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Biomedical subjects

C R Scriver

Publications and source records attributed to C R Scriver.

At least 199 records · Page 11Linked to original sources
PubMed1981

Autosomal hypophosphataemic bone disease responds to 1,25-(OH)2D3.

We diagnosed non X-linked hypophosphataemic bone disease in a 38-month-old girl. Findings included: genu varum, shortened stature, fasting hypophosphataemia (2.3-2.5 mg/100 ml; 0.74-0.81 mmol/l), diminished theoretical renal threshold for phosphate (TmP/GFR), and osteomalacia without rickets. One patient (the father) had fasting hypophosphataemia (2.3-2.7 mg/100 ml; 0.74-0.87 mmol/l) and low TmP/GFR without osteomalacia or shortened stature. Treatment of the girl with 1,25-(OH)2D3 (1 microgram a day) raised the level of serum phosphorus, improved tubular reabsorption of phosphate, and healed the bone deformity; this combination of responses is not present in X-linked hypophosphataemia. There was no correction of hypophosphataemia or TmP/GFR with 1,25-(OH)2D3 treatment (1-3 micrograms a day) in the father.

Adult↗
PubMed1981

Effect of 1,25-dihydroxyvitamin D3 on phosphate homeostasis in the X-linked hypophosphatemic (Hyp) mouse.

We studied the effect of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on homeostasis of inorganic phosphate (Pi) in murine hypophosphatemia (Hyp), a homologue of X-linked hypophosphatemia (XLH) in man. Normal mice given 1,25-(OH)2D3 (83 pg/g.d) by continuous subcut, infusion x 10 d) had a significant rise in plasma calcium (Ca) (p less than 0.001), plasma Pi (p less than 0.025) and fractional Ca excretion (p less than 0.001), without change in fractional Pi excretion or Na+-stimulated Pi transport in purified renal brush-border membrane vesicles (BBMV). Hyp littermates did not respond to this dose of 1,25-(OH)2D3. At 415 pg/g.d, Hyp mice had increased plasma Ca (p less than 0.001), fractional Ca excretion (p less than 0.001), and plasma Pi (p less than 0.001) but no change in either fractional Pi excretion or Na+-stimulated Pi transport in BBMV. At this dose, 1,25-(OH)2D3 also stimulated Pi transport by everted sacs of Hyp small intestine (p less than 0.001). No deficiency of Pi transport was found in untreated Hyp intestine. We conclude that 1,25-(OH)2D3 improves Pi homeostasis in the Hyp phenotype by its effect on intestine; the defect in renal Pi reabsorption remains unchanged.

Animals↗
PubMed1981

X-linked hypophosphatemia: effect of calcitriol on renal handling of phosphate, serum phosphate, and bone mineralization.

Eleven patients with the Mendelian phenotype of x-linked hypophosphatemia (XLH) were treated with calcitriol [1,25-(OH)2D3] and phosphate. Ten patients had received prior treatment with ergocalciferol and phosphate. Five subjects were prepubertal and six were postpubertal. Response to calcitriol was measured under nonfasting and overnight fasting protocols. Bone biopsies were obtained before and after treatment. Calcitriol (mean dose, 30 ng/kg. day) 1) raised serum phosphorus uniformly in prepubertal patients but in only two of six postpubertal subjects; 2) did not change the theoretical renal phosphate threshold in the total patient group and thus had no effect on the primary transport defect in XLH; 3) improved trabecular bone mineralization in the total patient group, as determined by bone histomorphometry. The beneficial effect on extracellular phosphorus homeostasis was attributed to improved intestinal absorption of phosphorus; improvement in bone mineralization may reflect an additional effect of 1,25-(OH)2D3 on bone itself in XLH. Mild transient hypercalcemia occurred during 0.6% of 3545 treatment days and was readily controlled by adjusting the dosage of 1,25-(OH)2D3.

Adolescent↗
PubMed1981

Outcome of early and long-term management of classical maple syrup urine disease.

The outcome of 8,400 treatment days in the lives of four patients with classical maple syrup urine disease (MSUD) (present ages: 1 3/12, 5 7/12, and 8 11/12 years) are described. Each diagnosis was made by clinical signs rather than by newborn screening. Acute-phase treatment beginning on the 11th day of life comprised peritoneal dialysis, intravenous lipid, and early intestinal alimentation. Mean age at discharge from hospital was 29 days. There were 16 readmissions to the hospital for the group (89 days, 1.05% treatment days) without any serious neurologic symptoms. The mean level of plasma leucine for the group (for levels below 1 mM) during treatment was 0.42 mM (normal for age range, 0.077 +/- 0.021 mM [mean +/- SD]). Plasma leucine exceeded 1 mM during 1.02% of treatment days (representing 8.6% of 1,042 measurements. Mean levels of plasma valine and isoleucine were 60% and 70% of the plasma leucine value for the group. Tolerance for dietary leucine did not exceed 620 mg/day in any patient. Somatic growth was normal and the mean current IQ/development quotient (DQ) score is 101 (range 89 to 117); the three oldest patients attend regular schools. A characteristic EEG pattern resembling the teeth of a comb was observed in three patients during the acute phase in the newborn period but not during long-term treatment. These results were obtained in an ambulatory program with home visiting.

Child↗
PubMed1981

Metabolic abnormalities in the idiopathic Fanconi syndrome: studies of carbohydrate metabolism in two patients.

Two patients with idiopathic Fanconi syndrome and glucose intolerance were studied from a metabolic perspective. They had fasting hyperglycemia, massive glucosuria, insulinopenia, ketosis, and elevated serum free fatty acids. There was a markedly blunted insulin secretory response to glucagon, tolbutamide, glucose, and arginine. One patient had the findings of diabetic retinopathy and a sensory neuropathy. Neither patient could convert galactose to glucose, but they did not have galactosemia. As a result of these studies, and previous reports in which similar changes were noted, we conclude that diabetes mellitus may occur in patients who have had idiopathic Fanconi syndrome for many years.

Adolescent↗
PubMed1980

The relationship of 4-aminobutyric acid metabolism to ammoniagenesis in renal cortex.

Mitochondrial 4-aminobutyrate aminotransferase in rat kidney can utilize pyruvate as the acceptor for the amino group of 4-aminobutyrate. Renal 4-aminobutyrate aminotransferase activity at saturating equimolar concentration of 4-aminobutyrate and 5 mM pyruvate is 42.8 +/- 2.5 mumol/g protein per h (mean +/- S.E.M.) or 70% of 4-aminobutyrate aminotransferase activity with equimolar alpha-ketoglutarate. 4-Aminobutyrate aminotransferase in brain does not transaminate with pyruvate. Since pyruvate is an important mitochondrial metabolite in kidney, net disposal of glutamate via the 4-aminobutyrate pathway is possible. The renal 4-aminobutyrate pathway in the rat has other distinctive features when compared with the pathway in rat brain. Most inhibitors of rat neuronal glutamate decarboxylase were ineffective against the renal form of the enzyme, but 20 mM semicarbazide inhibited the latter form by 80% (P < 0.001) in vitro and reduced renal 4-aminobutyrate content by 75% (P < 0.001) in vivo. In the presence of 20 mM semicarbazide, ammoniagenesis by rat renal cortex slices incubated in 1 mM glutamine was inhibited 26% (P < 0.01). Semicarbazide was proportionately less effective (15% inhibition) when ammonia-genesis was stimulated (+243%) in slices prepared from chronically acidotic animals, and was no deterrant to ammoniagenesis when non-acidotic slices were incubated in supraphysiologic concentrations of 10 mM glutamine. We conclude that whereas integrity of the renal 4-aminobutyrate pathway may contribute to glutamate disposal and thus ammoniagenesis under physiologic conditions, the pathway is a passive participant in the overall process of ammoniagenesis.

4-Aminobutyrate Transaminase↗
PubMed1980

Age-dependent serum sulfate levels in children and adolescents.

We measured inorganic sulfate in 100 microliters of deproteinized serum by microassay, using the 133Ba precipitation method. Infants and children under 3 yr (n = 46), children from 3 to 9 yr of age (n = 27) and adolescents (10-18 yr, n = 12) in a hospitalized population, and healthy adults (n = 10), were studied. An age-dependent curvilinear regression for serum sulfate characterizes the first group: the mean serum sulfate value falls from 0.47 mmol/l on the first day of life to 0.33 mmol/l at 36 months. Thereafter the mean value is about 0.33 mmol/l. The 95% confidence intervals were defined for each group.

Adolescent↗
PubMed1980

Alkaline phosphatase activity does not mediate phosphate transport in the renal-cortical brush-border membrane.

We studied (1) the effect of primary modulators of phosphate transport, namely the hypophosphataemic mouse mutant (Hyp) and low-phosphorus diet, on alkaline phosphatase activity in mouse renal-cortex brush-border membrane vesicles and (2) the effect of several primary inhibitors of alkaline phosphatase on phosphate transport. Brush-border membrane vesicles from Hyp-mouse kidney had 50% loss of Na+-dependent phosphate transport, but only 18% decrease in alkaline phosphatase activity. The low-phosphorus diet effectively stimulated Na+/phosphate co-transport in brush-border membrane vesicles (+ 118%), but increased alkaline phosphatase activity only slightly (+13%). Levamisole (0.1 mM) and EDTA (1.0 mM) inhibited brush-border membrane-vesicle alkaline phosphatase activity of 82% and 93% respectively, but had no significant effect on Na+/phosphate co-transport. We conclude that alkaline phosphatase does not play a direct role in phosphate transport across the brush-border membrane of mouse kidney.

Alkaline Phosphatase↗
PubMed1980

Cord-blood tyrosine levels in the full-term phenylketonuric fetus and the "justification hypothesis".

The "justification hypothesis" attributes mental retardation in phenylketonuria (PKU) to an inability of the heterozygous mother to deliver an appropriate amount of tyrosine to the PKU fetus who, in turn, is unable to correct for this deficiency because of its genetic constitution. We tested this hypothesis by measuring concentrations of tyrosine and phenylalanine in cord blood obtained at delivery from nine infants with PKU and five infants with persistent (non-PKU) hyperphenylalaninemia (PHP). For each of these specimens there were four control cord-blood specimens from infants born on the same day and, generally, in the same hospital. PKU and PHP groups were similar with respect to cord-blood tyrosine and phenylalanine values. There was no biologically significant deficiency of tyrosine in cord blood of the pooled PKU and PHP deficiency of tyrosine in cord blood of the pooled PKU and PHP groups (54 +/- 10 microM, mean +/- SD) compared with controls (61 +/- 16 microM, P = 0.13). On the other hand, phenylalanine in cord blood of the pooled PKU and PHP groups was significantly increased (144 +/- 30 microM, mean +/- SD) compared with controls (128 +/- 24, P = 0.004). The mangitude of the differences in cord-blood tyrosine and phenylalanine between control and PKU subjects are so small that it is unlikely that they have any consequences for physical and mental development. The justification hypothesis, as it pertains to blood tyrosine at term, is not upheld.

Female↗
PubMed1980

Tubular reabsorption of alpha-aminoisobutyric acid in the pre-steady-state. Evidence for a cell-to-lumen flux.

We investigated time-dependent and concentration-dependent renal handling of alpha-aminoisobutyric acid (AIB) in the rat during seven consecutive 30-min clearance periods after onset of AIB infusion. Following low-level rapid venous infusion of AIB (9.75 mumol/kg in 30 s), plasma [AIB] fell exponentially in the initial three periods and in linear fashion (-0.00158 microM/min) thereafter. Although filtered AIB fell in proportion to plasma [AIB] during the early clearance periods (5--125 min), fractional excretion of AIB (FEAIB) rose (delta FEAIB = + 0.077 +/- 0.010, mean +/- SD) and stabilized only in later clearance periods (125--215 min). Saturable intrarenal binding does not explain rising FEAIB with falling plasma [AIB] because sequential infusions of AIB, 120 min apart, also elicited the phenomenon after each infusion. During continuous infusions of AIB, time dependence of FEAIB was also observed, in the early interval (5--95 min), after onset of AIB infusion at various concentrations of plasma [AIB] below 3 mM approximately. Measurement of concentration-dependent net tubular reabsorption of AIB in the fourth through seventh clearance periods (near the steady state) revealed progressive saturation over the whole range of plasma [AIB] (0--12 mM), yet with a collapse of net reabsorption in the plasma [AIB] range 2--4 mM. Measurements of renal tissue AIB in these experiments revealed that cellular AIB is of sufficient magnitude and bears such a relationship to plasma AIB and FEAIB that it could contribute to an observable cell-to-lumen movement of amino acid in the "pre-steady-state" situation and could account for the rise in FEAIB following AIB infusion and the collapse in tubular reabsorption of AIB at 2--4 mM plasma [AIB].

Absorption↗