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Biomedical subjects

I Warren

Publications and source records attributed to I Warren.

12 recordsLinked to original sources
PubMed1997

Effect of solid and liquid diet on uptake of large particulates across intestinal epithelium in rats.

The effect of diet composition on the uptake of particulates across the gastrointestinal epithelium has been examined in fasted male weanling Sprague-Dawley rats by estimating the systemic uptake of orally administered 2-microns latex polystyrene microspheres. Using a tissue solubilization assay, particle transfer in animals maintained on a fluid diet was determined. A larger number of particles was transferred from the gut lumen to the internal organs, including the mesenteric lymph node, spleen, bone marrow, liver, kidney, and heart of animals fed solid pelleted diet than those maintained on a fluid-diet 4 hr after oral administration of particles. The increase in particle number in rats fed the solid diet was only statistically significant (P < 0.05) for brain tissue in the analysis for trend. However, the number of particles retained in the proximal region of the gut at the end of this period was greater in animals fed the fluid diet. This work demonstrates that diet composition is important in gastrointestinal transepithelial translocation of microspheres.

Adolescent↗
PubMed1992

Increased globotriaosylceramide in familial dysautonomia.

Familial Dysautonomia (FD) is an autosomal recessive disease of unknown etiology, occurring primarily in Ashkenazi Jews. Patients are neurologically impaired, with deficits primarily in autonomic and sensory functions. The biochemical and genetic defects have remained elusive, precluding carrier detection and prenatal diagnosis. High-performance liquid chromatography data indicated up to a threefold increase in the neutral glycosphingolipid globotriaosylceramide in Dysautonomic fibroblasts and lymphoblasts. Total ganglioside values, measured by colorimetric, fluorometric or specific sodium borohydride incorporation, were decreased. Affected fibroblasts exhibited a range of pleomorphic phenotypes, such that the usual swirl-like confluent growth pattern of normal fibroblasts was distorted to varying degrees, suggesting abnormalities in the FD plasma membrane, possibly affecting cell-cell contacts. The glycosphingolipid increase could not be accounted for on the basis of markedly decreased alpha-galactosidase activity, as in Fabry's disease, where patients also display decreased autonomic function.

Cell Line↗
PubMed1989

Simultaneous fractionation of four placental neutral glycosphingolipids with a continuous gradient.

We describe a method for isolating milligram quantities of the four neutral glycosphingolipids, glucocerebroside, lactosylceramide, traiosylceramide, and globoside, from human placental tissue. This procedure is carried out on a silicic acid column eluted with a continuous chloroform-methanol gradient (19:1 to 4:1); the four glycosphingolipids elute as separate fractions with no need for further separation. The method is simple, rapid, and yields sufficient material to use as analytical standards for several hundred runs. The lipids have been identified by NMR spectroscopy. Placental tissue is freely available in most centers and is an excellent untapped source for these compounds. Given that lactosylceramide is not commercially available and that triaosylceramide (ceramide trihexoside) cannot be obtained in a reliable state, this technique represents an effective solution to this dilemma.

Glycosphingolipids↗
PubMed1986

Regulation of renal sulfoglycolipid biosynthesis.

The in vitro activity of the renal galactolipid sulfotransferase and the level of sulfated glycolipids in the rat kidney have been correlated as a function of age. The galactolipid sulfotransferase was found to be greatly reduced in the young as compared with the adult animal. The relatively minor changes in the sulfated glycolipid content of the kidney with age suggests that an increase in sulfoglycolipid turnover occurs during growth. An inhibitory activity was detected in the homogenate supernate of the young animal capable of reducing the in vitro sulfotransferase activity of the adult. Assay of the human renal galactolipid sulfotransferase showed that this enzyme activity is deleted in samples of the blastematous form of Wilm's renal tumor. The results suggest that the rate of synthesis of renal sulfoglycolipids may prove a marker of renal development, perhaps by post translational regulation.

Aging↗
PubMed1985

HPLC analysis of urinary sulfatide: an aid in the diagnosis of metachromatic leukodystrophy.

Metachromatic leukodystrophy (MLD) presents as six separate variant forms, four allelic and two non-allelic. It is diagnosed in the laboratory by a decrease in the fibroblast or leukocyte arylsulfatase A activity, generally against an artificial substrate. Since residual enzyme activity is not always an indicator of presence or absence of disease, it may be helpful to supplement this information with that of the presence or absence of sulfatide storage in the body. We have improved the HPLC analysis of sulfatide by the use of a sulfated internal standard, sulfatoxymonoalkylmonoacylgalactosylglycerol. Normal urines contain approximately 0 to 0.2 nmol sulfatide/mg creatinine, whereas MLD urines may contain 5 to 7.5 nmol/mg. There is no increase in plasma sulfatide compared to controls in the age group of MLD patients which we studied (up to 4 years).

Cerebroside-Sulfatase↗
PubMed1983

HPLC analysis of neutral glycolipids: an aid in the diagnosis of lysosomal storage disease.

Concentrations of GL-la (glucocerebroside) (8.36 nmol/ml), GL-2a (lactosylceramide) (4.03 nmol/ml), GL-3a (globotriosylceramide) (2.25 nmol/ml) and GL-4a (globotetraosylceramide) (2.87 nmol/ml) have been determined in normal plasma and compared to concentrations in the plasma from patients with Gaucher, Krabbe, Fabry, Sandhoff and Tay-Sachs diseases as well as with hypercholesterolemia. HPLC analysis of perbenzoylated glycolipid derivatives (isolated and purified by modification of an existing procedure) was performed on samples equivalent to 50 to 100 microliter of plasma. The sensitivity could be readily increased ten-fold. We have employed a novel internal standard-monogalactosyl diglyceride, a plant glycolipid, commercially available in pure form. Analysis was performed on a 5 micron ultrasphere silica column, using a gradient of isopropanol in hexane rather than the more usual dioxane in hexane. Our gradient exhibited an essentially flat baseline precluding the necessity of a reference cell. Recoveries of glycolipids added to plasma (95%), experimental yields (60%) and standard curves are presented and discussed. A method is also presented for the separation of GL-la and monogalactosyl diglyceride derivatives for rapid (8 minute) isocratic analysis of multiple samples from Gaucher patients. The benefits of such a simple, reproducible HPLC technique are discussed.

Chromatography, High Pressure Liquid↗
PubMed1980

Neonatal gut function, measured by the one hour blood D (+) xylose test: influence of gestational age and size.

D(+) Xylose absorption, assessed by one hour blood xylose levels, has been measured after intraduodenal infusion of the sugar in 35 infants of differing gestational age and size. The test was performed between the 2nd and 6th days of life. Full-term appropriately grown infants had higher blood xylose levels (1.41+/-0.07 mmol/l) at one hour than pre-term appropriately grown infants (1.17+/-0.07 mmol/l; P less than 0.05), or 'light for dates' infants, both full-term (0.73+/-0.06 mmol/l; P less than 0.001) and pre-term (0.96+/-0.17 mmol/l; P less than 0.05). Serial studies of 11 infants were made two to five times between the 3rd and 20th day of life. The levels for one hour xylose rose in all groups, but the 'light for dates' infants showed the least rise. There was no sign of catch-up in this group, and some results appeared to fall further behind those of appropriately grown infants. These results suggest that the primal small intestine is maturing in the perinatal period, and that intrauterine growth retardation may impair intestinal absorption. The nutritional significance is not known.

Administration, Oral↗