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Biomedical subjects

D W Lundgren

Publications and source records attributed to D W Lundgren.

29 records · Page 2Linked to original sources

Fluctuations of unbound whole blood polyamine levels during the menstrual cycle.

Perchloric acid-extractable whole blood spermidine and spermine concentrations were determined over a 4-week period in three men, four women, and one ovariectomized woman. Individual male spermidine/spermine ratios showed little fluctuation and similar values were obtained for each of the three males studied. Male spermidine and spermine concentrations, although stable for each male, varied from one subject to the next. Individual female spermidine/spermine ratios, as well as individual concentrations, fluctuated substantially when compared to those valued obtained for males; female ratios appear to rise and fall as a function of the menstrual cycle. The spermidine/spermine ratios obtained from a normal female receiving oral contraceptive, as well as those from an ovariectomized female, were characteristic of values obtained form men. It is suggested that a sex-related hormone(s) influences sperimidine and spermine concentrations in females.

Adult↗

Distribution of spermidine and spermine in blood from cystic fibrosis patients and control subjects.

Previous studies have shown an abnormality of the spermidine-to-spermine (Spd/Spm) ratio in whole blood of cystic fibrosis homo-and heterozygotes. To investigate Spd and Spm distribution amoung blood components as a possible cause of the abnormality, blood was fractionated using Rabinowitz's glass bead technique and Boyum's Ficoll-Hypaque method. Free (unconjugated) polyamines were extracted with perchloric acid and quantitated on an amino acid analyzer. In controls, mean +/- SEM concentrations in nmoles/10(9) cells of Spd and Spm, respectively, were 1.02 +/- 0.08 and 0.894 +/- 0.28 for erythrocytes; 126 +/- 31 and 357 +/- 105 for lymphocytes; 36 +/- 16 and 240 +/- 33 for granulocytes; and less than 0.5 and less than 0.5 nmoles/ml for plasma. When converted to the concentration in whole blood, it was found that greater than 90% of Spd and over 70% of Spm was associated with erythrocytes. While the higher cellular concentration in leukocytes was not unexpected, the fact that Spd and Spm in whole blood were primarily associated with erythrocytes was a new finding. Comparison with controls revealed that the Spd/Spm ratio in both whole blood and erythrocytes was significantly higher in the group of cystic fibrosis patients.

Cell Fractionation↗

Polyamine alterations in blood of male homozygotes and heterozygotes for cystic fibrosis.

The polyamines, spermidine and spermine, have been measured in whole blood extracts from control volunteers, patients with cystic fibrosis, and obligate cystic fibrosis heterozygotes. Male homo- and heterozygotes for cystic fibrosis exhibit a consistent and significant decrease in blood spermine resulting in an elevated spermidine/spermine ratio when compared to control males. In contrast, control females exhibited reduced spermidine and spermine levels as compared to control males. Blood from female cystic fibrosis homo- and heterozygotes showed similar results. The sex difference is probably due to fluctiations of blood polyamines during the menstrual cycle. Abnormal polyamine levels are the first observation of an alteration of a low molecular weight metabolite characteristic of both male homo- and heterozygotes for cystic fibrosis.

Cystic Fibrosis↗

Neonatal glycine encephalopathy: biochemical and neuropathologic findings.

A patient with neonatal glycine encephalopathy who had severe neurologic retardation, spasticity, and seizures died at 17 years of age. Glycine concentration was markedly elevated in brain tissue, especially in the cerebellum. Neuropathologic study revealed spongy myelinopathy throughout the central nervous system and calcium oxalate crystals in the cerebellum, which are probably derived from degradation of glycine. Myelinopathy appeared to be static compared to neonatal patients. The neurologic manifestations of neonatal glycine encephalopathy are probably due to neurotransmitter abnormalities, not to myelin damage.

Adolescent↗

Cyclooxygenase inhibitors decrease apoptosis initiated by actinomycin D, cycloheximide, and staurosporine in amnion-derived WISH cells.

Apoptosis is a process by which external or developmental factors induce a specific series of events leading to cell death. Recently, apoptotic cells have been described in rat amnion membrane at late gestation, suggesting apoptosis may be involved in membrane rupture. Mechanisms controlling amnion cell apoptosis are unknown. The objective of this study was to investigate whether cyclooxygenase and prostaglandins are integral to apoptosis in amnion, as reported in intestinal epithelial cells and renal mesangial cells. Amnion-derived WISH cells underwent apoptosis in a dose- and time-dependent manner after incubation with actinomycin D, cycloheximide, or staurosporine, as determined by cell viability, DNA fragmentation analysis, and fluorescent in situ fragmentation analysis. Cells cultured with increasing doses of these agents also demonstrated concomitant increases in prostaglandin E2 output. WISH cell coincubation with these agents and the cyclooxygenase inhibitors indomethacin or piroxicam resulted in dose-dependent decreases in both prostaglandin E2 and apoptosis. Cultures incubated with 0.5 microgram/mL actinomycin D showed 80.7% cell apoptosis after 12 hours compared with 1.1% in untreated cultures. After 24 hours incubation with actinomycin D, 0.8% of the original cell number remained attached to the plate. In cultures coincubated with 0.5 microgram/mL actinomycin D and 100 mumol/L indomethacin, only 19.2%, 24.7%, and 39.3% of the cells were found to be apoptotic after 12, 24, and 48 hours in culture, respectively. Similar trends were observed after the use of cycloheximide or staurosporine in combination with indomethacin or prioxicam. These data suggest that cyclooxygenase and/or prostaglandins play a role in programmed cell death of amnion-derived WISH cells in culture.

Amnion↗