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Biomedical subjects

R Folman

Publications and source records attributed to R Folman.

14 recordsLinked to original sources

Increased rates of polypeptide chain elongation in placental explants from human diabetics.

Average rates of polypeptide chain elongation were determined in placental explants of first trimester and term placentas from both normal and diabetic human pregnancies. Average ribosome half-transit times were determined by measuring the kinetics of transfer of labeled polypeptides from polysomal-bound to released polypeptides. The average half-transit time decreases from 75 sec per ribosome in first trimester explants to 56 sec per ribosome in term placentas. The average polypeptide molecular weights synthesized by explants from first trimester and in term are 49,300 and 49,600, respectively, which are not significantly different. The average elongation rates for first trimester and term placental explants are 172 and 231 amino acids per minute per ribosome, respectively, which are significantly different. Moreover, the average polypeptide molecular weight synthesized by term placentas from diabetic pregnancies is 48,200, while the average ribosome half-transit time is 40 sec. Thus, ribosomes from explants of term placenta from diabetics move along the average message at a much higher speed than do ribosomes in normal term tissue. The assembly rate of amino acid into polypeptide in explant of placenta of diabetic mothers is 314 amino acids per minute, which is significantly faster than 231 amino acids per minute in normal term tissue. These findings indicate that during placental development and in diabetic pregnancy there is a large change in the actual rates at which amino acids are added to the nascent polypeptide chain--i.e., the rates in polypeptide chain elongation. Therefore, translation-level regulation of protein synthesis in placenta plays a significant part in the magnitude of the response to developmental and other physiological stimulations.

Chorion

RNA synthesis in cultured human placenta.

The in vitro synthesis of RNA in the human placental tissue, incubated in organ culture, was investigated. We followed the synthesis of the poly A(-) and poly A(+) RNA fractions, and investigated the distribution of the newly synthesized RNA among the subcellular fractions isolated from first and third trimester placentas. The poly A(-) RNA was the major fraction of the RNA synthesized in vitro. The incorporation of [3H]uridine into the poly A(+) RNA fraction was very low. As protein synthesis occurred during the entire incubation period, we suggest the presence of a pool of mRNA molecules in the form of mRNP particles.

DNA

Teratogenicity of bromocryptine in pregnant rats.

The teratogenicity of bromocryptine (CB-154, Sandoz, Basel) was studied in three groups of pregnant rats which received 0.625 mg/kg/day, 1.25 mg/kg/day, and 2.5 mg/kg/day bromocryptine, respectively, i.m. and in a control group of pregnant rats which received the solvent only. There was no significant difference in the birth rate, fetal resorption rate, male/female ratio and malformation rate between the four groups. There was a significant elevation of the average fetal and placental weights between the experimental and the control fetuses. Bromocryptine does cross the placental barrier and in our study might act as growth promoting factor.

Abnormalities, Drug-Induced

The in vitro synthesis and secretion of alkaline phosphatase from first trimester human decidua.

We studied the in vitro synthesis and secretion of alkaline phosphatase by human first trimester decidual tissue incubated in organ culture. Decidua synthesizes two different alkaline phosphatase isoenzymes; heat stable and heat labile. decidual tissue maintains a constant pool of alkaline phosphatases. The synthesis of alkaline phosphatase may be the driving force for its secretion. The de novo synthesis and secretion rate of alkaline phosphatases were also investigated. The higher specific radioactivities of the secreted enzymes than those found in the tissue may suggest that newly synthesized alkaline phosphatase is preferentially released. The intracellular distribution of the alkaline phosphatase isoenzymes was compared as well. The characteristics of the two isoenzymes are different in human decidua of maternal origin from those previously reported in the human placenta originating from embryonic stem cells.

Alkaline Phosphatase

The synthesis and secretion of human placental lactogen (hPL) in cultured term placenta.

We studied the in vitro synthesis and secretion of hPL by human term placental tissue incubated in organ culture. Placental tissue maintains a constant pool of hPL. The synthesis of hPL may be the driving force for its secretion. The de novo synthesis and secretion rates of hPL were also investigated. The higher specific radioactivities of the secreted hPL than those found in the tissue may suggest that newly synthesized hPL is preferentially released. The intracellular distribution of hPL was also compared.

Female

Synthesis and secretion of alkaline phosphatase in vitro from first-trimester and term human placentas.

The synthesis and secretion of alkaline phosphatases in vitro by human placental tissue incubated in organ culture were studied. First-trimester placenta synthesizes and secretes two different alkaline phosphatase isoenzymes (heat-labile and heat-stable), whereas in term placenta nearly all the alkaline phosphatase synthesized and secreted is heat-stable. The specific activities of alkaline phosphatases in first-trimester and term placental tissue remain constant throughout the time course of incubation. In the media, specific activities increase with time. Hence, alkaline phosphatase synthesis seems to be the driving force for its own secretion. The rates of synthesis de novo and of alkaline phosphatases were measured. The specific radioactivities of the secreted alkaline phosphatases were higher than the corresponding specific radioactivities in the tissue throughout the entire incubation period. The intracellular distribution of the alkaline phosphatase isoenzymes was compared.

Alkaline Phosphatase

Isolation of ribonuclease-free polysomes from human placenta.

Human placenta is known to have a high level of polysome-bound ribonuclease which has hindered the isolation of intact polyribosomes from this tissue. We describe conditions for preparing polysomes devoid of apparent ribonuclease activity from both first trimester and term placenta. This stable preparation was achieved by utilizing buffer at low pH containing 300 mM LiCl and precipitating the polysomes chemically with 200 mM MgCl2. The yield of polysomes obtained by this procedure is 2-2.5 fold greater than that obtained by the conventional method of preparing placental polysomes. The polysomes are considered pure as judged by the ratios of absorbance 260/280 and 260/235. Moreover, the yield of polysomes obtained is greater than 95% of the tissue content and the profile of the polysomes is probably representative of the in vivo population. This is concluded from experiments in which a known amount of labelled chick polysomes was added to fresh placental tissue and the recovery of label and its distribution was analyzed.

Cell Fractionation

The synthesis and secretion of human chorionic gonadotropin by tissue slices from first trimester placentas.

Placental tissue slices from first trimester placentas synthesize and secrete proteins labeled by radioactive glucosamine are preferentially secreted as compared to proteins in general. One of the proteins synthesized and secreted is hCG. Processing and secretion of proteins, including hCG, by the tissue slices need a two-hour period. Both secretion and glycosylation of the protein can take place independently of protein synthesis. A method was developed for the specific determination of newly synthesized radioactive hCG in placental tissue.

Chorionic Gonadotropin

Recurrence of the hemolytic uremic syndrome in a 3 1/2-year-old child, 4 months after second renal transplantation.

Terminal renal failure secondary to the hemolytic uremic syndrome (HUS) developed 18 months after initial transplantation and 4 1/2 months after the child received his second cadaveric renal allograft. Recurrence of the syndrome was evidenced by gross hematuria and hypertension after a 'flu-like' illness, sudden decrease in platelet count and hemoglobin, and erythrocyte fragmentation. Renal biopsy findings were compatible with HUS. Evidence is presented that the HUS was a recurrence of the original disease.

Cadaver