PubMed Health⌕ Search

Biomedical subjects

D B Caplan

Publications and source records attributed to D B Caplan.

14 recordsLinked to original sources
PubMed1992

Subacute necrotizing encephalopathy: oxidative phosphorylation defects and the ATPase 6 point mutation.

Subacute necrotizing encephalopathy (SNE) or Leigh's disease is associated with various defects in oxidative phosphorylation (OXPHOS). However, the relationships between these OXPHOS defects and nuclear DNA or mitochondrial DNA (mtDNA) mutations is still unclear. We evaluated three SNE pedigrees (two singleton cases and a pedigree) biochemically for OXPHOS abnormalities and genetically for four mtDNA point mutations. There was a complex I defect in all three pedigrees that was associated with a complex III defect in two individuals. An mtDNA mutation in the ATPase, subunit 6 gene (np 8993) was present in one SNE pedigree. This mutation was maternally inherited, heteroplasmic, produced marked clinical and biochemical heterogeneity between pedigree members, and varied along the maternal lineage at levels ranging from 0% to > 95% of the total mtDNAs. These mtDNA mutations were not present in the other two pedigrees. These observations emphasize the importance of screening for OXPHOS defects and mtDNA mutations in SNE cases.

Adenosine Triphosphatases↗
PubMed1991

Aerosol alpha 1-antitrypsin treatment for cystic fibrosis.

In cystic fibrosis neutrophil-dominated inflammation on the respiratory epithelial surface results in a chronic epithelial burden of the destructive enzyme, neutrophil elastase. alpha 1-antitrypsin (alpha 1AT), the main inhibitor of neutrophil elastase in lung, was given in aerosol form to 12 cystic fibrosis patients. It suppressed neutrophil elastase in the respiratory epithelial lining fluid (ELF) and restored the ELF anti-neutrophil elastase capacity when ELF alpha 1AT reached 8 mumol/l. This treatment also reversed the inhibitory effect of cystic fibrosis ELF on pseudomonas killing by neutrophils, which suggests that it may augment host defence in cystic fibrosis.

Adult↗
PubMed1986

Biliary atresia: an evolving perspective.

From 1967 to 1984, 50 of our patients with extrahepatic biliary atresia had surgical exploration. Of 40 biliary drainage procedures, bile drained in 21 (52%). Thirty-four patients had portoenterostomy, three had portocholecystostomy, and the most recent six patients had a valved hepatoduodenal conduit. Successful biliary drainage was related to the presence of microscopic ducts at the porta hepatis in 20 of 21 infants. Twenty patients are alive, 12 from two to six years postoperatively (one with a liver transplant). Seven have normal serum bilirubin values. Height and weight exceed the 50th percentile in 5/15 patients studied. Multiple episodes of cholangitis have occurred in 11 patients with portoenterostomy and two with hepatoduodenal conduits. In 12 patients, hemorrhage from the stoma necessitated closure of the stoma before 1 year of age. Five of the six patients with hepatoduodenal conduit are alive two years postoperatively.

Bile Ducts↗
PubMed1986

Low levels of pyridoxal 5'-phosphate in patients with cystic fibrosis.

To determine the effect of cystic fibrosis on the regulation of plasma pyridoxal 5'-phosphate (PLP), the biologically active form of vitamin B6, we measured this compound in plasma from 56 patients with cystic fibrosis. The concentration of PLP in plasma was assayed by a radioenzymatic technique. The results of this study showed that PLP concentration was decreased significantly (6.44 +/- 5.20 ng/mL, mean +/- SD; median 4.45 ng/mL) in patients with cystic fibrosis as compared with a group of hospitalized children with neither cystic fibrosis nor hepatic disease serving as a control group (13.2 +/- 5.04 ng/mL, mean +/- SD; median 12.5 ng/mL). Additionally, 25% of the population with cystic fibrosis exhibited exceedingly low plasma PLP level (less than 2.75 ng/mL). In patients with cystic fibrosis, significant inverse linear associations were found between plasma PLP and serum levels of SGOT and SGPT (PLP v SGOT: r = -.60, P less than .03; PLP v SGPT: r = -.50, P less than .03). This study demonstrated that a deficiency of plasma PLP is a common abnormality in cystic fibrosis and that the low PLP level may be a reflection of impaired vitamin B6 metabolism associated with this disorder.

Adolescent↗
PubMed1985

Platelet-monoamine oxidase activity in Reye's syndrome.

Platelet and liver monoamine oxidase (MAO) activity (mean +/- SD) was evaluated in patients with liver-biopsy-proven Reye's syndrome. MAO was measured by a radioenzymatic technique with [3H]tyramine as a substrate. A marked decrease in MAO activity [3.3 +/- 2.4 nmol of [3H]4-hydroxyphenylacetic acid formed X (mg protein)-1 X h-1] was observed in platelets on admission in all patients (n = 13) with Reye's syndrome when compared with hospitalized patients without liver disease (n = 8) [9.8 +/- 2.5 nmol of [3H]4-hydroxyphenylacetic acid formed X (mg protein)-1 X h-1] and with liver disease (n = 10) [9.1 +/- 2.0 nmol of [3H]4-hydroxyphenylacetic acid formed X (mg protein)-1 X h-1]. Following recovery from the disease, platelet MAO approached levels that were not significantly different from those of controls. Contrastingly, reduction of hepatic MAO in Reye's syndrome was similar to that seen in patients with liver disease of different etiologies. These studies suggest that reduced platelet MAO activity is a specific abnormality in Reye's syndrome, and it may be representative of generalized impairment of mitochondrial function in these patients. Furthermore, the pattern of liver and platelet MAO activity in Reye's syndrome may allow for the differentiation of this disease from other hepatopathologic conditions.

Adolescent↗
PubMed1979

Evidence for hypertyraminemia in Reye's syndrome.

Utilizing a specific and sensitive radioimmunoassay, palsma and urine tyramine were measured in 14 consecutive patients with liver biopsy-proven Reye's syndrome. Plasma tyrosine was measured in 11 of these patients. The results revealed significant (P less than .003) elevation in plasma (3.4 +/- .52 ng/ml) (mean +/- SEM) and urine (1.00 +/- .26 mg/24 hr) tyramine as well as plasma tyrosine (204 +/- 52.5 mumole/liter) at the onset of the disease when compared to the levels of tyramine and tyrosine in a group of hospitalized patients without hepatic disorders. Furthermore, there was a positive correlation between plasma tyramine and days in coma (r = .86; P less than .001), and between plasma tyramine and tyrosine (r = 0.80; P less than .001). These data suggest that there is s substantial disturbance of tyrosine metabolism in Reye's syndrome and that the accumulation of this amino acid and its metabolite, tyramine, may contribute to the encephalopathy of this disease.

Adolescent↗
PubMed1978

Quantitative changes of serum lipoprotein-X after cholestyramine administration in infants with cholestatic biliary tract and liver disease.

Lipoprotein-X (LP-X) was determined before and after the administration of cholestyramine in fifty-five infants with persistent cholestatic jaundice to differentiate between intra- and extrahepatic disease. In twenty-seven infants with biliary atresia, serum LP-X prior to cholestyramine ranged from 0.87 to 11.42 g/l (mean: 3.43 g/l; the average concentration was significantly lower (P less than 0.001) in males. After cholestyramine, LP-X rose in twenty-three, remained the same in two, and decreased slightly in two infants. Serum LP-X was present in twenty of the twenty-eight infants with intrahepatic cholestasis prior to cholestyramine in concentrations from 0.84 to 14.19 g/l (mean: 3.13 g/l). After cholestyramine, LP-X decreased in all by an average of 78% (P less than 0.005). The other eight infants did not have LP-X before or after cholestyramine. This study shows that LP-X in the serum of infants with cholestatic jaundice indicates severe cholestasis, but is not itself diagnostic of biliary atresia. The differentiation of biliary atresia from other diseases is readily achieved, as the administration of cholestyramine for 2-3 weeks causes a marked decrease of serum LP-X in patients with patent extrahepatic bile ducts. The absence of serum LP-X excludes biliary atresia.

Bile Ducts, Intrahepatic↗