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Biomedical subjects

G L Feldman

Publications and source records attributed to G L Feldman.

At least 55 records · Page 3Linked to original sources
PubMed1988

Recombinations between IRP and cystic fibrosis.

A candidate gene for cystic fibrosis was recently isolated by selective cloning of HpaII-tiny-fragment islands; it maps considerably closer to CF than does MET or D7S8 (pJ3.11), and DNA polymorphisms from this region are in marked disequilibrium with CF. cDNA cloning has shown that this protein has a growth factor-like structure and shows homology to the murine and human proto-oncogene int-1; it is designated IRP (int-1-related protein). DNA sequences from the IRP locus that recognize RFLPs are proving to be highly informative for prenatal diagnosis. We report five crossovers that have been identified which occur either within the IRP locus or between IRP and CF; these recombinants demonstrate that CF maps between the DNA markers D7S8 and KM.19.

Cystic Fibrosis↗
PubMed1981

Deficient acetyl CoA carboxylase activity in multiple carboxylase deficiency.

Multiple carboxylase deficiency has previously been characterized by deficient activity of three biotin-dependent enzymes: propionyl CoA carboxylase, pyruvate carboxylase and beta-methylcrotonyl CoA carboxylase. We have demonstrated that the activity of a fourth carboxylase, acetyl CoA carboxylase (ACC), is also deficient in fibroblasts from two patients with this disorder. Furthermore, ACC activity increased six- to eight-fold when cells from these patients were incubated in culture medium containing supplemental biotin. If the primary defect in multiple carboxylase deficiency is due to deficient activity of holocarboxylase synthetase, our results would indicate that there may be a common holocarboxylase synthetase, or at least a common subunit, for all the carboxylases. Finally, since ACC catalyzes the initial step in fatty acid biosynthesis, our results further suggest the importance of dietary supplementation with fatty acids in addition to treating these patients with pharmacologic doses of biotin.

Acetyl-CoA Carboxylase↗
PubMed1981

Biochemical characterization of biotin-responsive multiple carboxylase deficiency: heterogeneity within the bio genetic complementation group.

Three biotin-dependent enzymes, pyruvate carboxylase (PC), propionyl CoA carboxylase (PCC), and beta-methylcrotonyl CoA carboxylase (beta MCC), were biochemically characterized in fibroblasts from two patients with neonatal multiple carboxylase deficiency. Genetic complementation analyses indicated that both cell lines, designated lines 1 and 2, were deficient in the various carboxylase activities and belonged to the bio complementation group. The activities of the three carboxylases became normal when line 2 cells were incubated in medium supplemented with biotin (1 mg/l) for 24 hrs, whereas 4-6 days were required to achieve maximum activities of PC, PCC, and beta MCC (57%, 46%, and 29% of mean normal enzyme activity, respectively) in line 1 cells incubated in medium containing up to 10 mg/1 biotin. Furthermore, PC activity in line 2 continued to increase under apparent gluconeogenic conditions in culture, but not in line 1. Thermostability studies suggested that biotin stabilizes PC and beta MCC in both cell lines. PC in line 1 cells incubated with or without biotin was less stable than that in normal or line 2 cells, and the less than normal increase of enzyme activities in line 1, especially that of PC, may represent incomplete biotination. These results indicate that there is biochemical heterogeneity within the bio complementation group. Immunotitration with antibodies prepared against purified pig heart PCC demonstrated normal quantities of cross-reacting material in both lines and no differences in the amount of this material after incubation with supplemental biotin, despite the seven- to 20-fold increase in PCC activity. Thus, the increase in carboxylase activity in both bio lines appears to represent activation of rpe-existing apocarboxylase rather than de novo enzyme synthesis. The primary defect in this form of multiple carboxylase deficiency may be in a common holocarboxylase synthetase or in biotin transport. If the defect is in the synthetase, the differences noted between the two bio lines could be explained by a difference in the enzyme's Km for biotin.

Biotin↗
PubMed1980

Evidence for two genetic complementation groups in pyruvate carboxylase-deficient human fibroblast cell lines.

We have examined genetic complementation in pyruvate carboxylase deficiency by comparing the enzyme activity in polyethylene glycol-induced heterokaryons with that in unfused mixtures of fibroblasts from three affected children. Complementation, manifested as a three- to sevenfold increase in pyruvate carboxylase activity, was observed in fusions between a biotin-responsive multiple carboxylase (pyruvate carboxylase, propionyl CoA carboxylase, and beta-methylcrotonyl CoA carboxylase) deficient fibroblast line and two other lines deficient only in pyruvate carboxylase activity. Kinetic analysis of complementing pyruvate carboxylase deficient lines, measured by the rate of restoration of enzyme activity as a function of time, revealed that maximum restoration was achieved within 10-24 hr after fusion. This profile is similar to those oberved for fusions between the multiple carboxylase deficient line and two lines deficient in propionyl CoA carboxylase activity that are known to represent different gene mutations. Although the patients with pyruvate carboxylase deficiency had similar clinica findings, our studies indicate that pyruvate carboxylase deficiency is genetically heterogeneous, with at least two distinct, probably intergenic, complementation groups.

Biotin↗
PubMed1977

The fetal trimethadione syndrome: report of an additional family and further delineation of this syndrome.

We describe a family in which seven pregnancies resulted in four infants who died and in three abortions. During these pregnancies the mother took trimethadione (Tridione), as well as other anticonvulsants. Two normal children were born after treatment with all medications were stopped. There have now been 53 reported pregnancies in which the fetuses were exposed to trimethadione or paramethadione; 48 (87%) resulted in fetal loss or a child born with congenital malformations. The most common defects include malformed ears, cleft palate, cardiac defects, urogenital malformations, and skeletal abnormalities. Delayed mental and physical development were also seen. These findings constitute a clinical entity termed the fetal trimethadione syndrome. The malformation rate is believed to be due to the teratogenic effects of trimethadione. Physicians need to be aware of the danger of trimethadione and related drugs during pregnancy and should withhold these medications during this period.

Abnormalities, Drug-Induced↗
PubMed1975

The influence of exogenous PMS and HCG on the arachidonic acid content of the immature rat ovary.

The influence of exogenous PMS and/or HCG, on the arachidonic acid (C 20:4omega6) content of the immature rat ovary was examined. Changes in ovarian arachidonate content associated with hormone administration were assessed in total lipid extracts, and in several neutral and phospholipid fractions. Both relative percentage and absolute amounts of arachidonic acid in several lipids were measured as well as uptake of radioactivity into total lipid resulting from the administration of 3H-labeled arachidonic acid in vivo. On the basis of these studies, we conclude (1) PMS, with or without HCG promotes increased uptake of exogenous arachidonic acid into ovarian total lipids; (2) Arachidonic acid is a mojor fatty acid constituent from noncholine containing phosphatides at the onset of normal estrous (ca. 38 days) even in the animals which received no PMS or HCG; (3) Changes in ovarian arachidonic acid levels following gonadotropin administration are more striking in the two phospholipid fractions than in the two neutral lips examined; (4) PMS is associated with a rapid outpouring of ovarian lipid, accompanied by a high turnover of arachidonic acid which is enhanced or modified temporally by added HCG in vivo. These results provide the first quantitative evidence that gonadotropins may regulate prostaglandin biosynthesis in the ovary by their effects on the uptake, storage, or release of arachidonic acid, a major PG precursor, from specific ovarian lipids. While the data strongly suggest that the regulation of one or more ovarian esterases (cholesterol esterase, lipase, phospholipase) is the mechanism by which gonadotropins regulate PG biosynthesis, a direct action on PG synthetase is not ruled out.

Animals↗
PubMed1975

Photokeratoscopy in the fitting of soft contact lenses.

Our ultimate goal is to develop a photokeratoscopic system that will enable the fitter to select an initial lens of the proper design and power to fit a given eye and with reasonable assurance that further fitting will rarely be required. Our studies in this direction have carried us through to a prefitting screening system for the Bausch and Lomb Soflens that greatly increases the probability of successful fitting (and which demonstrates the importance of corneal shape in the successful fit of this lens) to a highly promising experimental system that is applicable to larger lenses with spherical base curves. The development of this computer-assisted fitting system is highly desirable. It will make the fitting a much simpler and efficient process with much less trauma to the eye and a marked reduction in the risk of accidental infection than with trial lens fitting. But, a second desirable effect that is not readily apparent is the use of the computer to drive fabrication equipment to manufacture lenses on a custom-fit basis to obtain the maximum in physiological tolerance that these lenses are capable of delivering. In either case, the patient is the ultimate beneficiary and that should always be our major goal.

Adolescent↗