Search PubMed⌕ Search

Biomedical subjects

I Cetin

Publications and source records attributed to I Cetin.

At least 37 records · Page 2Linked to original sources

Post-zygotic origin of complete maternal chromosome 7 isodisomy and consequent loss of placental PEG1/MEST expression.

Maternal UPD of chromosome 7 is associated with pre- and postnatal growth retardation (IUGR, PNGR) and Silver-Russell syndrome (SRS [MIM 180860]). We report a case of IUGR in a newborn with SRS stigmata. Using combined haplotyping and cytogenetic-FISH studies we characterized the lymphocytes, umbilical cord and four placental cotyledons. The results are consistent with complete maternal isodisomy 7 and trisomy 7 mosaicism of post-zygotic origin. The trisomic cell line was prevalent in trophoblast cells from two placental cotyledons. Trisomy 7 of post-zygotic origin is a frequent finding, but maternal isodisomy 7, due to trisomic rescue has never been reported. PEG1/MEST expression was evaluated on placenta cDNA and a specific transcript was revealed only in the cotyledons with a high percentage of trisomic cells and the presence of the paternal chromosome 7 contribution, but not in the placental biopsies with maternal isodisomy 7. The histological features of the four placental fragments revealed that isodisomy 7 correlates with a pattern of cotyledonary hyper-ramification due to an increase of the branching angiogenesis, which could be the result of a defect of angiogenesis caused by the absence of PEG1 product. The severe hypo-ramification of the two cotyledons, showing trisomy 7 mosaicism, may be due to the triplicate dosage of genes on chromosome 7. The delayed fetal growth could be the phenotypic effect of the imbalance between imprinted and non-imprinted genes on chromosome 7 in the fetus or the result of abnormal placental function during pregnancy.

Adult↗

Reduction of subcutaneous mass, but not lean mass, in normal fetuses in Denver, Colorado.

OBJECTIVE: To test the hypothesis that reduced birth weight in normal fetuses born at moderately high altitude (Denver), compared with the birth weight in normal fetuses born at sea level (Milan), is caused by a reduction in both lean mass and subcutaneous fat mass. STUDY DESIGN: Ninety-four normal singleton pregnancies (46 in Denver, 48 in Milan) had serial ultrasonographic axial images obtained to assess subcutaneous tissues of fetuses as a measure of body fat. The abdominal wall thickness and mid upper arm and mid thigh were examined. The equation was: Subcutaneous tissue equals total cross-sectional area minus bone and muscle area. Lean mass included the area of muscle and bone, head circumference, and femur length. RESULTS: Gestational age at delivery was similar between groups. Birth weight was less at Denver's altitude (2991 +/- 79 g versus 3247 +/- 96 g; P =.04). Abdominal wall thickness, mid upper arm, and mid thigh subcutaneous tissues measurements were significantly reduced at Denver's altitude and increased further in significance with advancing gestational age. Lean mass measurements were similar between groups. CONCLUSIONS: The reduced birth weight of the newborns in Denver was the result of a reduction in fetal subcutaneous fat tissue and not lean mass. Ultrasonography can be used to follow subcutaneous measurements longitudinally and to detect differences, and potentially disease processes, in study populations.

Adipose Tissue↗

Macrophage migration inhibitory factor in the human endometrium: expression and localization during the menstrual cycle and early pregnancy.

Macrophage migration inhibitory factor (MIF) was discovered as an activated T-lymphocyte-derived protein that inhibits the random migration of macrophages in vitro. Subsequently, knowledge of the physiological actions of MIF was extended to include its role as a proinflammatory cytokine that affects several functions of macrophages and lymphocytes. Previous reports have suggested an involvement of MIF in reproduction. However, no data are currently available on the presence of this cytokine in the human endometrium. In this study, the expression and tissue localization of MIF was evaluated in specimens of cycling endometrium, first trimester placenta bed biopsy, and isolated endometrial glands by Western blot analysis, immunohistochemistry, ELISA, and reverse transcription-polymerase chain reaction. The results demonstrated that MIF is expressed in human endometrium across the menstrual cycle and in early pregnancy. Immunohistochemical localization identified the protein in glandular epithelium, in stromal and predecidualized stromal cells of cycling endometrium, as well as in the decidua of first-trimester placenta. The proinflammatory features and specific actions of MIF on lymphoid cells suggest its potential involvement in several aspects of endometrial physiology.

Blotting, Western↗

Amino acid interconversions in the fetal-placental unit: the animal model and human studies in vivo.

Fetal growth and development are dependent upon the adequate provision of oxygen and substrates from the maternal circulation. The need for amino acids is related to protein synthesis, interconversion to other substrates, and oxidation. Amino acids cross the placenta by active transport systems, and their concentrations in the fetus are higher than in the mother. In addition, most amino acids are extensively metabolized within the placenta, and, for some nonessential amino acids, placental synthesis has been demonstrated in chronically catheterized fetal lambs. Interorgan cycling between the fetal liver and placenta has been hypothesized for nonessential amino acids like glycine and serine. Amino acids are oxidized within the fetal tissues, particularly in liver and muscle, with differences between amino acids and in relation to metabolic state. In human pregnancies, maternal-fetal transfer rates have been investigated in vivo by stable isotope methodologies performed at fetal blood sampling. The transfer rate of nonessential amino acids like glycine is significantly lower than for essential amino acids like leucine, confirming glycine synthesis in the fetoplacental unit also in human pregnancies. Moreover, when a steady state model is applied, the fetal-maternal ratio for [1-(13)C]leucine is significantly reduced in pregnancies associated with intrauterine growth restriction, reflecting a decrease in leucine placental transfer and/or an increase in protein catabolism in the fetoplacental unit. This reduction is proportional to the degree of severity of intrauterine growth restriction but is significant also in those intrauterine growth-restricted fetuses with normal oxygenation and acid-base status.

Amino Acids↗

The endocrine and metabolic profile of the growth-retarded fetus.

Intrauterine growth retardation (IUGR) is characterized by the failure of the fetus to grow at a normal rate in utero and is associated with a number of endocrine and metabolic changes. Our knowledge of the placental nutrient supply and the endocrine status of the fetal-placental unit during pregnancies involving IUGR has greatly increased over the past decade as a result of the availability of fetal blood samples obtained under relatively steady state conditions. These studies have provided evidence that the supply of glucose is impaired only under severe conditions, whereas placental transfer of amino acids is reduced even in fetuses with normal oxygenation and feto-placental blood flow. Moreover, significant in utero relationships have been reported between fetal weight and circulating levels of growth factors such as insulin-like growth factor-I and leptin. When measured per kg fetal weight, however, levels of leptin are significantly higher in growth-retarded fetuses, with abnormal feto-placental blood flow and reduced oxygen content. The metabolic and endocrine changes observed should be interpreted in relation to the severity of the disease.

Adaptation, Physiological↗

Mutations in coagulation factors in women with unexplained late fetal loss.

BACKGROUND: Factor V and prothrombin-gene mutations are independent risk factors for venous thrombosis; it is debated whether a mutation in the gene encoding methylenetetrahydrofolate reductase, an enzyme involved in homocysteine metabolism, also increases the risk of venous thrombosis. Whether any of these mutations is associated with an increased risk of late fetal death is not known. METHODS: We studied 67 women with a first episode of unexplained late fetal loss (fetal death after 20 weeks or more of gestation) and 232 women who had had one or more normal pregnancies and no late fetal losses. All the women were tested for the presence of three gene mutations. Women with other thrombophilic conditions were excluded from the study. RESULTS: Eleven of the 67 women with late fetal loss (16 percent) and 13 of the 232 control women (6 percent) had either the factor V or the prothrombin mutation. The relative risks of late fetal loss in carriers of the factor V and prothrombin mutations were 3.2 (95 percent confidence interval, 1.0 to 10.9) and 3.3 (95 percent confidence interval, 1.1 to 10.3), respectively. Thirteen percent of the women whose fetuses died and 20 percent of the control women were homozygous for the mutation in the methylenetetrahydrofolate reductase gene (relative risk, 0.8; 95 percent confidence interval, 0.5 to 1.2). CONCLUSIONS: Both the factor V and the prothrombin mutations are associated with an approximate tripling of the risk of late fetal loss.

Abortion, Spontaneous↗

Fetal plasma leptin concentrations: relationship with different intrauterine growth patterns from 19 weeks to term.

The relationship between in utero fetal growth and fetal leptin concentrations was investigated between 19 and 41 wk in 40 normal (appropriate for gestational age, AGA) fetuses, in 25 intrauterine growth-restricted (IUGR) fetuses, and in 18 fetuses from gestational diabetic mothers (GDM), representing different intrauterine growth patterns. Umbilical venous plasma leptin concentrations were determined at the time of either in utero fetal blood sampling or delivery. Plasma leptin was measurable as early as 19 wk of gestation. A significant difference was observed between umbilical venous and arterial plasma leptin concentrations (0.6+/-0.6 ng/mL; p<0.01). In AGA and in IUGR fetuses, significant positive relationships were found between fetal leptin concentrations and both gestational age (p<0.001) and fetal weight (p<0.001). Leptin concentrations were significantly higher in AGA than IUGR only after 34 wk (p<0.05), but leptin per kilogram fetal weight (leptin/kg) was not significantly different. In IUGR with abnormal umbilical arterial Doppler velocimetry and fetal heart rate, leptin/kg significantly higher than in IUGR with normal biophysical and biochemical parameters was found (p<0.05). Both circulating plasma leptin and leptin/kg were significantly higher in GDM than in normal fetuses (p<0.001) and correlated with abdominal fat mass measured by ultrasound. No gender differences were observed in any group of fetuses. These findings indicate a clear relationship between fetal leptin concentrations and fetal fat mass. Data in severe IUGR suggest the presence of increased leptin concentrations associated with in utero signs of fetal distress.

Diabetes, Gestational↗

Umbilical amino acid uptake at increasing maternal amino acid concentrations: effect of a maternal amino acid infusate.

OBJECTIVE: Our purpose was to establish whether, in normal human pregnancies, the maternal intravenous infusion of amino acids can increase fetal amino acid uptake and amino acid concentrations. STUDY DESIGN: Twenty-six normal pregnancies were studied at the time of cesarean delivery (38-40 weeks' gestation). In 10 cases an amino acid formulation (Freamine 8.5% III, Baxter) was infused into a maternal vein before cesarean delivery. Maternal blood samples were obtained during the course of the study. Umbilical venous and arterial samples were obtained from the clamped segment of the cord. There were no differences between the 2 groups for fetal and placental weights and for fetal oxygenation and acid-base balance. RESULTS: Maternal amino acid concentrations increased significantly in the group receiving infusions. Significant increases in umbilical venous concentrations were observed for most amino acids, except for histidine and threonine. The amino acid umbilical arteriovenous differences per mole of oxygen (AA/O(2) ratio) increased significantly for leucine, isoleucine, valine, methionine, phenylalanine, arginine, glycine, serine, alanine, and proline. There were no significant increases for lysine, histidine, and threonine. CONCLUSION: An increase in maternal concentrations leads to an increase in the delivery of most amino acids to the fetus.

Adult↗

Steady state maternal-fetal leucine enrichments in normal and intrauterine growth-restricted pregnancies.

The aim of this study was to compare the fetal/maternal (F/M) leucine-enrichment ratio in normal (AGA) and intrauterine growth-restricted (IUGR) pregnancies at the time of fetal blood sampling (FBS). A maternal primed-constant infusion of L-[1-13C]-leucine was given in six AGA and 14 IUGR pregnancies, divided into three groups according to the pulsatility index (PI) of the umbilical artery and to fetal heart rate (FHR): group 1 (normal FHR and PI, four cases); group 2 (normal FHR and abnormal PI, five cases); and group 3 (abnormal FHR and PI, five cases). Maternal arterialized samples were taken at time zero and every 20 min for 125+/-7 min. Umbilical venous samples were obtained after 114+/-42 min of infusion. Under steady state conditions, there was a significant linear relationship between maternal leucine disposal rate and maternal leucine concentration. The comparison of fetal to maternal leucine enrichment showed a progressive dilution of the fetal enrichment relative to the mother between AGA and IUGR of group 1 (0.89 versus 0.78, p < 0.02), group 2 (0.71, p < 0.001), and group 3 (0.62, p < 0.001), and also among the three IUGR groups. The F/M leucine molar percent enrichment (MPE) ratio showed a positive correlation with the umbilical venous oxygen content and an inverse correlation with fetal lactate concentration. We conclude that the dilution in the fetal/maternal leucine-enrichment ratio correlates with the severity of growth restriction and reflects decreased transplacental leucine flux and/or increased protein breakdown within the fetoplacental compartments.

Adult↗

Pathophysiology of intrauterine growth retardation: role of the placenta.

The placenta is essential for normal fetal development. Failure of the placenta can result in many fetal conditions, for example, intrauterine growth retardation (IUGR). Placentas from pregnancies complicated by IUGR show vascular damage, which may lead to the onset of pregnancy-induced maternal hypertension. Accurate placental assessment may, therefore, indicate which fetuses are at risk of IUGR and so improve clinical evaluation and management of both the fetus and the mother. Placental development and function can be assessed by a number of methods, including measurement of placental weight at mid-gestation (placental growth in the second trimester correlates strongly with placental weight at birth), assessment of fetal and placental circulation (an association between perinatal morbidity and abnormal blood velocity profiles has been established) and assessment of placental metabolism and nutritional transfer (a reduction in transfer of nutrients may be an early indicator of IUGR.

Female↗

Association between the activity of the system A amino acid transporter in the microvillous plasma membrane of the human placenta and severity of fetal compromise in intrauterine growth restriction.

Primarily, our objectives were to compare system A amino acid transporter activity in the microvillous plasma membrane (MVM) of placentas from normally grown (appropriate for gestational age, AGA) and intrauterine growth-restricted (IUGR) fetuses delivered during the third trimester, as a whole and in relation to the severity of IUGR. Ten AGA and 16 IUGR pregnancies were studied at the time of elective cesarean section performed between 28 and 40 wk of gestation. Severity of IUGR pregnancies was assessed primarily by Doppler velocimetry and fetal heart rate monitoring. Placental MVM vesicles were prepared, and system A activity in these was measured. The transporter activity was significantly lower in IUGR compared with AGA pregnancies. Within the IUGR group system A activity was only significantly lower, compared with AGA, in cases that presented with a reduction in umbilical blood flow. We conclude that placental MVM system A activity is lower in IUGR compared with AGA pregnancies delivered during the third trimester. System A activity is related to the severity of IUGR.

Alkaline Phosphatase↗

Maternal concentrations and fetal-maternal concentration differences of plasma amino acids in normal and intrauterine growth-restricted pregnancies.

OBJECTIVES: Our purpose was to determine whether maternal amino acid concentration changes during gestation in pregnancies with intrauterine growth restriction as in normal pregnancies and to verify whether these changes are related to changes in fetal-maternal differences. STUDY DESIGN: Amino acid concentrations were measured in 5 nonpregnant women, in 11 second-trimester and 10 third-trimester pregnant women with appropriate-for-gestational-age fetuses, and in 23 pregnant women with intrauterine growth restriction. Umbilical venous amino acids were measured at the time of fetal blood sampling. The severity of intrauterine growth restriction was assessed by Doppler velocimetry and fetal heart rate and by evaluation of oxygenation and acid-base balance. RESULTS: In normal pregnant women the maternal concentration of most amino acids was significantly lower in both the second and third trimesters compared with nonpregnant women. In intrauterine growth restriction the maternal concentrations of most essential amino acids were significantly higher than in appropriate-for-gestational-age pregnancies. This observation, coupled with lower fetal amino acid concentrations in intrauterine growth restriction, leads to significantly lower fetal-maternal differences. CONCLUSIONS: Normal pregnant women have a significant decrease in amino acid concentrations compared with nonpregnant women, whereas in intrauterine growth restriction maternal amino acids are reduced less, Significantly lower fetal-maternal concentration differences are present in intrauterine growth restriction, independent of the degree of severity.

Adult↗

In vivo placental transport of glycine and leucine in human pregnancies.

L-[1-13C]Glycine and L-[1-13C]leucine were infused as a bolus into 12 pregnant patients carrying normal fetuses before fetal blood sampling at gestational ages ranging from 20 to 37 wk. Maternal venous samples were obtained every 2-3 min for 15 min after the bolus infusion. Fetal samples were obtained from the umbilical vein within 15 min of the bolus. Amino acid plasma enrichments (molar percent enrichment) were determined by gas chromatography-mass spectroscopy and their concentrations by ion exchange chromatography. The ratios of glycine and leucine transfer were assessed from fetal/maternal enrichment ratios for each amino acid. We now report that over the gestational age range of 20-37 wk, under relatively undisturbed fetomaternal conditions (fetal blood sampling), human placental glycine transfer is limited, with a glycine/leucine ratio = 0.16 +/- 0.02. We hypothesize that, in human pregnancies, the relative rates of in vivo transplancental transport of amino acids can be assessed indirectly utilizing fetal blood sampling and stable isotope methodology. The application of this approach to leucine and glycine demonstrates that the transfer of leucine is rapid (demonstrable in seconds), whereas that of glycine is more limited.

Adult↗

Total knee arthroplasty complicated by Corynebacterium jeikeium infection.

Corynebacterium jeikeium is a slow-growing multiresistant micro-organism. It causes serious opportunistic infections in patients with long hospital stays who receive broad-spectrum antibiotics. It can be isolated from blood and other sites in neutropenic, immunosuppressed bone marrow recipients and in patients with indwelling catheters. Cases of infection related to bone and joint replacements are rare. This case is the first where Corynebacterium jeikeium has been isolated from an infected knee following total knee arthroplasty.

Aged↗

Fetal blood sampling during pregnancy: risks and diagnostic advantages.

A review is provided on the use of fetal blood sampling during pregnancy. Informations on the technique, its indications, risks and benefits are provided. In addition, the application of fetal blood sampling in cases of intrauterine growth retardation as well as some metabolic features of intrauterine life are discussed.

Blood Specimen Collection↗

Diagnostic value of blood sampling in fetuses with growth retardation.

BACKGROUND: Fetuses with intrauterine growth retardation are delivered if they have evidence of distress, as manifested by abnormalities in the fetal heart rate and umbilical-artery blood flow. We studied whether umbilical-blood sampling might provide further information useful for management. METHODS: We measured hemoglobin and lactate concentrations, oxygen content, pH, blood gas levels, and base deficit in umbilical-vein blood and correlated these measurements with the heart rate and umbilical-artery wave forms recorded by Doppler velocimetry in 56 fetuses with growth retardation. Twenty-one fetuses had normal heart rates and normal results of velocimetry, 24 had normal heart rates and abnormal results of velocimetry (indicative of decreased diastolic flow), and 11 had abnormal heart rates and abnormal results of velocimetry. RESULTS: None of the 21 fetuses with normal heart rates and velocimetry had hypoxia or acidemia. Of the 24 fetuses with normal heart rates and abnormal velocimetry, 4 (17 percent) had moderate lactic acidosis, 1 (4 percent) had a low pH value, and 3 (12 percent) had hypoxia. Of the 11 fetuses with abnormal heart rates and velocimetry, 7 (64 percent) had lactic acidosis, low blood oxygen content, and low pH values. The absence of end-diastolic flow increased the risk of hypoxia and acidemia. The proportion of fetuses with elevated hemoglobin concentrations was similar among the three groups. CONCLUSIONS: Assessment of fetal oxygenation and acid-base balance is not indicated in fetuses with growth retardation if their heart rates and the results of velocimetry are normal. If the results of velocimetry are abnormal, fetal-blood sampling can distinguish fetuses that have growth retardation alone from those that also have hypoxia and acidosis, and thus may aid in determining the optimal time of delivery.

Acidosis↗

An evaluation of fetal glucogenesis in intrauterine growth-retarded pregnancies.

The presence of fetal glucogenesis was evaluated in nine patients with pregnancies complicated by intrauterine growth retardation (IUGR) at the time of fetal blood sampling (FBS) between 29 and 35 weeks of pregnancy. Eight were singleton pregnancies and one was a twin pregnancy in which blood samples were obtained from both twins. A maternal primed-constant infusion of D(U-13C]glucose was performed, and the presence of fetal glucogenesis was assessed by a comparison of steady-state maternal and fetal glucose enrichments. No significant difference was present between maternal and fetal molar percent excess ([MPE] P = .97), and the mean fetal to maternal (F/M) MPE ratio (0.99 +/- 0.01) was not significantly different from 1 (P = .76). F/M MPE ratio was independent of the time of FBS and umbilical venous glucose and lactate concentrations. Thus fetal glucogenesis is not demonstrable in a group of fairly severe growth-retarded fetuses after an overnight fast with this relatively noninvasive approach.

Adult↗