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Biomedical subjects

D M Nelson

Publications and source records attributed to D M Nelson.

At least 73 records · Page 4Linked to original sources
PubMed1990

Human placental insulin binding in normal and well-controlled diabetic patients.

Previous studies of insulin binding to placentas of both insulin-dependent and untreated gestational diabetic patients have described placentas from diabetics to contain fewer insulin receptors than placentas from nondiabetic gravidas. However, these studies were done using membrane fractions prepared from the placentas and at a time when adequacy of antepartum glycemic control in the diabetic patients was not routinely evaluated by self blood sugar measurement or hemoglobin A1 assay. The current study compares specific 125I-insulin binding in vitro to intact placental villi from 15 normal patients with insulin binding to intact villi obtained from 15 insulin-dependent diabetic mothers whose fasting and postprandial blood sugars and hemoglobin A1 levels were maintained in a range normal for term pregnancy. We demonstrate that insulin binding to intact placental villi is the same in this group of diabetic patients as in the nondiabetic patients.

Adult↗
PubMed1990

Trophoblast interaction with fibrin matrix. Epithelialization of perivillous fibrin deposits as a mechanism for villous repair in the human placenta.

The authors have used morphometric, immunocytochemical, and electron optical techniques to study fibrin deposits associated with villi from 14 normal term placentas, and have examined the response of cultured cellular trophoblast to fibrin matrix in vitro. Morphometric analysis of 3477 villous profiles showed that 5.5% of villi examined had fibrin deposition at sites of syncytial denudation and that fibrin deposition was highly associated with villous epithelial denudation, as evidenced by loss of cytokeratin staining. The perivillous fibrin deposits were strongly immunoreactive for the B beta chain of fibrin II, consistent with local thrombolytic cleavage of fibrinogen to fibrin. Deposits were frequently surfaced by a discontinuous layer of cytokeratin-positive trophoblastic cells that showed type IV basement membrane collagen immunoreactivity at the interface between trophoblast and fibrin. Ultrastructurally, damage to the syncytial trophoblast was apparent at the edge of some deposits, where syncytial denudation was accompanied by a fibrin coating of residual cellular trophoblast and the trophoblastic basal lamina. Other deposits were surfaced by syncytial trophoblast with underlying cellular trophoblast and a new basal lamina external to the basal lamina of the villous core. Cultured cellular trophoblast grown on a fibrin matrix, but not on uncoated plastic, showed morphologic differentiation into a trophoblast layer like that on term villi. The authors suggest that epithelialization of perivillous fibrin deposits is a form of villous repair and that trophoblast-fibrin interactions can modulate trophoblastic differentiation.

Chorionic Villi↗
PubMed1989

High glucose levels decrease proliferation of cultured human fetal cells from placenta.

We used the placenta as a source of undifferentiated cells to study the effect high glucose levels can have on human fetal cell proliferation in vitro. Cells were subcultured in a modified minimum essential medium with 10% fetal bovine serum containing either 5.5 mmol/L (100 mg/dl) D-glucose (control), 11 mmol/L (200 mg/dl) D-glucose, or 22 mmol/L (400 mg/dl) D-glucose. Cells grown in mannitol-containing media were used as controls for osmolality. After 3 and 7 days' growth in different media, the labeling index was determined by autoradiographic analysis, and cell numbers were determined with a Coulter counter. The labeling indices for cells grown 3 days in 11 or 22 mmol/L D-glucose were 89% (p less than 0.002) and 84% (p less than 0.001), respectively, of control cells grown in 5.5 mmol/L D-glucose. After 7 days' growth, the labeling indices of cells grown in 11 or 22 mmol/L D-glucose were 84% (p less than 0.002) and 70% (p less than 0.001), respectively, of cells grown in 5.5 mmol/L D-glucose media. There was a significant decrease in the number of cells present at both 3 and 7 days in cultures grown in 22 mmol/L D-glucose compared with control. We conclude that a few day's exposure to high glucose levels can have an effect on proliferation of human placental cells in vitro. We suggest that a glucose effect on proliferation of other cells derived from the products of conception might be one mechanism contributing to abnormal development in some pregnancies of diabetic women.

Autoradiography↗
PubMed1989

Aspirin differentially affects thromboxane and prostacyclin production by trophoblast and villous core compartments of human placental villi.

Low-dose aspirin has been used as prophylactic treatment for preeclampsia and fetal growth retardation, but the physiologic mechanisms for the beneficial effect of this therapy are unknown. We studied the effects of aspirin on eicosanoid production by different compartments of normal term human placental villi. Duplicate parallel incubations (n = 7) of whole villi, villous core tissues, and trophoblast were established on Millicell platform dishes in minimum essential medium in the presence or absence of 1 x 10(-4) or 1 x 10(-5) mol/L aspirin. Production rates of thromboxane A2 and prostacyclin were estimated by radioimmunoassay of their stable hydrolysis products, thromboxane B2 and 6-keto-prostaglandin F1 alpha, respectively. Our results indicate that 1 x 10(-4) mol/L aspirin inhibits thromboxane production in whole villi and villous core tissues denuded of their trophoblast layer but not in isolated trophoblast cells. The same concentration of aspirin also inhibits prostacyclin production in the isolated villous core but not in whole villi and not in isolated trophoblast. We conclude that aspirin can selectively inhibit thromboxane production in whole placental villi and differentially affects thromboxane and prostacyclin production by the trophoblast and villous core compartments.

Aspirin↗
PubMed1989

Thromboxane and prostacyclin production by different compartments of the human placental villus.

We separated the trophoblast and villous core of human placental villi to compare thromboxane (Tx) and prostacyclin production in these two compartments with eicosanoid production by intact villi. TxB2 and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), the stable metabolites of TxA2 and prostacyclin, respectively, were measured in serum-free media from 48-h incubations of intact villi, villous core tissue denuded of its trophoblast layer, and trophoblast cells. In villi, the medium TxB2 concentrations increased rapidly to a peak level of 20 +/- 9 (+/- SE) (n = 11) pg/microgram protein at 48 h; 6-keto-PGF1 alpha was first detected in medium at 20 h, and it increased to 19.6 +/- 4.0 pg/micrograms protein (n = 11) by 48 h. Compared to villi, villous core tissue denuded of its surface trophoblast layer had a 7-fold greater TxB2 level (136 +/- 17 pg/micrograms protein; n = 11) by 48 h, but a comparable level of 6-keto-PGF1 alpha (22.5 +/- 3.7 pg/micrograms protein). Trophoblast cultures produced predominantly TxB2 (109 +/- 18 pg/micrograms protein; n = 11) and had the lowest 6-keto-PGF1 alpha production among the three groups (11.4 +/- 2.6 pg/micrograms protein). At 48 h, the mean TxB2/6-keto-PGF1 alpha ratio was 1.0 in medium from intact villi, 6.2 in medium from villous core tissue, and 13.3 in medium from trophoblast cells. Indomethacin inhibited production of both eicosanoids in all cultures. Our studies indicate that intact placental villi produce equal amounts of Tx and prostacyclin, the trophoblast compartment produces predominantly Tx, and the villous core compartment produces an increased amount of Tx when denuded of its trophoblast layer. These data also suggest that the trophoblast produces an inhibitor or provides a catabolic function that limits villous core Tx production.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Pertussis toxin-sensitive G protein mediation of PGE2 inhibition of cAMP metabolism and phasic glucose-induced insulin secretion in HIT cells.

Although prostaglandin E2 (PGE2) is known to inhibit glucose-induced insulin secretion, it is uncertain whether PGE2 actions on the beta-cell are direct, whether they are equipotent for both phases of hormone secretion, and whether the same mechanism of action prevails throughout. Study of the HIT cell, a clonal line of pancreatic beta-cells, provides answers to these questions because perifusion with glucose and 3-isobutyl-1-methylxanthine stimulates biphasic insulin secretion. Perifusion with PGE2 decreased both the first and second phases of glucose-induced insulin release to 47 +/- 4% of controls. Pretreatment with pertussis toxin partly prevented PGE2 inhibition to 80 +/- 4% of controls for first phase and 79 +/- 4% of controls for second phase. To evaluate whether the partial prevention of PGE2 inhibition seen with pertussis toxin pretreatment was caused by Gi heterotrimer association between the preincubation period and the end of perifusion, PGE2 actions were also examined during continuous treatment with pertussis toxin. Under these conditions, PGE2 inhibition of both phases was totally prevented. However, no difference was observed in membrane protein ADP ribosylation when cells were examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis after pretreatment or continuous treatment with pertussis toxin. Cyclic AMP (cAMP) accumulation was inhibited by PGE2 (from 3263 +/- 153 to 1549 +/- 158 fmol/10(6) cells) but less so after pretreatment with pertussis toxin (correlation between insulin release and cAMP accumulation during perifusion; n = 18, r = .85, P less than .001). Thus, PGE2 equally inhibits both phases of glucose-induced insulin secretion and cAMP generation through a pertussis toxin-sensitive G protein-mediated direct effect on the pancreatic beta-cell.

1-Methyl-3-isobutylxanthine↗
PubMed1988

Cord blood acid-base status in neonates delivered by Silastic vacuum cup extraction: comparison with forceps and spontaneous deliveries.

Umbilical cord blood gases were measured as objective parameters of neonatal outcome in patients delivered by Silastic vacuum extractor and were compared with those values from patients delivered spontaneously, by forceps, or by sequential use of vacuum and forceps. The results demonstrated no clinically significant differences among the groups in cord blood pH, pCO2, pO2, base excess, or bicarbonate values. These observations provide reassurance that the Silastic vacuum extractor is a safe alternative for vaginal delivery of the appropriately selected term fetus.

Acid-Base Equilibrium↗
PubMed1986

Morphology and glycoprotein synthesis of uterine glandular epithelium in human basal plate at term: an ultrastructural and autoradiographic study.

This study describes the morphologic features of uterine glandular epithelium in human basal plate at term and identifies this epithelium as an active site of glycoprotein synthesis. Wedge biopsies were obtained from the basal plate at the time of repeat cesarean section from 11 normal pregnant patients at term. Biopsy specimens were either processed immediately for microscopic examination or incubated in vitro with 25 microCi/cc of 3H-galactose or 3H-leucine. Tissues incubated with tritiated compounds (2-hour pulse +/- 3-hour chase in nonradioactive medium) were either processed for light microscopic autoradiographic analysis or extracted for determination of trichloroacetic-acid-precipitable tritiated macromolecules in tissues and medium. Profiles of cuboidal-columnar glandular epithelium were identified in the decidual component of the basal plate region adjacent to spiral arterioles and perpendicular to the inner layers of myometrial muscle. Autoradiographic and biochemical studies identified the glandular epithelium, as well as large decidual cells, to be major sites of incorporation of both 3H-galactose and 3H-leucine and to be prime sources for secretion of tritiated macromolecules that appeared in the medium during in vitro incubation of basal plate tissue. Ultrastructurally, the glandular epithelium was noted to rest on a basal lamina, to have lateral cell membranes with numerous desmosomes, and to exhibit an apical surface with microvilli projecting into a luminal space. Cytologic features of the cells included abundant profiles of rough endoplasmic reticulum, multiple mitochondria with lamellar cristae, a well-developed perinuclear but nonpolarized Golgi apparatus,and nuclei containing predominantly euchromatin.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoradiography↗
PubMed1986

Reversal of a developmental restriction in neural crest-derived cells of avian embryos by a phorbol ester drug.

Neural crest cells and some of the crest-derived cells of dorsal root ganglia (DRG) of early avian embryos give rise to pigment cells when placed in culture. DRG from older embryos, however, fail to do so under comparable culture conditions. This age-dependent loss of melanogenic ability might be explained either by the death of a subpopulation of latent melanoblasts within early DRG, or the imposition of additional developmental restrictions in multipotent DRG cells. We show here that 12-O-tetradecanoylphorbol-13-acetate (TPA) causes some DRG cells to undergo pigmentation in cultures from older embryos, indicating that the loss of melanogenic ability in older embryos is not due to cell death. These pigment cells also display morphogenetic properties of normal melanocytes, including the ability to invade feather primordia. In addition to DRG, various other neural crest-derivatives contain cells similarly affected by TPA, including cells within sympathetic ganglia and peripheral nerves. We suggest that TPA reverses the developmental restriction of melanogenic ability that is normally imposed on neural crest-derived cells that migrate to various sites in avian embryos where melanogenesis does not normally occur.

Animals↗
PubMed1986

Association of prolonged, preterm premature rupture of the membranes and abruptio placentae.

Nine patients with prolonged, preterm premature rupture of the membranes (PROM) had associated abruptio placentae confirmed at delivery. Antepartum vaginal bleeding during the course of expectant management was the most common feature in the clinical course of the patients who developed abruptio placentae. Other clinical and laboratory findings suggesting the diagnosis were not present consistently. Retrospective analysis of all patients with prolonged, preterm PROM led to an estimated risk of 4% for the development of abruptio placentae during the course of expectant management of such patients. This risk estimate is three to eight times greater than that for the development of abruptio placentae in pregnancy generally. A high index of suspicion for abruptio placentae is appropriate when patients with prolonged, preterm PROM develop vaginal bleeding or any other suggestive clinical signs or symptoms of abruptio placentae during the course of expectant management.

Abruptio Placentae↗
PubMed1985

Glycosylated serum protein levels in diabetic and nondiabetic pregnant patients: an indicator of short-term glycemic control in the diabetic patient.

Measurement of the level of nonenzymatic glycosylation of blood proteins with more rapid turnover times than hemoglobin has been suggested as an indicator of time-averaged glucose control in nonpregnant diabetic patients. Using affinity chromatography, we have measured the levels of glycosylated serum proteins during pregnancy in 14 normal volunteers and 15 insulin-dependent diabetic patients. No relationship was noted between the percentage of glycosylated serum proteins in serum from normal patients and the gestational age at the time of sampling in the second and third trimesters of pregnancy. When the relative frequency distribution of glycosylated serum protein levels in normal patients was compared with that in diabetic patients, a significant difference was noted between the two groups, with a higher percentage of glycosylated serum protein levels in diabetic patients being at elevated values compared to those in normal patients. Normal patients had measured glycosylated serum protein levels of 12.5% +/- 2.2% whereas diabetic patients had glycosylated serum protein levels of 14.0% +/- 3.6%. When peak fasting serum glucose and high Chemstrip glucose levels were compared with glycosylated serum proteins in the diabetic population, a significant correlation for each was noted. The best correlation resulted from a comparison of an average Chemstrip glucose level (mean of 49 glucose values during the previous week) and the glycosylated serum protein value obtained at the end of that week. This inexpensive assay can be adapted to any clinical laboratory and should provide an objective means to evaluate short-term glycemic control, complementing the evaluation provided by self-glucose monitoring (immediate control) and intermittent assay of glycosylated hemoglobin (long-term control).

Adolescent↗
PubMed1985

Hereditary antithrombin III deficiency and pregnancy: report of two cases and review of the literature.

The pregnancy and the serum antithrombin III levels during the antenatal and postpartum period of two patients with hereditary antithrombin III deficiency is described. Both antithrombin III antigen and activity levels dropped to their lowest levels immediately after delivery. A review of the literature emphasizes the high risk for thromboembolism in patients with hereditary antithrombin III deficiency. Important considerations for the obstetrician concerning hereditary antithrombin III deficiency are discussed, including: 1) the need to therapeutically anticoagulate these patients postpartum, 2) the need to consider prophylactic anticoagulation throughout pregnancy especially in patients with a history of thrombosis, 3) the practical aspects of assaying antithrombin III in plasma rather than serum, 4) the normally low antithrombin III levels in normal newborns, and 5) the need to provide prepregnancy counseling, including information about the autosomal dominant inheritance of hereditary antithrombin III deficiency.

Adult↗
PubMed1984

Calcium levels in normal and hypertensive pregnant patients.

Epidemiologic studies of hypertension in nonpregnant patients have suggested that abnormal calcium metabolism contributes to the genesis of hypertension. We have studied serum ionized calcium, total calcium, phosphorus, magnesium, total protein, and albumin in 16 normal pregnant women, 12 gravid patients with chronic hypertension, and 31 gravid patients with pregnancy-induced hypertension. In contradistinction to the reported difference in ionized calcium between nonpregnant normal and hypertensive patients, we have found no difference in serum ionized calcium between our groups.

Adult↗
PubMed1983

Gonadotropin and lipoprotein receptor levels in rat luteal cells of early pregnancy.

Dispersed cells from rat corpora lutea isolated on pregnancy days, 5, 7, 10 and 13, yielded three distinct sub-populations of luteal cells when centrifuged in a continuous, 0-40%, Metrizamide density gradient. Bands I and II (refract. ind. 1.340-1.346) constituted highly enriched, functional, luteal cell fractions. The more dense fraction (Band III, refract. ind. 1.348-1.355), while contaminated with non-luteal cells, also contained cells capable of progesterone production. Progesterone synthesis by all three sub-populations was stimulated by LH, and each sub-population bound [125I]-labeled hCG and [125I]-labeled HDL with high affinity. However, the concentrations of LH/hCG and lipoprotein binding sites were greater in Band I + II than in Band III. Progesterone secretion during the selected days of pregnancy, being high on days 5 and 13 with a nadir on day 10, was shown to correlate with the concentration of LH/hCG-binding sites present on Band I + II cells. This correlation was not seen when comparing Band III cells. The concentration of HDL-binding sites did not vary significantly with the sub-populations of luteal cells isolated on the selected days of pregnancy.

Animals↗
PubMed1983

Plutonium--its behavior in natural water systems and assimilation by man.

There are a number of factors which must be considered in establishing whether or not the inadvertent intrusion of a sizable amount of plutonium-bearing material into a natural water system may have a significant impact on the health of those individuals who use that system as a drinking water resource. These factors include the chemical form(s) and solubility of plutonium in natural waters, its behavior in relation to natural processes (geochemical and biological), its fate in water treatment systems, and its uptake by man from drinking water. From the results obtained in our investigations of the behavior in natural water systems, it appears that (1) the chemical forms of plutonium dissolved in natural waters are Pu(IV) and Pu(V), (2) the soluble plutonium in many waters is bound to the organic constituents which probably enhances plutonium solubility, (3) the natural process responsible for the removal of plutonium from water is adsorption onto sediments, and (4) in water treatment systems, soluble plutonium is oxidized to the VI state and this form is not removed. From our investigations of gastrointestinal absorption, it appears that the value for f1, the fraction transferred from the gut to blood, is surely greater than 1 X 10(-3) and may be as high as 2 X 10(-1). Consideration of these and other factors indicates that, in the event of an accident, the concentration of plutonium could, in certain small natural water systems, approach and perhaps even exceed, the MPC for plutonium. However, the impact on the health of the affected population would not be inordinately high.

Humans↗
PubMed1983

Peripartum heart failure due to primary pulmonary hypertension.

Despite the high incidence of sudden death in pregnant patients with primary pulmonary hypertension (PPH) and heart failure, no data are available that thoroughly elucidate the peripartum hemodynamic alterations occurring in these patients. The present report describes the clinical course of a pregnant patient with PPH and provides data regarding peripartum hemodynamic alterations. Hemodynamic parameters were stable during labor and delivery, but pulmonary vascular resistance rose gradually while cardiac output fell after parturition. Dobutamine caused a modest but unsustained increase in cardiac output. Nitroprusside produced a significant sustained augmentation of cardiac output from 3.5 to 5.0 liters/min due to reduction of systemic and pulmonary vascular resistances, and permitted restoration of hemodynamic stability and resolution of heart failure. The authors believe that pregnant patients with PPH and severe heart failure in whom abortion is not possible should have complete hemodynamic monitoring during parturition and for several days thereafter. Segmental epidural anesthesia and lateral positioning of the patient minimize hemodynamic alterations during labor and delivery. Nitroprusside and dobutamine may be effective for treatment of congestive heart failure.

Adult↗