Search PubMed⌕ Search

Biomedical subjects

C R Scriver

Publications and source records attributed to C R Scriver.

At least 127 records · Page 7Linked to original sources
PubMed1988

Lysinuric protein intolerance mutation is not expressed in the plasma membrane of erythrocytes.

We measured mediated fluxes of L-lysine and L-ornithine across the plasma membrane of erythrocytes from control subjects and patients homozygous for the lysinuric protein intolerance (LPI) mutation. We found no differences in net uptake or efflux of cationic amino acids in control and LPI cells, contrary to our findings in cultured skin fibroblasts. We conclude that expression of the LPI (y+) transport system for cationic amino acids varies between tissues and that measurements of fluxes in erythrocytes cannot be used for diagnosis of LPI.

Adult↗
PubMed1988

Newborn urine screening experience with over one million infants in the Quebec Network of Genetic Medicine.

We screened urine for chemical individuality in over 1 million newborn infants, by various chromatographic (thin-layer), chemical and spectrophotometric methods, 12 procedures in all. The programme is part of the Quebec Network of Genetic Medicine. Voluntary urine screening began in 1971 and has evolved with changes in choice of tests and times of sample collection. Urine samples were collected on filter paper at either 5, 14 or 21 days after birth; results were best with the 21-day test. Compliance is over 94% with the latter and over 98% with requests for repeat samples. Screening is centralized in one laboratory; follow-up diagnosis, counselling and management are done at four regional centres. Incidence of phenotypes ranged from 1:4300 live births (for expressed cystinuria alleles) to 1 per million (for hyperargininaemia). Over 20 inherited Mendelian disorders were identified. 30 patients required aggressive medical management. We show how this programme can be used for neuroblastoma screening.

Chromatography, Thin Layer↗
PubMed1988

Initiation and characterization of primary mouse kidney epithelial cultures.

Primary cultures of murine renal epithelial cells were established from a preparation of proximal tubule fragments. Confluent cultures exhibited multiple dome formation, indicating the presence of tight junctions and an intact transcellular transport process. Ultrastructural analysis revealed a monolayer of polarized cells, with a sparse but clearly defined microvillar surface facing the growth medium and a basolateral surface attached to the substratum. Cultures grown on collagen gels did not show domes. The epithelial monolayer exhibited several differentiated functions of the proximal tubule: a) parathyroid hormone (PTH)-stimulated cAMP synthesis; b) production of 24,25-dihydroxyvitamin D3 from 25-hydroxyvitamin D3; c) high alkaline phosphatase activity; and d) Na+-dependent transport of phosphate (Pi) and alpha-methylglucoside (alpha-MG). The sugar uptake was selectively inhibited by phlorizin, a competitive inhibitor of glucose uptake at the luminal membrane. Kinetic analysis revealed independent transport systems for Pi and alpha-MG, with Km values corresponding to the high affinity systems identified in brush border membrane vesicles derived from the proximal tubule. Pi uptake by the epithelial monolayers was regulated by the concentration of Pi in the growth medium. Phorbol esters and PTH did not exert an effect on Pi and alpha-MG transport in mouse primary cultures. The present study demonstrates that primary cultures provide a useful in vitro preparation to investigate renal proximal tubular function.

24,25-Dihydroxyvitamin D 3↗
PubMed1988

Oral findings in patients with autosomal dominant hypophosphatemic bone disease and X-linked hypophosphatemia: further evidence that they are different diseases.

Oral examinations were performed on 5 patients with hypophosphatemic bone disease (HBD) (2 males and 3 females), 14 patients with X-linked hypophosphatemia (XLH), and 4 affected XLH relatives (6 males and 12 females). The control subjects were the unaffected siblings and parents of the patients and unrelated healthy, gender- and age-matched subjects. Serum phosphorus values were the same by disease type and gender in patients with HBD and XLH. They shared certain dental abnormalities, in particular pulpal necrosis and large pulp spaces. However, only patients with XLH had Class III malocclusions and mild enamel defects, and males with XLH had more severe occlusal and enamel defects than females with XLH. Different dental phenotypes are further evidence that XLH and HBD are different diseases. The dental abnormalities were not prevented by treatment, instituted early in life, which raised serum phosphorus to the near normal range.

Adolescent↗
PubMed1988

Decreased transport in renal basolateral membrane vesicles from hypertaurinuric mice.

Basolateral membrane vesicles were prepared from mouse kidney by use of a Percoll density gradient method. The preparation was enriched ninefold in Na+-K+-ATPase with minimal contamination by other cellular membranes. The basolateral membranes were a mixture of sealed inside-out and right-side-out vesicles (30%) and leaky vesicles or sheets (70%). Taurine uptake into basolateral membrane vesicles was osmotically sensitive, sodium dependent, temperature sensitive, inhibited by beta-alanine, and saturable (apparent Km, 360 microM; Vmax, 25.4 pmol.mg protein-1.15 s-1), indicating transport by a carrier-mediated process. The function of this transporter was examined in an inbred mouse strain, C57BL/6J, which has selective hypertaurinuria, presumably a result of decreased basolateral membrane permeability to taurine [Rozen et al., Am. J. Physiol. 244 (Renal Fluid Electrolyte Physiol. 13): F150-F155, 1983]. The sodium-dependent component of taurine uptake was significantly lower in C57BL/6J vesicles relative to control (C3H/HeJ strain): 2.9 +/- 0.7 vs. 9.4 +/- 0.3 (SE) pmol.mg protein-1.15 s-1, respectively; P less than 0.001. The interstrain difference in uptake was specific for taurine and could not be ascribed to differences in vesicle purification, integrity, orientation, or size. These findings indicate that the renal basolateral membrane is the site of a transport defect, which explains decreased net taurine reabsorption in vivo in the C57BL/6J strain, and corroborate earlier observations in the renal cortical slice preparation.

Animals↗
PubMed1988

Primary cultures of renal epithelial cells from X-linked hypophosphatemic (Hyp) mice express defects in phosphate transport and vitamin D metabolism.

Mutation in a gene (symbol Hyp) on the X chromosome causes hypophosphatemia in the mouse. The murine phenotype is a counterpart of X-linked hypophosphatemia in man. Both exhibit impaired renal reabsorption of phosphate in vivo. In vitro studies in the Hyp mouse have shown decreased Na+-dependent phosphate transport at the brush border membrane and abnormal mitochondrial vitamin D metabolism. To determine whether the mutant renal phenotype is intrinsic to the kidney or dependent upon putative extrinsic humoral factor(s) for its expression, we established primary cultures of renal epithelial cells from normal and Hyp male mouse kidneys. The cells are derived from proximal tubule. Initial uptake rates of phosphate and alpha-methyl-D-glucopyranoside (alpha-MG), a metabolically inert analogue of D-glucose, were measured simultaneously in confluent monolayers exhibiting epithelial polarity and tight junctions. The mean phosphate/alpha-MG uptake ratio in Hyp cultures was 82% of that in normal cells (P less than 0.01, n = 96). Moreover, the production of 24,25-dihydroxyvitamin D3 was significantly elevated in confluent cultures of Hyp cells relative to normal cells. These results imply that the Hyp gene is expressed in situ in renal epithelium and suggest that humoral factors are not necessary for the mutant renal phenotype in X-linked hypophosphatemia of mouse and man.

Animals↗
PubMed1987

Feasibility of chemical screening of urine for neuroblastoma case finding in infancy in Quebec.

Neuroblastoma is the most common fatal solid tumour of childhood. Studies in Japan suggest that screening urine at 6 months for tumour-derived metabolites greatly improves early case finding and prognosis. The incidence rate of neuroblastoma in Quebec is at least 1 per 10,330 live births, higher than that of all other diseases responding to early treatment except congenital hypothyroidism screened for in the Quebec Network of Genetic Medicine. The feasibility of chemical screening of urine for elevated levels of homovanillic acid and vanillylmandelic acid in Quebec was assessed. The cost-effectiveness of screening 100,000 infants per year would be high (cost-benefit ratio 2.4), with a net saving of about $280,000 and eight lives per year. The estimated cost of adding neuroblastoma screening to the existing urine metabolite screening program is $70,700. The apparent sensitivity of the proposed test is 0.859 and the rate of false-positive results about 0.1%, both acceptable values. The attitude of potential participants toward the present urine screening program and the addition of a "tumour test" was positive. The results indicate that a pilot study of neuroblastoma screening in Quebec could be undertaken.

Attitude to Health↗
PubMed1987

Audiometric evidence for two forms of X-linked hypophosphatemia in humans, apparent counterparts of Hyp and Gy mutations in mouse.

Two forms of X-linked hypophosphatemia occur in the mouse. One form, caused by the Hyp gene, is a counterpart of human X-linked hypophosphatemic "vitamin D-resistant rickets". The other, recently characterized, is caused by a different gene (Gy) closely linked to Hyp on the mouse X-chromosome. The Gy mutation also impairs cochlear function in the mouse. We measured hearing in 22 patients with X-linked hypophosphatemia; five, including 2 mother-son pairs, had sensorineural hearing deficits due to cochlear dysfunction. We suggest the disease in these persons may be the human counterpart of the Gy phenotype in the mouse, which implies there are 2 forms of X-linked hypophosphatemia in humans.

Adult↗
PubMed1987

Hyperphenylalaninemia due to deficiency of 6-pyruvoyl tetrahydropterin synthase. Unusual gene dosage effect in heterozygotes.

We have identified deficient biopterin synthesis in four probands and one sib with persistent postnatal hyperphenylalaninemia. The metabolic findings were associated with a benign clinical presentation and normal biopterin level in cerebrospinal fluid in the newborn period, indicating the peripheral (hepatic) form of this autosomal recessive phenotype. Impaired development was apparent at 3 months in one proband not treated early. Treatment with oral tetrahydropterin restored adequate phenylalanine hydroxylase activity; it also maintained or improved CNS function. The deficient enzyme in these subjects is 6-pyruvoyl tetrahydropterin synthase (PTS). Erythrocyte activity of PTS in homozygotes (or compound heterozygotes) is less than 10% of normal. Heterozygotes have 20%-50% of normal PTS activity (enzyme phenotype), a finding compatible with a range of gene dosage effects, some abnormal. The metabolic phenotype in heterozygotes (urine biopterin excretion) did not correlate with erythrocyte PTS activity. The complex relationship between erythrocyte PTS activity, and biopterin synthesis in these families indicates genetic heterogeneity at the PTS locus.

Alcohol Oxidoreductases↗