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Biomedical subjects

C Sibley

Publications and source records attributed to C Sibley.

17 recordsLinked to original sources
PubMed2006

Imprinted genes, placental development and fetal growth.

In mammals, imprinted genes have an important role in feto-placental development. They affect the growth, morphology and nutrient transfer capacity of the placenta and, thereby, control the nutrient supply for fetal growth. In particular, the reciprocally imprinted Igf2-H19 gene complex has a central role in these processes and matches the placental nutrient supply to the fetal nutrient demands for growth. Comparison of Igf2P0 and complete Igf2 null mice has shown that interplay between placental and fetal Igf2 regulates both placental growth and nutrient transporter abundance. In turn, epigenetic modification of imprinted genes via changes in DNA methylation may provide a mechanism linking environmental cues to placental phenotype, with consequences for development both before and after birth. Changes in expression of imprinted genes, therefore, have major implications for developmental programming and may explain the poor prognosis of the infant born small for gestational age and the wide spectrum of adult-onset diseases that originate in utero.

Animals↗
PubMed2006

Regulation of placental efficiency for nutrient transport by imprinted genes.

Intrauterine growth and development can impact upon the long-term health of an individual. The fetus is dependent upon the placenta for its supply of nutrients and oxygen from the mother. In turn, the functional capacity of the placenta to supply that demand is under the control of the fetal and maternal genomes. Recent evidence suggests that imprinted genes, a class of genes found in placental mammals whose expression depends on their parental origin, have multiple roles in the placenta. The imprinted genes regulate the growth and transport capacity of the placenta, thereby controlling the supply of nutrients. They may also regulate the growth rate of fetal tissues directly, thereby controlling nutrient demand by the fetus. Recent studies using mice with deletions or disruption of imprinted genes with an altered balance between placental and fetal growth and changes in placental efficiency are indicative of feto-placental signalling of fetal nutrient demand. We propose that signalling mechanisms involving growth demand signals and nutrient transporters are likely to occur and are important for fine tuning normal fetal growth.

Animals↗
PubMed1999

System A amino acid transporter activity in human placental microvillous membrane vesicles in relation to various anthropometric measurements in appropriate and small for gestational age babies.

Fetal growth and development is dependent on the transfer of amino acids from maternal to fetal blood across the microvillous plasma membrane (MVM) and basal plasma membrane of placental syncytiotrophoblast. The aim of this study was to determine the relationship of system A amino acid transporter (SysA) activity in MVM to a variety of measurements of size at birth in a group of term small for gestational age (SGA) babies and in a group of appropriate for gestational age (AGA) babies. Mean SysA activities (nmol/mg vesicle protein/30 s +/- SEM) were: SGA, 0.027 +/- 0.004 (n = 25) and AGA, 0.045 +/- 0.005 (n = 24); p = 0.006. Spearman rank correlations were calculated for SGA (n = 19-25) and AGA (n = 21-24) groups for SysA activity against the following anthropometric measurements: abdominal circumference, birth weight, length, midarm circumference (MAC), head circumference, midarm circumference:head circumference ratio, placental weight (PW), placental ratio (placental weight:birth weight), birth weight:length ratio, Ponderal index (birth weight/length3) and triceps and subscapular skin-fold thicknesses (tsft and ssft). In SGA babies, SysA activity was positively correlated (p < 0.05) with subscapular skin-fold thicknesses (r = 0.48), triceps skin-fold thicknesses (r = 0.42), PW (r = 0.42), and placental ratio (r = 0.46). In AGA babies, the only significant correlation was an inverse one with placental ratio (r = -0.50). These data suggest there are differences in the relationship between placental SysA activity and fetal proportion in term AGA compared with SGA babies.

Amino Acid Transport Systems↗
PubMed1998

Electrical potential difference between exocelomic fluid and maternal blood in early pregnancy.

The forces that drive transfer of solutes between maternal blood and embryo in early human pregnancy are poorly understood. The aim of this study was to determine whether there is an electrical potential difference (PD) between maternal blood and the exocelomic cavity and between maternal blood and the amniotic cavity in the normal human conceptus at or before 10 wk of pregnancy. We measured PD between a saline-filled catheter in a forearm vein of women undergoing termination of pregnancy for psychological reasons in the first trimester and a second saline-filled catheter in the exocelomic cavity or amniotic cavity of their conceptus. The mean (+/- SE) maternal blood/exocelomic cavity PD in eight women was 8.7 +/- 1.0 mV and the mean maternal blood/amniotic cavity PD in four of the women was 6.7 +/- 1.3 mV, embryo side negative for both sets of measurement. These data show that there is a PD between maternal and embryonic extracellular fluid in the first trimester that will directly influence exchange of ions between the two compartments.

Amniotic Fluid↗
PubMed1997

Placental transporter activity and expression in relation to fetal growth.

The question of whether there are causative or compensatory changes in placental transport physiology affecting fetal growth is considered. Reductions in uterine and umbilical blood flow in growth retardation will reduce maternofetal exchange of lipophilic solutes, such as O2 and CO2, but will not have a major effect on the transfer of hydrophilic solutes. These solutes are transferred across the placenta by paracellular diffusion, transporter protein-mediated transport and endocytosis-exocytosis. Neither paracellular diffusion nor endocytosis-exocytosis has been investigated in relation to fetal growth. The weight of evidence is that there is no change in the activity and expression of the syncytiotrophoblast GI UTI glucose transporter in fetal growth retardation. However, there is strong evidence that the activity of the system A amino acid transporter, per milligram of placental membrane protein, is altered in relation to fetal growth, but in a complex manner. There is also some weaker evidence that the activity of the Na(+)-H+ exchanger, per milligram of placental membrane protein, is directly related to birth-weight. There are no data for other solute transporters; a considerable amount of work still remains to be done in order to understand the relationship between placental function and fetal growth rate.

Animals↗
PubMed1995

Mechanisms of alphafetoprotein transfer in the perfused human placental cotyledon from uncomplicated pregnancy.

We investigated the mechanisms of alphafetoprotein (AFP) transfer across the human placenta by correlating measurements of AFP transfer with cytochemical localization of AFP. Placental cotyledons were dually perfused in vitro with either the fetal or maternal perfusate containing umbilical cord plasma as a source of AFP. Steady state AFP clearance, corrected for release of endogenous AFP, was 0.973 +/- 0.292 microliter/min per gram in the fetal to maternal direction (n = 10), significantly higher (P < 0.02) than that in the maternal to fetal direction (n = 5; 0.022 +/- 0.013 microliter/min per gram). Clearance of a similarly sized protein, horseradish peroxidase was also asymmetric but clearance of the small tracer creatinine was not. Using a monoclonal antibody, we localized AFP to fibrinoid deposits in regions of villi with discontinuities of the syncytiotrophoblast, to cytotrophoblast cells in these deposits, to syncytiotrophoblast on some villi, and to trophoblast cells in the decidua. We conclude that AFP transfer in the placenta is asymmetric and that there are two available pathways for AFP transfer: (a) from the fetal circulation into the villous core and across fibrinoid deposits at discontinuities in the villous syncytiotrophoblast to enter the maternal circulation; and (b) AFP present in the decidua could enter vessels that traverse the basal plate.

Biological Transport↗
PubMed1991

Choriocarcinoma cells increase the number of differentiating human cytotrophoblasts through an in vitro interaction.

The human placenta arises from the zygote through single cell intermediates called cytotrophoblasts that in turn give rise to a syncytium. In culture, mononucleated cytotrophoblasts exhibit little, if any, cell division but are converted to multinucleated cells. Choriocarcinoma, the malignant tumor of placenta trophoblast, comprises a mixed population of dividing cellular intermediates that resemble cytotrophoblasts but are less differentiated. Because the choriocarcinoma intermediates arise from dividing cells, the tumor may contain one or more cell types in abundance not present in the population of isolated placental cells. To study placental differentiation through cell-cell interaction, choriocarcinoma cell lines were co-cultured with placenta-derived cytotrophoblasts, and placental hormone biosynthesis, as a marker of differentiation was examined. We reasoned that intermediates formed by the tumor might interact with and complement those intermediates in the placenta-derived cytotrophoblast population. Co-culturing either the JAr or JEG choriocarcinoma cell lines with cytotrophoblasts elevated the synthesis of the chorionic gonadotropin alpha and beta subunits 10-20 fold, and human placental lactogen 5-fold. The effect was specific for these trophoblast-derived cells, since comparable quantities of Chinese hamster ovary or HeLa cells did not affect the placental cytotrophoblast culture. Further experiments suggested that the source of enhanced synthesis was the cytotrophoblasts. We propose that an interaction between cytotrophoblasts and choriocarcinoma cells occurs, which results in an increased number of differentiating cytotrophoblasts. Such co-cultures may represent a model system for examining choriocarcinoma cell interaction with normal cells, a process known to occur in vivo. The data are also consistent with the hypothesis that the regulated chorionic gonadotropin production in the placenta is determined by interaction among trophoblast cells at different stages of differentiation.

Animals↗
PubMed1990

Rh immunization by the partial D antigen of category DVa.

Reported here is the first example of a partial D antigen stimulating the production of anti-D: stimulation was of fetal origin. During her second pregnancy, anti-D developed in the serum of a D-negative mother who had received Rh immunoglobulin after the birth of her first D-positive child. Her second baby had moderate neonatal jaundice and was successfully treated by phototherapy. Subsequently the red cells of the father and of the first child were shown to carry a partial D antigen of category DVa type. Six available batches of Rh immunoglobulin reacted with DVa cells.

Adult↗
PubMed1980

The immunoglobulin mu chains of membrane-bound and secreted IgM molecules differ in their C-terminal segments.

The B lymphocytes synthesizes two forms of IgM molecules during its development from a stem cell to a mature antibody-secreting plasma cell. The monomeric receptor IgM molecule is affixed to the plasma membrane and triggers the later stages of B cell differentiation, whereas the pentameric secreted IgM molecule is an effector of humoral immunity. The structural differences between membrane-bound and secreted IgM molecules are reflected in the differences between their heavy or mu chains. We have previously determined the complete amino acid sequence of a murine secreted mu (microsecond) chain. In this study, we have compared the structures of the secreted and membrane-bound mu (micron) heavy chains by peptide mapping, micro-sequence and carboxypeptidase analyses. These studies demonstrate that the micron and microsecond chains are very similar throughout their VH, C mu 1, C mu 2, C mu 3 and C mu 4 domains. The micron and microsecond chains differ in the amino acid sequence of their C-terminal segments. These studies in conjunction with those carried out on the micron and microsecond mRNAs and the C mu gene suggest that the micron and microsecond chains from a given B cell are identical except for their 41 and 20 residue C-terminal segments, respectively. The amino acid sequence of the 41 residue C membrane terminal segment predicted from the corresponding micron mRNA is in agreement with all the protein studies reported in this paper.

Amino Acid Sequence↗
PubMed1980

Endotoxemia of cirrhosis: an observation not substantiated.

Physiologic similarities between cirrhotic and septic patients have implicated systemic endotoxemia as a possible mediator of the hemodynamic, neurologic, and hematologic complications observed in patients with cirrhosis of the liver. The recently reported high prevalence of endotoxin in ascites, as well as in portal and systemic plasma, has further incriminated endotoxin of gut origin as the responsible agent. Limulus amebocyte lysate tests were performed upon peripheral plasma of 38 cirrhotic patients; portal plasma and ascites were assayed in 14 and 11 of these patients, respectively. No endotoxin was detectable. We believe that the ubiquity of endotoxin, with the attendant opportunities for specimen contamination, is the most likely explanation for the recently reported high prevalence of endotoxin in the plasma and ascites of cirrhotic patients.

Adult↗
PubMed1979

Amino acid sequence of a mouse immunoglobulin mu chain.

The complete amino acid sequence of the mouse mu chain from the BALB/c myeloma tumor MOPC 104E is reported. The C mu region contains four consecutive homology regions of approximately 110 residues and a COOH-terminal region of 19 residues. A comparison of this mu chain from mouse with a complete mu sequence from human (Ou) and a partial mu chain sequence from dog (Moo) reveals a striking gradient of increasing homology from the NH2-terminal to the COOH-terminal portion of these mu chains, with the former being the least and the latter the most highly conserved. Four of the five sites of carbohydrate attachment appear to be at identical residue positions when the constant regions of the mouse and human mu chains are compared. The mu chain of MOPC 104E has a carbohydrate moiety attached in the second hypervariable region. This is particularly interesting in view of the fact that MOPC 104E binds alpha-(1 leads to 3)-dextran, a simple carbohydrate. The structural and functional constraints imposed by these comparative sequence analyses are discussed.

Amino Acid Sequence↗
PubMed1979

Laboratory suggestions: Improving the sensitivity of the Fletcher factor assay.

The prolonged activated partial thromboplastin times observed with Fletcher factor (prekallikrein)-deficient plasmas become nearly normal after the plasma is incubated with contact surfaces or with an activator. Those shorter times may lead to relatively flat reference curves for Fletcher factor assays under certain conditions. The authors examine in detail the effect of incubation time upon the sensitivity of Fletcher factor assays. Four different surface activators were used in the tests to determine the optimal activation for each type. An incubation time of 1 min produced maximal sensitivity with each surface activator tested. All reagents remained stable for at least an hour at 37.5 C.

Blood Coagulation Tests↗