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Biomedical subjects

D Sidiropoulos

Publications and source records attributed to D Sidiropoulos.

15 recordsLinked to original sources

Stimulation of phospholipase C by guanine-nucleotide-binding protein beta gamma subunits.

We have previously shown that soluble fractions obtained from human HL-60 granulocytes contain a phospholipase C which is markedly stimulated by the stable GTP analogue guanosine 5'-[3-O-thio]triphosphate (Camps, M., Hou, C., Jakobs, K. H. and Gierschik, P. (1990) Biochem. J. 271, 743-748]. To investigate whether this stimulation was due to a soluble alpha subunit of a heterotrimeric guanine-nucleotide-binding protein or a soluble low-molecular-mass GTP-binding protein, we have examined the effect of purified guanine-nucleotide-binding protein beta gamma dimers on the phospholipase-C-mediated formation of inositol phosphates by HL-60 cytosol. We found that beta gamma subunits, purified from bovine retinal transducin (beta gamma t), markedly stimulated the hydrolysis of phosphatidylinositol 4,5-bisphosphate by this phospholipase C preparation. The stimulation of phospholipase C by beta gamma t was not secondary to a phospholipase-A2-mediated generation of arachidonic acid, was prevented by the GDP-liganded transducin alpha subunit and was additive to activation of phospholipase C by guanosine 5'-[3-O-thio]triphosphate. Beta gamma t also stimulated soluble phospholipase C from human and bovine peripheral neutrophils, as well as membrane-bound, detergent-solubilized phospholipase C from HL-60 cells. Stimulation of soluble HL-60 phospholipase C was not restricted to beta gamma t, but was also observed with highly purified beta gamma subunits from bovine brain. Fractionation of HL-60 cytosol by anion-exchange chromatography revealed the existence of at least two distinct forms of phospholipase C in HL-60 granulocytes. Only one of these forms was sensitive to stimulation by beta gamma t, demonstrating that stimulation of phospholipase C by beta gamma subunits is isozyme specific. Taken together, our results suggest that guanine-nucleotide-binding protein beta gamma subunits may play an important and active role in mediating the stimulation of phospholipase C by heterotrimeric guanine-nucleotide-binding proteins.

Animals

Bile acid pattern in human amniotic fluid.

Individual bile acids were determined in twenty-nine amniotic fluid specimens obtained from twenty-six women between the 32nd and 41st week of gestation. Total bile acid concentration ranged from 0.4 to 4.8 mumol/l with a mean of 1.57 mumol/l. Besides the two major bile acids of man, cholic acid and chenodeoxycholic acid, 3beta-hydroxy-5-cholenoic acid was found in all, lithocholic acid in ten and deoxycholic acid in nine of the twenty-nine amniotic fluid samples. 3beta-Hydroxy-5-cholenoic acid averaged 39.8% of total bile acids during 32-37 weeks of gestation and 20.2% at term (P less than 0.01). These findings point towards important differences between fetal and adult bile metabolism and may reflect maturation of hepatic bile acid biosynthesis near term.

Amniotic Fluid

[Screening of newborn infants in cystic fibrosis. Evaluation of a 4-year study in Switzerland].

The results of an evaluation over 4 years (1973-1976) of 16,620 BM-tests (Boehringer-Mannheim newborn screening for cystic fibrosis) at 8 hospitals in Switzerland are presented and the data from analysis of albumin, protein and alpha1-antitrypsin concentrations, and on trypsin-inhibitory capacity of the meconia are discussed. 99.5% of the tests were negative. Of the remaining 0.5% BM-positive tests, the diagnosis of cystic fibrosis required confirmation by sweat test and clinical course in 6 cases, or 0.04% of the total collective. The test was false-negative in 2 cases (0.012%), of which one had a primary pulmonary form of cystic fibrosis. The study shows that the BM-test, as screening test for cystic fibrosis, makes it possible to distinguish between "normal" and "suspect". By calculating the ratio albumin to alpha1-antitrypsin, it would be possible to verify the probability of a reliable diagnosis as early as a few days after birth. As before, however, it would be indispensable to confirm the diagnosis of cystic fibrosis by a sweat test with pilocarpin iontophoresis. By consistent screening in all obstetric and pediatric clinics it would be possible to improve early diagnosis still further.

Cystic Fibrosis

[Detection of 3 beta-hydroxy-5-cholenoic acid in human amniotic fluid].

Studies of the bile acids of human meconium suggest that a fetal pathway of bile acid synthesis exists which leads to formation of 3beta-hydroxy-5-cholenoic acid, a bile acid not found in serum of healthy pregnant women. To obtain additional support for this hypothesis, cholic, chenodeoxycholic, and 3beta-hydroxy-5-cholenoic acid were measured in amniotic fluid specimens from 18 pregnant women without liver disease. The finding of a considerable percentage of 3beta-hydroxy-5-cholenoic acid (mean: 34 molar %; range 3-71 molar % of total bile acids) in amniotic fluid strengthens the hypothesis that a fetal pathway of bile acid synthesis exists which begins with oxidation of the cholesterol side chain.

Adolescent

Hormonal mechanism of milk secretion in the newborn.

The mechanism inducing milk secretion in 10 puerperal women and in their children (Witch's milk) was studied by means of sequential hormone measurements starting at delivery and continued during the first postpartum week. Determinations included prolactin (PRL), growth hormone (GH), estradiol 17beta (E217beta), and progesterone (PG). Hormonal levels in the newborns closely paralleled those of the mothers. In both groups, the onset of milk secretion coincided with the disappearance of sex steroids from plasma in the presence of elevated PRL concentrations. Response to TRH (8 microng/kg) revealed adequate PRL reserve, and failure of this peptide to modify basal GH in the neonates was suggestive of appropriate hypothalamic control. The role of estrogens in the induction of pituitary hyperplasia during pregnancy is discussed.

Estradiol

Determination of bile acid concentration in human amniotic fluid for prenatal diagnosis of intestinal obstruction.

Bile acid concentration was measured in amniotic fluid obtained for standard indications from 11 healthy pregnant women without polyhydramnios (28 to 42 weeks of gestation) and from 9 patients with polyhydramnios (28 to 38 weeks of gestation). Two of the latter women delivered infants with intestinal obstruction distal to the papilla of Vater, a condition that causes regurgitation of bile into the amniotic fluid. In the women without polyhydramios, the total bile acid concentration ranged from 1.4 to 2.4 micronmol/liter. In the seven patients with polyhydramnios not associated with fetal intestinal obstruction, the bile acid concentration in amniotic fluid was not significantly different (0.9 to 1.9 micronmol/liter). By contrast, the bile acid concentration in amniotic fluid specimens from the two patients with polyhydramnios who gave birth to children with intestinal obstruction was considerably elevated (30.3 to 83.1 micronmol/liter). These findings suggest that determination of bile acid concentration in amniotic fluid permits prenatal diagnosis of intestinal obstruction distal to the papilla of Vater.

Amniotic Fluid

[Statistic evaluation of anamnestic and clinical findings in a premature labor collective of 245 cases].

245 cases of premature birth were compared from the point of view of frequency of aetiologically significant factors with 200 cases of normal birth. The perinatal progress of these premature and normal births was also followed up. It was possible to obtain statistical confirmation of the connection between prematurity and frequent occurrence of some of these parameters. Prominent amongst these are previous abortions and premature births, cervical insufficiency and malformation of the uterus, multiple pregnancies and anomalous foetal position, also placental insufficiency. Increased mortality and morbidity--including perinatal complications--were recorded at the same time. Knowledge of predisposing factors will in many cases make it possible to recognize in good time when pregnancies may be at risk and give adequate supervision and treatment where appropriate.

Abortion, Habitual

Outcome of 100 randomly positioned children of very low birthweight at 2 years.

Prematurely born children often show a tendency to adopt extensor motor patterns during the first years of life. These children and especially those children of very low birthweight are considered to be at high risk for abnormal development. Positioning in an ordinary manner or in a more flexed position imposed at random during the neonatal period until discharge from hospital did not have a statistically significant influence on the development of these children at 24 months after term. Analysis of the optimality score of the 100 randomly selected children, born consecutively at the University Women's Hospital, Bern, showed a significant influence of prenatal optimality and congenital malformations on their later outcome.

Child Development