 0.01 versus control); and in four untreated patients with autosomal dominant hypophosphatemic (non-rachitic) bone disease, 30.2 +/- 6.3 (not significantly different from the controls). The difference in bone disease between X-linked hypophosphatemia (severe) and hypophosphatemic bone disease (mild) at comparable low serum levels of phosphate implies that 1,25-(OH)2D and phosphate may have independent roles in the pathogenesis of defective bone mineralization.

Adolescent↗
PubMed1978

Genetics and Medicine: an evolving relationship.

The rapid expansion of knowledge in human and medical genetics has revealed at least 6 percent average heterozygosity per structural gene locus, in excess of 2300 Mendelian (single gene) variants and several hundred chromosomal variants in man. This means that with the exception of monozygous twins, no two individuals are alike in their phenotype. Therefore, each person has a relative state of health, and genetic factors contribute significantly to disease. The ubiquity of genetic diversity requires the development of services for genetic screening, diagnosis, and counseling to prevent and treat a major portion of disease in modern society. Specific programs in Quebec and Canada illustrate how individuals and populations can be served by such services. Better education of citizens and health professionals in human genetics is essential for the further improvement of genetics services in society.

Blood Chemical Analysis↗
PubMed1978

The defect in transcellular transport of phosphate in the nephron is located in brush-border membranes in X-linked hypophosphatemia (Hyp mouse model).

We purified renal cortex brush-border membranes from mutant hemizygous hypophosphatemic (Hyp/Y) mice and male control (+/Y) littermates. Tenfold purification of mutant and wild-type membranes was obtained. Phosphate enters +/Y brush-border membrane vesicles by a saturable Na+-dependent arsenate-inhibited component and also by a diffusional component observed in the presence of a potassium gradient. Phosphate is not bound or incorporated significantly by mouse brush-border membrane vesicles. Parallel studies with rat renal cortex brush-border membrane vesicles revealed that phosphate and D-glucose transport in rat and mouse vesicles are similar and have the characteristics reported by other workers. Brush-border membrane vesicles prepared from Hyp/Y renal cortex have significant (p less than 0.001) partial loss of phosphate transport on the Na+-dependent arsenate-inhibited component. D-Glucose transport is not affected. Our previous studies reveal that other components of transcellular phosphate flux in kidney are normal. Therefore, we conclude that the mutant gene product in the Hyp mouse is confined to the brush-border membrane. Stability of the X-chromosome in mammalian evolution implied that the same gene product is involved in the classic human disease, familial 'vitamin D 'resistant' X-linked hypophosphatemia.

Animals↗